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-...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-09-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.700045/full |
| _version_ | 1818731892010123264 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Polina Shindiapina |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-17T23:24:53Z |
| format | Article |
| id | doaj.art-11e102a0fff440d19a1c2e8eecf7cba8 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-17T23:24:53Z |
| publishDate | 2021-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-11e102a0fff440d19a1c2e8eecf7cba82022-12-21T21:28:47ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-09-011210.3389/fimmu.2021.700045700045Immune Recovery Following Autologous Hematopoietic Stem Cell Transplantation in HIV-Related Lymphoma Patients on the BMT CTN 0803/AMC 071 TrialPolina Shindiapina0Polina Shindiapina1Maciej Pietrzak2Michal Seweryn3Eric McLaughlin4Xiaoli Zhang5Mat Makowski6Elshafa Hassan Ahmed7Elshafa Hassan Ahmed8Sarah Schlotter9Rebecca Pearson10Rhonda Kitzler11Anna Mozhenkova12Jennifer Le-Rademacher13Richard F. Little14Gorgun Akpek15Ernesto Ayala16Steven M. Devine17Lawrence D. Kaplan18Ariela Noy19Uday R. Popat20Jack W. Hsu21Lawrence E. Morris22Adam M. Mendizabal23Amrita Krishnan24William Wachsman25William Wachsman26Nita Williams27Nidhi Sharma28Craig C. Hofmeister29Stephen J. Forman30Willis H. Navarro31Willis H. Navarro32Joseph C. Alvarnas33Richard F. Ambinder34Gerard Lozanski35Robert A. Baiocchi36Robert A. Baiocchi37Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, United StatesComprehensive Cancer Center, The Ohio State University, Columbus, OH, United StatesDepartment of Biomedical Informatics, The Ohio State University, Columbus, OH, United StatesBiobank Lab, Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Łódź, Łódź, PolandDepartment of Biomedical Informatics, The Ohio State University, Columbus, OH, United StatesDepartment of Biomedical Informatics, The Ohio State University, Columbus, OH, United StatesEmmes Company, Rockville, MD, United StatesComprehensive Cancer Center, The Ohio State University, Columbus, OH, United StatesDepartment of Veterenary Biosciences, College of Veterenary Medicine, The Ohio State University, Columbus, OH, United StatesCollege of Medicine, The Ohio State University, Columbus, OH, United StatesDepartment of Pathology, The Ohio State University, Columbus, OH, United StatesDepartment of Pathology, The Ohio State University, Columbus, OH, United StatesComprehensive Cancer Center, The Ohio State University, Columbus, OH, United StatesDivision of Clinical Trials and Biostatistics, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, United States0National Cancer Institute, National Institutes of Health, Bethesda, MD, United States1Pacific Central Coast Health Centers, San Luis Obispo, CA, United States2Department of Internal Medicine, Hematology & Oncology, Mayo Clinic, Jacksonville, FL, United States3Center for International Blood and Marrow Transplant Research, National Marrow Donor Program/Be The Match, Minneapolis, MN, United States4Department of Medicine, University of California, San Francisco, San Francisco, CA, United States5Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, United States6Department of Stem Cell Transplantation and Cellular Therapy, University of Texas, MD Anderson Cancer Center, Houston, TX, United States7Division of Hematology and Oncology, Department of Medicine, University of Florida, Gainesville, FL, United States8Blood and Marrow Transplant Program at Northside Hospital, Atlanta, GA, United StatesEmmes Company, Rockville, MD, United States9Department of Hematology & Hematopoietic Cell Transplantation, City of Hope Comprehensive Cancer Center, Duarte, CA, United States0Moores University of California San Diego Cancer Center, La Jolla, CA, United States1Veterans Affairs San Diego Healthcare System, San Diego, CA, United StatesComprehensive Cancer Center, The Ohio State University, Columbus, OH, United StatesComprehensive Cancer Center, The Ohio State