Frontiers in Immunology (Sep 2021)
Immune Recovery Following Autologous Hematopoietic Stem Cell Transplantation in HIV-Related Lymphoma Patients on the BMT CTN 0803/AMC 071 Trial
- Polina Shindiapina,
- Polina Shindiapina,
- Maciej Pietrzak,
- Michal Seweryn,
- Eric McLaughlin,
- Xiaoli Zhang,
- Mat Makowski,
- Elshafa Hassan Ahmed,
- 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. Hsu,
- Lawrence E. Morris,
- Adam M. Mendizabal,
- Amrita Krishnan,
- William Wachsman,
- William Wachsman,
- Nita Williams,
- Nidhi Sharma,
- Craig C. Hofmeister,
- Stephen J. Forman,
- Willis H. Navarro,
- Willis H. Navarro,
- Joseph C. Alvarnas,
- Richard F. Ambinder,
- Gerard Lozanski,
- Robert A. Baiocchi,
- Robert A. Baiocchi
Affiliations
- Polina Shindiapina
- Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, United States
- Polina Shindiapina
- Comprehensive Cancer Center, The Ohio State University, Columbus, OH, United States
- Maciej Pietrzak
- Department of Biomedical Informatics, The Ohio State University, Columbus, OH, United States
- Michal Seweryn
- Biobank Lab, Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Łódź, Łódź, Poland
- Eric McLaughlin
- Department of Biomedical Informatics, The Ohio State University, Columbus, OH, United States
- Xiaoli Zhang
- Department of Biomedical Informatics, The Ohio State University, Columbus, OH, United States
- Mat Makowski
- Emmes Company, Rockville, MD, United States
- Elshafa Hassan Ahmed
- Comprehensive Cancer Center, The Ohio State University, Columbus, OH, United States
- Elshafa Hassan Ahmed
- Department of Veterenary Biosciences, College of Veterenary Medicine, The Ohio State University, Columbus, OH, United States
- Sarah Schlotter
- College of Medicine, The Ohio State University, Columbus, OH, United States
- Rebecca Pearson
- Department of Pathology, The Ohio State University, Columbus, OH, United States
- Rhonda Kitzler
- Department of Pathology, The Ohio State University, Columbus, OH, United States
- Anna Mozhenkova
- Comprehensive Cancer Center, The Ohio State University, Columbus, OH, United States
- Jennifer Le-Rademacher
- Division of Clinical Trials and Biostatistics, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, United States
- Richard F. Little
- 0National Cancer Institute, National Institutes of Health, Bethesda, MD, United States
- Gorgun Akpek
- 1Pacific Central Coast Health Centers, San Luis Obispo, CA, United States
- Ernesto Ayala
- 2Department of Internal Medicine, Hematology & Oncology, Mayo Clinic, Jacksonville, FL, United States
- Steven M. Devine
- 3Center for International Blood and Marrow Transplant Research, National Marrow Donor Program/Be The Match, Minneapolis, MN, United States
- Lawrence D. Kaplan
- 4Department of Medicine, University of California, San Francisco, San Francisco, CA, United States
- Ariela Noy
- 5Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, United States
- Uday R. Popat
- 6Department of Stem Cell Transplantation and Cellular Therapy, University of Texas, MD Anderson Cancer Center, Houston, TX, United States
- Jack W. Hsu
- 7Division of Hematology and Oncology, Department of Medicine, University of Florida, Gainesville, FL, United States
- Lawrence E. Morris
- 8Blood and Marrow Transplant Program at Northside Hospital, Atlanta, GA, United States
- Adam M. Mendizabal
- Emmes Company, Rockville, MD, United States
- Amrita Krishnan
- 9Department of Hematology & Hematopoietic Cell Transplantation, City of Hope Comprehensive Cancer Center, Duarte, CA, United States
- William Wachsman
- 0Moores University of California San Diego Cancer Center, La Jolla, CA, United States
- William Wachsman
- 1Veterans Affairs San Diego Healthcare System, San Diego, CA, United States
- Nita Williams
- Comprehensive Cancer Center, The Ohio State University, Columbus, OH, United States
- Nidhi Sharma
- Comprehensive Cancer Center, The Ohio State University, Columbus, OH, United States
- Craig C. Hofmeister
- 2Winship Cancer Institute, Emory University, Atlanta, GA, United States
- Stephen J. Forman
- 9Department of Hematology & Hematopoietic Cell Transplantation, City of Hope Comprehensive Cancer Center, Duarte, CA, United States
- Willis H. Navarro
- 3Division of Hematology/Oncology/Transplantation, University of Minnesota, Minneapolis, MN, United States
- Willis H. Navarro
- 4Global Research and Development, Atara Biotherapeutics, Inc., San Francisco, CA, United States
- Joseph C. Alvarnas
- 9Department of Hematology & Hematopoietic Cell Transplantation, City of Hope Comprehensive Cancer Center, Duarte, CA, United States
- Richard F. Ambinder
- 5Division of Hematologic Malignancies, Sidney Kimmel Comprehensive Cancer Center (SKCCC), Johns Hopkins Medical Institutions, Baltimore, MD, United States
- Gerard Lozanski
- Department of Pathology, The Ohio State University, Columbus, OH, United States
- Robert A. Baiocchi
- Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, United States
- Robert A. Baiocchi
- Comprehensive Cancer Center, The Ohio State University, Columbus, OH, United States
- DOI
- https://doi.org/10.3389/fimmu.2021.700045
- Journal volume & issue
-
Vol. 12
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.
Keywords
- human immunodeficiency virus (HIV)
- hematopoeietic stem cell transplantation
- Hodgkin lymphoma (HL)
- Non-Hodgkin lymphoma
- multiple myeloma
