(also see mesenchymal stem cells, granulocyte transfusion, autoimmune diseases, regulatory issues, acute radiation injury, other items)

v. HIV Positive Patients

A. Unrelated cord blood transplantation for a human immunodeficiency virus-1-seropositive patient with acute lymphoblastic leukemia. Tomonari A, Takahashi S, Shimohakamada Y, Ooi J, Takasugi K, Ohno N, Konuma T, Uchimaru K, Tojo A, Odawara T, Nakamura T, Iwamoto A, Asano S. Bone Marrow Transplant. 2005;36:261-2.

The authors describe the first case of an HIV-infected patient with ALL who underwent umbilical cord blood transplantation (UCBT).

A 23-year-old woman was confirmed as seropositive for HIV. She was diagnosed as Philadelphia chromosome-positive ALL and achieved hematological complete remission after two courses of chemotherapy. She received HAART (highly active antiretroviral therapy) during and after the chemotherapy and her HIV-RNA level continued to be below detectable levels.

She underwent a UCBT from an unrelated donor with mismatches at two loci. The conditioning regimen included 12 Gy TBI and 120 mg/kg cyclophosphamide. GVHD prophylaxis consisted of cyclosporine and methotrexate. HAART was discontinued on day +28. On day +33 her WBC remained below 100/µl and all bone marrow cells were of recipient origin. Therefore, at day +40 a second UCBT was performed from an unrelated donor with a one-locus mismatch at HLA-DR. The conditioning regimen included 40/m² fludarabine for 3 days. Cyclosporine was administered for GVHD prophylaxis. Neutrophil engraftment was achieved on day +27 and full donor chimerism was documented on day +28.

The HIV-RNA level increased to 3 x 10⁶ copies/ml on day +38 but returned to below detectable levels from day +195, and the CD4 count increased to above 300/µl from day +170. An RT-PCR analysis showed continuous negative test results for the p190^BCR-ABL transcript until the last follow-up evaluation at 15 months post UCBT.

The authors state that these results suggest that UCBT is feasible for HIV-infected patients on HAART, although further studies are warranted.

B. Treatment of human immunodeficiency virus-related lymphoma with haematopoietic stem cell transplantation. Molina A, Zaia J, Krishnan A. Blood Rev. 2003;17:249-58.

The advent of highly active antiretroviral therapy (HAART) and its co-administration with chemotherapy in patients with human immunodeficiency virus (HIV)-related lymphoma has lead to the exploration of potentially curative combination chemotherapy and myeloablative therapy followed by autologous haematopoietic stem cell transplantation (ASCT). Applying the same principles used for patients with HIV-negative aggressive lymphoma, in 1998 the authors developed a program of high-dose therapy and ASCT for patients with HIV-related lymphoma and Hodgkin's disease. These studies have primarily included patients with chemosensitive lymphoma in relapse or first remission with poor-risk features at diagnosis. Filgrastim (G-CSF)-primed peripheral blood stem cell mobilization and apheresis have been successful while patients were receiving HAART and chemotherapy.

The authors report the results of ASCT in 19 patients with HIV-related lymphoid malignancies, representing the largest single-institution experience reported to date. Most patients received a chemotherapy-based conditioning regimen consisting of high-dose carmustine, etoposide and cyclophosphamide. Early infections, namely bacteremias and neutropenic fever were similar to those observed in the HIV-negative transplant setting. Opportunistic infections were rare and easily treatable. There were three early deaths, two from relapsed lymphoma and one from multi-organ failure in an older patient. The remaining 16 patients are alive and in remission.

The authors conclude that ASCT is well tolerated, can result in long-term remissions, and is potentially curative in selected HIV-related lymphoma patients with chemosensitive relapse and high-risk disease in first remission defined by the age-adjusted International Prognostic Index criteria (i.e., two or three of the following: elevated LDH, advanced stage, and poor performance status). Acquisition of resistance to HAART remains as a potential problem for HIV-positive patients who are cured of their lymphoma.

C. Should HIV-positive patients with lymphoma be offered stem cell transplants? Krishnan A, Zaia J, Forman SJ. Bone Marrow Transplant. 2003;32:741-8.

Advances in effective antiretroviral therapy for HIV infection have made high-dose therapy and autologous stem cell transplantation possible in patients with HIV-associated lymphomas. Regimen-related toxicity is not significantly increased when antiretroviral therapy is combined with high-dose chemoradiotherapy. Durable engraftment can be seen with autologous stem cell rescue. Infectious complications can be managed with a combination of surveillance and prophylaxis. Long-term remissions of these high-risk lymphomas can be achieved with this approach. This suggests that patients with HIV-associated lymphomas should be considered for autologous transplantation in a manner similar to HIV-negative lymphoma patients.