Abstract
We report a first in-depth comparison of immune reconstitution in patients with HIV-related lymphoma following autologous hematopoietic cell transplant (AHCT) recipients (n=37, lymphoma, BEAM conditioning), HIV(-) AHCT recipients (n=30, myeloma, melphalan conditioning) at 56, 180, and 365 days post-AHCT, and 71 healthy control subjects. Principal component analysis showed that immune cell composition in HIV(+) and HIV(-) AHCT recipients clustered away from healthy controls and from each other at each time point, but approached healthy controls over time. Unsupervised feature importance score analysis identified activated T cells, cytotoxic memory and effector T cells [higher in HIV(+)], and naïve and memory T helper cells [lower HIV(+)] as a having a significant impact on differences between HIV(+) AHCT recipient and healthy control lymphocyte composition (p<0.0033). HIV(+) AHCT recipients also demonstrated lower median absolute numbers of activated B cells and lower NK cell sub-populations, compared to healthy controls (p<0.0033) and HIV(-) AHCT recipients (p<0.006). HIV(+) patient T cells showed robust IFNγ production in response to HIV and EBV recall antigens. Overall, HIV(+) AHCT recipients, but not HIV(-) AHCT recipients, exhibited reconstitution of pro-inflammatory immune profiling that was consistent with that seen in patients with chronic HIV infection treated with antiretroviral regimens. Our results further support the use of AHCT in HIV(+) individuals with relapsed/refractory lymphoma.
Highlights
Improved outcomes in treatment of HIV-associated lymphomas have been achieved in the era of combined antiretroviral therapy [cART] by using multi-agent, dose-intense immunochemotherapeutic regimens, suggesting that HIV-positive [HIV (+)] patients can tolerate intensive approaches with curative intent [1,2,3,4,5,6]
We found that immune reconstitution followed distinct avenues in HIV(+) and HIV(-) autologous hematopoieticcell transplant (AHCT) recipients, with HIV(-) cohort achieving similarity with healthy controls and HIV(+) cohort reconstituting immune features associated with chronic, controlled HIV infection at 1 year post-transplant
Proportions in HIV(+) AHCT recipients. These findings suggest that HIV(+) AHCT recipients reconstitute as pro-inflammatory immune phenotypes, that are similar to cancer-free HIV(+) subjects on cART
Summary
Improved outcomes in treatment of HIV-associated lymphomas have been achieved in the era of combined antiretroviral therapy [cART] by using multi-agent, dose-intense immunochemotherapeutic regimens, suggesting that HIV-positive [HIV (+)] patients can tolerate intensive approaches with curative intent [1,2,3,4,5,6]. In HIV-related NHL, the risk of relapse exceeded 11% after a median follow up of 4.5 years in patients that achieved CR with initial chemotherapy in a prospective observational study of 254 patients [11]. Multiple groups have performed autologous hematopoieticcell transplant (AHCT) in limited numbers of HIV(+) patients with high-risk lymphoma in the era of HIV viral load control with cART. BMT CTN 0803/AMC 071/NCT01141712 was the first interventional, Phase 2 prospective trial investigating the safety and efficacy of a unified myeloablative conditioning regimen followed by AHCT in 40 patients with controlled HIV infection and chemotherapy sensitive relapsed/refractory HIV-associated lymphoma. A prospective multicenter study of AHCT for early consolidation in 16 patients with high or high–intermediate risk HIV-related NHL showed a 50-month OS and PFS of 93.7% [18]
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