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

Autor:	Shindiapina P; Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, United States.; Comprehensive Cancer Center, The Ohio State University, Columbus, OH, United States., Pietrzak M; Department of Biomedical Informatics, The Ohio State University, Columbus, OH, United States., Seweryn M; Biobank Lab, Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Łódź, Łódź, Poland., McLaughlin E; Department of Biomedical Informatics, The Ohio State University, Columbus, OH, United States., Zhang X; Department of Biomedical Informatics, The Ohio State University, Columbus, OH, United States., Makowski M; Emmes Company, Rockville, MD, United States., Ahmed EH; Comprehensive Cancer Center, The Ohio State University, Columbus, OH, United States.; Department of Veterenary Biosciences, College of Veterenary Medicine, The Ohio State University, Columbus, OH, United States., Schlotter S; College of Medicine, The Ohio State University, Columbus, OH, United States., Pearson R; Department of Pathology, The Ohio State University, Columbus, OH, United States., Kitzler R; Department of Pathology, The Ohio State University, Columbus, OH, United States., Mozhenkova A; Comprehensive Cancer Center, The Ohio State University, Columbus, OH, United States., Le-Rademacher J; Division of Clinical Trials and Biostatistics, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, United States., Little RF; National Cancer Institute, National Institutes of Health, Bethesda, MD, United States., Akpek G; Pacific Central Coast Health Centers, San Luis Obispo, CA, United States., Ayala E; Department of Internal Medicine, Hematology & Oncology, Mayo Clinic, Jacksonville, FL, United States., Devine SM; Center for International Blood and Marrow Transplant Research, National Marrow Donor Program/Be The Match, Minneapolis, MN, United States., Kaplan LD; Department of Medicine, University of California, San Francisco, San Francisco, CA, United States., Noy A; Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, United States., Popat UR; Department of Stem Cell Transplantation and Cellular Therapy, University of Texas, MD Anderson Cancer Center, Houston, TX, United States., Hsu JW; Division of Hematology and Oncology, Department of Medicine, University of Florida, Gainesville, FL, United States., Morris LE; Blood and Marrow Transplant Program at Northside Hospital, Atlanta, GA, United States., Mendizabal AM; Emmes Company, Rockville, MD, United States., Krishnan A; Department of Hematology & Hematopoietic Cell Transplantation, City of Hope Comprehensive Cancer Center, Duarte, CA, United States., Wachsman W; Moores University of California San Diego Cancer Center, La Jolla, CA, United States.; Veterans Affairs San Diego Healthcare System, San Diego, CA, United States., Williams N; Comprehensive Cancer Center, The Ohio State University, Columbus, OH, United States., Sharma N; Comprehensive Cancer Center, The Ohio State University, Columbus, OH, United States., Hofmeister CC; Winship Cancer Institute, Emory University, Atlanta, GA, United States., Forman SJ; Department of Hematology & Hematopoietic Cell Transplantation, City of Hope Comprehensive Cancer Center, Duarte, CA, United States., Navarro WH; Division of Hematology/Oncology/Transplantation, University of Minnesota, Minneapolis, MN, United States.; Global Research and Development, Atara Biotherapeutics, Inc., San Francisco, CA, United States., Alvarnas JC; Department of Hematology & Hematopoietic Cell Transplantation, City of Hope Comprehensive Cancer Center, Duarte, CA, United States., Ambinder RF; Division of Hematologic Malignancies, Sidney Kimmel Comprehensive Cancer Center (SKCCC), Johns Hopkins Medical Institutions, Baltimore, MD, United States., Lozanski G; Department of Pathology, The Ohio State University, Columbus, OH, United States., Baiocchi RA; Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, United States.; Comprehensive Cancer Center, The Ohio State University, Columbus, OH, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2021 Sep 03; Vol. 12, pp. 700045. Date of Electronic Publication: 2021 Sep 03 (Print Publication: 2021).
DOI:	10.3389/fimmu.2021.700045
Abstrakt:	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.)
Databáze:	MEDLINE
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