Autologous Stem Cell Transplant for HIV-Associated Lymphoma: A Systematic Review and Meta-Analysis

Background: The advent of highly active antiretroviral therapy (HAART) has significantly improved the prognosis of individuals living with Human Immunodeficiency Virus (HIV). However, HIV-associated lymphoma remains a significant cause of morbidity and mortality in this population. Autologous stem cell transplantation (ASCT) is a potential curative treatment for patients with relapsed aggressive lymphoma. However, the immunosuppressive nature of HIV poses unique challenges in the management of these patients. This study aims to review and summarize ASCT experience in patients with HIV-associated lymphoma. We performed a systematic review to evaluate feasibility and efficacy of ASCT in patients with HIV-associated lymphoma.

Method: PubMed, Cochrane, Embase and ClinicalTrials.Gov were searched between Jan 1, 1996, and Dec 31, 2023, for published studies reporting ASCT outcomes in patients with HIV-associated lymphoma. Studies that were non-English language studies, retrospective or included less than 10 eligible patients were excluded. Studies and sub-studies of first-line ASCT were included in the analysis of toxicity and excluded from the analysis of efficacy. Data regarding demographics, CD4 count, viral load, HAART use, non-relapse post-transplant mortality, overall survival (OS), and progression free survival (PFS) were abstracted. Metanalysis of pooled results was completed using MedCalc Statistical Software version 22.032 where feasible.

Results: 342 titles were screened for eligibility, 275 were selected for abstract review, and 40 were identified for full-text review. Six prospective studies were included, none were randomized controlled trials. One of these six prospective studies was included in the analysis of toxicity, but excluded from the analysis of efficacy, as ASCT was used in first line. The prospective trials included data on 134 transplanted patients: 33 with HL, 131 with NHL. 90% (92 of 102 evaluable) patients were male. Median age in the trials was 39 – 47 years. Median CD4 count ranged from 174 to 249 and all patients were receiving HAART at time of transplant. Pooled estimate of non-relapse mortality in the first 6 months post transplant was 5.39% (95% CI 2.28 – 9.73) using a random effects model. Three unique prospective trials provided OS and PFS estimates with variable follow-up after ASCT for relapsed/refractory (R/R) HIV-associated aggressive lymphoma. Data on 52 patients from two trials was amenable to pooled analysis. Estimated 2-year OS was 79.8% (95% CI 68.1 – 89.3), 80.5% (95% CI 60.2 – 94.7) and 78.7% (95% CI 63.3 – 90.2) for R/R HIV-lymphoma, R/R HIV-HL and R/R HIV-NHL respectively. Estimated 2-year PFS was 77.9% (95% CI 65.9 – 87.8), 80.5% (95% CI 60.2 – 94.7), and 75.9% (95% CI 61.0 – 88.1) for all R/R HIV-lymphoma, R/R HIV-HL and R/R HIV-NHL respectively.

Conclusion: This is the first systematic review summarizing the safety and efficacy of ASCT for HIV-associated lymphoma. Although no comparative trials are available, non-relapse mortality post-transplant is similar to what has been reported in historical trials. OS and PFS appears encouraging, but prospective data are limited, and comparative data is entirely lacking.