Participants must have pathologically confirmed, newly diagnosed high-risk acute myeloid leukemia, as defined by at least one of the following criteria:\r\n* Age >=  years\r\n* Age >=  years with adverse risk karyotype, as per European Leukemia Net Guidelines\r\n* Age >=  years with antecedent or underlying myelodysplastic syndrome, chronic myelomonocytic leukemia (CMML) or myeloproliferative neoplasm\r\n* Age >= years with acute myeloid leukemia (AML) with myelodysplastic syndrome (MDS)-related changes\r\n** Note: For patients in category A, a sample to evaluate patient cytogenetics will be sent at the time of diagnosis per standard clinical care and the absence of favorable risk cytogenetics must be confirmed by day ; if the cytogenetic analysis reveals that the patient harbors favorable risk cytogenetics, or if the cytogenetic results are not received prior to day , the participant will be removed from the study; patients removed due to presence of favorable cytogenetics would be considered to be inevaluable and will be replaced; in addition, patients who receive less than half of their total alisertib dose during induction would be considered to be inevaluable and will be replaced
Complete first remission (CR) at high risk for relapse
Complete first remission (CR) at high risk for relapse
Acute lymphoblastic leukemia (B- or T-acute lymphoblastic leukemia [ALL])\r\n* Complete response (CR)-ultra high risk features\r\n** Unfavorable cytogenetics\r\n** Hypodiploidy\r\n** Induction failure\r\n** Minimal residual disease (MRD) positive after consolidation\r\n* CR\r\n** Any of the high risk features listed in CR\r\n** B-ALL: any relapse considered eligible for transplant \r\n** T-ALL\r\n* CR -any
Acute Lymphoblastic Leukemia (ALL) in first complete remission (CR) that is NOT considered favorable-risk as defined by the presence of at least one of the following: Adverse cytogenetics such as t(;), t(;), t(;), other Mixed Lineage Leukemia (MLL) rearrangements; White blood cell counts of greater than ,/mcL (B-ALL) or greater than ,/mcL (T-ALL)at diagnosis; Recipient age older than  years at diagnosis; Time to CR greater than  weeks
Acute Myelogeneous Leukemia (AML) in CR that is NOT considered as favorable-risk. Favorable risk is defined as having one of the following: t(.) without CKIT mutation, inv() without CKIT mutation or t(;), normal karyotype with mutated NPM and not FLT-ITD, normal karyotype with double mutated CEBPA, Acute promyelocytic leukemia (APL) in first molecular remission at end of consolidation
Subjects must have histologically documented acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), myelodysplastic syndrome (MDS), myeloproliferative disorders (MPD), chronic myeloid leukemia (CML), non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL) or multiple myeloma (MM) as follows:\r\n* Acute myeloid leukemia (AML) with one or more of the following criteria:\r\n** Poor risk cytogenetics, including -, q-, -, q-, t(;); complex cytogenetics (>=  abnormalities); or normal cytogenetics with Fms-like tyrosine kinase  (Flt) internal tandem duplications (ITD), in first or subsequent complete remission (CR)\r\n** Relapsed or primary refractory AML with =< % blasts in the peripheral blood\r\n** Subjects in CR who required two cycles of induction to achieve remission may be included at the discretion of the treating physician\r\n** Standard risk or intermediate risk cytogenetics in second or subsequent CR (enrolled at the discretion of the treating physician)\r\n* Acute lymphoblastic leukemia (ALL) with one of the following criteria:\r\n** Second or subsequent CR\r\n** Any partial remission (PR) (no circulating blasts)\r\n** High-risk ALL in first CR including (Philadelphia chromosome positive [Ph+], t(:)), complex karyotype, hypodiploidy (<  chromosomes), positive minimal residual disease (MRD) after induction, and other high risk features in adults per treating physician\r\n* Myelodysplasia, intermediate- (score .-.) or high risk (score > .) by the International Prognostic Score System\r\n* Myeloproliferative disorders (include chronic myelomonocytic leukemia [CMML], agnogenic myeloid metaplasia [AMM] or idiopathic myelofibrosis, and juvenile myelomonocytic leukemia [JMML]) with excess blasts (> %)\r\n* Chronic myeloid leukemia (CML) with one of the following criteria:\r\n** Second or subsequent chronic phase\r\n** Accelerated phase\r\n** Blast crisis\r\n* Non-Hodgkin's lymphoma (NHL) meeting one of the following criteria:\r\n** Relapse after autologous stem cell transplantation with evidence of responsive disease\r\n** Subject with chemosensitive relapse who have no option for autologous stem cell transplantation due to blood or marrow involvement or failure to mobilize autologous stem cells or are not considered eligible for autologous transplant by their treating physician\r\n* Hodgkins lymphoma: relapse after autologous hematopoietic cell transplant (HCT), chemorefractory disease\r\n* Multiple myeloma: per National Comprehensive Cancer Network (NCCN) guidelines
Acute myeloid leukemia, including biphenotypic acute leukemia or mixed-lineage leukemia:\r\n* All patients must be in CR as defined by hematologic recovery and < % blasts by morphology/flow cytometry in a representative bone marrow sample with cellularity >= % for age; patients who do not have high-risk features (for example preceding myelodysplastic syndrome [MDS], high-risk cytogenetics, >=  cycles to obtain CR, erythroblastic or megakaryocytic leukemia or >= CR) must be discussed with the principal investigator (PI) prior to enrollment and at the Patient Care Conference or equivalent group such as the pediatric leukemia board as an alternative\r\n* Patients in whom adequate marrow/biopsy specimens cannot be obtained to determine remission status by morphologic assessment, but have fulfilled criteria of remission by flow cytometry, recovery of peripheral blood counts with no circulating blasts, and/or normal cytogenetics (if applicable) may still be eligible; reasonable attempts must be made to obtain an adequate specimen for morphologic assessment, including possible repeat procedures; these patients must be discussed with the PI prior to enrollment; patients persistently aplastic for greater than one month since completing last chemotherapy are also eligible with PI approval
Acute lymphoblastic leukemia, including biphenotypic acute leukemia or mixed-lineage leukemia:\r\n* All patients must be in CR as defined by < % blasts by morphology; flow cytometry in a representative bone marrow sample with cellularity >= % for age; patients who do not have high-risk disease (high risk CR, greater than one cycle to obtain CR or >= CR) must be discussed with the PI prior to enrollment and at the Patient Care Conference or equivalent group such as the pediatric leukemia board as an alternative\r\n* Patients in whom adequate marrow/biopsy specimens cannot be obtained to determine remission status by morphologic assessment, but have fulfilled criteria of remission by flow cytometry, recovery of peripheral blood counts with no circulating blasts, and/or normal cytogenetics (if applicable) may still be eligible; reasonable attempts must be made to obtain an adequate specimen for morphologic assessment, including possible repeat procedures; these patients must be discussed with the principal investigator Ann Dahlberg prior to enrollment; patients persistently aplastic for greater than one month since completing last chemotherapy are also eligible with PI approval
Patients with one of the high risk myeloid diseases as outlined below. Patients must have less than % blasts on the last bone marrow (BM) evaluation prior to starting the conditioning regimen. Diseases included on this protocol include:\r\n* Acute myeloid leukemia (AML) in first complete remission (CR) with intermediate or high risk features as defined below:\r\n** Cytogenetic abnormalities which are not considered good risk cytogenetic features (i.e t(:), t(:), inv  without c-kit mutations. And/or\r\n** Therapy related AML with history of antineoplastic therapy (radiation and/or chemotherapy) And/or\r\n** Normal karyotype with mutations of FLT, RUNX, TP mutation, ASXL or any others that are considered to be high risk\r\n* AML in >= nd remission\r\n* Myelodysplastic syndrome, myeloproliferative neoplasms, or MDS/myeloproliferative neoplasms (MPN) overlap syndrome with:\r\n** International prognostic scoring system risk score intermediate- (INT-) or high risk at the time of transplant evaluation. And/or\r\n** Any risk category if life-threatening cytopenia exists And/or\r\n** Karyotype or genomic changes that indicate high risk for progression to acute myelogenous leukemia, including abnormalities of chromosome  or , mutations of TP, or complex or monosomal karyotype.\r\n* Chronic myelomonocytic leukemia (CMML): CMML- or CMML-.\r\n* Chronic myeloid leukemia (CML) with the following features:\r\n** Patients who have failed or are intolerant to BCR-ABL tyrosine kinase inhibitors. And/or\r\n** CML with BCR-ABL mutation consistent with poor response to tyrosine kinase inhibition (e.g Tl mutation)\r\n* Patients with severe aplastic anemia.
For ALL: patients must belong to one of the following high risk categories: \r\n* Primary refractory as defined by failure to achieve CR after induction and at least one salvage therapy \r\n* Second or subsequent relapse \r\n* Relapse after allogeneic or autologous stem cell transplantation (requirement for second relapse does not apply post-transplant) \r\n* All variants of ALL including T-ALL, B / myeloid, lymphoblastic leukemia lymphoma are eligible
Eligible patients with a histopathological confirmed diagnosis of hematologic malignancy in one of the following categories:\r\n* Acute myelogenous leukemia:\r\n** Patients with de novo or secondary disease in unfavorable risk group including poor risk cytogenetics according to National Comprehensive Cancer Network (NCCN) guidelines for acute myelogenous leukemia (AML) i.e., monosomal karyotype, -, q-, -, q-, q-non t (;), inv (), t (;), t (;), t (;) and complex karyotypes (>=  unrelated abnormalities), or all patient in intermediate risk groups accept patients with FLT-NPM+ disease\r\n** Patients with active disease\r\n** Patients with chemosensitive active disease\r\n* Acute lymphocytic leukemia:\r\n** Patients with de novo or secondary disease according to NCCN guidelines for acute lymphocytic leukemia (ALL) hypoploidy (<  chromosomes); t (v;q): MLL rearranged; t (;) (q;q.); complex cytogenetics ( or more chromosomal abnormalities); high white blood cell (WBC) at diagnosis (>= , for B lineage or >= , for T lineage); iAMPloss of q, and abnormal p\r\n** Patients with active disease\r\n** Patients with chemosensitive active disease\r\n* Myelodysplastic syndrome in high-intermediate (int-) and high risk categories
Patients with B-lineage ALL in hematologic complete remission (CR) with molecular failure (ie, had never achieved an MRD-negativity status before inotuzumab ozogamicin) or had a molecular relapse (i.e., became MRD positive after having been MRD negative) starting at any time point after  months of frontline therapy. Molecular disease or minimal residual disease is defined by a value of at least of ^- by multicolor flow cytometry
Acute myelogenous leukemia (AML):\r\n* Complete first remission (CR) at high risk for relapse such as any of the following:\r\n** Known prior diagnosis of myelodysplasia (MDS) or myeloproliferative disorder.\r\n** Therapy-related AML.\r\n** White cell count at presentation > ,.\r\n** Presence of extramedullary leukemia at diagnosis.\r\n** Any unfavorable subtype by French-American-British (FAB) or World Health Organization (WHO) classification.\r\n** High-risk cytogenetics (e.g. those associated with MDS, abnormalities of , , , complex karyotype) or high risk molecular abnormalities.\r\n** Requirement for  or more inductions to achieve CR.\r\n** Any patient with newly diagnosed AML with intermediate risk cytogenetics who elects allograft with curative intent over consolidation chemotherapy.\r\n** Any patient unable to tolerate consolidation chemotherapy as would have been deemed\r\nappropriate by the treating physician.\r\n** Other high risk features not defined above.\r\n* Complete second remission (CR).\r\n* Primary refractory or relapsed AML with less than % blasts before transplant. Persistent/relapsed AML with cytogenetic, flow cytometric, or molecular aberrations in >= % of cells are eligible.
Acute lymphoblastic leukemia (ALL):\r\n* Complete first remission (CR) at high risk for relapse such as any of the following:\r\n** White cell count at presentation > , for B-cell lineage and > , for T-cell lineage.\r\n** Presence of any high-risk cytogenetic abnormalities such as t(;), t(;), t(;) or other MLL rearrangements (q) or other high-risk molecular abnormality.\r\n** Failure to achieve complete remission after four weeks of induction therapy.\r\n** Persistence or recurrence of minimal residual disease on therapy.\r\n** Any patient with newly diagnosed ALL >=  years-old.\r\n** Any patient unable to tolerate consolidation and/or maintenance chemotherapy as would have been deemed appropriate by the treating physician.\r\n** Other high risk features not defined above.\r\n* Complete second remission (CR).\r\n* Primary refractory or relapsed ALL with less than % blasts before transplant. Persistent/relapsed ALL with cytogenetic, flow cytometric or molecular aberrations in >= % of cells are eligible.
