Allogeneic Hematopoietic Stem Cell Transplantation in HIV-Positive Patients with Malignant and Non-Malignant Disorders: A Report from the Center for International Blood and Marrow Transplant Research (CIBMTR).

Previous reports suggest feasibility and curative potential of autologous transplantation for HIV-associated lymphomas. Anecdotal reports suggest that allogeneic hematopoietic stem cell transplantation (AlloHCT) may also be feasible in HIV-positive patients. To further evaluate AlloHCT in HIV-positive patients, we retrospectively evaluated 27 HIV-positive patients with malignant (n=20) or non-malignant disorders (n=7), who received AlloHCT between 1987 and 2003 and were reported to the CIBMTR.

The median age at transplant was 32 years (range 9–49) and 78% of recipients were male. The donors were: HLA identical siblings, 19 (70%); syngeneic, 5 (19%); and unrelated, 3(11%). Indications for HCT were diverse and included: non-Hodgkin lymphoma, 10; chronic myeloid leukemia, 3; acute myeloid leukemia, 2; myelodysplastic syndrome, 2; acute lymphoblastic leukemia, 2; other acute leukemia, 2; aplastic anemia, 2; and other non-malignant disorders including HIV disease, 5. Twenty-one (78%) patients were transplanted prior to 1996. The conditioning regimens were: high-dose (≥ 1000 cGY) total body irradiation (TBI) based, 13 (48%); chemotherapy only, 13 (48%); and, low-dose (200cGY) TBI containing, 1 (4%). Twenty-three (85%) patients received bone marrow and 4 (15%) peripheral blood grafts.

Rate of neutrophil engraftment at 28 days was 77%. The cumulative incidence (95% CI) of grades II – IV acute GVHD (excludes syngeneic transplants) was 9% (1 – 25). For patients alive at 100 days (n = 11), the cumulative incidence of chronic GVHD at 1 and 2 years was 36% (12 – 65). At a median follow-up of 59 months, 6 patients are alive. Twenty-one patients died at a median of 58 days (2 – 479) but only 3 (14%) due to relapse. The probability of survival at 2-years was 22%. Treatment related mortality (TRM) at 100 days and 2-years were 44% and 67%, respectively. Causes of TRM were: pulmonary toxicity, 7; infections, 3; organ failure, 3; HIV disease, 2; and others, 3. Deaths related to pulmonary toxicity appear to be higher in patients receiving high-dose TBI based conditioning (5/13) compared to the other conditioning regimens (2/14). CD4 counts (×10⁹/L) and viral loads (log copies) are available on few patients and some patients had multiple values post-transplant. In the 3 months prior to transplant, the median CD4 count (n = 8) was 106 (0–1200) and the median viral load (n = 5) was 1.7 (1.6 – 5). At 3 months post transplant, the median CD4 count (n = 15) was 20 (0 – 286). After 6 months post transplant, the median CD4 count (n = 9) and viral load (n = 9) were 640 (302 – 1061) and 1.7 (1.7 – 4.4), respectively.

Of the 6 patients transplanted after 1996, 4 survive compared to 2 of 21 patients transplanted prior to 1996, presumably related to the effect of improved supportive care strategies and highly active anti-retroviral therapy. There appears to be a decreased incidence of acute GVHD in the HIV-positive patients although survival early on was poor and the numbers of patients evaluated small. This may be due to T cell deficiency and abnormal antigen presentation in HIV infected patients.

These data suggest that AlloHCT is feasible for HIV-positive patients with malignant and non-malignant disorders and provide the framework for the design of future prospective studies.