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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.

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.

Patients will be placed on a study arm after receiving a Donor Search Prognosis Score, which is based on HLA allele frequencies and race/ethnicity. This score predicts the likelihood of successfully identifying a 10/10 matched unrelated donor.Worse search prognosis is associated with racial and ethnic minority status but not with other patient and disease biology characteristics that might influence the success of hematopoietic cell transplantation (HCT). Thus, the use of donor search prognosis in this trial as a tool for biologic assignment to matched unrelated donors vs. mismatched donors provides a mechanism to minimize bias from disease characteristics.

Donor Search Prognosis Score

Stephanie J Lee, MD, MPH

Stefan Ciurea, MD

The purpose of this study is to determine if a search strategy of searching for an HLA-matched unrelated donor for allogeneic transplantation if possible then an alternative donor if an HLA-matched unrelated donor is not available versus proceeding directly to an alternative donor transplant will result in better survival for allogeneic transplant recipients within 2 years after study enrollment.

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.

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.

Clinical Transplant-Related Long-term Outcomes of Alternative Donor Allogeneic Transplantation (BMT CTN 1702)

To compare overall survival in patients transplanted for malignant diseases, according to the donor search prognosis and the alternative donor used.

To compare relapse in patients transplanted for malignant diseases, according to the donor search prognosis and the alternative donor used.

To compare disease-free survival, treatment-related mortality, and acute and chronic GVHD in patients transplanted for malignant diseases, according to the donor search prognosis and the alternative donor used.

To compare treatment-related mortality in patients transplanted for malignant diseases, according to the donor search prognosis and the alternative donor used.

To compare acute and chronic GVHD in patients transplanted for malignant diseases, according to the donor search prognosis and the alternative donor used.

To describe survival in patients with acquired aplastic anemia and sickle cell disease after transplantation, according to the donor search prognosis and the alternative donor used.

To describe acute and chronic GVHD in patients with acquired aplastic anemia and sickle cell disease after transplantation, according to the donor search prognosis and the alternative donor used.

In patients with AML or ALL in first complete remission or early stage MDS treated with a limited subset of conditioning and GVHD prophylaxis regimens and transplanted with either matched unrelated donors or haploidentical related donors (QOL Substudy), to compare QOL, according to the donor search prognosis and alternative donor used.

In patients with AML or ALL in first complete remission or early stage MDS treated with a limited subset of conditioning and GVHD prophylaxis regimens and transplanted with either matched unrelated donors or haploidentical related donors (QOL Substudy), to describe the incidence of primary graft failure, according to the donor search prognosis and alternative donor used.

In patients with AML or ALL in first complete remission or early stage MDS treated with a limited subset of conditioning and GVHD prophylaxis regimens and transplanted with either matched unrelated donors or haploidentical related donors (QOL Substudy), to describe the incidence of chronic GVHD, according to the donor search prognosis and alternative donor used.

In patients with AML or ALL in first complete remission or early stage MDS treated with a limited subset of conditioning and GVHD prophylaxis regimens and transplanted with either matched unrelated donors or haploidentical related donors (QOL Substudy), to describe time until off systemic immunosuppression, according to the donor search prognosis and alternative donor used.

In patients with AML or ALL in first complete remission or early stage MDS treated with a limited subset of conditioning and GVHD prophylaxis regimens and transplanted with either matched unrelated donors or haploidentical related donors (QOL Substudy), to describe the incidence of acute grade III-IV and chronic GVHD requiring immunosuppression-free, relapse-free survival (GRFS), according to the donor search prognosis and alternative donor used.

In patients with AML or ALL in first complete remission or early stage MDS treated with a limited subset of conditioning and GVHD prophylaxis regimens and transplanted with either matched unrelated donors or haploidentical related donors (QOL Substudy), to describe the incidence of moderate-severe chronic GVHD relapse-free survival (CRFS), according to the donor search prognosis and alternative donor used.

In patients with AML or ALL in first complete remission or early stage MDS treated with a limited subset of conditioning and GVHD prophylaxis regimens and transplanted with either matched unrelated donors or haploidentical related donors (QOL Substudy), to describe the incidence of current CRFS (still on systemic treatment for cGVHD), according to the donor search prognosis and alternative donor used.

In patients with AML or ALL in first complete remission or early stage MDS treated with a limited subset of conditioning and GVHD prophylaxis regimens and transplanted with either matched unrelated donors or haploidentical related donors (QOL Substudy), to describe the number of hospital days in the first 100 post-transplant days, according to the donor search prognosis and alternative donor used.

In patients with AML or ALL in first complete remission or early stage MDS treated with a limited subset of conditioning and GVHD prophylaxis regimens and transplanted with either matched unrelated donors or haploidentical related donors (QOL Substudy), to describe the incidence of infections, according to the donor search prognosis and alternative donor used.

In patients with AML or ALL in first complete remission or early stage MDS treated with a limited subset of conditioning and GVHD prophylaxis regimens and transplanted with either matched unrelated donors or haploidentical related donors (QOL Substudy), to describe the incidence of immune reconstitution, according to the donor search prognosis and alternative donor used.

In patients with AML or ALL in first complete remission or early stage MDS treated with a limited subset of conditioning and GVHD prophylaxis regimens and transplanted with either matched unrelated donors or haploidentical related donors (QOL Substudy), to describe the late effects after transplantation, according to the donor search prognosis and alternative donor used.

Compare overall survival between Very Likely to find a matched unrelated donor search prognosis patients and Very Unlikely to find a matched unrelated donor search prognosis patients who are evaluable.

To estimate and compare the cumulative incidence of receiving a transplant according to donor search prognosis, regardless of donor search prognosis

To describe barriers to achieving transplantation with different donor search strategies, regardless of donor search prognosis

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