Within 60 days after bone marrow biopsy confirmed remission after the patients recover from their last course of chemotherapy, the goal will be to consent the eligible patient prior to the remission confirmation bone marrow biopsy at the end of the planned chemotherapy); ideally, the research samples will be collected during the bone marrow biopsy, and the patient will be enrolled to the study within 2 weeks of the bone marrow biopsy; if there is delay to enroll the patient after the bone marrow biopsy and research sample collection, it is ok not to repeat bone marrow biopsy within 4 weeks, after the last bone marrow biopsy, if there is no sign of disease relapse; a repeat bone marrow biopsy should be done if the delay of enrollment is more than 4 weeks after the last bone marrow biopsy; patients with confirmed remission within 60 days after the last bone marrow biopsy, without research samples collection, should have a repeat bone marrow biopsy conducted within two weeks prior to enrolling on the study
Bone marrow involvement (> 25%)\r\n* Note: bone marrow aspiration/biopsy can be performed at the time of diagnosis and does not need to be repeated unless there is a change in peripheral blood counts or it was performed more than 14 days prior to study entry
Patients with bone marrow failure syndromes
One of the following Ph-like ALL genetic lesions must be present in the diagnostic bone marrow or peripheral blood sample:
STEP I: Patients must be diagnosed with symptomatic standard-risk multiple myeloma (SR-MM) as defined by all of the following (except gene expression profile [GEP]70 status if unknown):\r\n* No evidence of t(14;16) by fluorescence in situ hybridization (FISH) testing on bone marrow or not available\r\n* No evidence of t(14:20) by FISH testing on bone marrow or not available\r\n* No evidence of deletion 17p by FISH testing on bone marrow\r\n* FISH should be from within 90 days of registration\r\n** NOTE: If the FISH result states that no immunoglobulin heavy chain (IgH) abnormality is present, both t(14;16) and t(14;20) can be considered negative; in addition, if the patient has a t(11;14) or t(4;14) translocation present, they can be considered negative for t(14;16) and t(14;20); if testing for t(14;16) or t(14;20) could not be performed for lack of sufficient material or non-availability of the probe in the test panel, patients can be enrolled on the study\r\n* Standard Risk GEP70 signature within the past 90 days (only if GEP has been done and results are available)\r\n** NOTE: GEP testing is NOT a requirement for the study; if the test has been done, patients found to have a GEP70 status of high-risk will not be eligible\r\n* Serum lactate dehydrogenase (LDH) =< 2 x upper limit of normal (ULN) within the past 28 days\r\n* No more than 20% circulating plasma cells on peripheral blood smear differential or 2,000 plasma cells/microliter on white blood cell (WBC) differential of peripheral blood within the past 90 days\r\n** NOTE: This is NOT the plasma cell % from the marrow aspirate
Diagnostic bone marrow and peripheral blood specimens must be submitted for immunophenotyping and selected molecular testing, and the establishment of BCR/ABL status; testing will be performed by the Eastern Cooperative Oncology Group (ECOG)-American College of Radiation Imaging Network (ACRIN) Leukemia Translational Research Laboratory (LTRL) and reported to the institution\r\n* NOTE: IT IS ESSENTIAL THAT A SAMPLE CONTAINING SUFFICIENT BLAST CELLS BE SUBMITTED TO THE ECOG-ACRIN LTRL AT BASELINE SO THAT SUBSEQUENT BONE MARROW ASSESSMENTS OF MRD CAN BE DONE; IN ADDITION TO ALLOWING THE LTRL TO CONFIRM ELIGIBILITY BASED ON BLAST CELL IMMUNOPHENOTYPE AND BCR/ABL STATUS, IT IS ALSO IMPERATIVE THAT AN ADEQUATE NUMBER OF BLASTS BE BANKED FOR ANALYSIS BY DRS MULLIGHAN/WILLMAN. WITHOUT ADEQUATE BASELINE SAMPLES, PATIENTS WILL NOT BE ABLE TO BE TREATED AND RANDOMIZED ON THIS PROTOCOL; IF A BONE MARROW ASPIRATE IS NOT AVAILABLE FOR LTRL SUBMISSION AT BASELINE, IT IS IMPERATIVE THAT DR PAIETTA FROM THE LTRL IS CALLED TO DISCUSS THE PERIPHERAL BLOOD WBC AND BLAST COUNT BEFORE BLOOD ONLY IS SUBMITTED\r\n* NOTE: Hydroxyurea can be given for up to 5 days prior to initiation of protocol therapy for control of leukocyte count and/or other symptoms or signs; corticosteroids can be given after pre-registration to the protocol and submission of baseline marrow and blood samples for control of leukocyte count and/or other symptoms or signs prior to initiation of protocol therapy if needed; if corticosteroids are given prior to pre-registration, contact the study chair as the patient may still be eligible to participate
New diagnosis of B lineage ALL must be made upon bone marrow or peripheral blood immunophenotyping; cases with myeloid antigen expression, but unequivocal lymphoid immunophenotype, are eligible
Mature B ALL (Burkitt’s-like leukemia) is excluded from enrollment in this trial; pre-study bone marrow biopsy and aspirate must be completed =< 1 week prior to registration
Patients must have maintained peripheral blood evidence of a remission and must have a CR or CRi, confirmed on restaging bone marrow (BM) aspirate and biopsy
Bone marrow aspirates must be submitted for centralized minimal residual disease (MRD) assessment performed by the ECOG-ACRIN Leukemia Translational Research Laboratory
For patients pre-registering before the start of radiation therapy documentation of bone marrow aspirate and biopsy containing < 10% clonal plasma cells; radiation therapy should preferably begin within 28 days after bone marrow biopsy
Bone marrow aspirate and biopsy containing < 10% clonal plasma cells performed after completion of RT and within 28 days prior to registration
Patients must have bone marrow biopsy performed within 42 days prior to registration
Patients must be newly diagnosed with a clinical diagnosis of APL (initially by morphology of bone marrow or peripheral blood)\r\n* Bone marrow is highly preferred but in cases where marrow cannot be obtained at diagnosis, peripheral blood will be accepted
Patients with isolated myeloid sarcoma (myeloblastoma, chloroma, including leukemia cutis) but without evidence of APL by bone marrow or peripheral blood morphology are excluded
All newly diagnosed patients must have evidence of ALL in their marrow or peripheral blood with at least 20% lymphoblasts present in blood or bone marrow collected within 28 days prior to registration; all relapsed/refractory patients (Cohort 2) must have at least 5% lymphoblasts present in blood or bone marrow collected within 28 days prior to registration; for relapsed/refractory patients, pathology and cytogenetics reports (both from time of original diagnosis) must be submitted at time of registration; if a bone marrow aspirate cannot be obtained despite an attempt (dry tap), appropriate immunohistochemistry (IHC) testing, including CD19, must be performed on the bone marrow biopsy to determine lineage; for ALL in marrow or peripheral blood, immunophenotyping of the blood or marrow lymphoblasts must be performed to determine lineage (B cell, T cell or mixed B/T cell); appropriate marker studies including cluster of differentiation (CD)19 (B cell), must be performed; co-expression of myeloid antigens (CD13 and CD33) will not exclude patients; if possible, the lineage specific markers (myeloid cells) should be determined; the blood/bone marrow sample for these assays must be obtained within 28 days prior to registration; patients with only extramedullary disease in the absence of bone marrow or blood involvement are not eligible
Registration Step 3 – Maintenance: Patients must have documented CR or CRi within 28 days prior to registration; note that bone marrow examination is only required if there are clinical signs/symptoms of progression; if progression is a concern due to the length of the time for count recovery, a bone marrow examination is recommended
Hemoglobin >= 8.0 g/dL for patients with solid tumors and known bone marrow metastatic disease
Subjects without bone marrow metastases must have an ANC > 750/?l to begin treatment.
