This is a multicenter, interventional and observational study to understand factors affecting the likelihood of transplantation in patients without a human leukocyte antigen (HLA) matched family donor and to compare outcomes associated with pursuing an HLA-identical unrelated versus other alternative donor graft sources. Alternative donors are defined as any donor other than an HLA-matched or 1 antigen-mismatched related donor. Patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), myelodysplastic syndromes (MDS), Non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), acquired aplastic anemia (AA) or sickle cell disease (SCD) are eligible. The primary comparison for the interventional study will be between two arms based on biologic assignment, analyzed on an intention-to-treat basis: Arm 1: Patients who are Very Likely to find a matched unrelated donor (MUD), defined as having a \>90% chance of finding an 8/8 HLA-matched unrelated donor, for whom a fully matched unrelated donor will be pursued; and Arm 2: Patients who are Very Unlikely to find a MUD, defined as having a \<10% chance of finding an 8/8 HLA-matched unrelated donor, for whom a haploidentical, cord blood, or mismatched unrelated donor transplant will be pursued. Patients with a Less Likely chance of finding a MUD, i.e., those not falling into the other two groups (a 26% chance), will be enrolled onto the observational component of the study and analyzed for all relevant endpoints but will not be included in the primary comparison.
Inclusion Criteria:
Patients fulfilling the inclusion criteria will be eligible for enrollment in this study. Of those who consent, only patients who lack a suitable HLA-identical or 1 allele or antigen mismatched related donors are evaluable. Patients with an HLA-identical sibling or 1 allele or antigen mismatched family member donor are evaluable as long as the center deems the family member donor as unsuitable for other reasons. Patients may co-enroll with other interventional or observational studies.
1. Patients of all ages with AML, ALL, MDS, NHL, HL, AA, or SCD are eligible.
2. Any planned conditioning regimen and GVHD prophylaxis approach is eligible.
3. Patients must be considered suitable allogeneic transplant candidates at the time of enrollment based on medical history, physical examination, and available laboratory tests. Specific testing for organ function is not required for eligibility but, if available, these tests should be used by the treating physician to judge transplant suitability.
4. Patient and physician must intend to proceed with allogeneic HCT within the next 6 months if a suitable donor is identified.
5. Center plans to follow the algorithm for alternative donor identification: (a) for subjects who are Very Likely to find a MUD, attempt to identify a matched unrelated donor; (b) for a subjects who are Very Unlikely to find a MUD, proceed expeditiously to a haploidentical, cord blood or mismatched unrelated donor.
6. Signed informed consent, and assent if applicable. Consent may be signed prior to completion of family typing but patients will only be considered evaluable upon confirmation that there is no suitable HLA-identical or 1 allele or antigen mismatched related donor available.
Exclusion Criteria:
1. Prior allogeneic HCT (prior autologous transplant is allowed)
2. Previous formal unrelated donor search
