Absence of donor specific HLA antibodies
DONOR: For a partially HLA-mismatched transplant, the patient must lack antibodies against donor HLA molecules; specifically, complement dependent cytotoxicity and flow cytometric crossmatch assays must be negative, and the mean fluorescence intensity (MFI) of any anti-donor HLA antibody by solid phase immunoassay should be < 3000; consult with Immunogenetics for the clinical significance of any anti-donor antibody; desensitization to remove anti-donor antibody should only be performed for patients who have no other donor options
Have evidence of recipient donor specific anti-HLA antibodies.
Anti-donor HLA antibodies. Additional exclusion criteria:
Presence of anti-donor HLA antibodies (positive anti-donor HLA antibody is defined as a positive cross-match test of any titer by complement-dependent cytotoxicity or flow cytometric testing or the presence of anti-donor HLA antibody to the high expression loci HLA-A, B, C, DRB1, or DPB1 with mean fluorescence intensity (MFI) > 1000 by solid phase immunoassay).
Recipient HLA antibodies against donor HLA
Presence of donor-specific antibodies against chosen graft source
Suitable related haploidentical donor identified:\r\n* Must be matched at least at 5 of 10 HLA antigens (A, B, C, DRB1, DQ)\r\n* Must not be matched at more than 7 of 10 HLA antigens\r\n* Recipient should not have HLA antibodies to potential donor; if the recipient does have HLA antibodies to the potential donor, an alternative donor is preferred; however, if there are no suitable alternative donors, the donor to whom the patient has HLA antibodies can be utilized as long as the antibody titer is less than 2000 median fluorescence intensity (MFI); if the titer is > or = to 2000 MFI, the recipient must undergo successful antibody desensitization prior to enrollment on this study; any patients who have demonstrated donor specific antibodies will not be evaluated for the end points measured in this study but will be followed for treatment related toxicities\r\n* Haploidentical donors that are ABO compatible with the recipient are preferred; Minor ABO incompatibility is preferred to major ABO incompatibility; major ABO incompatibility between recipient and donor is the least preferred but still acceptable for this study\r\n* It is preferred that the haploidentical donor must be available to donate on day -1 and day 0 at Roswell Park Cancer Institute (RPCI), so that fresh product can be processed by the RPCI stem cell lab and administered to the patient on day 0; while less preferable, cryopreserved product may be utilized on this protocol
Patients with donor specific HLA antibodies with a titer greater than 2000 MFI (whether or not they have undergone a desensitization protocol)
Presence of donor directed HLA antibodies
DONOR: Absence of pre-existing donor-specific anti-HLA antibodies (DSA) in the recipient; Patients with pre-existing DSA could undergo desensitization per City of Hope (COH) standard operating procedures [SOP] and should have DS < 2000 prior to conditioning at discretion of principal investigator (PI)
DONOR: Positive anti-donor HLA antibody
Presence of anti-donor HLA antibodies (positive anti-donor HLA antibody is defined as a positive cross-match test of any titer by complement-dependent cytotoxicity or flow cytometric testing or the presence of anti-donor HLA antibody to the high expression loci HLA-A, B, C, or DRB1 with mean fluorescence intensity [MFI] > 1000 by solid phase immunoassay)
Presence of donor specific antibodies (DSA) with mean fluorescence intensity (MFI) of > 2000 as assessed by the single antigen bead assay, < 6 weeks prior to starting transplant conditioning
DONOR: Recipient derived anti-donor HLA antibodies identified as “unacceptable\ by Luminex assay; exceptions may be made by the Director of the Histocompatibility Laboratory in conjunction with the recipient’s physician and a plan for desensitization
DONOR: Positive anti-donor HLA antibody
DONOR: Lack of recipient anti-donor HLA antibody; Note: in some instances, low level, non-cytotoxic HLA specific antibodies may be permissible if they are found to be at a level well below that detectable by flow cytometry; this will be decided on a case-by-case basis by the principal investigator (PI) and one of the immunogenetics directors
Positive patient anti-donor HLA antibody, which is deemed clinically significant.