Subject must be willing to provide fresh bone marrow samples during Screening (and prior to study treatment, if required).
Bone marrow aspirate samples have been collected.
Willing and able to undergo a pre-treatment bone marrow aspirate and biopsy and subsequent bone marrow aspirates and biopsies during treatment Specifically for participants in Arm A:
Patient consent to collection of fresh bone marrow biopsy and aspirate for exploratory research obtained from a procedure performed no more than 28 days prior to initiating treatment on cycle 1, day 1
Not willing to undergo, not a candidate for, or not having a donor for immediate (within 3 months from the Screening date) bone marrow transplantation.
Participants with any abnormal cytogenetics in the bone marrow not related to the lymphoma, and not deemed to be constitutional
Patients are able and willing to provide bone marrow biopsies/aspirates as requested by the protocol
Bone marrow specimen will be required at study entry; available deoxyribonucleic acid (DNA) sample from pre-induction bone marrow (BM) will be used for calibration step for MRD evaluation by gene sequencing
A bone marrow biopsy must be performed within four weeks prior to cycle 1 day 1 treatment to establish the baseline fibrosis score, and consent is required prior to that bone marrow biopsy to assure tissue is collected for protocol mandated testing
Bone marrow biopsy within 28 days of study drug infusion demonstrating at least 5% plasma cell involvement
Receipt of radiotherapy to >25 % of bone marrow.
Patients with relapsed or refractory SAA or very SAA defined:\r\n* Bone marrow (< 25% cellular)\r\n* Peripheral cytopenias (at least 2 of 3)\r\n** ANC < 500 per ml\r\n** Platelets < 20,000 per ml\r\n** Absolute reticulocytes (retic) < 60,000 or corrected retic < 1%\r\n* Very severe: as above, but ANC < 200\r\n* Disease may be designated as acquired or inherited if previous counts known (these other bone marrow failure disorders that are characterized by aplastic anemia may go by additional names such as dyskeratosis congenita or paroxysmal nocturnal hemoglobinuria [PNH])\r\n* Failed at least one course of immunosuppressive therapy (if presumed acquired disease); patients with inherited disease will be characterized as refractory and do not require immunosuppressive first
If post allogeneic SCT must not have less than 50% donor chimerism in either peripheral blood or bone marrow
Known bone marrow disorders which may interfere with bone marrow recovery or participants with delayed recovery from prior chemoradiotherapy
? 30% bone marrow blasts with at least 20% cellularity at mid-cycle bone marrow biopsy or residual AML on subsequent~ day 28 bone marrow biopsy by morphology, flow, PCR or FISH
Agree to undergo a tumor/bone marrow biopsy of at least one metastatic site
Suitable for imminent bone marrow transplant, or within 4 weeks of one.
During the 4 weeks prior to inclusion in study, subjects must have a baseline bone marrow examination including all of the following:\r\n* Cytomorphology to confirm bone marrow blasts;\r\n* Cytogenetics; AND\r\n* Eastern Cooperative Oncology Group (ECOG) status 0-2
Bone marrow cellularity < 25% or marrow cellularity < 50% but with < 30% residual hematopoietic cells.
In the haplo cohort, the potential donor must be willing to donate bone marrow.
Have histologically or cytologically confirmed recurrent AML as defined by >= 5% myeloblasts by manual aspirate differential of bone marrow biopsy
Able to provide bone marrow biopsy samples
Bone marrow: > 25% donor T-cell chimerism in peripheral blood, obtained after 3 weeks post-transplant; ANC >1 x 10E9/L
Myelodysplastic syndromes: diagnosis of very low or low risk MDS (biologically defined as low-risk MDS) by Revised-International Prognostic Score (R-IPSS), pathologically confirmed by a bone marrow aspirate and biopsy prior to registration; blast count must be < 20%\r\n* Bone marrow aspirate can be obtained from the subject at any time after the subject has given consent; the subject must be registered to the study within 30 days of obtaining the aspirate; (Note: if diagnostic bone marrow is obtained within 30 days prior to registration, a portion of the bone marrow aspirate collected may be used for research baseline sample to alleviate a second biopsy)
Newly diagnosed lower GI grade II-IV aGVHD with clinical diagnosis based on modified Keystone criteria1 following allogeneic HSCT using bone marrow, peripheral blood stem cells, or cord blood. Grading of aGVHD will be based on International Bone Marrow Transplant Registry (IBMTR) criteria.
< 25% bone marrow involvement of cellular marrow with lymphoma as determined by bilateral bone marrow aspirate and biopsy; NOTE: the percent involvement should be estimated by the hematopathologist using all of the biopsy material
Marrow cellularity =< 15% (as determined on all bone marrow samples)
Documentation of CT7, MAGE-A3, or WT1 expression in the bone marrow and/or bone marrow aspirate
In morphologic remission (< 5% marrow blasts) based on bone marrow (BM) biopsy performed +/- 5 days of day 28 post-transplantation
Bone marrow fibrosis that leads to a dry tap
Known bone marrow dysplasia
Evidence of relapsed/recurrent/residual disease as assessed by bone marrow aspirate and biopsy performed within 42 days prior to study entry
Measurable MRD in bone marrow within 28 days prior to registration (MPF method)
Leukocytes ? 750/mcL\r\n* If these cytopenias are not judged by the investigator to be due to underlying disease (i.e. potentially reversible with anti-neoplastic therapy); a subject will not be excluded because of pancytopenia ? grade 3 if it is due to disease, based on the results of bone marrow studies
Platelets ? 50,000/mcL\r\n* If these cytopenias are not judged by the investigator to be due to underlying disease (i.e. potentially reversible with anti-neoplastic therapy); a subject will not be excluded because of pancytopenia ? grade 3 if it is due to disease, based on the results of bone marrow studies
Evidence of myelodysplasia or cytogenetic abnormality indicative of myelodysplasia on any bone marrow biopsy prior to initiation of therapy.
