Key factors for the success of autologous hematopoietic stem cell transplantation in HIV-infected patients with lymphoproliferative diseases

Abstract Introduction: Modern antiretroviral therapy (ART) has increased the life expectancy of HIV patients, but 9% of the 40.1 million infected people develop malignant neoplasms, which remain the leading cause of death. Aggressive B-cell lymphomas (plasmablastic - PL, diffuse large B-cell - DLBCL, relapsed/refractory forms) require complex treatment. Autologous hematopoietic stem cell transplantation (auto-HSCT) is an effective method for consolidating remission, but mortality can reach 20%. Materials and methods: Since 2024, a recearch has been initiated at the Loginov Moscow State Medical Research Center to evaluate the effectiveness of blood stem cell mobilization and collection, as well as to assess the efficacy and safety of auto-HSCT in HIV-positive patients with aggressive and recurrent B-cell lymphomas. At the time of the interim analysis, 10 patients were included in the study. The median age was 43 years (33–59 years). Distribution by nosology and disease status was as follows: PL in the first complete remission (n=2), resistant Hodgkin's lymphoma (rHL) (n=3); DLBCL (n=3); PL in the second complete remission (n=1), PL in partial remission (PR) (n=1). Mobilization of HSCs was performed according to the protocol «Hd-Cy/Hd-Ara-C + G-CSF». The Benda-EAM regimen was used as a conditioning regimen before auto-HSCT. All patients underwent a comprehensive examination to exclude active infections against the background of immunosuppression: PCR test (Cytomegalovirus, Epstein-Barr virus), Serology (Herpes simplex virus, toxoplasmosis), hepatitis: HBV (HBsAg, anti-HBcore IgG, PCR HBV DNA), HCV (anti-HCV, PCR HCV RNA), Tuberculosis (IGRA, T-SPOT.TB). ART regimen adjustments were made in 40% of patients taking into account drug-drug interactions with chemotherapy regimens. The effectiveness of the therapy was confirmed by the absence of HIV RNA in the blood serum using the PCR method (Abbot Real Time HIV-1 test system). The immune status (CD4+ lymphocytes) exceeded 150 cells/μl. Results: The mean number of CD34+ cells collected by apheresis was 4.4 × 10⁶/kg of patient body weight (2.09–7.97 × 10⁶/kg), indicating adequate mobilization of HSCs. The median time to recovery of neutrophil levels >0.5 × 10⁹/l was 11 days (9–12 days). The median duration of observation after auto-HSCT was 5.5 months. Mortality in the early post-transplant period reached 10% (n=1; cause of death — septic shock). Complete remission was maintained in 9 out of 10 patients (90%) at the follow-up points. In one case, progression of plasmablastic lymphoma was recorded (зrobably due to resistance (3 lines of PCT + TP53 mutation)). The structure of infectious complications in the post-transplant period included: febrile neutropenia (n=3), sepsis (pseudomonas aeruginosa) (n=1); mucositis grades I–III (n=3), enterocolitis (n=2), CMV viremia (n=1). According to virological monitoring, reactivation of either HIV infection or opportunistic infections was not recorded in any patient. Additionally, it was demonstrated that after auto-HSCT, there was no significant decrease in the level of CD4+ lymphocytes. Discussion and Conclusions. In the era of ART and immunochemotherapy, the results of treatment of HIV-associated lymphomas in AUTO-HSCT are determined by factors that depend on both the characteristics of the lymphoproliferative disease itself and the presence of persistent infections against the background of an immunocompromised state. The study demonstrates that the efficacy and safety of auto-HSCT in patients with HIV infection and aggressive B-cell lymphomas are comparable to those in HIV-negative recipients. Careful pretransplant screening for opportunistic infections is a mandatory component of the safety of auto-HSCT in HIV-positive patients. The key predictors of successful mobilization, collection of HSCs and performance of auto-HSCT are achieving complete remission and modern ART, taking into account drug-drug interactions. The absence of HIV reactivation indicates the absence of a negative effect of the auto-HSCT procedure on the control of viral replication. Preservation of immune status (CD4+ lymphocyte level >150 cells/μl) after Auto-HSCT confirms the safety of this intervention in immunocompromised patients with HIV infection. Further analysis of the efficacy and safety results of the procedure is currently ongoing, and the possibility of including patients in CAR-T cell therapy programs is also being considered.