Patients with the following hematologic malignancies:\r\n* Acute myelogenous leukemia (AML): High-risk AML including:\r\n** Antecedent hematological disease (e.g., myelodysplasia [MDS])\r\n** Treatment-related leukemia\r\n** Complete remission (CR) with poor-risk cytogenetics or molecular markers (e.g. Flt  mutation, q, del , del , complex cytogenetics)\r\n** CR or CR\r\n** Induction failure or st relapse with =< % blasts in the marrow\r\n* Acute lymphoblastic leukemia (ALL)\r\n** High-risk CR including:\r\n*** Poor-risk cytogenetics (e.g., Philadelphia chromosome t(;) or q rearrangements)\r\n*** Presence of minimal disease by flow cytometry after  or more cycles of chemotherapy\r\n** No CR within  weeks of initial treatment\r\n** Induction failure with =< % blasts in the marrow\r\n** CR or CR\r\n* Myelodysplastic syndromes (MDS), intermediate, high or very high risk by the revised international prognostic scoring system (IPSS-R)\r\n* Chronic myelogenous leukemia (CML) in second chronic phase after accelerated or blast crisis\r\n* Myelofibrosis (MF):\r\n** Intermediate- or high risk by Dynamic International Prognostic Scoring System (DIPSS)-plus OR\r\n** Monosomal karyotype OR\r\n** Presence of inv()/i(q) abnormalities OR\r\n** Other unfavorable karyotype OR leukocytes >=  x ()/L AND\r\n** Circulating blasts =< %\r\n* Relapsed or refractory lymphoid malignancies (including non-Hodgkin lymphoma, Hodgkin lymphoma) meeting the following criteria:\r\n** Disease status: Stable disease, partial remission or nd and rd complete remission\r\n** Have relapsed after autologous transplant or who have failed to collect for an autologous transplant
The patient must have a diagnosis of one of the following (one must be yes):\r\n* Bone marrow failure disorders:\r\n** Acquired bone marrow failure disorders include aplastic anemia, paroxysmal nocturnal hemoglobinuria (PNH):\r\n*** SAA must have failed at least one cycle of standard immunosuppressive therapy with calcineurin inhibitor plus anti-thymocyte globulin (ATG)\r\n*** PNH must have failed treatment or not tolerated treatment with eculizumab or progressed during or after treatment with eculizumab\r\n** Hereditary bone marrow failure disorders include Diamond-Blackfan anemia, Shwachman-Diamond syndrome, Kostmann syndrome, and congenital amegakaryocytic thrombocytopenia\r\n* Other non-malignant hematologic or immunologic disorders that require transplantation:\r\n** Quantitative or qualitative congenital platelet disorders (including but not limited to congenital amegakaryocytopenia, absent-radii syndrome, Glanzmanns thrombasthenia)\r\n** Quantitative or qualitative congenital neutrophil disorders (including but not limited to chronic granulomatous disease, congenital neutropenia)\r\n** Congenital primary immunodeficiencies (including but not limited to severe combined immunodeficiency syndrome, Wiskott-Aldrich syndrome, CD ligand deficiency, T-cell deficiencies)\r\n** Hemoglobinopathies (including sickle cell disease and thalassemia)\r\n* Acute leukemias:\r\n** Acute myeloid leukemia (AML) - antecedent myelodysplastic syndrome, secondary\r\nAML, intermediate cytogenetics, high risk cytogenetic abnormalities or normal cytogenetics with high-risk\r\nmolecular mutations (including but not limiting to Flt-ITD mutation), or other high risk features as per clinical judgment of the study principal investigator (PI) (or in the absence of the study PI, another equally qualified clinician)\r\n** Acute lymphoblastic leukemia (ALL) - B cell or T cell\r\n* Chronic myelocytic leukemia (CML):\r\n** Chronic phase (intolerant or unresponsive to imatinib and/or tyrosine kinase inhibitors)\r\n** Second chronic phase or accelerated phase who are ineligible for conventional myeloablative transplantation\r\n* Myeloproliferative and myelodysplasia syndromes:\r\n** Myelofibrosis (with/without splenectomy) with intermediate to high risk features\r\n** Advanced polycythemia vera not responding to therapy\r\n** Myelodysplastic syndrome (MDS) with an Revised International Prognostic Scoring System (IPSS-R) score of intermediate or higher\r\n** Secondary MDS with any IPSS score\r\n** Chronic myelomonocytic leukemia (CMML)\r\n* Lymphoproliferative disease:\r\n** Chronic lymphocytic leukemia (CLL), low-grade non-Hodgkin lymphoma (NHL) (recurrent or persistent) cytotoxic therapy refractory or with less than  months duration of complete response (CR) between courses of conventional therapy\r\n** Multiple myeloma (MM) progressive disease after auto bone marrow transplantation (BMT), tandem allo after prior auto\r\n** Waldenstroms macroglobulinemia (failed one standard regimen)\r\n** T or B cell lymphoma with poor risk features\r\n** Hodgkin disease:\r\n*** Received and failed frontline therapy\r\n*** Failed or not eligible for autologous transplantation
PHASE I: Patients who have/are either:\r\n* Transplanted in hematologic first complete remission with evidence of minimal residual disease within  days of allogeneic transplantation\r\n** Pre- or post-transplant minimal residual disease defined by:\r\n*** Any detectable acute lymphocytic leukemia (ALL) (by flow cytometry, cytogenetics, or polymerase chain reaction [PCR] techniques) as per clinical indication\r\n* In second or third complete remission at the time of allogeneic transplantation\r\n* Treated with reduced intensity regimens\r\n* Lymphoid blast crisis of chronic myelogenous leukemia (CML)\r\n* Are relapsed or refractory to at least  line of chemotherapy
Must have one of the following hematologic malignancies: a. Acute myelogenous leukemia (AML), induction failure, high-risk for relapse first remission (with intermediate-risk or high-risk cytogenetics, flt mutation positive and/or evidence of minimal residual disease by flow cytometry), secondary leukemia from prior chemotherapy and/or arising from myelodysplastic syndrome (MDS), Langerhan's cell histiocytosis, any disease beyond first remission. b. Myelodysplastic syndrome (MDS): MDS International Prognostic Scoring System (IPSS) INT- will be enrolled only if the subjects have failed previous leukemia treatments and are transfusion-dependent. MDS may be primary or therapy related, including patients that will be considered for transplant. Including the following categories: ) Revised IPSS intermediate and high risk groups, ) MDS with transfusion dependency, ) Failure to respond or progression of disease on hypomethylating agents, ) Refractory anemia with excess of blasts, ) Transformation to acute leukemia, ) Chronic myelomonocytic leukemia, ) Atypical MDS/myeloproliferative syndromes, ) Complex karyotype, abn(g), -/g-, -/g-, abn(p), abn(p). c. Acute lymphoblastic leukemia (ALL) patients with the following will be considered: induction failure, primary refractory to treatment (do not achieve complete remission after first course of therapy) or are beyond first remission including second or greater remission or active disease. Patients in first remission are eligible if they are considered high risk, defined as any of the following detected at any time: with translocations ; or ;, hypodiploidy, complex karyotype, secondary leukemia developing after cytotoxic drug exposure, and/or evidence of minimal residual disease, or acute biphenotypic leukemia which excludes >  chromosomal abnormalities, or double hit non-Hodgkin's lymphoma. Non-Hodgkin's lymphoma (NHL) in second or third complete remission or relapse (including relapse post autologous hematopoietic stem cell transplant), or relapsed double hit lymphoma. Small lymphocytic lymphoma (SLL), or chronic lymphocytic leukemia (CLL) with progressive disease with progression after standard of care therapy or have failed/been intolerant to ibrutinib. Chronic myelogenous leukemia (CML) second chronic phase or accelerated phase. Hodgkin's disease (HD): Induction failure after the first complete remission, or relapse (including relapse post autologous hematopoietic stem cell transplant), or those with active disease.
Diagnosed with one of the following high-risk malignancies, which require hematopoietic cell transplant (HCT) but do not have an available human leukocyte antigen (HLA)-matched (/) related or unrelated donor\r\n* High risk acute lymphoblastic leukemia (ALL) in first complete remission (CR) or greater\r\n* High risk acute myelogenous leukemia (AML) in CR or greater\r\n* High risk undifferentiated acute leukemia\r\n* High risk myelodysplastic syndrome (MDS)\r\n* Chronic myelogenous leukemia (CML) failing or intolerant to tyrosine kinase inhibitors (TKIs) or in accelerated, blastic phase, or in second or subsequent chronic phase\r\n* Juvenile myelomonocytic leukemia (JMML)\r\n* Lymphoma, (Hodgkin and non-Hodgkin lymphoma [NHL] including marginal zone, follicular lymphoma, chemotherapy-sensitive large-cell, mantle cell lymphoma, gray zone, and Burkitts lymphoma in remission)
IMMUNE RECONSTITUTION STUDY ONLY: Diagnosed with one of the following high-risk malignancies, which require HCT but do not have an available HLA-matched (/) related or unrelated donor\r\n* High risk acute lymphoblastic leukemia (ALL) in CR or greater\r\n* High risk acute myelogenous leukemia (AML) in CR or greater\r\n* High risk myelodysplastic syndrome (MDS)\r\n* Chronic myelogenous leukemia (CML) failing or intolerant to TKIs or in accelerated, blastic phase, or in second or subsequent chronic phase\r\n* Juvenile myelomonocytic leukemia (JMML)\r\n* Lymphoma, (Hodgkin and NHL including marginal zone, follicular lymphoma, chemotherapy-sensitive large-cell, mantle cell lymphoma, gray zone, and Burkitt's lymphoma in remission
Acute myeloid leukemia (AML): second or greater complete remission (CR); first CR (CR) in patients >=  years old; CR in <  years old that is NOT considered as favorable risk\r\n* Favorable risk AML is defined as having one of the following:\r\n* t(,) without cKIT mutation\r\n* inv() or t(;) without cKIT mutation\r\n* Normal karyotype with mutated NPM but FLT-ITD wild type\r\n* Normal karyotype with double mutated CEBPA\r\n* Acute prolymphocytic leukemia (APL) in first molecular remission at the end of consolidation
Acute lymphoblastic leukemia (ALL)/lymphoma: second or greater CR; CR unable to tolerate consolidation chemotherapy due to chemotherapy-related toxicities; CR high-risk ALL; high risk ALL is defined as having one of the following:\r\n* Evidence of high risk cytogenetics, e.g. t(;), t(;), t(;), other MLL rearrangements, IKZF\r\n* Recipient age  years and older at diagnosis\r\n* White blood cell counts of greater than ,/mcL (B-ALL) or greater than ,/mcL (T-ALL) at diagnosis\r\n* Central nervous system (CNS) leukemia involvement during the course of disease \r\n* Slow cytologic response (> % lymphoblasts in bone marrow on day  of induction therapy)\r\n* Evidence of persistent immunophenotypic or molecular minimal residual disease (MRD) at the end of induction and consolidation therapy
Patients with high risk myeloid or lymphoid malignancies prior to stem cell transplant with increased risk of disease relapse after stem cell transplant, including but not limited to conditions listed below\r\n* Refractory acute myelogenous or lymphoid leukemia\r\n* Relapsed acute myelogenous or lymphoid leukemia\r\n* Myelodysplastic syndromes with % or more blasts or with residual dysplastic changes prior to stem cell transplant, or with poor risk cytogenetic changes, such as -, - or complex karyotype, or with poor molecular mutations, especially p mutation\r\n* Chronic myelogenous leukemia in chronic phase  or more, blast phase presently, or second accelerated phase\r\n* Recurrent or refractory malignant lymphoma or Hodgkins disease with high risk relapse features or not in complete remission\r\n* High risk chronic lymphocytic leukemia not in complete remission or with high risk relapse features, such as p mutation, or p deletion et al.\r\n* Acute leukemia (including AML, ALL) with minimal residual disease determined by accepted methods, including multiple color flow cytometry; next generation sequencing (NGS) or molecular testing\r\n* Acute leukemia with poor risk cytogenetic changes
Acute lymphocytic leukemia (ALL) in complete remission (CR) with high-risk features including adverse cytogenetic such as t(;), t(;), t(;), or MLL gene rearrangements; in second or greater morphologic remission; persistent minimal residual disease
Acute myeloid leukemia (AML) in CR with intermediate-risk disease and persistent detectable minimal residual disease (MRD), or with high-risk features defined as: greater than  cycle of induction therapy required to achieve remission; preceding myelodysplastic syndrome (MDS) or myeloproliferative disease; presence of FLT mutations or internal tandem duplications, DNMTa, TET, MLL-partial tandem duplication (PTD), ASXL, PHF; FAB M or M classification; adverse cytogenetics including: -, del q, -, delq, abnormalities involving q, q, q, q, q, , +, complex [>  abnormalities]
Acute lymphoid leukemia (ALL) in first complete remission (CR) with high risk for relapse including:\r\n* t(;) or detected BCR-ABL translocation by genomic methodologies\r\n* BCR-ABL-Like B-ALL including mutations of IKZF or CRLF\r\n* Translocations or mutations involving q (MLL) gene\r\n* Hypodiploid karyotype\r\n* Deletion of p\r\n* Loss of p or TP mutation\r\n* T-lymphocyte lineage antigen expression (T-ALL)\r\n* Central nervous system (CNS) or other extramedullary involvement\r\n* White blood cell (WBC) count >= , cells/uL at diagnosis
Acute myeloid leukemia (AML) in CR with intermediate or high risk features including:\r\n* Cytogenetic abnormalities associated with myelodysplastic syndrome including abnormalities of chromosome  or \r\n* History of anti-neoplastic therapy (radiation or chemotherapy)\r\n* Extramedullary involvement\r\n* WBC count >= , cells/uL at diagnosis\r\n* Rearrangements or mutations of q (MLL)\r\n* Abnormalities of chromosome \r\n* TP mutation or loss of p\r\n* Complex or monosomal karyotype \r\n* Normal karyotype with mutations of FLT, RUNX, or ASXL
Has previously untreated, de novo, non-M acute myeloid leukemia (AML) with intermediate-risk disease (intermediate-I or intermediate-II) as defined by ELN criteria OR normal cytogenetics (after analysis of  or more metaphases) with mutated nucleophosmin (NPM) without FMS-related tyrosine kinase -internal tandem duplication (FLT-ITD); monoallelic CEBPA mutations are not considered favorable risk and are therefore eligible