Diagnosis of myelofibrosis or other malignancy with moderate-severe bone marrow fibrosis.
Myeloblasts account for less than 20% of leukocytes on peripheral blood and bone marrow aspirate
Myeloblast count ? 20% in peripheral blood or bone marrow aspirate
Hemoglobin ?8.0 g/dL (Grade ?2) maintained for ?1 week from any prior transfusion. Note: Grade ?3 neutropenia, thrombocytopenia, or anemia is permitted if the abnormality is related to bone marrow involvement with hematological malignancy (as documented by bone marrow biopsy/aspirate obtained since the last prior therapy).
Adults up to 68 y/o with any of following: acute leukemia (ALL or AML), myelodysplasia, aplasia, and/or therapy (chemotherapy or radiation) induced bone marrow aplasia or hypoplasia with thrombocytopenia (platelet count ? 5,000 and ? 70,000/?L) for a minimum of 2 days. May include bone marrow transplant or peripheral or cord blood stem cell recipients, but not subjects with Graft-vs-Host disease.
Patients with known bone marrow metastatic disease will not be eligible
Patients must have > 20% plasma cells in the bone marrow aspirate differential <60 days prior to enrollment. The required bone marrow evaluation will need to be repeated for patients who received more than 1 cycle of anti-myeloma therapy (corticosteroid with or without other anti-myeloma agents)
In subjects previously treated with blinatumomab, CD19 tumor expression in bone marrow or peripheral blood.
Platelets >= 75,000/uL, if plasma cell percentage on bone marrow biopsy aspirate or core is > 30%, platelet eligibility requirement will be adjusted to 60,000/ul
Patients with cytopenias attributable to bone marrow lymphomatous bone marrow involvement per current bone marrow biopsy may be enrolled if other inclusion criteria are met
Bone marrow dysplasia
Patients with newly diagnosed AML based on the World Health Organization classification who have persistent leukemia after a course or more of treatment with induction chemotherapy (the diagnosis of persistent disease, which is defined as > 10% blasts by evaluation of bone marrow biopsy or bone marrow aspirate)
Be willing to provide tissue from bone marrow biopsies
Be willing to provide tissue from a bone marrow biopsy if suspected involvement and/or lymph node at enrollment as well as a repeat bone marrow biopsy (if involved at diagnosis) after 3 of therapy and at the time of progression and/or completion of therapy whichever comes first
Has acute promyelocytic leukemia as diagnosed by morphologic examination of bone marrow, by fluorescent in situ hybridization or cytogenetics of peripheral blood or bone marrow, or by other accepted analysis.
Another bone marrow malignancy
Bone marrow dysplasia
Documented complete remission with full donor engraftment (by short tandem repeat [STR] identity testing) on day +30 bone marrow biopsy
Confirmed histologic diagnosis on bone marrow biopsy and aspirate within 14 days of trial entry prior to starting cycle 1.
Greater than 50% lymphoblasts on screening bone marrow aspirate or biopsy
Corticosteroids and hydroxyurea are permitted after screening bone marrow biopsy is performed and for up to 7 days prior to starting study therapy
During the 8 weeks prior to inclusion in study, subjects must have a baseline bone marrow examination including all of the following:\r\n* Cytomorphology to confirm bone marrow blasts\r\n* Cytogenetics
> 10% bone marrow blasts at transplant if no history of AML and > 5% if had previous progression to AML (in a bone marrow biopsy 4 weeks prior to start of conditioning on study)
All patients must be willing to undergo a mandatory serial bone marrow aspirate and/or biopsy at screening and subsequently following treatment for the assessment of biomarker/pharmacodynamics and disease status. Exceptions may be considered after documented discussion with Novartis.
Bone marrow aspirate after completion of therapy demonstrates detectable DTCs (via IHC)
Hemoglobin >= 8.0 g/dL – may be waived if abnormalities are due to disease related bone marrow involvement, within 14 days of study registration (within 30 days for pulmonary and cardiac assessments)
Patients with prolonged pre-existing hematological toxicities including known indicators of bone marrow failure or abnormality
CELL PROCUREMENT: Relapsed or refractory precursor B cell ALL:\r\n* Second or greater bone marrow relapse OR\r\n* Any bone marrow relapse >100 days after allogeneic stem cell transplant OR\r\n* Primary refractory ALL defined as no complete response after 2 cycles of a standard of care chemotherapy regimen OR\r\n* For adult subjects: first bone marrow relapse with duration of first complete response (CR) < 1 year OR CR1 duration >= 1 year and refractory to >= 1 cycle of therapy for treatment of relapse\r\n* Subjects with isolated non-central nervous system (CNS) extramedullary disease will be eligible as long as the time-of-remission criteria above for bone marrow relapses or primary refractory ALL are met and the biopsy for extramedullary disease confirms CD19 expression\r\n* For pediatric subjects: first bone marrow or isolated non-CNS extramedullary relapse refractory to 1 cycle of standard therapy for relapsed ALL\r\n* While active CNS3 leukemia will be excluded, subjects with concurrent CNS3 disease and bone marrow relapse who have responded to CNS-directed therapy prior to enrollment will be allowed to participate; intrathecal chemotherapy will be allowed to continue between lymphodepleting chemotherapy and cell infusion\r\n* Subjects with CNS2 disease and concurrent bone marrow relapse will be eligible; intrathecal chemotherapy will be allowed to continue between lymphodepleting chemotherapy and cell infusion
Presence of >= 10% blast by morphologic examination of bone marrow aspirate or biopsy
Outside diagnostic material is acceptable as long as peripheral blood and/or bone marrow slides are reviewed at the study institution; flow cytometric analysis of peripheral blood and/or bone marrow should be performed according to institutional practice guidelines
Bone marrow aspirates/biopsies should be performed within 30 +/- 3 days from registration to confirm disease remission status
Unwilling or unable to undergo serial bone marrow aspirate/biopsy
Persisting (> 8 weeks) severe pancytopenia due to hematologic disorder or due to previous therapy rather than disease (ANC < 0.5 x 109/L or platelets < 30 x 109/L) - to be confirmed via bone marrow biopsy, as part of normal clinical care, prior to signing of consent.