University, Columbus, OH, United States2Winship Cancer Institute, Emory University, Atlanta, GA, United States9Department of Hematology & Hematopoietic Cell Transplantation, City of Hope Comprehensive Cancer Center, Duarte, CA, United States3Division of Hematology/Oncology/Transplantation, University of Minnesota, Minneapolis, MN, United States4Global Research and Development, Atara Biotherapeutics, Inc., San Francisco, CA, United States9Department of Hematology & Hematopoietic Cell Transplantation, City of Hope Comprehensive Cancer Center, Duarte, CA, United States5Division of Hematologic Malignancies, Sidney Kimmel Comprehensive Cancer Center (SKCCC), Johns Hopkins Medical Institutions, Baltimore, MD, United StatesDepartment of Pathology, The Ohio State University, Columbus, OH, United StatesDivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, United StatesComprehensive Cancer Center, The Ohio State University, Columbus, OH, United StatesWe 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.https://www.frontiersin.org/articles/10.3389/fimmu.2021.700045/fullhuman immunodeficiency virus (HIV)hematopoeietic stem cell transplantationHodgkin lymphoma (HL)Non-Hodgkin lymphomamultiple myeloma |
| spellingShingle | 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 Immune Recovery Following Autologous Hematopoietic Stem Cell Transplantation in HIV-Related Lymphoma Patients on the BMT CTN 0803/AMC 071 Trial Frontiers in Immunology human immunodeficiency virus (HIV) hematopoeietic stem cell transplantation Hodgkin lymphoma (HL) Non-Hodgkin lymphoma multiple myeloma |
| title | Immune Recovery Following Autologous Hematopoietic Stem Cell Transplantation in HIV-Related Lymphoma Patients on the BMT CTN 0803/AMC 071 Trial |
| title_full | Immune Recovery Following Autologous Hematopoietic Stem Cell Transplantation in HIV-Related Lymphoma Patients on the BMT CTN 0803/AMC 071 Trial |
| title_fullStr | Immune Recovery Following Autologous Hematopoietic Stem Cell Transplantation in HIV-Related Lymphoma Patients on the BMT CTN 0803/AMC 071 Trial |
| title_full_unstemmed | Immune Recovery Following Autologous Hematopoietic Stem Cell Transplantation in HIV-Related Lymphoma Patients on the BMT CTN 0803/AMC 071 Trial |
| title_short | Immune Recovery Following Autologous Hematopoietic Stem Cell Transplantation in HIV-Related Lymphoma Patients on the BMT CTN 0803/AMC 071 Trial |
| title_sort | immune recovery following autologous hematopoietic stem cell transplantation in hiv related lymphoma patients on the bmt ctn 0803 amc 071 trial |
| topic | human immunodeficiency virus (HIV) hematopoeietic stem cell transplantation Hodgkin lymphoma (HL) Non-Hodgkin lymphoma multiple myeloma |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.700045/full |
| work_keys_str_mv | AT polinashindiapina immunerecoveryfollowingautologoushematopoieticstemcelltransplantationinhivrelatedlymphomapatientsonthebmtctn0803amc071trial AT polinashindiapina immunerecoveryfollowingautologoushematopoieticstemcelltransplantationinhivrelatedlymphomapatientsonthebmtctn0803amc071trial AT maciejpietrzak immunerecoveryfollowingautologoushematopoieticstemcelltransplantationinhivrelatedlymphomapatientsonthebmtctn0803amc071trial AT michalseweryn immunerecoveryfollowingautologoushematopoieticstemcelltransplantationinhivrelatedlymphomapatientsonthebmtctn0803amc071trial AT ericmclaughlin immunerecoveryfollowingautologoushematopoieticstemcelltransplantationinhivrelatedlymphomapatientsonthebmtctn0803amc071trial AT xiaolizhang immunerecoveryfollowingautologoushematopoieticstemcelltransplantationinhivrelatedlymphomapatientsonthebmtctn0803amc071trial AT matmakowski immunerecoveryfollowingautologoushematopoieticstemcelltransplantationinhivrelatedlymphomapatientsonthebmtctn0803amc071trial AT elshafahassanahmed immunerecoveryfollowingautologoushematopoieticstemcelltransplantationinhivrelatedlymphomapatientsonthebmtctn0803amc071trial AT elshafahassanahmed immunerecoveryfollowingautologoushematopoieticstemcelltransplantationinhivrelatedlymphomapatientsonthebmtctn0803amc071trial AT sarahschlotter