Immune Recovery Following Autologous Hematopoietic Stem Cell Transplantation in HIV-Related Lymphoma Patients on the BMT CTN 0803/AMC 071 Trial.

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.
Competing Interests: PS, Seattle Genetics, Research funding. AK, Celgene, Consultancy, Speakers Bureau, Millennium/Takeda, Consultancy, Speakers Bureau, Onyx, Consultancy, Speakers Bureau, Janssen, Consultancy, Speakers Bureau. Hofmeister, Signal Genetics, Inc., Membership on an entity’s Board of Directors or advisory committees, Celgene, Research Funding; Arno Therapeutics, Inc., Research Funding, Incyte, Corp, Membership on an entity’s Board of Directors or advisory committees, Janssen, Pharmaceutical Companies of Johnson & Johnson, Research Funding, Karyopharm Therapeutics, Research Funding, Takeda Pharmaceutical Company, Research Funding, Teva, Membership on an entity’s Board of Directors or advisory committees. SF, Mustang Therapeutics, Other, Construct licensed by City of Hope. WN, Atara Biotherapeutics, employment, stock ownership. GL, Boehringer Ingelheim, Research Funding, Beckman Coulter, Research Funding, Stemline Therapeutics Inc., Research Funding, Genentech. RB, Prelude Therapeutics, Research Funding and Scientific Advisory Board, Viracta, Scientific Advisory Board. AN, Janssen, Membership on a Board or Advisory Committee; Medscape, Honoraria; Morphosys, Membership on a Board or Advisory Committee; Pharmacyclics, Research Funding, Honoraria; Rafael Pharma, Research Funding; Epizyme, Membership on a Board or Advisory Committee; Physician Education Resource, Consulting. MM and AMM are employed by EMMES Company. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2021 Shindiapina, Pietrzak, Seweryn, McLaughlin, Zhang, Makowski, Ahmed, Schlotter, Pearson, Kitzler, Mozhenkova, Le-Rademacher, Little, Akpek, Ayala, Devine, Kaplan, Noy, Popat, Hsu, Morris, Mendizabal, Krishnan, Wachsman, Williams, Sharma, Hofmeister, Forman, Navarro, Alvarnas, Ambinder, Lozanski and Baiocchi.)