Patients with bone marrow metastatic disease will not be eligible
Confirmed diagnosis of SAA (acquired or inherited), either from initial diagnosis or follow-up assessments, defined as:\r\n* Bone marrow hypocellularity is required and relative to patient’s age (normocellularity is 100- patient age in years)\r\n** Often marrow cellularity < 50% but with < 30% residual hematopoietic cells may be applied where appropriate at the discretion of the principal investigator (PI)\r\n* Two out of three of the following (in peripheral blood): neutrophils < 0.5 x 10^9/L, platelets < 20 x 10^9/L (without transfusions), reticulocyte count < 60 x 10^9/L
The potential donor must be willing to donate bone marrow
Isolated extramedullary leukemia without also meeting bone marrow criteria for acute leukemia (ie, ?20% blasts in bone marrow aspirate)
Elevated expression above of WT1 in pre-treatment bone marrow or peripheral blood by either of two methods:\r\n* Increased expression of WT1 determined if the number of copies of WT1 divided by the number of copies of ABL x 10^4 is > 250 for bone marrow, or > 50 for peripheral blood; \r\n* Demonstration of WT1 overexpression will be determined by immunohistochemical staining (IHC) in blasts as compared to adjacent normal myeloid and erythroid precursors, as determined by a Fred Hutchinson/Seattle Cancer Care Alliance pathologist
ELIGIBILITY FOR APHERESIS/BLOOD COLLECTION:\r\n* Human leukocyte antigen (HLA)-A*02:01 expression\r\n* Elevated expression above of WT1 in bone marrow or peripheral blood: increased expression of WT1 will be determined if the number of copies of WT1 divided by the number of copies of ABL x 10^4 is > 250 for bone marrow, or > 50 for peripheral blood; or when available, demonstration of WT1 overexpression will be determined by immunohistochemical staining (IHC) in blasts as compared to adjacent normal myeloid and erythroid precursors, as determined by Fred Hutchinson/Seattle Cancer Care Alliance hematopathology
Elevated expression above baseline of WT1 in bone marrow or peripheral blood
Either bone marrow or peripheral blood is allowed
Outside diagnostic material is acceptable as long as peripheral blood and/or bone marrow slides are reviewed at the study institution by appropriate clinical staff; flow cytometric analysis of peripheral blood and/or bone marrow should be performed according to institutional practice guidelines
High risk AML and MDS patients will be included; cohort 1: morphological relapse after stem cell transplant: \r\n* MDS patients: re-appearance of dysplastic changes in the bone marrow, with or without increase in bone marrow last count, which is pathologically consistent with myelodysplastic syndrome; \r\n* AML patients: bone marrow blast count >= 5%
Congenital bone marrow failure syndrome
Bone marrow tumour infiltration <25% tumour cells.
Subjects must be able and willing to provide bone marrow biopsies/aspirates as requested by the protocol
Patients with disease only in the bone may not have received Xofigo/radium 223 to avoid ongoing DNA damage in bone marrow
Depressed bone marrow
ANC ? 750 - cannot be transfused (must be ? 72 hours from last neutrophil infusion) However, the plt and ANC requirements can be waived if low counts thought to be secondary to leukemia or tumor bone marrow infiltration
Subjects must have bone marrow with >= 5% blasts (M2 or M3 marrow) definitively identified either on a bone marrow aspirate or biopsy sample, as assessed by morphology, immunohistochemical studies, flow cytometry, karyotype, cytogenetic testing such as fluorescent in situ hybridization (FISH) or other molecular studies
Bone marrow depression or hematologic parameters in the range that would increase the risk for severe bleeding
Gastrointestinal or bone marrow or spleen only patients are allowable
Non-secretory disease measurable with bone marrow biopsy or radiography.
Myelodysplastic syndrome. If clinically significant anemia or pancytopenia exists, documentation of a bone marrow aspirate within 24 months prior to the first dose of PRTX-100 showing no evidence of myelodysplasia is required.
Patients with solid tumors not metastatic to bone marrow:
Bone marrow specimen from diagnosis (or pre-induction) will be required at study entry; available deoxyribonucleic acid (DNA) sample will be used for calibration step for MRD evaluation by gene sequencing
Multiple myeloma in complete remission is defined as per Durie BG et al.:\r\n* Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and =< 5% plasma cells in the bone marrow; CR requires two consecutive assessments by serum and urine immunofixation made at any time prior to enrollment; CR also requires no known evidence of progressive or new bone lesions if radiographic studies are performed; confirmation with repeat bone marrow is not needed
Received previous radiotherapy to approximately > 25% of bone marrow
Bone marrow (BM) harvest required to reach adequate cell dose for transplant
INCLUSION CRITERIA FOR ADDITIONAL PTCy-MILs INFUSION AT RELAPSE: Donor CD3+ chimerism >= 30% measured in peripheral blood or bone marrow
No option for immediate bone marrow transplant unless patient refuses this therapy
To be eligible for this protocol the patient must have AML not in remission defined as greater than >= 5% myeloblasts by aspirate morphology as determined by a bone marrow aspirate and biopsy obtained within 2 weeks of study registration\r\n* In the event induction treatment results in a hypoplastic bone marrow status (< 10% cellularity), precluding accurate enumeration of blast percentages, the patient is still eligible if the preceding bone marrow aspirate contained >= 5% myeloblasts; to meet this condition, prior induction therapy must have been completed a minimum of 21 days prior to this result
Able and willing to provide bone marrow biopsies/aspirates as requested by the protocol.
