Reduced-intensity conditioning allogeneic stem cell transplantation in HIV patients with hematologic malignancies: yes, we can

To the editor:

The early enthusiasm for allogeneic stem cell transplantation (ASCT) in patients with HIV infection was tempered by the high transplantation-related mortality and rapid progression of HIV infection after allografting, casting serious doubts about the feasibility of this curative modality in HIV⁺ patients with hematologic malignancies.^1-3  While the development of reduced-intensity conditioning (RIC) regimens has improved the outcomes of ASCT in general, its role in the HIV⁺ patient population remains to be defined.

We used a uniform strategy of RIC consisting of fludarabine (30 mg/m²/day, days −7 to −3), busulfan (0.8 mg/kg/dose intravenously × 8 doses) with (n = 2) or without (n = 1) thymoglobulin in 3 HIV⁺ patients with advanced hematologic malignancies (Table 1). Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus (0.03 mg/kg/day intravenously, commencing on day −2) and mini-dose methotrexate (5 mg/m² on days +1, +3, +6, and +11). To assess donor-cell chimerism, pretransplantation peripheral blood samples were used to identify polymerase chain reaction (PCR)–short tandem repeat informative fragments for each donor/recipient pair. After transplantation, lineage-specific chimerism analysis was performed as previously described.⁴  Patients' HIV-RNA PCR (COBAS Ampliprep/COBAS TaqMan HIV-1 real time PCR test), CD4, and CD8 counts were determined at baseline and on days +90, +180, and +360. All investigations were approved by The Ohio State University Institutional Review Board and Clinical Scientific Review Committee, and complied with the recommendations of the Declaration of Helsinki.

Median patient age was 51 years (range, 39-55 years). One patient each had AML [unique patient number (UPN) 1], Burkitt lymphoma (UPN2) and plasmablastic lymphoma (CD138⁺, CD20⁻, HHV8⁺, EBER1⁻, EBER2⁻; UPN3). All patients were in second complete remission (CR) at the time of transplantation. Median pre-ASCT CD4 count was 339 cells/uL (range, 189-457 cells/μL). HIV RNA viral load at baseline was undetectable in 2 patients and 814 copies/mL in UPN1. Donors included sibling (n = 1) or unrelated volunteers (n = 2). Highly active antiretroviral therapy (HAART) was not interrupted during RIC-ASCT. All patients successfully engrafted. Only UPN3 developed transient grade II acute GVHD. At median follow-up of 651 days, all patients are alive and off immunosuppression without active GVHD. UPN2 relapsed at day +160, but subsequently achieved CR after a donor lymphocyte infusion. Posttransplantation HIV RNA viral loads remain undetectable in 2 patients. UPN1, with a 20-year history of heavily pretreated HIV/AIDS, developed elevated HIV RNA viral loads (15 000 copies/mL) 18 months after ASCT, which responded to switching HAART to tipranavir and lamivudine. No AIDS-related opportunistic infections were seen. The details of other infectious complications are summarized in Table 1. Donor-cell chimerism and immune reconstitution after ASCT were prompt (Table 1).

Initial experience with RIC-ASCT in HIV⁺ patients (n = 2), showed development of acute retroviral syndrome after transplantation, likely secondary to interruption of HAART.⁵  Uninterrupted HAART was attempted in another study using nonmyeloablative conditioning ASCT (n = 2), but disease relapse and GVHD appeared problematic, probably due to nominal intensity of the conditioning regimen and less aggressive GVHD prophylactic strategy used.⁶  Our study provides critical preliminary evidence that in the modern era, RIC-ASCT with uninterrupted HAART is safe and feasible in HIV⁺ patients. Moreover, our data suggest that for HIV⁺ patients lacking sibling donors, unrelated donors are acceptable, and that in this patient population, administration of thymoglobulin (for GVHD prophylaxis) and donor lymphocyte infusion (after relapse) does not cause any unexpected toxicities.

In conclusion, our encouraging experience strongly argues that HIV⁺ patients with advanced hematologic malignancies should no longer be routinely denied the potentially curative modality of RIC-ASCT.