Patients must have one of the following hematologic malignancies: acute myelogenous leukemia (AML), induction failure, high-risk for relapse first remission (with intermediate-risk or high-risk cytogenetics including complex karyotype, abnormal [abn][q], -/q-, -/q-, abn[p], abn[p], myeloid/lymphoid or mixed-lineage leukemia [MLL] gene re-arrangement and t [;], fms related tyrosine kinase  [flt] mutation positive and/or evidence of minimal residual disease by flow cytometry), secondary leukemia from prior chemotherapy and/or arising from myelodysplastic syndromes (MDS), any disease beyond first remission
Acute lymphoblastic leukemia (ALL): Induction failure, primary refractory to treatment (do not achieve complete remission after first course of therapy) or are beyond first remission including second or greater remission or active disease; patients in first remission are eligible if they are considered high risk, defined as any of the following detected at any time: with translocations ; or ;, hypodiploidy, complex karyotype, secondary leukemia developing after cytotoxic drug exposure, and/or evidence of minimal residual disease or acute biphenotypic leukemia, or double hit non-Hodgkin's lymphoma
Acute myeloid leukemia (AML) and related precursor neoplasms: nd or greater complete remission (CR); first complete remission (CR) in patients >  years old; CR in =<  years old that is NOT considered as favorable-risk; favorable risk AML is defined as having one of the following:\r\n* t(,) without cKIT mutation\r\n* inv() or t(;) without cKIT mutation \r\n* Normal karyotype with mutated NPM and wild type FLT-ITD\r\n* Normal karyotype with double mutated CEBPA\r\n* Acute prolymphocytic leukemia (APL) in first molecular remission at the end of consolidation
Acute lymphoblastic leukemia (ALL)/lymphoma: second or greater CR; CR unable to tolerate consolidation chemotherapy due to chemotherapy-related toxicities; CR high-risk ALL; high risk ALL is defined as having one of the following:\r\n* Evidence of high risk cytogenetics, e.g. t(;), t(;), t(;), other MLL rearrangements, IKZF\r\n*  years of age or older at diagnosis\r\n* White blood cell counts of greater than ,/mcL (B cell [B]-ALL) or greater than ,/mcL (T cell [T]-ALL) at diagnosis\r\n* Central nervous system (CNS) leukemia involvement during the course of disease\r\n* Slow cytologic response (> % lymphoblasts in bone marrow on day  of induction therapy)\r\n* Evidence of persistent immunophenotypic or molecular minimal residual disease (MRD) at the end of induction and consolidation therapy
Cohort : High risk AML and MDS patients who are in complete remission morphologically with no evidence of minimal residual disease by flow cytometry or cytogenetic or molecular testing after allogeneic stem cell transplantation
Acute myeloid leukemia: High risk first complete remission (CR) (as evidenced by preceding myelodysplasia [MDS], high risk cytogenetics, >=  cycles to obtain CR, erythroblastic or megakaryocytic leukemia, FLT- ITD +; second or higher complete response [CR+]); all patients must be in CR as defined by hematological recovery, AND < % blasts by light microscopy within the bone marrow with a cellularity of >= %
High risk for relapse defined as: st CR with high risk features for relapse (including history of prior malignancy treated with chemotherapy or radiotherapy, or history of myelodysplastic syndrome, myeloproliferative disorder, chronic myelomonocytic leukemia, myelodysplastic syndrome [MDS]/myeloproliferative neoplasm [MPN] or other hematologic malignancy thought to have evolved to AML [i.e., secondary AML, (sAML)]; high risk cytogenetics at diagnosis; fms-related tyrosine kinase  [FLT] mutated at diagnosis; or presence or minimal residual disease assessed by polymerase chain reaction [PCR], cytogenetics, and/or flow cytometry at time of enrollment) nd CR regardless of disease characteristics at the time of diagnosis
Patients with B-lineage acute lymphocytic leukemia (ALL) in hematologic complete remission (CR) with molecular failure (ie, had never achieved an MRD-negativity status before blinatumomab) or had a molecular relapse (ie, became MRD positive after having been MRD negative) starting at any time point after  months of frontline therapy; molecular disease or minimal residual disease is defined by a value of at least of  x ^- by multicolor flow cytometry
Patients likely to have a significantly better durable response to allogeneic transplant alone (better than % progression free longer than  years) includes: those with myeloproliferative diseases or hemoglobinopathies with over % T cell subset engraftment (assessed around  days post transplant); it is not anticipated that any such patients would be transplanted within our program, however but those in first remission acute myeloid leukemia (AML) patients with good risk standard genetics or normal genetics with either nucleophosmin (NPM) or CCAAT/enhancer binding protein alpha (CEBPA) mutations, first chronic phase chronic myelogenous leukemia (CML) without kinase gene mutations, follicular lymphoma patients in first remission who only required  regimen to attain remission all would be excluded from this protocol
Eligible patients will have a histopathologically confirmed diagnosis of hematologic malignancy in one of the following categories: \r\n* Acute myelogenous leukemia \r\n** In first complete remission (CR) with poor risk cytogenetics according to National Comprehensive Cancer Network (NCCN) guidelines for acute myeloid leukemia (AML): monosomal karyotype, -, q-,-,q-,q-non t(;), inv (), t(;), t(;), t(;) and complex karyotypes (>=  unrelated abnormalities [abn]) and normal cytogenetics with fms-related tyrosine kinase  (FLT)-internal tandem duplications (ITD) mutation \r\n** In second complete remission (CR) or third complete remission (CR) \r\n** With chemosensitive primary refractory disease \r\n* Acute lymphocytic leukemia \r\n** In CR with poor risk cytogenetics: \r\n*** For adults according to NCCN guidelines for acute lymphoblastic leukemia (ALL): hypoploidy (<  chromosomes); t(v;q): mixed lineage leukemia (MLL) rearranged; t(;) (q;q.); complex cytogenetics ( or more chromosomal abnormalities); high white blood cell (WBC) at diagnosis (>= , for B lineage or >= , for T lineage) \r\n*** For pediatrics t(;), intrachromosomal amplification of chromosome  (iAMP)loss of q, and abnormal p \r\n** In CR or CR \r\n** With chemosensitive primary refractory disease \r\n* Myelodysplastic syndrome in high-intermediate (int-) and high risk categories
Patients with neoplastic hematological disorders with indication of allogeneic transplant according to the National Comprehensive Cancer Network (NCCN) or other standard guidelines as follows:\r\n* Acute lymphoblastic leukemia (ALL) with high-risk features or relapsed disease.\r\n* Hodgkin or non-Hodgkin lymphoma (HL or NHL): relapsed disease where remission duration is less than  year, relapse after previous autologous transplant, or failure to achieve complete remission (CR) with chemotherapy\r\n* Myeloid malignancy (acute myeloid leukemia [AML] with intermediate/high-risk features [per NCCN criteria] or relapsed disease, OR chronic myeloid leukemia [CML] in hematological remission or chronic phase)
Acute myelogenous leukemia (AML): high-risk AML including:\r\n* Antecedent hematological disease (e.g., myelodysplasia [MDS])\r\n* Treatment-related leukemia\r\n* Complete remission (first complete remission [CR]) with poor-risk cytogenetics or molecular markers (e.g. fms-related tyrosine kinase  [Flt ] mutation, q, del , del , complex cytogenetics)\r\n* Second complete remission (CR) or third complete remission (CR) or induction failure or st relapse with either\r\n** =< % blasts in the marrow or \r\n** =< % blasts in the peripheral blood
Subjects must meet one of the disease classifications listed below:\r\n* Acute leukemias (includes T lymphoblastic lymphoma); remission is defined as < % blasts with no morphological characteristics of acute leukemia (e.g., Auer Rods) in a bone marrow with > % cellularity, peripheral blood counts showing absolute neutrophil count (ANC) > /ul, including patients in complete remission with incomplete platelet recovery (CRp)  \r\n** Acute lymphoblastic leukemia in high risk first complete remission (CR) as defined by at least one of the following: \r\n*** Adverse cytogenetics such as t(;), t(;), t(;), mixed lineage leukemia (MLL) rearrangements \r\n*** White blood cell counts > ,/mcL\r\n*** Patients over  years of age\r\n*** Time to complete remission >  weeks\r\n*** Presence of extramedullary disease\r\n** Acute myelogenous leukemia in high risk CR as defined by at least one of the following: \r\n*** Greater than  cycle of induction therapy required to achieve remission \r\n*** Preceding myelodysplastic syndrome (MDS) \r\n*** Presence of Fms-like tyrosine kinase  (Flt) abnormalities\r\n*** French-American-British classification (FAB) M or M leukemia or\r\n*** Adverse cytogenetics for overall survival such as:\r\n**** Those associated with MDS \r\n**** Complex karyotype (>=  abnormalities)\r\n**** Any of the following: inv() or t(;), t(;), t(;), +  [alone or with other abnormalities except for t(;), t(;), inv() or t(;)], t(;)(q;p.)\r\n** Acute leukemias in nd or subsequent remission\r\n** Biphenotypic/undifferentiated leukemias in st or subsequent complete remission (CR)\r\n** High-risk MDS status-post cytotoxic chemotherapy\r\n** Myelofibrosis\r\n* Burkitts lymphoma: second or subsequent CR\r\n* Lymphoma\r\n** Chemotherapy-sensitive (complete or partial response) large cell, mantle cell or Hodgkins lymphomas that have failed at least  prior regimen of multi-agent chemotherapy and are ineligible for an autologous transplant or relapsed/progressed after autologous stem cell transplant\r\n** Marginal zone B-cell lymphoma or follicular lymphoma that has progressed after at least two prior therapies (excluding single agent Rituxan) and are ineligible for an autologous transplant or relapsed/progressed after autologous stem cell transplant
Disease Criteria: \r\n* ALL in complete remission (CR) at the time of transplant; remission is defined as less than .% bone marrow lymphoblasts by morphology, as determined by a bone marrow aspirate obtained within  weeks of study registration\r\n* Philadelphia chromosome positive ALL is allowed\r\n* Lymphoid blastic crisis of chronic myelogenous leukemia (CML) will be included (provided that patients achieve CR)
Patients with one of the following diseases: acute myeloid leukemia (AML): a. first complete remission with high-risk features defined as: (i) greater than  cycle of induction therapy required to achieve remission; (ii) preceding myelodysplastic syndrome (MDS); (iii) presence of FLT mutations or internal tandem duplication or other mutations associated with poor-risk AML (e.g. DNMTA, TET); (iv) French-American-British Classification (FAB) M or M classification; (v) adverse cytogenetics: -, deletion (del) q, -, delq, abnormalities involving q, q, q, q, q, , + or complex karyotype (>  abnormalities); (vi) treatment-related AML, or b. second or greater remission; patients beyond second remission have to be in complete remission (CR) at transplant to be eligible, or c. primary induction failure with partial response to therapy who achieve adequate cytoreduction
Acute myeloid leukemia in first remission with any of the following high risk features defined as:\r\n* Adverse cytogenetics: -, deletion (del) q, -, delq, abnormalities involving q, q, q, q, q, , + or complex karyotype (>  abnormalities)\r\n* Preceding myelodysplastic or myeloproliferative syndrome\r\n* Presence of high risk molecular abnormalities including FLT mutations, DNMTA, TET; ras; kit\r\n* FrenchAmericanBritish (FAB) monosomy (M) or M classification\r\n* Treatment related acute myeloid leukemia (AML)\r\n* Residual cytogenetic or molecular abnormalities
High risk hematologic malignancy\r\n* High risk acute lymphoblastic leukemia (ALL) in complete remission  (CR); examples include, but not limited to: t(;), hypodiploid, minimal residual disease (MRD) > % at the end of induction, M or greater marrow at the end of induction, infants with mixed-lineage leukemia (MLL) fusion or t(;)\r\n* ALL in high risk complete remission  (CR); examples include, but not limited to t(;), bone marrow (BM) relapse <  months CR, T-ALL, very early (<  months CR) isolated central nervous system (CNS) relapse\r\n* ALL in complete remission  (CR) or subsequent\r\n* Acute myeloid leukemia (AML) in high risk CR (diagnosis of AML includes myeloid sarcoma); examples include but not limited to: preceding myelodysplastic syndrome (MDS), q-, -, -, French-American-British Cooperative group (FAB) M, FAB M not t(;), MRD > or = % on day  (AML), MRD > .% after two cycles of induction, M marrow after once cycle of induction, M marrow after two cycles of induction, fms-related tyrosine kinase  (FLT)-internal tandem duplication (ITD)\r\n* AML in CR or subsequent\r\n* AML in relapse with < % blasts in BM\r\n* Therapy related AML, with prior malignancy in CR >  months\r\n* MDS, primary or secondary\r\n* NK cell, biphenotypic, or undifferentiated leukemia in CR or subsequent\r\n* Chronic myeloid leukemia (CML) in accelerated phase, or in chronic phase with persistent molecular positivity or intolerance to tyrosine kinase inhibitor\r\n* Hodgkin lymphoma in CR or subsequent after failure of prior autologous HCT, or unable to mobilize stem cells for autologous HCT\r\n* Non-Hodgkin lymphoma in CR or subsequent after failure of prior autologous HCT, or unable to mobilize stem cells for autologous HCT\r\n* Juvenile myelomonocytic leukemia (JMML)\r\n* One of the following hematologic malignancies that are refractory (includes chemoresistant relapse or primary induction failure)\r\n** ALL\r\n** AML\r\n** CML (blast crisis)\r\n** Hodgkin or non-Hodgkin lymphoma
Patients must have a histologically and cytological confirmed acute myeloid leukemia, high risk AML defined as:\r\n* Age > , or\r\n* Presence of complex cytogenetic abnormalities (with >  cytogenetic abnormalities), del (q, -, -), t(,), q () or high risk mutations by fluorescence in situ hybridization (FISH) eg mixed lineage leukemia (MLL) , FMS-like tyrosine kinase  positive (FLT- +), or\r\n* Secondary AML, or\r\n* A white blood cell count of >  x ^/L\r\n* Failure to achieve complete remission (CR) with single standard induction