Bone marrow with tumor cells seen on routine morphology
Patients with a diagnosis of acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or myelodysplastic syndromes (MDS) with fewer than 10% myeloblasts or lymphoblasts in the bone marrow and no blasts in the peripheral blood on morphologic analysis performed within 30 days of start of the conditioning regimen; if remission bone marrow is available beyond 30 days a new bone marrow evaluation is required to assess remission status\r\n* The diagnosis of AML, ALL, or MDS will be based on World Health Organization (WHO) criteria\r\n* Pre-transplant bone marrow sample must be evaluable for assessment of remission status (i.e. aspirate smear containing particles and/or evaluable bone marrow core biopsy)\r\n* Patients with leukemia infiltration in the central nervous system (CNS) are eligible if cerebrospinal fluid (CSF) cytospin is negative for myeloblasts or lymphoblasts at time of enrollment\r\n* If the patient has an intra-abdominal chloroma on presentation, and has a partial response or complete response to treatment (size reduction of chloroma and marrow blast < 10%), the patient is eligible; however the chloroma must be included as part of the treatment target
Relapsed or refractory AML as defined by one of the following criteria:\r\n* First relapse within 12 months after date of first complete response (CR) or complete response with incomplete bone marrow recovery (CRi)\r\n* Persistent AML documented by bone marrow biopsy at least 28 days after day 1 of the first induction cycle of cytotoxic chemotherapy\r\n* Hypercellular bone marrow with greater than 20% cellularity and 10% blasts at least 14 days after first induction cycle day 1
Bone marrow with >= 5% lymphoblasts
Histologic proof of neuroblastoma or positive bone marrow for tumor cells with increased urine catecholamines
Patients must have documented WT1 positive disease; for purpose of this study, this is defined as detectable presence of WT1 expression by immunohistochemistry or by WT1 transcript via real time-polymerase chain reaction (RT-PCR) on a bone marrow or other plasma cell-related biopsy specimen prior to autologous stem cell transplantation; bone marrow or other biopsy specimen from time of diagnosis from patients diagnosed at MSKCC or outside hospital may be requested for assessment of WT1 expression by IHC
Diagnosis of AML according to World Health Organization (WHO) diagnostic criteria (at least 20% blasts in the peripheral blood or bone marrow), with French-American-British Cooperative group (FAB) classification other than M3 (acute promyelocytic leukemia), documented by bone marrow aspiration and biopsy performed within 14 days prior to administration of 1st dose of remission induction chemotherapy; if a bone marrow aspirate and biopsy were obtained within 28 days prior to the first dose of remission induction therapy then these tests may be submitted for review at University of Southern California (USC) and a repeat screening bone marrow does not need to be conducted
No morphologic evidence of leukemia or active MDS as determined by JHH hematopathologist independent review of a bone marrow aspirate and biopsy done following the completion of therapy
Bone marrow hypocellular for age
Patients must be able to provide blood and bone marrow samples and undergo the procedures required for this protocol
In patients whose leukemic cells are available for evaluation, the expression of WT1 in the patient's bone marrow will be determined; if WT1 expression in the patient’s bone marrow is not highly expressed by polymerase chain reaction (PCR), the patient will be excluded from the study; patients with no evaluable leukemia will be eligible for enrollment based on the high frequency of positive leukemias (> 90%), and leukemia will be evaluated for WT1 expression if recurrence is detected
Donor myeloid engraftment (from peripheral blood or bone marrow) of at least 40% documented =< 60 days from protocol therapy; a bone marrow engraftment analysis should show the cluster of differentiation (CD)15+ fraction to be at least 40% for inclusion
No evidence of extranodal disease outside the chest including spleen and bone marrow.
Bone marrow (BM) harvest required to reach adequate cell dose for transplant
Willingness to undergo a pretreatment bone marrow biopsy and/or aspirate, or archival sample obtained since completion of most recent therapy (as appropriate to subjects with existing bone marrow disease or for whom bone marrow examination is a component of disease status assessment)
Demonstrate NOXA BH3 priming of ?40% by mitochondrial profiling in bone marrow or 30 - 39% for NOXA Exploratory Arm.
Evidence of poor bone marrow function (bone marrow cellularity less than 50% with at least one cytopenia) OR
Recipients will have satisfactory organ function (excluding bone marrow) and will have a Karnofsky activity assessment > 90% and will have:
Trephine biopsy is recommended (unless diagnosis can be confirmed by peripheral blood examination) in the event that bone marrow aspiration results in a \dry tap\
Diagnosis of hairy cell leukemia (HCL) established by bone marrow examination
If recent mold infection e.g. Aspergillus - must have minimum of 30 days of appropriate treatment before bone marrow transplant (BMT) and infection controlled and be cleared by Infectious Disease
Willing to provide research bone marrow aspirate specimen
Both granulocyte-colony stimulating factor (G-CSF) stimulated peripheral blood grafts and bone marrow grafts will be the priority, although bone marrow graft source will be allowed based upon donor preference
Presence of mutated BTK in ? 4% of peripheral blood or bone marrow CLL cells, or ?1% and rising on two separate measurements obtained at least 28 days apart.
Primary bone marrow failure;
Has a bone marrow examination performed within 14 days before baseline (C1D1).
Prior radiotherapy in the adjuvant setting allowed provided that less than 25% of the bone marrow had been irradiated
Patient with documented mastocytosis and evaluable disease based upon histological criteria: typical infiltrates of mast cells in a multifocal or diffuse pattern in skin and/or bone marrow biopsy
Relapsed following autologous bone marrow transplantation (BMT), or are ineligible, or refused BMT
Palliative bone-directed radiotherapy is permitted unless involving an area of ? 25% of bone marrow reserves and occurring within 5 weeks prior to the start of study treatment;
4. Sufficient and viable bone marrow aspirate or peripheral blood collection to use for the ex vivo sensitivity assay.
Is able and willing to provide protocol-defined bone marrow biopsies/aspirates Inclusion Criteria for Cohort 2 in Part 2 only:
Patients with >= 25% of the bone marrow radiated for other diseases
Other bone marrow failure syndromes or low grade (< 5% bone marrow blasts) MDS
Bone marrow biopsy (BMBx) within 28 days prior to first study treatment.
