Allogeneic Hematopoietic Stem Cell Transplantation in HIV-Positive Patients with High Risk Hematologic Malignancies

Recent studies have shown that Autologous Stem cell Transplantation (ASCT) in HIV+ patients (pts) with associated lymphoma along with highly active antiretroviral therapy (HAART) have similar results to those observed in immunocompetent pts. However there have been few reports describing Allogeneic Hematopoietic Stem Cell Transplantation (AlloHSCT) in HIV+ pts with high risk hematologic malignancies. The main difficulties associated to this procedure are infections and pharmacological interactions. We present the results of three HIV+ pts with hematologic malignancies treated with HAART and AlloHSCT.

• Pt # 1: 37 years old male diagnosed with HIV infection (AIDS-C3) in 1988, on HAART since 1996. In 1998 a diffuse large B cell lymphoma (DLBCL) IV-B was diagnosed. He achieved complete remission (CR) after CHOPx6, but relapsed one month later. After ESHAP he underwent AlloHSCT from an HLA-identical sibling in chemo-sensitive relapse. TBI+Cy was administered as conditioning treatment (CT) and Cyclosporine (CsA) as Graft versus Host Disease (GvHD) prophylaxis. HAART (3TC, NFV, EFV, d4T) was maintained during transplantation. The patient died on day (d) +6 due to respiratory distress without engraftment. Autopsy showed pulmonary aspergillosis with no evidence of toxicity or lymphoma.

• Pt # 2: 45 years old female. AIDS-C3 in 1994, on HAART since 1996. Diagnosed with high risk common acute lymphoblastic leukemia in 2005. She reached CR after Hyper-CVAD+Rituximab (R) x2 and received an AlloHSCT from an HLA-identical sibling using TBI+Cy as CT and CsA + Methotrexate (MTX) as GvHD prophylaxis. HAART (T20, d4T, ABC, 3TC) was maintained throughout the procedure. Engraftment occurred on +17d and full donor chimerism (FCh) on +26d. During transplantation Herpes Zoster infection, febrile neutropenia and CMV infection were observed and suitably treated. Acute GvHD grade III occurred on +30d, successfully treated with steroids, CsA and mycophenolate mofetil. Four months (m) after transplantation the patient showed extensive chronic GvHD (cGvHD) also treated with steroids and CsA. Despite adequate immunologic recovery since +6m (CD4+: 450 cells/mm³ and serum IgG: 683mg/dl) she developed Streptococcal pneumonia (+9m) encephalitis of unknown etiology (+12m) and streptococcal sepsis together with pneumonia (+20m). The patient remains in CR with negative HIV-viral load and no cGvHD 30m after transplant.

• Pt # 3: 44 years old male.

AIDS-C3 on HAART since 2000. He developed DLBCL-IVA in 2004 and reached CR after CHOP+R x6. Relapsed in 2006, showing refractoriness to ESHAP+R x5 and reaching 2^nd CR after ASCT with BEAM as CT. He relapsed again in 2007, and received MINE-R x3 and GIFOX-R x1 obtaining partial remission. An AlloHSCT from an HLA-identical sibling was designed using reduced CT (⁹⁰Y-Ibritumomab-tiuxetan, Rituximab, Fludarabine and Melphalan) and CsA + MTX as GvHD prophylaxis. HAART (DDI, T20, 3TC) was maintained during treatment, but stopped for 7 days due to mucositis. Engraftment was observed on +13d, with FCh on +32d. During transplantation the patient developed febrile neutropenia and CMV infection, successfully resolved. After CsA withdrawal on +70d, the patient showed two acute grade II GvHD episodes responsive to steroids and CsA. The patient remains in CR with cGVHD, on immunosupression, 9 months after transplant. He shows negative HIV-Viral load, CD4+ 65 cells/mm³ and serum IgG 559mg/dl. These pts show that AlloHSCT is a feasible treatment in HIV+ pts with high risk hematologic malignancies. Moreover we have not found significant interactions between immunosuppressive agents and HAART. Nevertheless early diagnosis of infection is critical in this setting.