By definition, patients with hematological malignancies or dyscrasias that require HSCT as part of cure-directed therapy are by definition high-risk and can be treated on this protocol; examples of high risk patients include but are not limited to: \r\n* Acute myeloid leukemia with high risk features as defined by: \r\n** Age greater than or equal to  \r\n** Secondary acute myeloid leukemia (AML) (prior therapy or hematologic malignancy) \r\n** Normal cytogenetics but fms-related tyrosine kinase  (FLT)/internal tandem duplication (ITD) positive \r\n** Any relapse or primary refractory disease \r\n** Greater than  cytogenetic abnormalities or any one of the following cytogenetic abnormalities: -/del(q), -/del(q), Abn(q), (q), (q), (q), (p), t(;), t(;), t(;), +, del(p), inv(), t(;), -, q  \r\n** Any single autosomal monosomy\r\n* Acute lymphoid leukemia in st or nd morphological remission; ALL with any morphological evidence of disease will not be eligible\r\n* Myelodysplasia (MDS) other than refractory anemia (RA), refractory anemia with rare sideroblasts (RARS), or isolated q- syndrome subtypes\r\n* Hodgkins or Non-Hodgkins lymphoma in nd or greater remission or with persistent disease\r\n* Myeloma with evidence of persistent disease after front-line therapy\r\n* Chronic myeloid leukemia (CML) resistant to signal transducer inhibitor (STI) therapy \r\n* Myelofibrosis and chronic myelomonocytic leukemia (CMML) \r\n* Essential thrombocytopenia or polycythemia vera with current or past evidence of evolution to acute leukemia\r\n* Patients with chronic lymphocytic leukemia (CLL), follicular non-Hodgkin lymphoma (NHL), or other lymphoid malignancies who have highly adverse cytogenetics (such as p deletion), are chemo-insensitive, are not responsive to highly effective novel treatments such as chimeric antigen receptor T-lymphocytes (CART) or Ibrutinib, or who have transformed disease\r\n* Any hematological malignancy not cited above which is thought to be high-risk with increased chance of post HSCT relapse\r\n* Any patient who has an aggressive disease that would normally be treated on a myeloablative study, but is prevented from doing so by factors in their past medical history; examples are patients with previous treatment with radiation therapy precluding TBI, or a past history of myeloablative therapy, precluding a nd myeloablative regimen\r\n* Patients with aplastic anemia may be treated on this protocol, with outcomes reported descriptively
Acute lymphoblastic leukemia (ALL/LL) in st remission clinical or molecular features indicating a high risk for relapse; or ALL >= nd remission
High risk acute myelogenous leukemia or high risk myelodysplastic syndrome (Revised International Prognosis Scoring System [r-IPSS] score  or above) status post allogeneic bone marrow transplant from matched related or unrelated donors; high risk acute myeloid leukemia (AML) patients in this study are defined as AML patients with residual leukemia at the time of transplant, very poor cytogenetics (i.e. deletion  or monosomy , deletion  or monosomy  and complex cytogenetics) or secondary AML; patients with acute promyelocytic leukemia are not eligible for this study
Any patient with a hematologic or oncologic diagnosis in which allogeneic HSCT is thought to be beneficial, and in whom front-line therapy has already been applied; patients will be considered high-risk if they have any of the following:\r\n* Eastern Cooperative Oncology Group (ECOG) performance status of =< \r\n* Acute leukemia: requiring more than one chemotherapy regimen to obtain st complete remission (CR); second or greater CR, st relapse; any Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL)\r\n* Chronic myelogenous leukemia (CML) nd chronic phase, accelerated phase, or blastic phase\r\n* Myelodysplastic syndromes (MDS) with International Prognostic Scoring System (IPSS) of intermediate  or greater\r\n* Any myeloproliferative disorder\r\n* Hodgkin lymphoma: relapsed, refractory, or primary induction failure\r\n* Non-Hodgkin lymphoma: relapsed, refractory, primary treatment failure, or not eligible for an autologous HSCT\r\n* Other conditions not listed will be assessed as high-risk by the principal investigator (PI)
Poor-risk acute leukemia in first remission, with remission defined as < % bone marrow blasts morphologically:\r\n* Acute myeloid leukemia (AML) with at least one of the following: AML arising from myelodysplastic syndrome (MDS) or a myeloproliferative disorder, or secondary AML; presence of fms-related tyrosine kinase  (Flt) internal tandem duplications; poor-risk cytogenetics: complex karyotype [>=  abnormalities], inv(), t(;), t(;), myeloid/lymphoid or mixed-lineage leukemia (MLL) rearrangement with the exception of t(;), or abnormalities of chromosome  or ; primary refractory disease\r\n* Acute lymphoblastic leukemia (ALL) (leukemia and/or lymphoma) with at least one of the following: adverse cytogenetics such as t(;), t(;), t(;), or MLL rearrangement; clear evidence of hypodiploidy; primary refractory disease\r\n* Biphenotypic leukemia
Acute lymphoblastic leukemia in high risk first complete remission (CR) as defined by at least one of the following: \r\n* Adverse cytogenetics including but not limited to t(;), t(;), t(;), mixed lineage leukemia (MLL) rearrangements\r\n* White blood cell counts > ,/mcL\r\n* Patients over  years of age\r\n* Time to complete remission >  weeks\r\n* Presence of extramedullary disease\r\n* Minimal residual disease\r\n* Other risk factors determined by the patients attending physician to be high risk features requiring transplantation
Acute myelogenous leukemia in high risk CR as defined by at least one of the following: \r\n* Greater than  cycle of induction therapy required to achieve remission\r\n* Preceding myelodysplastic syndrome (MDS)\r\n* Presence of fms-like tyrosine kinase receptor- (Flt) abnormalities\r\n* French-American-British (FAB) M or M leukemia, or\r\n* Adverse cytogenetics for overall survival such as: \r\n** Those associated with MDS\r\n** Complex karyotype (>=  abnormalities); or \r\n** Any of the following: inv() or t(;), t(;), t(;), +  [alone or with other abnormalities except for t(;), t(;), inv() or t(;)], t(;)(q;p.)]\r\n* Other risk factors determined by the patients attending physician to be high risk features requiring transplantation
Acute myelogenous leukemia (AML): \r\n* Complete first remission (CR) at high risk for relapse such as: \r\n** Known prior diagnosis of myelodysplasia (MDS) or myeloproliferative disorder; \r\n** Therapy related AML; \r\n** White cell count at presentation > ,; \r\n** Presence of extramedullary leukemia at diagnosis; \r\n** Any unfavorable subtype by French-American-British (FAB) or World Health Organization (WHO) classification; \r\n** High-risk cytogenetics (e.g. those associated with MDS, abnormalities of , , , Philadelphia chromosome, complex karyotype) or high risk molecular abnormalities;\r\n** Requirement for  or more inductions to achieve CR\r\n** Any patient with newly diagnosed AML with intermediate risk cytogenetics\r\n** Any patient unable to tolerate consolidation chemotherapy as would have been deemed appropriate by the treating physician\r\n* Complete second remission (CR)
Acute lymphoblastic leukemia (ALL): \r\n* Complete first remission (CR) at high risk for relapse such as: \r\n** White cell count at presentation > , for B-cell lineage and >, for T-cell lineage; \r\n** Presence of a high-risk cytogenetic abnormality such as t(;), t(;), t(;) or other MLL rearrangements (q) or other high-risk molecular abnormality; \r\n** Failure to achieve complete remission after four weeks of induction therapy; \r\n** Any patient with newly diagnosed ALL >=  years-old;\r\n** Any patient unable to tolerate consolidation and/or maintenance chemotherapy as would have been deemed appropriate by the treating physician\r\n* Complete second remission (CR)
Acute leukemia in morphologic relapse or with morphologic persistent disease (cytogenetic or molecular persistence/relapse in morphologic CR are eligible); MDS or CML or other myeloproliferative disorder with > % blasts; aggressive lymphoma or HL with POD after salvage chemotherapy
Acute myelogenous leukemia (AML) at the following stages:\r\n* High risk first complete remission (CR), defined as:\r\n** Having preceding myelodysplasia (MDS)\r\n** High risk cytogenetics (high-risk cytogenetics: del (q) , -, abn (q), t (;) complex karyotype (>=  abnormalities) with any minimal residual disease (MRD) status\r\n** Requiring >=  cycles chemotherapy to obtain complete response (CR)\r\n** High allelic ratio fms-related tyrosine kinase  (FLT)/internal tandem duplications positive (ITD+)\r\n** Standard risk cytogenetics with positive MRD at end of induction \r\n* Second or greater CR\r\n* First relapse with < % blasts in bone marrow
Acute lymphocytic leukemia (ALL) at the following stages:\r\n* High risk first remission, defined as:\r\n** Philadelphia chromosome positive (Ph+) ALL; or\r\n** Mixed lineage leukemia (MLL) rearrangement with slow early response [defined as having M (-% blasts) or M (> % blasts on bone marrow examination on day  of induction therapy); or\r\n** Hypodiploidy (<  chromosomes or deoxyribonucleic acid [DNA] index < .); or\r\n** End of induction M bone marrow; or\r\n** End of induction M marrow or MRD > % with M- marrow or MRD > % at day \r\n** High-risk infant ALL defined as age <  months at diagnosis with MLL (q) translocation\r\n* High risk second remission, defined as:\r\n** Bone marrow relapse <  months from induction; or >  months (mths) if a matched sibling donor is available\r\n** T-lineage relapse at any time; or,\r\n** Very early isolated central nervous system (CNS) relapse (<  months from diagnosis); or\r\n** Slow reinduction (M- at Day ) after relapse at any time\r\n* Any third or subsequent CR
Acute lymphocytic leukemia (ALL) at the following stages:\r\n* High risk first remission, as determined by treating physician as per current guidelines\r\n* Secondary remission, defined as:\r\n** Bone marrow relapse <  months from induction; or,\r\n** T-lineage relapse at any time; or,\r\n** Isolated CNS relapse or,\r\n** Slow reinduction (M- at day ) after relapse at any time\r\n* Any third of subsequent complete remission (CR)
Acute myelogenous leukemia (AML)\r\n* High risk first complete remission (CR), as determined by treating physician as per current guidelines\r\n* Second or greater CR\r\n* First relapse with < % blasts in bone marrow\r\n* Patients with therapy-related AML whose prior malignancy has been in remission for at least  months
Acute myeloid leukemia: high risk first complete remission (CR) as evidenced by: \r\n* High risk cytogenetics; t(;) or other mixed lineage leukemia (MLL) rearrangements; chromosome , , or  abnormalities; complex karyotype (>  distinct changes)\r\n* >=  cycles to obtain complete remission (CR)\r\n*Second CR (CR) or higher preceding myelodysplasia (MDS)\r\n* All patients must be in CR or early relapse (i.e., < % blasts in bone marrow [BM])
Acute myeloid leukemia: high risk first complete remission (CR) (as evidenced by preceding myelodysplastic syndrome [MDS], high risk cytogenetics such as those associated with MDS or complex karyotype, >  cycles to obtain complete response [CR] or erythroblastic and megakaryocytic); second or greater CR
Acute lymphoblastic leukemia/lymphoma: high risk CR as evidenced by high risk cytogenetics (e.g. t(;), t(;),t(;), other mixed-lineage leukemia (MLL) rearrangements, hypodiploidy or IKAROS family zinc finger  [IKZF]), >  cycle to obtain CR or evidence of minimal residual disease (MRD); patients in second or greater CR are also eligible
Acute myeloid leukemia (AML) and related precursor neoplasms: nd or greater complete remission (CR); first complete remission (CR) in patients >  years old; CR in =<  years old that is NOT considered as favorable-risk; favorable risk AML is defined as having one of the following:\r\n* t(,) without cKIT mutation\r\n* inv() or t(;) without cKIT mutation\r\n* Normal karyotype with mutated NPM and wild type FLT-ITD\r\n* Normal karyotype with double mutated CEBPA\r\n* Acute prolymphocytic leukemia (APL) in first molecular remission at the end of consolidation
Acute lymphoblastic leukemia (ALL)/lymphoma: second or greater CR; CR unable to tolerate consolidation chemotherapy due to chemotherapy-related toxicities; CR high-risk ALL; high risk ALL is defined as having one of the following:\r\n* Evidence of high risk cytogenetics, e.g. t(;), t(;), t(;), other MLL rearrangements, IKZF\r\n*  years of age or older at diagnosis\r\n* White blood cell counts of greater than ,/mcL (B-cell [B]-ALL) or greater than ,/mcL (T-cell [T]-ALL) at diagnosis\r\n* CNS leukemia involvement during the course of disease\r\n* Slow cytologic response (> % lymphoblasts in bone marrow on day  of induction therapy)\r\n* Evidence of persistent immunophenotypic or molecular minimal residual disease (MRD) at the end of induction and consolidation therapy
Patients must have one of the following hematologic malignancies: acute myelogenous leukemia (AML), induction failure, high-risk for relapse first remission (with intermediate-risk or high-risk cytogenetics, fms-related tyrosine kinase  [FLT] mutation positive and/or evidence of minimal residual disease by flow cytometry), secondary leukemia from prior chemotherapy and/or arising from myelodysplastic syndrome, any disease beyond first remission
Acute lymphoblastic leukemia (ALL): induction failure, primary refractory to treatment (do not achieve complete remission after first course of therapy) or are beyond first remission including second or greater remission or active disease; patients in first remission are eligible if they are considered high risk, defined as any of the following detected at any time: with t(;) or t(;), hypodiploidy, complex karyotype, secondary leukemia developing after cytotoxic drug exposure, and/or evidence of minimal residual disease, or acute biphenotypic leukemia, or double hit non-Hodgkin's lymphoma
AML and ALL in st complete remission (CR) at high risk of relapse based on negative prognostic factors (for the definition of high-risk of relapse see Appendix H).