Willing and able to undergo a pre-treatment bone marrow aspirate and biopsy and subsequent bone marrow aspirates and biopsies during treatment
Newly-diagnosed AML patients according to World Health Organization (WHO) classification who are considered candidates for intensive chemotherapy based upon examination of peripheral blood or bone marrow aspirate specimens or touch preparations of the bone marrow biopsy obtained within two weeks prior to randomization; a bone marrow aspirate is required for enrollment; however, on occasion there is discordance between percentage of myeloblasts on the differential of the peripheral blood or aspirate; the peripheral blood criteria are sufficient for diagnosis; confirmatory immunophenotyping will be performed centrally
Diagnostic bone marrow and peripheral blood specimens must be submitted for immunophenotyping and selected molecular testing
Consolidation cycle 1 must commence within sixty days of the bone marrow aspirate and biopsy that confirmed the presence of a CR or CRi
Patients must have maintained peripheral blood evidence of a remission and must have a CR or CRi, confirmed on restaging bone marrow (BM) aspirate and biopsy and cytogenetic analysis
Subjects must be able and willing to provide bone marrow biopsies/aspirates and buccal mucosal sample as requested by the protocol
Willing and able to undergo a pre-treatment bone marrow biopsy and subsequent on-treatment bone marrow biopsies
Definitive radiotherapy (> 10 fractions and maximal area of hematopoietic active Bone Marrow treated greater than 25%) within 4 weeks prior to Screening
Acquired bone marrow failure syndromes
Congenital bone marrow failure syndrome
DONOR: Able and willing to have up to 3 separate mobilized apheresis collections performed or if unable to undergo apheresis agrees to a bone marrow harvest (requires additional consent)
Bone marrow plasma cells must make up 30% or less of total bone marrow cells based on a bone marrow biopsy performed within 30 days of the start of protocol treatment
Patients who have not passed the nadir of bone marrow suppression from previous anti-myeloma therapy yet; if in doubt, serial complete blood counts (CBCs) with differential should be obtained
Bone marrow aspirates/biopsies should be performed within 28 (+ 4 day window) days from registration to confirm disease remission status
Bone marrow lymphoplasmacytosis with:
Beta-human chorionic gonadotropin (B-HCG) will be performed on all women of child-bearing potential as screening prior to enrollment on this trial; signal transducer and activator of transcription 3 (STAT3) levels in the bone marrow will also be measured prior to enrollment; the B-HCG, STAT3 testing and bone marrow biopsy costs are not considered standard of care and have been included in the proposed budget
A subject will not be excluded because of pancytopenia >= grade 3 if it is due to disease, based on the results of bone marrow studies
Patients who received radiotherapy to more than 25% of their bone marrow
Patients who received radiotherapy to more than 25% of their bone marrow
Patients must have documented WT1 + disease; for purpose of this study, this is defined as detectable presence of any WT1 transcript via RT-PCR on a bone marrow performed at MSKCC within 4 weeks prior to the administration of the first dose of vaccine
Pregnancy at the time of bone marrow transplant (BMT)
Bone marrow dysplasia
Patients must have a unilateral or bilateral bone marrow biopsy performed within 42 days prior to registration
Diagnosed with PMF, PPV-MF or PET-MF as confirmed by bone marrow biopsy
2nd or greater Bone Marrow (BM) relapse OR
Bone marrow with ? 5% lymphoblasts by morphologic assessment at screening
2nd or greater Bone Marrow (BM) relapse OR.
Bone marrow with ? 5% lymphoblasts by morphologic assessment at screening.
Must be willing to consent to two or more bone marrow aspirate procedures to be completed during study.
Inaspirable bone marrow.
quantifiable bone marrow infiltration documented in a bone marrow biopsy during screening
Willing and able to undergo bone marrow aspirate per protocol (with or without bone marrow biopsy per institutional guidelines).
At least Grade 2 marrow fibrosis according to the WHO Grading of Bone Marrow Fibrosis;
Morphological or cytological features of myelodysplasia and/or post chemotherapy aplasia on bone marrow (BM) assessment.
Myelodysplastic Syndrome (MDS) according to World Health Organization (WHO) criteria confirmed by bone marrow aspirate and biopsy within 12 weeks prior to first dose. A local laboratory report from this diagnostic bone marrow aspirate and biopsy must be approved by the sponsor
RAEB 1 - defined as having 5% to 9% myeloblasts in the bone marrow.
WHO defined AML with 20% to 30% myeloblasts in the bone marrow and <30% myeloblasts in peripheral blood who are deemed by the investigator to be appropriate for azacitidine based therapy.
Ability to undergo the study required bone marrow sample collection procedures.
Acute promyelocytic leukemia as diagnosed by morphologic examination of bone marrow, by fluorescent in situ hybridization or cytogenetics of peripheral blood or bone marrow, or by other accepted analysis.
Outside diagnostic material is acceptable as long as peripheral blood and/or bone marrow slides are reviewed at the study institution; flow cytometric analysis of peripheral blood and/or bone marrow should be performed according to institutional practice guidelines
Patients with elevated catecholamines (i.e., > 2 x ULN) only or bone marrow disease only are NOT eligible for this study
Hematological values within the limits independent of growth factor support or transfusion unless cytopenia is caused by the underlying disease, i.e., no evidence of additional bone marrow dysfunction (e.g., myelodysplastic syndrome, hypoplastic bone marrow)
Current use of any chemotherapy agent likely to cause myeloablation (severe or complete depletion of bone marrow).
Subjects with clonal evolution in Ph+ cells observed in ?2 metaphases at baseline bone marrow cytogenetic test, unless the same abnormalities were present at diagnosis. Patients with no evidence of clonal evolution, including those patients whose cytogenetic testing fails or bone marrow aspiration is a dry tap at 3 months, are eligible for the study
Bone marrow cellularity of >= 50% of age defined normal values by core biopsy; cellularity must be evaluated within 90 days of the dosimetry infusion and at least 21 days after receiving any cytoreductive/myelosuppressive chemotherapy
Radiotherapy to ? 25% of the bone marrow within 4 weeks prior to randomization
Product planned for infusion is bone marrow
Subject consents to serial bone marrow aspiration and biopsies as specified.
Must have measurable disease, including one of the following: absolute lymphocyte count greater than 5000/uL, lymphadenopathy greater than 1.5 cm in longest dimension, splenomegaly (palpable at least 1 cm below the costal margin or radiographically enlarged), bone marrow biopsy with residual CLL cells, or resultant bone marrow dysfunction (platelet count < 100 k/uL, hemoglobin < 10 g/dL)
Patients with known metastatic tumor in the bone marrow
Gastrointestinal or bone marrow or spleen only patients are allowable and will be analyzed separately
Have a diagnosis of CLL based on peripheral blood flow cytometry and/or bone marrow aspiration and biopsy OR diagnosis of SLL based on lymph node or bone marrow biopsy; patients with SLL need to have measurable disease
Platelets >= 75,000/uL, if plasma cell percentage on bone marrow biopsy aspirate or core is > 30%, platelet eligibility requirement will be adjusted to 60,000/uL
For purposes of this study, bone marrow aspirate and biopsy are not considered surgical procedures and therefore are permitted within 14 days prior to start of protocol therapy
Patients with Ewing sarcoma metastatic to the bone marrow are not required to meet bone marrow criteria for study eligibility and are not evaluable for hematologic toxicity
For subjects in the Phase 2 portion of the trial, central testing of IDH2 mutation of bone marrow aspirate and peripheral blood, is required during screening to confirm eligibility
The diagnosis and evaluation of AML or MDS will be made by bone marrow aspiration and/or biopsy. If an aspirate is unobtainable (i.e., a \dry tap\), the diagnosis may be made from the core biopsy.
Screening bone marrow aspirate and peripheral blood samples are required of all subjects. A bone marrow biopsy must be collected if adequate aspirate is not attainable unless:
A bone marrow aspirate and biopsy was performed as part of the standard of care within 28 days prior to the start of the study treatment; and
Slides of bone marrow aspirate, biopsy and stained peripheral blood smear are available for both local and central pathology reviewers; and
A bone marrow aspirate sample acquired within 28 days prior to the start of study treatment has been sent for cytogenetic analysis.
