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

Polina Shindiapina, Maciej Pietrzak, Michal Seweryn, Eric McLaughlin, Xiaoli Zhang, Mat Makowski, Elshafa Hassan Ahmed, Sarah Schlotter, Rebecca Pearson, Rhonda Kitzler, Anna Mozhenkova, Jennifer Le-Rademacher, Richard F. Little, Gorgun Akpek, Ernesto Ayala, Steven M. Devine, Lawrence D. Kaplan, Ariela Noy, Uday R. Popat, Jack W. HsuLawrence E. Morris, Adam M. Mendizabal, Amrita Krishnan, William Wachsman, Nita Williams, Nidhi Sharma, Craig C. Hofmeister, Stephen J. Forman, Willis H. Navarro, Joseph C. Alvarnas, Richard F. Ambinder, Gerard Lozanski, Robert A. Baiocchi

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number700045
JournalFrontiers in immunology
Volume12
DOIs
StatePublished - Sep 3 2021

Keywords

  • hematopoeietic stem cell transplantation
  • Hodgkin lymphoma (HL)
  • human immunodeficiency virus (HIV)
  • multiple myeloma
  • Non-Hodgkin lymphoma

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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