COHORT : patients with high risk disease having undergone an allogeneic hematopoietic stem cell transplant from a / human leukocyte antigen (HLA) matched donor with one of the following disease subtypes:\r\n* Acute myeloid leukemia (AML) in CR with high risk features (European Leukemia Network [ELN]) at presentation\r\n** Diagnostic sample with either t(;), t(;), q, inv , -, -, delp, complex cytogenetics, NPMwt-fltITD+, OR p mutation (mut); patients whose samples have mutations in RUNX or ASXL are also eligible (unless the patient has favorable cytogenetics)\r\n* AML in CR with measurable minimal residual disease (MRD) by molecular (e.g., myeloid mutation profile, polymerase chain reaction [PCR] for NPM, core-binding factor [CBF], mixed lineage leukemia [MLL]) or flow cytometry \r\n* AML not in CR (including patients with morphologic CR but with incomplete recovery, CRi)\r\n* Myelodysplastic syndrome (MDS) with complex cytogenetics, p deletion or p mutation, or JAK or RAS mutation\r\n* Treatment-related MDS or AML\r\n* Acute lymphoblastic leukemia (ALL) not in CR\r\n* ALL with MRD\r\n* Any hematologic malignancy relapsed or with persistent disease after allogeneic hematopoietic stem cell transplant\r\n* Multiple myeloma\r\n* Non-Hodgkin lymphoma (NHL) with chemoresistant disease at time of transplant\r\n* Any patient undergoing allogeneic hematopoietic stem cell transplant and an anticipated rate of relapse > % based upon published data and for which there is consensus amongst the Hematologic Malignancies Tumor Study Group that enrollment is appropriate
High-risk acute myeloid leukemia (AML) with predicted risk of relapse higher than %, which includes, but not limited to the following:\r\n* Patients in morphological remission (complete response  [CR] or beyond) with minimal residual disease as quantified either by flow cytometry, or by cytogenetics or molecular markers.\r\n* Patients with the following karyotypes in morphological complete remission (CR) or complete remission with incomplete hematologic recovery (CRi): European LeukemiaNet (ELN)-Intermediate I, Adverse, ELN-Intermediate-II. (Examples include monosomal karyotype, complex karyotype, mutant p, mutant RUNX, mutant ASXL, mutant FLT-ITD, mutant DNMTA, inversion , T(:), KIT mutated core binding factor AML)
Adult patients must have a hematological malignancy, as described below:\r\n* Acute leukemias:\r\n** Acute lymphoblastic leukemia (ALL) in first complete remission (CR) that is NOT considered favorable-risk as defined by the presence of at least one of the following:\r\n*** Adverse cytogenetics such as t(;), t(;), t(;), other mixed lineage leukemia (MLL) rearrangements\r\n*** White blood cell counts of greater than ,/mcL (B-ALL) or greater than ,/mcL (T-ALL) at diagnosis,\r\n*** Recipient age older than  years at diagnosis,\r\n*** Time to CR greater than  weeks\r\n** Acute myelogeneous leukemia (AML) in first complete remission (CR) that is NOT considered as favorable-risk; favorable risk is defined as having one of the following:\r\n*** t(,) without CKIT mutation\r\n*** inv() without CKIT mutation or t(;)\r\n*** Normal karyotype with mutated nucleophosmin (NPM) and not FLT-IND\r\n*** Normal karyotype with double mutated CCAAT/enhancer binding protein alpha (CEBPA)\r\n*** Acute promyelocytic leukemia (APL) in first molecular remission at end of consolidation\r\n** Acute leukemias in second (nd) or subsequent\r\n** Biphenotypic/undifferentiated/prolymphocytic leukemias in first or subsequent CR, adult T-cell leukemia/lymphoma in first or subsequent CR\r\n* Chronic myelogenous leukemia (CML) excluding refractory blast crisis; to be eligible in first chronic phase (CP) patient must have failed or be intolerant to imatinib mesylate\r\n* Myelodysplastic syndrome (MDS): International Prognostic Scoring System (IPSS) intermediate (Int)- or high risk (i.e., refractory anemia with excess blasts [RAEB], RAEB in transformation [RAEBt]) or refractory anemia with severe pancytopenia or high risk cytogenetics; blasts must be < %\r\n* Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), marginal zone B-cell lymphoma or follicular lymphoma that have progressed after at least two prior therapies; patients with bulky disease (nodal mass greater than  cm) should be considered for debulking chemotherapy before transplant\r\n* Lymphoplasmacytic lymphoma, mantle-cell lymphoma, prolymphocytic leukemia are eligible after initial therapy in CR+ or first or greater partial remission (PR+)\r\n* Large cell non-Hodgkin lymphoma (NHL) > CR/> PR; patients in CR/PR with initial short remission (<  months) are eligible\r\n* Lymphoblastic lymphoma, Burkitt lymphoma, and other high-grade NHL after initial therapy if stage III/IV in CR/PR or after progression if stage I/II <  year\r\n* Multiple myeloma beyond PR; patients with chromosome  abnormalities, first response lasting less than  months, or beta- microglobulin >  mg/L, may be considered for this protocol after initial therapy\r\n* Natural killer (NK) cell leukemia
Pediatric patients must have a hematological malignancy as described below:\r\n* AML: high risk CR (preceding MDS, intermediate to high risk cytogenetics, >=  cycles to obtain CR, French-American-British classification system [FAB] M); CR+, first relapse with < % blasts in bone marrow; morphologic complete remission with incomplete blood count recovery; therapy-related AML for which prior malignancy has been in remission for at least  months\r\n* ALL: high risk CR (Philadelphia chromosome positive [Ph+] ALL, MLL rearrangements with slow early response, hypodiploidy, end of induction M bone marrow, end of induction M with M- at day , evidence of minimal residual disease [MRD]); high risk CR (Ph+ALL, bone marrow relapse <  months from induction, T-lineage relapse at any time, very early isolated central nervous system (CNS) relapse, slow induction after relapse at any time, evidence of MRD); >= CR\r\n* NK cell lymphoblastic leukemia in any CR\r\n* Biphenotypic or undifferentiated leukemia in any CR or if in first relapse must have less than % blasts in bone marrow\r\n* Myelodysplastic syndrome (MDS) at any stage\r\n* Chronic myelogenous leukemia (CML) in chronic or accelerated phase\r\nEvidence of CNS leukemia must be treated and in CNS CR to be eligible for the study
Acute leukemia, primary refractory or beyond complete remission (CR), or minimal residual disease (MRD) positivity
High-risk acute myeloid leukemia in CR with any of the following features:\r\n* Complex karyotype (>=  clonal chromosomal abnormalities)\r\n* Any of the following high risk chromosomal abnormalities: \r\n** Monosomal karyotype (-, q-, -, q-)\r\n** t(q), t(;), inv(), t(;) t(;) t(;)\r\n** Normal karyotype with FLT-internal tandem duplication (ITD) mutation
Acute myelogenous leukemia high risk in first complete remission (CR) (as evidenced by preceding myelodysplastic syndrome (MDS), high risk cytogenetics such as those associated with MDS or complex karyotype, or >  cycles to obtain complete remission [CR]); second or greater CR; must be in remission by morphology; patients in morphologic relapse/ persistent disease defined as > % blasts in normocellular bone marrow OR any % blasts if blasts have unique morphologic markers (eg auer rods) or associated cytogenetic markers that allows morphologic relapse to be distinguished are not eligible for arms  or ; note cytogenetic evidence of disease alone without morphologic relapse is acceptable; also a small percentage of blasts that is equivocal between marrow regeneration versus (vs) early relapse is acceptable provided there are no associated cytogenetic markers consistent with relapse
Patients must have one of the following disease types:\r\n* Acute myeloid leukemia (AML) with any of the following:\r\n** In first complete remission (CR) with high-risk features defined by any of the following:\r\n*** Presence of any of the cytogenetics abnormalities: -/q-, -/q-, t(:), t(;), inv(), q, q abnormalities, or complex karyotype with  or more abnormalities per clone\r\n*** Need for  cycles of induction therapy to achieve CR\r\n*** Preceding history of myelodysplasia or the prior administration of chemotherapy for a non-myeloid malignancy (i.e., secondary AML)\r\n** Patients in second or subsequent complete remission (CR, CR, etc.)\r\n** Primary refractory or relapsed AML with peripheral blood blasts < .x^/l or with extramedullary disease (excluding active disease of the central nervous system)\r\n* Acute lymphoblastic leukemia (ALL) with any of the following:\r\n** In CR with high-risk features defined by any of the following cytogenetic abnormalities, including Ph+, t(;), q abnormalities, or t(;)\r\n** Patients in second or subsequent complete remission (CR, CR, etc.)\r\n** Primary refractory or relapsed ALL with peripheral blood blasts < .x^/l or with extramedullary disease (excluding active disease of the central nervous system)\r\n* Myelodysplasia with any of the following features: \r\n** Refractory anemia with excess blasts with -% blasts in the bone marrow (RAEB II)\r\n** Refractory anemia with excess blasts with -% blasts (RAEB I) and poor risk cytogenetics (i.e., chromosome  abnormalities or complex karyotype with at least  abnormalities per clone)\r\n** Refractory cytopenia with multilineage dysplasia (RCMD) and poor risk cytogenetics (i.e., chromosome  abnormalities or complex karyotype with at least  abnormalities per clone)\r\n* Chronic myelogenous leukemia (CML) with one of the following criteria:\r\n** Accelerated phase, defined by any of the following:\r\n*** Blasts -% of peripheral blood white cells or bone marrow cells\r\n*** Peripheral blood basophils at least %\r\n*** Persistent thrombocytopenia (<  x ^/l) unrelated to therapy, or persistent thrombocytosis (>  x ^/l) unresponsive to therapy \r\n*** Increasing spleen size and increasing white blood cell (WBC) count unresponsive to therapy\r\n*** Cytogenetic evidence of clonal evolution (i.e., the appearance of an additional genetic abnormality that was not present in the initial specimen at the time of diagnosis of chronic phase)\r\n*** Resistance to tyrosine kinase inhibitors (e.g., imatinib, dasatinib, nilotinib) defined as no complete cytogenetic response even if the above criteria are not met\r\n** First chronic phase provided a complete hematologic remission was not achieved by  months or a complete cytogenetic remission by  months and the patient had received in addition to imatinib  mg daily at least one of the following options: a) imatinib - mg daily, b) nilotinib, or c) dasatinib\r\n** Second or subsequent chronic phase provided a complete hematologic remission was not achieved by  months or a major cytogenetic remission (<  % Philadelphia chromosome + metaphases) by  months and the patient had received in addition to imatinib  mg daily at least one of the following options: a) imatinib - mg daily, b) nilotinib, or c) dasatinib\r\n* Patients with aggressive non-Hodgkins lymphoma (NHL), including diffuse large cell lymphoma, mediastinal B-cell lymphoma, transformed lymphoma, mantle cell lymphoma, and peripheral T cell lymphoma, who also have one of the following criteria:\r\n** Failure to achieve complete remission to primary induction therapy\r\n** Relapsed and refractory to at least one line of salvage systemic therapy
Hematologic malignancies diagnoses:\r\n* Acute lymphoblastic leukemia (ALL) with a history of bone marrow relapse in clinical remission (CR) # or greater, or in CR# if prior induction failure; or with an M marrow if unable to achieve CR\r\n* Philadelphia chromosome positive ALL patients who:\r\n** Have progressed through or relapsed following tyrosine kinase inhibitor (TKI) therapy or conventional myeloablative therapy OR\r\n** Are ineligible to receive tyrosine kinase inhibitor (TKI) therapy AND myeloablative hematopoietic stem cell transplant (HSCT)\r\n* Acute myelogenous leukemia (AML) with a history of bone marrow relapse in remission CR # or greater; or with an M marrow if unable to achieve CR; or in CR# if prior induction failure; or any of the following high-risk categories:\r\n** FMS-like tyrosine kinase /internal tandem duplication positive (FLT/ITD+) with high allelic ratio > . (HR FLT/ITD+) regardless of low risk features\r\n** Presence of monosomy , monosomy , or deletion (del)q, without inversion (inv)()/t(;) or t(;) cytogenetics or nucleophosmin (NPM) or CCAAT enhancer-binding protein (CEBP) alpha mutations\r\n** AML without inv()/t(;), t(;), NPM, CEPB alpha mutations, monosomy , monosomy , delq, or HR FLT/ITD+, but with evidence of residual AML (>= .%) at end of induction I\r\n* Hodgkins and non-Hodgkins lymphoma with refractory disease or relapse after at least one salvage regimen, or after autologous stem cell transplant\r\n* Juvenile myelomonocytic leukemia (JMML) with < % blasts in marrow and blood, who are not eligible for effective standard therapies\r\n* Chronic myelogenous leukemia (CML) with history of blast crisis (ALL/AML) or progressive disease failing tyrosine-kinase inhibitor (TKI)