immunerecoveryfollowingautologoushematopoieticstemcelltransplantationinhivrelatedlymphomapatientsonthebmtctn0803amc071trial AT rebeccapearson immunerecoveryfollowingautologoushematopoieticstemcelltransplantationinhivrelatedlymphomapatientsonthebmtctn0803amc071trial AT rhondakitzler immunerecoveryfollowingautologoushematopoieticstemcelltransplantationinhivrelatedlymphomapatientsonthebmtctn0803amc071trial AT annamozhenkova immunerecoveryfollowingautologoushematopoieticstemcelltransplantationinhivrelatedlymphomapatientsonthebmtctn0803amc071trial AT jenniferlerademacher immunerecoveryfollowingautologoushematopoieticstemcelltransplantationinhivrelatedlymphomapatientsonthebmtctn0803amc071trial AT richardflittle immunerecoveryfollowingautologoushematopoieticstemcelltransplantationinhivrelatedlymphomapatientsonthebmtctn0803amc071trial AT gorgunakpek immunerecoveryfollowingautologoushematopoieticstemcelltransplantationinhivrelatedlymphomapatientsonthebmtctn0803amc071trial AT ernestoayala immunerecoveryfollowingautologoushematopoieticstemcelltransplantationinhivrelatedlymphomapatientsonthebmtctn0803amc071trial AT stevenmdevine immunerecoveryfollowingautologoushematopoieticstemcelltransplantationinhivrelatedlymphomapatientsonthebmtctn0803amc071trial AT lawrencedkaplan immunerecoveryfollowingautologoushematopoieticstemcelltransplantationinhivrelatedlymphomapatientsonthebmtctn0803amc071trial AT arielanoy immunerecoveryfollowingautologoushematopoieticstemcelltransplantationinhivrelatedlymphomapatientsonthebmtctn0803amc071trial AT udayrpopat immunerecoveryfollowingautologoushematopoieticstemcelltransplantationinhivrelatedlymphomapatientsonthebmtctn0803amc071trial AT jackwhsu immunerecoveryfollowingautologoushematopoieticstemcelltransplantationinhivrelatedlymphomapatientsonthebmtctn0803amc071trial AT lawrenceemorris immunerecoveryfollowingautologoushematopoieticstemcelltransplantationinhivrelatedlymphomapatientsonthebmtctn0803amc071trial AT adammmendizabal immunerecoveryfollowingautologoushematopoieticstemcelltransplantationinhivrelatedlymphomapatientsonthebmtctn0803amc071trial AT amritakrishnan immunerecoveryfollowingautologoushematopoieticstemcelltransplantationinhivrelatedlymphomapatientsonthebmtctn0803amc071trial AT williamwachsman immunerecoveryfollowingautologoushematopoieticstemcelltransplantationinhivrelatedlymphomapatientsonthebmtctn0803amc071trial AT williamwachsman immunerecoveryfollowingautologoushematopoieticstemcelltransplantationinhivrelatedlymphomapatientsonthebmtctn0803amc071trial AT nitawilliams immunerecoveryfollowingautologoushematopoieticstemcelltransplantationinhivrelatedlymphomapatientsonthebmtctn0803amc071trial AT nidhisharma immunerecoveryfollowingautologoushematopoieticstemcelltransplantationinhivrelatedlymphomapatientsonthebmtctn0803amc071trial AT craigchofmeister immunerecoveryfollowingautologoushematopoieticstemcelltransplantationinhivrelatedlymphomapatientsonthebmtctn0803amc071trial AT stephenjforman immunerecoveryfollowingautologoushematopoieticstemcelltransplantationinhivrelatedlymphomapatientsonthebmtctn0803amc071trial AT willishnavarro immunerecoveryfollowingautologoushematopoieticstemcelltransplantationinhivrelatedlymphomapatientsonthebmtctn0803amc071trial AT willishnavarro immunerecoveryfollowingautologoushematopoieticstemcelltransplantationinhivrelatedlymphomapatientsonthebmtctn0803amc071trial AT josephcalvarnas immunerecoveryfollowingautologoushematopoieticstemcelltransplantationinhivrelatedlymphomapatientsonthebmtctn0803amc071trial AT richardfambinder immunerecoveryfollowingautologoushematopoieticstemcelltransplantationinhivrelatedlymphomapatientsonthebmtctn0803amc071trial AT gerardlozanski immunerecoveryfollowingautologoushematopoieticstemcelltransplantationinhivrelatedlymphomapatientsonthebmtctn0803amc071trial AT robertabaiocchi immunerecoveryfollowingautologoushematopoieticstemcelltransplantationinhivrelatedlymphomapatientsonthebmtctn0803amc071trial AT robertabaiocchi immunerecoveryfollowingautologoushematopoieticstemcelltransplantationinhivrelatedlymphomapatientsonthebmtctn0803amc071trial |