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Blood and Marrow Clinical Trials Network - Allogeneic Hematopoietic Cell Transplant for Hematological Cancers and Myelodysplastic Syndromes in HIV-Infected Individuals (BMT CTN-0903-BioLINCC)

Data Access NOTE: Please refer to the “Authorized Access” section below for information about how access to the data from this accession differs from many other dbGaP accessions.

Objectives: To evaluate the safety and effectiveness of allogeneic hematopoietic cell transplantation for patients with hematologic malignancies or myelodysplastic syndromes and coincident-HIV infection.

Background: Allogeneic hematopoietic cell transplantation (alloHCT) has been a safe and curative option for many patients with hematologic malignancies but was not well studied in the HIV+ population despite the interest in the HIV research community of the curative potential of alloHCT. Hematologic malignancies in people with HIV infection (HIV+) have been associated with poor outcomes due to opportunistic infections, but the development of antiretroviral therapy (ART) has increased the possibility of these patients achieving clinical outcomes comparable to those of the general population following stem cell transplant. The BMT CTN 0903 trial was designed to evaluate the safety and effectiveness of alloHCT for patients with HIV infection and hematologic malignancies.

Participants: Patients had documented HIV infection, were a minimum of 15 years of age and had acute myeloid leukemia (AML) or acute lymphocytic leukemia (ALL) in first or second complete remission (CR); Int-2 or high-risk myelodysplastic syndromes (MDS) with < 10% marrow blasts and no circulating myeloblasts after their most recent therapy; or Hodgkin or non-Hodgkin lymphoma beyond first CR with at least a partial response to last treatment. Patients had either an 8/8 matched related donor at HLA-A, -B, -C, (serologic typing or higher resolution) and -DRB1 (at high resolution using DNA based typing), or at least a 7/8 matched unrelated donor at HLA-A,-B, -C and -DRB1. A 7/8 matched related donor match was permitted only if an 8/8 unrelated donor could not be identified. A secondary matching criterion was the presence of homozygosity for CCR5delta32. AlloHCT using cord blood units or T-cell depletion was not allowed. Patients with history of prior alloHCT were excluded. Patients had to meet adequate organ function. Karnofsky/Lansky performance status ≥ 70% and could not have active central nervous system disease, HIV infection resistant to all antiretroviral therapy, or opportunistic infection unresponsive to treatment.

There were seventeen HIV-infected patients with acute leukemia, myelodysplasia (MDS), NHL or classical HL who were enrolled in the trial.

Design: Patients with HIV infection and hematological malignancies or myelodysplastic syndromes (MDS) were treated with either reduced-intensity conditioning (RIC) or myeloablative conditioning (MAC) followed by alloHCT. RIC or MAC was at the discretion of investigator. Where feasible, an attempt was made to identify hematopoietic cell donors who were homozygotes for the CCR5delta32 polymorphism. Graft-versus-host disease (GVHD) was treated per institutional standards.

Four regimens were permitted for conditioning. RIC regimens were: fludarabine and busulfan (Flu/Bu), and fludarabine and melphalan (Flu/Mel). MAC regimens were busulfan and fludarabine (Bu/Flu), or cyclophosphamide and total body irradiation (Cy/TBI). GVHD prophylaxis regimens included tacrolimus/methotrexate, tacrolimus/sirolimus, and post-transplant cyclophosphamide with tacrolimus/mycophenolate. Patients receiving busulfan-containing preparative regimens were not eligible to receive tacrolimus/sirolimus. A committee reviewed individual patient's HIV treatment history and ART options before initiation of the transplant conditioning regimen and advised changes to minimize potential drug interactions. It was recommended that ART be continued except ritonavir-containing regimens during MAC.

The goal of the study was to assess the 100-day non-relapse mortality. Secondary endpoints included 100-day disease status, percentage donor chimerism, hematologic function, infections, six-month overall survival (OS), incidence of acute and chronic GVHD, immunologic reconstitution, and impact of alloHCT upon measures of HIV persistence in blood including peripheral blood mononuclear (PBMC)-associated HIV DNA and infectious virus from resting CD4+T-cells using a quantitative virus outgrowth assay.

Follow-up visits occurred weekly through 8 weeks post-transplant, at 100 days, 6 months, 1 year, and 2 years.

Conclusions: There was no non-relapse mortality (NRM) at 100 days, or at 6 months, and therefore no evidence to suggest that NRM is prohibitive or more than that seen in non-HIV-infected patients. The cumulative incidence of grades II-IV acute GVHD was 41%. After year one, overall survival was 59%. In patients who achieved complete chimerism, cell-associated HIV DNA and inducible infectious virus in the blood were not detectable.