Long-Term Follow up of Patients with HIV-Associated Non-Hodgkin Lymphoma (NHL) after Autologous Stem Cell Transplantation (ASCT)

Background:The Blood and Marrow Transplant Clinical Trials Network 0803 study confirmed the safety and efficacy of ASCT in HIV-infected patients with lymphoma. Short term toxicity and transplant related mortality was low (5.2%) and engraftment, treatment-related mortality and survival outcomes were not statistically significantly different from that of age and diagnosis matched CIBMTR controls. However, median follow up in that trial was 24 months after ASCT, and the questions of second cancer incidence and other infections in a this population remain (Alvarnas et al, ASH 2014). Herein we report the long term outcomes of ASCT in HIV-infected patients.

Methods: Retrospective cohort trial of 52 HIV-infected patients who underwent ASCT for high-risk NHL at City of Hope from January 1, 1998 to December 31, 2011. Two patients were excluded from the analysis due to early post-transplant mortality: one patient died at day 22 due to multiorgan failure, and another died at day 72 due to relapsed lymphoma. Fifty patients with a minimum survival of 100-days post ASCT were evaluated for long-term outcomes. Estimation of event-free survival (EFS) and overall survival (OS) was computed using Kaplan-Meier curves and the cumulative incidence of relapse was estimated with competing risk of mortality.

Results: Median follow up was 5.43 years (range 0.30-14.96 years). Median age at the time of transplantation was 45 years (range 26-64 years of age). Prior to transplant, 23 patients (46%) were in complete remission and 27 (54%) were in partial remission. Most patients had aggressive NHL, with diffuse large B-cell lymphoma (48%) and Burkitt lymphoma (24%) being most common histologies. Other subtypes included Burkitt-like (10%), plasmablastic (10%), follicular lymphoma (2%), and T-cell lymphomas (6%). Nine patients relapsed (18%), at a median time of 97 days (range 54-253 days) post ASCT. Fifteen patients (30%) died; 8 out of 15 (53%) died due to relapse. Opportunistic infections (OI) occurred in 8 patients (16%) at a median of 0.68 years (range 0.17-10.82 years). Types of OI included CMV retinitis (1), HSV/Zoster (1), HPV (1), Candida esophagitis (1) and PJP (3). One patient died from OI (PJP). Seven patients (14%) developed a second primary malignancy (SPM) at median time to SPM of 5.63 years (range 1.02-14.35 years). Type of SPM included treatment-related myelodysplastic syndrome (t-MDS) with progression to acute myelogenous leukemia (AML) (2) observed at 3.2 years and 12.6 years, respectively, after ASCT; squamous cell carcinoma of the tongue (1), and skin cancers, including melanoma (1) at 14.3 years post ASCT, basal cell carcinoma (2) at 5.5 and 5.6 years post ASCT, and squamous cell carcinoma in situ (1) at 1.0 year post ASCT. Two patients died from the t-MDS.

Conclusions: Thirty-five of 50 patients (70%) were alive at the time of analysis confirming the efficacy of this procedure. EFS/OS at 1 year and 5 years post ASCT was 78% (95% CI:67.3%-90.4%)/82% (95% CI: 71.9%-93.4%) and 71.4% (95% CI:59.8%-85.3%)/73.3% (95% CI: 61.8%-86.9%), respectively. Relapse of NHL tended to occur early post-transplant. Cumulative incidence of relapse was 18% at 1 year post ASCT (95% CI: 8.8%-29.8%). Development of OI was also seen early post-ASCT. While SPM appeared as late as 14.35 years following ASCT, it was no higher than that seen in the non-HIV ASCT setting. This is the largest single institution study reporting long-term follow up of HIV-positive patients post ASCT for NHL and demonstrating that while SPM remain a long term concern neither SPM, OI or HIV infection were major factors in mortality.