Patients must have at least one of the following high-risk conditions listed below (criteria are consistent with existing criteria within Children's Oncology Group [COG] protocols):\r\n* Acute lymphocytic leukemia (ALL) in first complete remission (CR) as defined by at least one of the following:\r\n** Hypodiploidy\r\n** Induction failure\r\n** Minimal residual disease (MRD) after consolidation\r\n* Acute myeloid leukemia (AML) in CR with high risk features defined as:\r\n** High allelic ratio fms-related tyrosine kinase  (FLT)/internal tandem duplications (ITD) positive (+)\r\n** Monosomy \r\n** Del (q)\r\n** Standard risk cytogenetics with positive minimal residual disease at the end of Induction I chemotherapy (for patients being treated on or according to COG AAML who have had MRD studies sent to Seattle or performed at their local institution where the flow assay is sensitive enough to detect >= .% blasts)\r\n* Acute leukemias in nd or subsequent complete remission (CR) (CR >= )\r\n* Mixed phenotype/undifferentiated leukemias in st or subsequent CR\r\n* Secondary or therapy related leukemias in CR >= \r\n* Natural killer (NK) cell leukemia or NK cell lymphoblastic leukemia/lymphoma CR >= \r\n* Myelodysplastic syndrome (MDS)\r\n* Juvenile myelomonocytic leukemia (JMML) (patients are eligible if they are not eligible for COG)\r\n* Prior transplant eligible if =<  years old (yo), >=  year has elapsed since BMT, and patient is off immunosuppression for >=  months with no GVHD; patients who have had a prior chemotherapy based preparative regimen are allowed to receive a TBI based prep, regardless of their disease\r\n* No known active central nervous system (CNS) involvement or extramedullary involvement by malignancy; such disease treated into remission is permitted\r\n* Remission is defined as morphology with < % blasts with no morphological characteristics of acute leukemia (e.g., Auer Rods) in a bone marrow with > % cellularity
Enrollment on protocol for collection of PBMC/T cells may occur for the following patients with CD+ B-ALL\r\n* Patients whose disease meets one of the following  criteria:\r\n** Very high-risk (VHR)\r\n** Patients in first (st) or subsequent marrow relapse (isolated or combined), at the time of relapse, during retrieval therapy, or after achievement of complete remission (CR)\r\n** Refractory disease\r\n** Definitions of VHR B-ALL include the following:\r\n*** National Cancer Institute (NCI) high risk (HR)-acute lymphoblastic leukemia (ALL) and age >=  years at diagnosis\r\n*** Overt central nervous system disease (CNS-) leukemia at diagnosis\r\n*** Day /end of induction bone marrow (BM) minimal residual disease (MRD) > .%\r\n*** Induction failure (M BM at day /end of induction)\r\n*** Hypodiploidy (n <  chromosomes and/or a deoxyribonucleic acid [DNA] index < .)\r\n*** t(;) ALL (Philadelphia chromosome/Ph+ ALL) or Ph-like ALL\r\n*** t(;) ALL\r\n*** MLL gene rearrangement\r\n*** IKAROS family zinc finger  (Ikaros) (IKZF) deletions\r\n*** Intrachromosomal amplification of chromosome  (iAMP)\r\n* Please note patients that only meet the criteria for collection/storage of PBMCs will need to re-consented prior to infusion of genetically modified T-cells
Eligible diagnoses:\r\n* Myelodysplastic syndrome (MDS) including chronic myelomonocytic leukemia (CMML) with at least one of the following poor-risk features:\r\n** Poor-risk cytogenetics\r\n** International Prognostic Scoring System (IPSS) score of intermediate (INT)- of greater\r\n** Treatment-related or secondary MDS\r\n** MDS diagnosed before age \r\n** Progression on or lack of response to standard deoxyribonucleic acid (DNA)-methyltransferase inhibitor therapy\r\n** Life-threatening cytopenias, including those requiring frequent transfusions\r\n* Small lymphocytic lymphoma (SLL) or chronic lymphocytic leukemia (CLL) with p deletion, or with progression <  months after second or greater treatment regimen; must have the following to be an acceptable candidate as well:\r\n** =< % of bone marrow cellularity involved by SLL/CLL (to lower risk of graft rejection)\r\n** No lymph nodes >=  cm in any dimension\r\n** No massive splenomegaly, defined as >  cm below the left costal margin\r\n* T-cell prolymphocytic leukemia (PLL) in partial remission (PR) or better prior to transplantation; must also have =< % of bone marrow cellularity involved by PLL (to lower risk of graft rejection)\r\n* Interferon- or tyrosine kinase-refractory chronic myelogenous leukemia (CML) in first chronic phase, tyrosine kinase inhibitor (TKI)-intolerant CML in first chronic phase, or CML in second or subsequent chronic phase\r\n* Philadelphia chromosome negative myeloproliferative disease (including myelofibrosis)\r\n** Intermediate- or high risk score by Dynamic International Prognostic Scoring System (DIPSS) plus is required for a diagnosis of myelofibrosis\r\n* Multiple myeloma or plasma cell leukemia with a PR or better to the last treatment regimen, based on the International Myeloma Working Group (IMWG) criteria\r\n* Hematologic malignancy in complete remission with minimal residual disease (MRD) non detectable OR detectable by conventional cytogenetics, fluorescence in situ hybridization (FISH), flow cytometry, or molecular testing or hematologic malignancies in partial remission
This treatment is for patients with high risk hematologic malignancies; high risk is defined as:\r\n* Any patient with a hematologic malignancy with residual disease after treatment with  or more chemotherapy regimens in whom achievement of remission with additional chemoradiotherapy is felt to be unlikely\r\n* Patients without morphologic evidence of disease but with high risk features which would predict for relapse despite remission at HSCT such as adverse cytogenetics, rd or greater complete remission (CR), or failure to recover peripheral blood counts to normal ranges; while these patients do not have detectable disease by current methods, like all patients they have non-detectable disease which in their case is highly aggressive
Acute lymphoblastic leukemia, including biphenotypic acute leukemia or mixed-lineage leukemia\r\n* High risk first complete remission (CR) (for example, but not limited to: t(;), t(;), t(;) or other mixed-lineage leukemia [MLL] rearrangements, hypodiploid); or high risk (HR) as defined by referring institution treatment protocol greater than  cycle to obtain CR; second complete remission (CR) or greater\r\n* All patients must be in CR as defined by < % blasts by morphology/flow cytometry in a representative bone marrow sample with cellularity >= % for age\r\n* Patients in which adequate marrow/biopsy specimens cannot be obtained to determine remission status by morphologic assessment, but have fulfilled criteria of remission by flow cytometry, recovery of peripheral blood counts with no circulating blasts, and/or normal cytogenetics (if applicable) may still be eligible; reasonable attempts must be made to obtain an adequate specimen for morphologic assessment, including possible repeat procedures; these patients must be discussed with the principal investigator prior to enrollment
Diagnosis of high risk hematological malignancy:\r\n* Any acute leukemia in first complete remission (CR) considered at high risk for relapse, or second or third CR, or relapse/refractory less than % blasts in bone marrow, or aplasia post-therapy; this includes de novo acute leukemia or acute leukemia that is therapy related or arising from an antecedent hematologic disorder including myelodysplasia (MDS), chronic myeloid leukemia (CML) or other myeloproliferative disorder\r\n* Juvenile myelomonocytic leukemia (JMML) in CR, or relapse with less than % bone marrow blasts \r\n* CML with tyrosine kinase inhibitor failure in chronic or accelerated phase or evolved to acute leukemia (blast crisis, see above)\r\n* MDS or other myeloproliferative disorder with life-threatening cytopenia(s), and/or red blood cell or platelet transfusion dependence, or patients with aplasia, or patients with excess blasts less than % blasts in the bone marrow at work-up\r\n* Aggressive lymphoma: patients in first complete remission (CR) with disease at high risk of relapse or CR- \r\n* Indolent lymphoma or chronic lymphocytic leukemia (CLL): any disease status provided any transformed component is in CR\r\n* Hodgkin lymphoma that is primary refractory or relapsed not suitable for other therapy and in partial remission (PR) or CR or small volume stable disease
Enrolled in University Of Minnesota study MT- Allogeneic Bone Marrow Transplantation Using Less Intensive Therapy and fitting into one of the following disease categories:\r\n* Acute myelogenous leukemia - high risk first complete remission (CR) (as evidenced by preceding myelodysplastic syndrome [MDS], intermediate to high risk cytogenetics, >=  cycles to obtain complete remission (CR), erythroblastic or megakaryocytic leukemia; second complete remission (CR)+; all patients must be in CR as defined by hematological recovery (absolute neutrophil count [ANC] > . x ^/L), AND < % blasts by light microscopy within the bone marrow with a cellularity of >= %\r\n* Acute lymphocytic leukemia - high risk CR [t(;), t (:), t(;) or other mixed-lineage leukemia [MLL] rearrangements] or >  cycle to obtain CR; CR+; all patients must be in CR as defined by hematological recovery (ANC > . x ^/L), AND < % blasts by light microscopy within the bone marrow with a cellularity of >= %\r\n* Chronic myelogenous leukemia all types except blast crisis (note treated blast crisis in chronic phase is eligible)\r\n* Non-Hodgkin lymphoma or Hodgkins lymphoma demonstrating chemosensitive disease\r\n* Myelodysplastic syndrome with severe pancytopenia, leading to either transfusion dependency or increased risk for infections
Acute lymphocytic leukemia\r\n* Adult: (>=  years) >= second complete remission (CR) OR first CR (CR) with a high risk feature:\r\n** Matched sibling donor for recipient treated on adult leukemia regimen\r\n** t(:) or breakpoint cluster region (bcr)-Abelson (abl)+; t(:), t(:), t(:), q (mixed lineage leukemia [MLL] rearrangements) complex cytogenetics ( or more chromosomal abnormalities), hypodiploidy (<  chromosomes.; note that patients with acute lymphoblastic leukemia (ALL) blast crisis who emerge from chronic myelogenous leukemia (CML) are also eligible\r\n** Primary induction failure, defined as failure to achieve CR with primary induction chemotherapy\r\n** High white blood cell (WBC) (> , for B-cell ALL and > , for T-cell ALL) at diagnosis\r\n** Persistence of minimal residual disease despite induction chemotherapy\r\n* Pediatric (<  years): >= CR OR CR with high risk features\r\n** Matched sibling donor for recipient treated on adult leukemia regimen\r\n** Primary induction failure (M [> % with greater  cells counted] marrow at day ), M (-% blasts with greater than  cells counted) bone marrow or minimal residual disease (MRD) > % at day  who then fail at day  with either M or M bone marrow (BM) or MRD > %\r\n** Persistent leukemia and t(;) (MRD > % day  or MRD > .% end-consolidation)\r\n** q (MLL) rearrangements detected by cytogenetic or polymerase chain reaction (PCR) at initial diagnosis who are slow early responders (M/M at day  or MRD > .% at day )\r\n** Extreme hypodiploidy (<  chromosomes or deoxyribonucleic acid [DNA] index of < .) detected by cytogenetic/ploidy analysis
Acute myelogenous leukemia\r\n* Adult: (>=  years) >= CR OR CR with one of the following high risk features\r\n** Adverse or intermediate-risk cytogenetics including:\r\n*** Normal cytogenetics\r\n*** Complex karyotype (>  abnormalities)\r\n*** Inv () or t(;); t(;)(q;p.); +; -/p-; -; -; (t(;); t(;); -, q-; -, q-; trisomy ; t(;); t(:)(pq)\r\n*** Monosomy karyotype (presence of an autosomal monosomy in conjunction with at least one other autosomal monosomy or structural abnormality\r\n*** Any other karyotype EXCEPT t(;), t(;), inv(), or t(;), and M (; ) unless v-kit Hardy-Zuckerman  feline sarcoma viral oncogene homolog (c-Kit) mutation present and then eligible\r\n*** AML emerging from CML (blast crisis) are eligible\r\n** Primary induction failure, defined as failure to achieve CR with primary induction chemotherapy\r\n** Secondary AML, defined as AML related to antecedent myelodysplastic syndrome (MDS), myeloproliferative neoplasm (MPN), or cytotoxic chemotherapy\r\n** Hyperleukocytosis (white blood cells [WBC] > , at diagnosis)\r\n** Mutations in the FMS-like tyrosine kinase  (FLT) gene (FLT-length mutations [LM]; FLT-internal tandem duplications [ITDs])\r\n** Bilineage or biphenotypic leukemias are high risk features and eligible\r\n* Pediatric (<  years): >= CR OR CR with a high risk feature including\r\n** Primary induction failure (>= % blasts in marrow after induction)\r\n** Persistent leukemia (> % after first course of chemotherapy)\r\n** Complex karyotype monosomy , or -/-q, FLT ITD-allelic ratio (AR) (> .) EXCEPT if also inv()/t(;), t(,)\r\n** Normal cytogenetics or abnormal cytogenetics EXCEPT if also inv()/t(;), t(,) are eligible for SIBLING transplant only\r\n** Bilineage or biphenotypic leukemias are high risk features and eligible