Patients with relapsed/refractory disease must have morphologic proof (from bone marrow aspirate, smears or touch preps of bone marrow biopsy) of AML with >= 10% blasts within two weeks (14 days) prior to initiation of therapy\r\n* All immunophenotype and cytogenetic/molecular groups are eligible for participation except for acute promyelocytic leukemia (APL) (as proven by the presence of promyelocytic leukemia/retinoic acid receptor alpha [PML-retinoic acid-receptor-[RAR] alpha])
REGISTRATION INCLUSION CRITERIA: Presence of bone marrow ERBB2 overexpressing DTCs at the time of diagnosis; bone marrow aspiration will be performed in consented patients to evaluate DTCs following pre-registration provided patients meet all eligibility criteria
AML with a history of CMMoL: CMMoLAML must have bone marrow documentation of prior CMMoL
Patients must be available for follow-up evaluations at 30, 60, 180 days post bone marrow transplant (BMT) and yearly thereafter indefinitely
Bone marrow myelodysplasia and/or chromosomal abnormalities
Acute myeloid leukemia with a fms-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) who are in a complete remission or partial remission (less than 10% blasts in marrow) as documented by bone marrow biopsy and who plan to undergo a bone marrow transplantation
Patients with lack of engraftment (less than 90% donor deoxyribonucleic acid [DNA] in bone marrow or peripheral blood) after bone marrow transplant as evidence by RFLP (restriction fragment length polymorphism) are not eligible
Bone marrow with less than 15% lymphoma cells following salvage therapy; no evidence of myelodysplasia
Evidence of myelodysplasia on any bone marrow biopsy
ALL in first bone marrow relapse occurring > 18 months (> 540 days) from initial diagnosis; marrow must have >= 25% blasts (M3 marrow), either on an aspirate or biopsy sample, as assessed by morphology, flow cytometry, and/or immunohistochemistry; individuals with CNS, testicular or other extramedullary involvement are eligible as long as they also meet marrow involvement criteria
A bone marrow aspiration performed within 21 days prior to the start of pre-infusion preparative therapy confirms the patient is in CR1
Presence of circulating malignant lymphoid cells or bone marrow with lymphoma that constituted more than 25% of the cellular elements
Patients must have a bone marrow biopsy (bilateral preferred, unilateral acceptable) within 90 days prior to starting treatment
Less than 5% marrow involvement with NHL within 4 weeks of study as defined by unilateral bone marrow aspiration and biopsy
no more than 10% of the subject's bone marrow is irradiated
Patients with >= 20% bone marrow involvement or plasmacytoma amenable to resection under local anesthesia
Other bone marrow failure syndromes
Testing for extraneural metastasis by bone scan or bone marrow biopsy will not be performed routinely on this protocol; in the unlikely event that extraneural metastasis is detected on an evaluation performed at an outside institution prior to referral or because of clinical suspicion, such M4 patients will be eligible for protocol treatment on the high-risk arm
Recent bone marrow biopsy and cytogenetic analysis
Detectable tumor on radiographic studies or bone marrow biopsy prior to mobilization regimen
Bone marrow consistent with plasma cell dyscrasia
bone marrow exam is performed at screening and demonstrates quantifiable CLL.
Cytotoxic regimens are any that include agents that target the genetic and/or mitotic apparatus of the dividing cells, resulting in dose limiting toxicity to the bone marrow or gastrointestinal mucosa
First or greater bone marrow relapse from CR, or
Has already had a bone marrow biopsy and aspirate to assess remission status after induction therapy
DONOR: Meets institutional selection criteria for organ and bone marrow donation
Bone marrow biopsy must be negative for lymphoma.
Patients should be eligible for transplantation according to the Bone Marrow Transplant (BMT) Policy Manual
Requiring salvage chemotherapy for persistent/refractory or relapsed disease after at least one course of conventional chemotherapy, e.g. with “7+3”, as defined by persistence of >= 20% myeloid blasts on bone marrow aspirate or peripheral blood smear; a bone marrow biopsy is not routinely required, but should be obtained if the aspirate is dilute, hypocellular, or inaspirable; outside bone marrow examinations performed within the stipulated time period are acceptable for screening as long as the slides are reviewed at the study institution; flow cytometric analysis of the bone marrow aspirate should be performed according to institutional practice guidelines
Palliative radiation therapy (RT) for metastatic disease is allowed only if =< 25% of total body bone marrow was irradiated and < or = 35Gy administered to the pericardial area; 28 days must have elapsed since completion of RT with bone marrow recovery; soft tissue disease irradiated in the prior 2 months may not be designated as measurable disease
Monoclonal bone marrow plasmacytosis ?30% (evaluable disease)
Measurable disease by one of the following: radiographic criteria (>= 2 cm by computed tomography); lymphoma involving peripheral blood with more than 5000 leukemia cells/mm^3, or any degree of bone marrow infiltration on bone marrow biopsy; skin involvement with or without nodal or bone marrow involvement permitted for cutaneous lymphomas is also permitted
Prior pelvic radiation (e.g. external beam, brachytherapy, etc) that, in the opinion of the investigator, may lead to decreased bone marrow cellularity in a marrow sample obtained from a pelvic bone marrow biopsy
Extensive radiotherapy (to greater than 15% of bone marrow)
Ongoing anticoagulant therapy that cannot be held if necessary to permit bone marrow sampling.
Participants with known bone marrow disorders which may interfere with bone marrow recovery or participants with delayed recovery from prior chemoradiotherapy
Radiotherapy involving <25% of the hematopoietically active bone marrow within 21 days preceding first dose of study treatment
Radiotherapy involving ?25% of the hematopoietically active bone marrow within 42 days preceding first dose of study treatment
Prior radiotherapy to > 25% of bone marrow volume.
Pathological confirmation by bone marrow documenting the following:
All patients must be willing to undergo a mandatory bone marrow aspirate and/or biopsy at baseline for the assessment of biomarker/pharmacodynamics and disease status
DONOR: Meets institutional selection criteria for organ and bone marrow donation
Presence of phosphorylated p65 NF-kB component in at least 5% of bone marrow cells
Patient must be able/willing to undergo bone marrow aspirate and biopsy
Prior radiotherapy to >= 40% of bone marrow
Able to undergo bone marrow aspiration and biopsy at screening
Acute promyelocytic leukemia as diagnosed by morphologic examination of bone marrow, by fluorescent in situ hybridization or cytogenetics of peripheral blood or bone marrow, or by other accepted analysis
Patients must have peripheral blood and bone marrow aspirate specimens obtained within 28 days prior to registration submitted for translational medicine; with patient consent, residuals will be banked for future research
Relapsed/persistent disease according to standard criteria requiring salvage therapy; outside diagnostic material is acceptable as long as peripheral blood and/or bone marrow slides are reviewed at the study institution; flow cytometric analysis of peripheral blood and/or bone marrow should be performed according to institutional practice guidelines
Patients with severe pancytopenia not meeting the above criteria for cell counts due to documented, extensive MM involvement of the bone marrow (suggested by >= 50% bone marrow plasmacytosis) will be eligible for enrollment
Patients must have unilateral or bilateral bone marrow biopsy performed within 42 days prior to registration
Any amount of neuroblastoma tumor cells in the bone marrow based on routine morphology (with or without immunocytochemistry) in at least one sample from bilateral aspirates and biopsies.
