Allogeneic Peripheral Blood Stem Cell Transplantation for Hematological Malignancies in Patients with HIV.

Abstract

Optimal management of intercurrent hematological malignancy in patients with HIV, in particular the feasibility of allogeneic peripheral blood stem cell transplantation (PSCT), remains to be defined. We present our experience with allogeneic transplantation in a series of three patients with HIV. The first patient is a 38 yo man with secondary myelodysplasia in transformation to acute myeloid leukemia. He had had no AIDS-defining illnesses, and was maintained on second-line anti-retroviral therapy of Stavudine, Lamivudine and Tenofovir with an undetectable HIV viral load and CD4 count 58 cells/μL. He received a HLA-identical PSCT, conditioned with cyclophosphamide 60 mg/m2 and total body irradiation (TBI) 13.2 Gy in 6 fractions with standard graft-versus host disease (GVHD) and infective prophylaxis. Transplantation was complicated by severe BK-virus associated hemorrhagic cystitis and prolonged neutropenia with sepsis necessitating temporary withdrawal of anti-retrovirals. Engraftment occurred at day 48, and bone marrow aspirate (BMA) confirmed remission. Anti-retroviral therapy was re-introduced 12 months post-transplantation in response to a rising HIV viral load. He subsequently developed progressive renal impairment due to post-transplant glomerulopathy, but had no late infective complications and is otherwise well and in remission 21 months post-transplantation with HIV viral load 150 copies/mL and CD4 count 181 cells/μL. The second patient was a 41 yo man with multiply-relapsed acute myeloid leukemia in third complete remission. He had no AIDS-defining illnesses and was maintained on fifth-line anti-retroviral regimen of Emtricitabine, Tenofovir, and Fosamprenavir with an undetectable viral load and CD4 count 275 cells/μL. He received an HLA-Identical sibling PSCT, conditioned as above, with additional anti-microbial prophylaxis with Entecavir for HBV; Azithromycin for MAC and Ciprofloxacin for a previous Rhodococcal pulmonary infection. Transplantation was complicated by neutropenic sepsis, pericarditis, and grade 2 cutaneous GVHD. Engraftment occurred day 21; BMA confirmed remission. He remained well with no further infective complications until day 67, when he presented with drug resistant Pseudomonal sepsis, multi-organ failure and succumbed day 78. The third patient was a 24 yo man with multiply-relapsed T-cell acute lymphoblastic leukaemia in second complete remission without prior AIDS-defining illnesses, maintained on second-line anti-retroviral regimen of Tenofovir, Ritonavir, and Fosamprenavir, with an undetectable HIV viral load and CD4 count 204 cells/μL. He received an HLA-identical sibling PSCT conditioned with etoposide 60 mg/m2 and TBI 13.2 Gy in 6 fractions, with extended anti-microbial prophylaxis. This was complicated by neutropenic dental infection and grade 2 cutaneous GVHD, treated with steroid therapy. Engraftment occurred day 25; BMA confirmed remission. There were no late complications and he maintained an undetectable HIV viral load and CD4 counts >200 copies/mL. At day 101 he relapsed, was treated with palliative intent, and died day 105. This series illustrates that allogeneic transplantation is a feasible therapeutic modality for high-grade hematological malignancies in carefully selected patients. Careful optimization of HIV control, and preventive management of infective complications and drug toxicity are critical to successful outcomes.