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

• Type of Material: Article
• Authors: Polina Shindiapina, Ohio State University; Maciej Pietrzak, Ohio State University; Michal Seweryn, University of Lodz; Eric McLaughlin, Ohio State University; Xiaoli Zhang, Ohio State University; Mat Makowski, Emmes Company; Elshafa Hassan Ahmed, Ohio State University; Sarah Schlotter, Ohio State University; Rebecca Pearson, Ohio State University; Rhonda Kitzler, Ohio State University; Anna Mozhenkova, Ohio State University; Jennifer Le-Rademacher, Mayo Clinic; Richard F Little, National Institutes of Health, Bethesda; Gorgun Akpek, Pacific Central Coast Health Centers; Ernesto Ayala, Mayo Clinic; Steven M Devine, Center for International Blood and Marrow Transplant Research, National Marrow Donor Program/Be The Match; Lawrence D Kaplan, University of California San Francisco; Ariela Noy, Memorial Sloan Kettering Cancer Center; Uday R Popat, University of Texas, MD Anderson Cancer Center; Jack W Hsu, University of Florida; Lawrence E Morris, Northside Hospital, Atlanta; Adam M Mendizabal, Emmes Co; Amrita Krishnan, City of Hope Comprehensive Cancer Center; William Wachsman, Moores University of California San Diego Cancer Center; Nita Williams, Ohio State University; Nidhi Sharma, Ohio State University; Craig Hofmeister, Emory University; Stephen J Forman, City of Hope Comprehensive Cancer Center; Willis H Navarro, University of Minnesota, Minneapolis; Joseph C Alvarnas, City of Hope Comprehensive Cancer Center; Richard F Ambinder, Johns Hopkins Medical Institutions; Gerard Lozanski, Ohio State University; Robert A Baiocchi, Ohio State University
• Language: English
• Date: 2021-09-03
• Publisher: FRONTIERS MEDIA SA
• Publication Version: Final Published Version
• Copyright Statement: © 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
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3389/fimmu.2021.700045
• Title of Journal or Parent Work: FRONTIERS IN IMMUNOLOGY
• Volume: 12
• Start Page: 700045
• End Page: 700045
• Grant/Funding Information: Research reported in this publication was also supported by The Ohio State University Comprehensive Cancer Center and the National Institutes of Health under grant number P30 CA016058.; The study was coordinated by the AIDS Malignancy Consortium and supported in part by Public Health Service Grant No. UM1 CA121947 and the National Cancer Institute, National Institutes of Health, and the Department of Health and Human Services.; EHA is supported by NIH-T32 grant T32CA090223.; Funding for this Blood and Marrow Transplant Clinical Trials Network (BMT CTN) and AIDS Malignancy Consortium (AMC) study was provided by HHSN261200622012C-009 from the National Cancer Institute (NCI) and by the AIDS Malignancy Consortium (AMC) through NCI grant U01CA121947.; The BMT CTN infrastructure is supported in part by grant U10HL069294 to the Blood and Marrow Transplant Clinical Trials Network from the National Heart, Lung, and Blood Institute and NCI.; PS has received funding through an AMC Translational Fellowship funded by the AMC through the grant U01CA121947 in 2017-2019 and T32 fellowship through the grant T32 CA009338 from the NIH.
• Keywords: hematopoeietic stem cell transplantation; CODOX-M/IVAC; multiple myeloma; NATURAL-KILLER-CELLS; Life Sciences & Biomedicine; HIGH-DOSE THERAPY; NON-HODGKIN-LYMPHOMA; Immunology; CD4(+) T-CELLS; Hodgkin lymphoma (HL); Science & Technology; NK CELLS; Non-Hodgkin lymphoma; INFUSIONAL EPOCH CHEMOTHERAPY; B-CELLS; ANTIRETROVIRAL THERAPY; human immunodeficiency virus (HIV); IMMUNOLOGICAL RECOVERY
• Research Categories: Health Sciences, Oncology; Health Sciences, Medicine and Surgery

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.