DONOR: Lack of recipient anti-donor HLA antibody; Note: in some instances, low level, non-cytotoxic HLA specific antibodies may be permissible if they are found to be at a level well below that detectable by flow cytometry; this will be decided on a case-by-case basis by the PI and one of the immunogenetics directors; pheresis to reduce anti-HLA antibodies is permissible; however eligibility to proceed with the transplant regimen would be contingent upon the result
DONOR: Positive anti-donor HLA antibody
Positive leukocytotoxic crossmatch; specifically, complement dependent cytotoxicity and flow cytometric crossmatch assays must be negative, and the mean (or median) fluorescence intensity (MFI) of any anti-donor HLA antibody by solid phase immunoassay should be < 2000; if a screening assay against pooled HLA antigens is used, positive results must be followed with specificity testing using a single antigen assay; the MFI must be < 2000 unless the laboratory has validated higher threshold values for reactivity for HLA antigens, such as HLA-C, DQ, and DP, that may be enhanced in concentration on the single antigen assays; consult with principal investigator (PI) for the clinical significance of any anti-donor antibody
Lack of recipient anti-donor HLA antibody\r\n* Note: in some instances, low level, non-cytotoxic HLA specific antibodies may be permissible if they are found to be at a level well below that detectable by flow cytometry; this will be decided on a case-by-case basis by the principal investigator (PI) and one of the immunogenetics directors; pheresis to reduce anti-HLA antibodies is permissible; however eligibility to proceed with the transplant regimen would be contingent upon the success of the desensitization
Class I or II antibodies against donor HLA antigens
DONOR: Recipient derived anti-donor high-titer (> 3000 MFI) HLA antibody as determined by Luminex assay
No donor-specific antibodies (DSA) using solid phase micro particle technology (by Luminex phenotype panel or Luminex single antigen bead test) performed 30 days or less prior to transplant; as assessed by local laboratories; a positive anti-donor HLA antibody test is defined as the presence of an antibody against any one of the high expression HLA molecules (HLA-A, -B, -C, or –DRB1) with a mean fluorescence intensity (MFI) > 1000 by solid phase immunoassay
Negative T and B cell flow crossmatches with the designated donor; as assessed by local laboratories; if one or more of the crossmatches is positive, the participant will be considered a screen failure unless combined results of antibody and cross match testing implicate a non-HLA antibody as the cause of the positive flow crossmatch; in this case, the protocol chair must approve the participant as a screening success after consultation with the HLA laboratory director
Anti-donor HLA antibody using solid phase micro particle technology (by Luminex phenotype panel or Luminex single antigen bead test) performed 30 days or less prior to transplant as assessed by local laboratories; the director of the immunogenetics laboratory will be responsible for determining what level of antibody is considered a positive anti-donor HLA antibody result
DONOR; Lack of recipient anti-donor HLA antibody\r\n* Note: In some instances, low level, non-cytotoxic HLA specific antibodies may be permissible if they are found to be at a level well below that detectable by flow cytometry; this will be decided on a case-by-case basis by the PI and one of the immunogenetics directors; pheresis to reduce anti-HLA antibodies is permissible; however eligibility to proceed with the transplant regimen would be contingent upon the success of the desensitization
DONOR: lack of recipient anti?donor HLA antibody\r\n* Note: in some instances, low level, non?cytotoxic HLA specific antibodies may be permissible if they are found to be at a level well below that detectable by flow cytometry; this will be decided on a case?by?case basis by the principal investigator (PI) and one of the immunogenetics directors; pheresis to reduce anti?HLA antibodies is permissible; however eligibility to proceed with the transplant regimen would be contingent upon the success of the desensitization
Presence of antibodies to a mismatched donor HLA antigen
Absence of donor-specific antibodies (DSA) to the mismatched HLA-locus
Patient will be screened for antibodies targeting mismatched HLA antigens in potential haploidentical donors (donor specific antibodies, DSA); antibody screen and confirmatory testing using Luminex single antigen-bead test will be done
Baseline positive donor-specific anti-HLA antibody testing
Known presence of HLA antibodies against the non-shared donor haplotype
Known presence of HLA antibodies against the non-shared donor haplotype
Recipients with donor sensitive antibodies (DSA), defined by 2000 or higher median fluorescence intensity (MFI) against one or more class I or II antigens