For patients enrolling in Stage 2, the bone marrow evaluation determined locally within the previous 6 months indicates the presence of MRD.
Unable to tolerate bone marrow biopsy
Relapsed disease is defined as the reappearance of leukemia cells in the bone marrow or peripheral blood or elsewhere in the body (other tissues/organs) after the attainment of a CR.
Available donor able to undergo a bone marrow harvest; for matched unrelated donor transplants only: peripheral blood stem cells may be collected if donor is unavailable for bone marrow harvest or if adequate bone marrow cannot be collected
Substantial radiotherapy to the bone marrow within 6 weeks prior to enrollment.
Bone marrow cellularity less than 25% or marrow cellularity less than 50% but with less than 30% residual hematopoietic cells
At pre-ASCT evaluation patients must meet the International Neuroblastoma Response Criteria (INRC) for CR, VGPR, or PR for primary site, soft tissue metastases and bone metastases; patients who meet those criteria must also meet the protocol specified criteria for bone marrow response as outlined below:\r\n* =< 10% tumor (of total nucleated cellular content) seen on any specimen from a bilateral bone marrow aspirate/biopsy\r\n* Patient who have no tumor seen on the prior bone marrow, and then have =< 10% tumor on any of the bilateral marrow aspirate/biopsy specimens done at pre-ASCT and/or pre-enrollment evaluation will also be eligible (note that per INRC this would have been defined as “overall” response of progressive disease [PD])
Pathological confirmation by bone marrow documenting the following:
Patients must have histologically confirmed diagnosis of Philadelphia-negative ALL by bone marrow biopsy or aspirate
Patients must have >= 5% leukemic blasts in the bone marrow and/or increasing levels of MRD in the bone marrow as assessed by flow cytometry; if an adequate bone marrow sample cannot be obtained, patients may be enrolled if there is unequivocal evidence of leukemia in the peripheral blood
Stage II Arm B: prior CDK4/6 inhibitor treatment, bone marrow transplant or extensive radiotherapy to ?25% of bone marrow
Subjects must have presence of < 20% bone marrow blasts per bone marrow biopsy/aspirate at screening.
No morphological evidence of disease (defined as marrow myeloblast percentage of < 5% and/or documentation from hematopathologist indicating no morphological evidence of leukemia) on day 14 bone marrow examination (range, day 14-17; day 1 refers to the first day of IC) following remission IC
Any evidence of fibrosis on morphological examination of bone marrow at the time of AML diagnosis
No evidence of recurrent disease on bone marrow evaluation done within 21 days of enrollment
Presence of clinically significant bone marrow fibrosis on the bone marrow examination immediately prior to UCBT
Patients undergoing additional procedures during the same anesthetic such as bone marrow aspirate or biopsy will be excluded
Subjects who are scheduled for bone marrow ablation chemotherapy
Patient has had prior bone marrow procedures
Patient is receiving additional potentially painful interventions (e.g. central line insertion/removal) concurrent with the bone marrow procedure
Patients with at least ONE of the following sites of measurable disease according to International Workshop Criteria87: A) Measurable tumor on MRI or CT scan. Measurable is defined as at least one lesion 20 mm in at least one dimension; for spiral CT, measurable is defined as 10 mm in at least one dimension. For patients with persistent disease, a biopsy of bone marrow, or bone, or a soft tissue site, must have demonstrated viable tumor. If lesion was radiated, biopsy must have been done at least 4 weeks after radiation completed. B) Bone marrow with tumor cells seen on routine morphology (not by NSE staining only) of bilateral aspirate and/or biopsy on one bone marrow sample, except for patient who tested positive subsequent to their last treatment regimen or patients who had a negative marrow within three months of study entry.
Patients with known bone marrow reticulin fibrosis (>= grade 2) (only applicable to patients with CML)
AML patients with persistent disease from the recent treatment defined as > 5% blast and/or > 20% cellularity and reported as persistent residual disease by a pathological report of the patient's bone marrow biopsy 14 days +/- 2 days from the initiation of cytarabine
Bone marrow aspirates/biopsies should be performed within 23 ± 7 days from registration to confirm disease remission status
Phase 1 only: known bone marrow fibrosis; Phase 2 only: Bone marrow fibrosis grade 2 or greater;
Bilateral bone marrow aspirates and biopsy
Able to begin study treatment between day 60 and day 100 after the transplant and meets the following transplant related requirements:\r\n* Sustained neutrophil (absolute neutrophil count [ANC] > 1000/mcL) and platelet (> 30,000/mcL) engraftment\r\n* > 50% donor chimerism in blood or bone marrow\r\n* No evidence of recurrent disease on most recent bone marrow evaluation (day 21 or 28 post-transplant is acceptable)\r\n* No morphologic evidence of relapse (< 5% bone marrow blasts)\r\n* Ability to be treated in the outpatient setting (not an inpatient)
HL\r\n* No clinical evidence of disease or disease-related symptoms\r\n* A post-treatment residual mass of any size is permitted as long as it is PET negative\r\n* Spleen and liver must be non-palpable and without nodules\r\n* If a pre-treatment bone marrow biopsy was positive, an adequate bone marrow biopsy from the same site must be cleared of infiltrate; if this is indeterminate by morphology, immunohistochemistry should be negative
Must consent to bone marrow aspirate or biopsy.
If post allogeneic SCT must not have less than 50% donor chimerism in either peripheral blood or bone marrow
Is willing to provide bone marrow biopsies and comply with protocol-defined evaluations
Subject must be willing and able to undergo bone marrow aspirate per protocol (with or without bone marrow biopsy per institutional guidelines).
Patients who have had RT in more than 35% of the bone marrow.
Collection of a bone marrow, fluid or tissue sample that is expected to have enough cells to run the assay
Failure to recover from Grade 3 or 4 toxicity from previous treatment (unrelated to malignant bone marrow involvement)