Patients with a diagnosis of acute myeloid leukemia (AML) (World Health Organization classification: >= % blasts in the bone marrow and/or peripheral blood) or myelodysplastic syndrome (MDS) (International Prognostic Scoring System intermediate- or higher) that at the time of allogeneic transplantation were in: - induction failure, relapsed disease or second or greater remission; patients in first complete remission that required more than  cycle of treatment to achieve the remission, or that have AML evolving from MDS, or that had the following abnormalities: FLT mutation, deletion of chromosome  or , mixed-lineage leukemia (MLL) gene rearrangement, or more than or equal to  cytogenetics abnormalities; patients with de novo or therapy-related MDS, chronic myelomonocytic leukemia (CMML) or AML are also eligible, regardless of cytogenetics or molecular rearrangements
Acute myelogenous leukemia (AML) in induction failure, relapse, past first remission, or first complete remission (CR) considered at risk for relapse
Patients who are to receive an allogeneic hematopoietic cell transplant as treatment for a leukemia or myelodysplastic syndrome that has an expected risk of relapse exceeding % will be eligible to have donor-derived WT peptide sensitized T cells generated prior to or at the time of transplant for immediate use post transplant at such time that the patient is found to have minimal residual disease or relapse; this includes patients with:\r\n* Acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), or MDS refractory to primary induction therapy\r\n* ALL or AML at any stage later than first ( degree) relapse\r\n* Chronic myelogenous leukemia (CML) secondary ( degree) or greater chronic phase after chemotherapy\r\n* CML in persistent accelerated phase or blast crisis\r\n* High risk MDS (refractory anemia with excess blasts [RAEB] and RAEB in transformation [T]) which has failed to respond or has recurred following induction chemotherapy
Patients must have one of the following hematologic malignancies: acute myelogenous leukemia (AML), induction failure, high-risk for relapse first remission (with intermediate-risk or high-risk cytogenetics, fms-related tyrosine kinase  [flt] mutation positive and/or evidence of minimal residual disease by flow cytometry), secondary leukemia from prior chemotherapy and/or arising from myelodysplastic syndrome (MDS), Langerhan's cell histiocytosis, any disease beyond first remission; or
Acute lymphoblastic leukemia (ALL): induction failure, primary refractory to treatment (do not achieve complete remission after first course of therapy) or are beyond first remission including second or greater remission or active disease; patients in first remission are eligible if they are considered high risk, defined as any of the following detected at any time: with translocations ; or ;, hypodiploidy, complex karyotype, secondary leukemia developing after cytotoxic drug exposure, and/or evidence of minimal residual disease, or acute biphenotypic leukemia, or double hit non-Hodgkin's lymphoma; or
Acute myeloid leukemia (AML) in >= first (st) remission - excluding those in st remission with good risk cytogenetic features (i.e. t(;), t(;), inv )
Acute lymphoblastic leukemia (ALL)/lymphocytic leukemia (LL) in st remission with clinical or molecular features indicating a high risk for relapse; or ALL > second (nd) remission
Acute Myelogenous Leukemia (AML) in high risk st or subsequent CR
MDS or high-risk AML, morphologically confirmed and based on World Health Organization criteria), who are transplant candidates with an available human leukocyte antigen (HLA)-matched sibling or unrelated donor with at least / match\r\n* Definition of high-risk AML:\r\n** Age >=  years\r\n** Age <  years with any of the following:\r\n*** Secondary AML\r\n*** Poor risk cytogenetics, which include abnormalities of chromosome , , or , trisomy , q abnormalities, t(;), q-, and complex karyotype\r\n*** Fms-related tyrosine kinase  (FLT) mutation\r\n*** Disease status >= second complete remission (CR) at time of HCT\r\n*** Detectable disease at time of HCT
One of the following:\r\n* Acute leukemia past first remission, in first or subsequent relapse, in second or greater remission; patients in first remission should have with intermediate or high cytogenetic risk factors or fms-related tyrosine kinase  (flt) mutation; patients with relapsed disease; patients with primary induction failure or relapse are eligible if they have < % bone marrow blasts, and no circulating blasts\r\n* Myelodysplastic syndrome with intermediate or high risk International Prognostic Scoring System (IPSS) score, or treatment related myelodysplastic syndrome (MDS)\r\n* Chronic myeloid leukemia (CML) resistant to tyrosine kinase treatment in a first or subsequent chronic phase or after transformation to accelerated phase or blast crisis\r\n* Chronic lymphocytic leukemia (CLL), lymphoma or Hodgkins disease which has failed to achieve remission or recurred following initial chemotherapy; patients must have at least a PR to salvage therapy, or low bulk untreated relapse (<  cm largest mass)\r\n* Multiple myeloma which has relapsed or progressed and has achieved a partial response to salvage chemotherapy
Acute myeloid leukemia\r\n* Not in remission (pediatric patients <  years)\r\n* Not in remission (-% blasts in the bone marrow for adult patients >=  years and =<  years)\r\n* Evidence of pre-transplant minimal residual disease (MRD) by flow cytometry, FISH or cytogenetics
Patients must have one of the following hematologic malignancies: \r\n* Acute myelogenous leukemia (AML), induction failure, high-risk for relapse first remission (with intermediate-risk or high-risk cytogenetics, fms-like tyrosine kinase [flt] mutation positive and/or evidence of minimal residual disease by flow cytometry), secondary leukemia from prior chemotherapy and/or arising from myelodysplastic syndrome (MDS), Langerhans cell histiocytosis, any disease beyond first remission; or\r\n* Myelodysplastic syndrome (MDS): primary or therapy related; or\r\n* Acute lymphoblastic leukemia (ALL): induction failure, primary refractory to treatment (do not achieve complete remission after first course of therapy) or are beyond first remission including second or greater remission or active disease; patients in first remission are eligible if they are considered high risk, defined as any of the following detected at any time: with translocations ; or ;, hypodiploidy, complex karyotype, secondary leukemia developing after cytotoxic drug exposure, and/or evidence of minimal residual disease, or acute biphenotypic leukemia, or double hit non-Hodgkin's lymphoma; or \r\n* Non-Hodgkin's lymphoma (NHL): in primary induction failure, second or third complete remission, refractory disease, or relapse (including relapse post autologous hematopoietic stem cell transplant); double hit lymphomas in first remission or more advanced disease; or \r\n* Small lymphocytic lymphoma (SLL), or chronic lymphocytic leukemia (CLL) with progressive disease following standard therapy; or,\r\n* Chronic myelogenous leukemia (CML) second chronic phase or accelerated phase; or,\r\n* Hodgkin's disease (HD): induction failures, second or third complete remission, or relapse (including relapse post autologous hematopoietic stem cell transplant)
High-risk hematologic malignancy\r\n* Very high risk acute lymphocytic leukemia (ALL) in first complete remission (CR); examples include, but not limited to hypodiploid M or greater marrow at the end of induction, infants with mixed lineage leukemia (MLL) fusion or t(;)\r\n* ALL in high risk second complete remission (CR); examples include but not limited to bone marrow (BM) relapse <  months (mo); CR, T-ALL, very early (<  mo CR) isolated central nervous system (CNS) relapse\r\n* ALL in third complete remission (CR) or subsequent\r\n* Acute myeloid leukemia (AML) in high risk CR; examples include but not limited to preceding myelodysplastic syndromes (MDS), q-, -, -, French American British (FAB) M, FAB M not t(;), minimal residual disease (MRD) >= % on day  (AML), M marrow after induction , M marrow after two cycles of induction, fms-related tyrosine kinase  (FLT)-internal tandem duplication (ITD)\r\n* AML in CR or subsequent\r\n* Therapy related AML, with prior malignancy in CR >  mo\r\n* MDS, primary or secondary\r\n* NK cell, biphenotypic, or undifferentiated leukemia in CR or subsequent\r\n* Chronic myelogenous leukemia (CML) in accelerated phase, or in chronic phase with persistent molecular positivity or intolerance to tyrosine kinase inhibitor\r\n* Hodgkin lymphoma in CR or subsequent after failure of prior autologous HCT, or unable to mobilize stem cells for autologous HCT\r\n* Non-Hodgkin lymphoma in CR or subsequent\r\n* Juvenile myelomonocytic leukemia (JMML)\r\n* Refractory hematologic malignancies (ALL, AML, CML in blast crisis, Hodgkin or non-Hodgkin lymphoma) due to chemoresistant relapse or primary induction failure\r\n* All patients with evidence of CNS leukemia must be treated and be in CNS CR to be eligible for study
Inclusion Criteria:\n\n        Donor:\n\n          -  Donor eligibility will be determined according to applicable federal, state and local\n             regulations and institutional standards\n\n          -  - years of age\n\n          -  / HLA-matched sibling\n\n          -  Fulfill individual Transplant Center criteria to serve as a mobilized blood cell donor\n\n          -  Serum creatinine <.mg/dl\n\n        Recipient:\n\n          -   to  years of age\n\n          -  / HLA antigen matched sibling willing to donate PBSC for transplant\n\n          -  Fulfill individual Transplant Center Criteria for transplant\n\n          -  One of the following diagnoses:\n\n               -  Acute myelogenous leukemia (AML) in st remission or beyond with <% marrow\n                  blasts and no circulating blasts. Marrow must be done within  days of the start\n                  of transplant conditioning regimen in alignment with other pre-transplant\n                  assessments.\n\n               -  Acute lymphoblastic leukemia (ALL) in st remission or beyond with <% marrow\n                  blasts and no circulating blasts\n\n               -  Myelodysplastic syndrome, either intermediate-,, or high risk by International\n                  Prognostic Scoring System or transfusion dependent\n\n               -  Chronic myelogenous leukemia (CML) failing or intolerant to tyrosine kinase\n                  inhibitor based therapy\n\n               -  Non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) in nd or greater complete\n                  remission, partial remission, or in relapse (but with at least stable disease\n                  after most recent therapy)\n\n               -  Chronic lymphocytic leukemia (CLL), relapsing after at least one prior regimen,\n                  or in remission with p deletion\n\n          -  Serum creatinine must be <.mg/dl\n\n          -  Total bilirubin and AST <x normal\n\n          -  Infectious disease marker (IDM) monitoring will be performed per institutional\n             standards\n\n          -  Karnofsky performance status of % or greater.\n\n          -  Patients who have undergone a prior autologous transplantation are eligible for a\n             reduced intensity transplant only\n\n        Exclusion Criteria:\n\n        Donor:\n\n          -  Donor unwilling or unable to give informed consent, or unable to comply with the\n             protocol including required follow-up and testing\n\n          -  Donor already enrolled on another investigational agent study\n\n          -  Pregnant or breast feeding females, or females not willing or able to use adequate\n             contraception if sexually active\n\n        Recipient:\n\n          -  Patient unwilling or unable to give informed consent, or unable to comply with the\n             protocol including required follow-up and testing\n\n          -  Patients with active, uncontrolled infection at the time of the transplant preparative\n             regimen\n\n          -  Pregnant or breast feeding females, or females not willing or able to use adequate\n             contraception if sexually active\n\n          -  Patients with a history of previous CNS tumor involvement showing active symptoms or\n             signs along with documented disease on lumbar puncture and MRI of the brain within \n             days of start of conditioning\n\n          -  A condition, which, in the opinion of the clinical investigator, would interfere with\n             the evaluation of primary and secondary endpoints.
Acute myelogenous leukemia (AML) in first remission that required more than  cycle of treatment to achieve remission or with the following cytogenetic abnormalities: FLT mutation, deletion/monosomy of chromosome  or , MLL gene rearrangement, or more than or equal to  cytogenetics abnormalities; also patients in second or greater remission
Poor-risk acute leukemia in first remission, with remission defined as < % bone marrow blasts morphologically:\r\n* Acute myeloid leukemia (AML) with at least one of the following:\r\n** AML arising from myelodysplastic syndromes (MDS) or a myeloproliferative disorder, or secondary AML\r\n** Presence of FMS-like tyrosine kinase- (Flt) internal tandem duplications\r\n** Poor-risk cytogenetics\r\n** Primary refractory disease\r\n* Acute lymphoblastic leukemia (ALL) (leukemia and/or lymphoma) with at least one of the following:\r\n** Poor-risk cytogenetics\r\n** Clear evidence of hypodiploidy\r\n** Primary refractory disease\r\n* Biphenotypic leukemia
Acute lymphocytic leukemia (ALL) in first complete remission (CR) with high-risk features including adverse cytogenetics such as t(;), t(;), t(;), or mixed-lineage leukemia (MLL) gene rearrangements; ALL in second or greater remission or ALL with relapsed disease, peripheral blood blasts < /microliter, ALL patients must show response to most recent received chemotherapy
Acute myeloid leukemia (AML) in CR with intermediate-risk disease or high-risk features defined as: \r\n* Greater than  cycle of induction therapy required to achieve remission\r\n* Preceding myelodysplastic syndrome (MDS) or myeloproliferative disease\r\n* Presence of fms-related tyrosine kinase  (FLT) mutations or internal tandem duplications\r\n* French-American-British (FAB) M or M classification\r\n* Adverse cytogenetics, -, del q, -, delq, abnormalities involving q, q, q, q, q, , + (>  abnormalities), peripheral blood blasts < /microliter, AML patients must show response to most recent received chemotherapy
Patients must meet one of the following:\r\n* Acute myeloid leukemia (AML) in first (st) remission - for patients whose AML does not have \good risk\ cytogenetic features (i.e. t[;], t[;], inv  without v-kit Hardy-Zuckerman  feline sarcoma viral oncogene homolog [c-kit] mutations)\r\n* Acute leukemias of ambiguous lineage in >= st remission\r\n* Secondary AML in remission\r\n* AML in >= second (nd) remission\r\n* Acute lymphoblastic leukemia (ALL) in st remission with clinical or molecular features indicating a high risk for relapse; or ALL >= nd remission\r\n* Chronic myelogenous leukemia (CML) failing to respond or not tolerating imatinib, dasatinib or nilotinib in first chronic phase of disease; CML in accelerated phase, second chronic phase, or in complete remission (CR) after accelerated phase or blast crisis\r\n* Non-Hodgkin lymphoma (NHL) with chemo responsive disease in any of the following categories:\r\n** Intermediate or high grade lymphomas who have failed to achieve a first CR or have relapsed following a st remission who are not candidates for autologous transplants\r\n** Any NHL in remission which is considered not curable with chemotherapy alone and not eligible/appropriate for autologous transplant\r\n* Myelodysplastic syndrome (MDS): refractory anemia (RA)/refractory cytopenia with multilineage dysplasia (RCMD) with high risk cytogenetic features or transfusion dependence, refractory anemia with excess blasts (RAEB)- and RAEB-\r\n* Chronic myelomonocytic leukemia (CMML): CMML- and CMML-
Must have a high risk hematologic malignancy as defined below; if the patient does not meet defined eligibility requirements as stipulated below, the principal investigator (PI) must be contacted to determine eligibility:\r\n* Acute myeloid leukemia (AML)\r\n** Patients with AML in the first complete remission (CR) with intermediate or high risk disease\r\n** Patients with AML in first CR with high-risk disease as defined by one of the following abnormalities; CR is defined as an M marrow (< % blasts by morphology), no evidence of extramedullary disease, and an absolute neutrophil count >= . x ^/L; cases where the ANC is < . x ^/L and rising will also be considered; the PI will need to approve such cases for enrollment; complete remissions without platelet recovery (CRp) will be considered complete remissions
Indicators of High-risk Disease are as follows:\r\n*** Fms-related tyrosine kinase  (Flt)/internal tandem duplication (ITD)+ (If quantitative testing was performed, the allelic ratio must be > .)\r\n*** Residual marrow disease (>= .%) detected by multidimensional flow cytometry after completing at least one cycle of induction chemotherapy\r\n*** Secondary AML; if the AML is secondary to treatment for another malignancy, the first malignancy must be in a complete remission\r\n*** High-risk cytogenetic abnormalities: Different high-risk cytogenetic criteria have been defined for adult and pediatric AML; we will, therefore, use two sets of cytogenetic criteria, one based on Childrens Oncology Group (COG) criteria for pediatric patients and one based on Southwestern Oncology Group (SWOG)/Eastern Oncology Group (ECOG) or Medical Research Council (MRC) criteria for adult patients; examples of high-risk cytogenetics: adult patients (>=  years): -/deletion (del) (q), -/del (q), inversion (inv)q, del (q), abnormality (abn)q, abn q, abnq, abnP, translocation (t)(;), t(;), complex karyotypes (>=  unrelated abnormalities); pediatric patients (<  years): -/del(q), -\r\n*** Other abnormalities associated with a higher risk for AML relapse; there are an increasing number of abnormalities being identified that have been associated with an intermediate or high risk of relapse, but have yet to be incorporated into cooperative group risk classification systems; patients with AML characterized by these abnormalities will be considered; the PI will need to approve such cases for enrollment\r\n** Patients with a partial first remission (PR, defined as an M marrow (-% blasts by morphology), no evidence of extramedullary disease, and an absolute neutrophil count >= . x ^/L; cases where the ANC is < . x ^/L and rising will also be considered; the PI will need to approve such cases for enrollment\r\n** Patients in nd or greater complete or partial remission\r\n* Myelodysplastic syndrome\r\n** Adult patients (>=  years) with secondary disease or de novo disease that meets criteria for intermediate, high or very high-risk disease based on the Revised International Prognostic Scoring System; Intermediate risk (.-. points), high risk (.- points), very high risk (>  points) \r\n** Pediatric patients with myelodysplastic syndrome (MDS), regardless of subtype, will be eligible\r\n* Acute lymphoblastic leukemia (ALL):\r\n** Given the poor prognosis of adults (>=  years) with ALL, adults in st or greater complete remission will be eligible; CR is defined as an M marrow (< % blasts), no evidence of extramedullary disease, and an absolute neutrophil count >= . x ^/L; cases where the ANC is < . x ^/L and rising will also be considered; the PI will need to approve such cases for enrollment; complete remissions without platelet recovery (CRp) will be considered remissions\r\n** Given the generally good prognosis of children (<  years) with ALL, they will have to meet one of the criteria listed below; additionally, children who are enrolled on a COG ALL trial for newly diagnosed or relapsed disease will have to meet the criteria for bone marrow transplant (BMT) outlined in that trial; CR is defined as an M marrow (< % blasts), no evidence of extramedullary disease, and an absolute neutrophil count (ANC) >= . x /L; cases where the ANC is < . x ^/L and rising will also be considered; the PI will need to approve such cases for enrollment; complete remissions without platelet recovery (CRp) will be considered remissions\r\n*** In st complete remission with a very high risk for relapse:\r\n**** Hyplodiploidy (<  chromosomes, as evidenced by the results of routine analysis of G-banded chromosomes, deoxyribonucleic acid (DNA) index (< .), or other appropriate methodology)\r\n**** > % residual marrow blasts by flow cytometry at the end of induction\r\n**** > .% residual marrow blasts by flow cytometry at the end of consolidation\r\n**** Early T-Cell Precursor (ETP) phenotype\r\n*** In nd complete remission with B-lineage disease after a marrow relapse occurring less than  months from diagnosis\r\n*** In nd complete remission with T-lineage disease or Philadelphia chromosome positive (Ph+) disease after a marrow relapse occurring at any time\r\n*** In a nd complete remission with T-lineage disease after an extra-medullary relapse occurring less than  months from diagnosis\r\n*** In rd or greater complete remission after a marrow or extramedullary relapse\r\n*** Other indications for transplant in pediatric patients with ALL must be approved by the study PI with a note to file reflecting study team discussion
Acute Lymphoblastic Leukemia (ALL) in first complete remission (CR) that is NOT considered favorable-risk as defined by the presence of at least one of the following:\r\n* Adverse cytogenetics such as t(;), t(;), t(;), other mixed lineage leukemia (MLL) rearrangements\r\n* White blood cell counts of greater than ,/mcL (B-ALL) or greater than ,/mcL (T-ALL) at diagnosis\r\n* Recipient age older than  years at diagnosis\r\n* Time to CR greater than  weeks
Acute Myelogenous Leukemia (AML) in first complete remission (CR) that is NOT considered as favorable-risk; favorable risk is defined as having one of the following:\r\n* t(,) without CKIT mutation\r\n* inv() without CKIT mutation or t(;)\r\n* Normal karyotype with mutated nucleophosmin (NPM) and not fms-related tyrosine kinase (FLT)-IND\r\n* Normal karyotype with double mutated CCAAT enhancer binding protein alpha (CEBPA)\r\n* Acute promyelocytic leukemia (APL) in first molecular remission at end of consolidation
Acute myeloid leukemia (AML) with any of the following:\r\n* In first remission (CR) with intermediate risk or high-risk cytogenetic and/or molecular features\r\n* Patients in second or subsequent complete remission (CR, CR, etc.)\r\n* Primary refractory or relapsed AML with no more than any one of the following adverse additional features according to modified Center for International Blood and Marrow Transplant Research (CIBMTR) criteria\r\n** Duration of first CR <  months\r\n** Poor risk cytogenetics or molecular features (FLT- internal tandem duplication [ITD]; complex karyotype with >=  clonal abnormalities, q-/-, q-/-, q abnormalities, inv(), monosomal karyotype)\r\n** Circulating peripheral blood blasts at time of enrollment\r\n** Karnofsky performance status < %
Considered at high risk for relapse as defined by:\r\n* The presence of >=  of the following: failure to achieve complete response (CR) post initial treatment; relapsed disease with an initial remission duration of <  months; or extranodal involvement at the start of pre-transplant salvage therapy
Acute lymphoblastic leukemia (ALL) second or greater complete remission (CR); first complete remission (CR) unable to tolerate consolidation chemotherapy due to chemotherapy-related toxicities; CR high-risk ALL; high risk ALL is defined as having one of the following:\r\n* Evidence of high risk cytogenetics such as t(;), t(;), t(;), other MLL rearrangements, IKZF\r\n*  years of age or older at diagnosis\r\n* White blood cell counts of greater than ,/mcL (B-ALL) or greater than ,/mcL (T-ALL) at diagnosis\r\n* Central nervous system (CNS) leukemia involvement during the course of disease\r\n* Slow cytologic response (> % lymphoblasts in bone marrow on day  of induction therapy)\r\n* Evidence of persistent immunophenotypic or molecular minimal residual disease (MRD) at the end of induction and consolidation therapy
Acute myelogenous leukemia (AML) and related precursor neoplasms: nd or greater complete remission (CR); first complete remission (CR) in patients >  years old; CR in =<  years old that is NOT considered as favorable-risk; favorable risk is defined as having one of the following:\r\n* t(,) without cKIT mutation\r\n* inv() or t(;) without cKIT mutation\r\n* Normal karyotype with mutated NPM and wild type FLT-ITD\r\n* Normal karyotype with double mutated CEBPA\r\n* Acute prolymphocytic leukemia (APL) in first molecular remission at end of consolidation
Acute myeloid leukemia (AML) in first remission with high-risk features or in second or higher remission
Acute lymphoblastic leukemia (ALL) in first remission with high-risk features or in second or higher remission