Characteristics of Graft-Versus-Host Disease (GvHD) After Post-Transplantation Cyclophosphamide Versus Conventional GvHD Prophylaxis

Rima M Saliba; Amin M Alousi; Joseph Pidala; Mukta Arora; Stephen R Spellman; Michael T Hemmer; Tao Wang; Camille Abboud; Sairah Ahmed; Joseph H Antin; Amer Beitinjaneh; David Buchbinder; Michael Byrne; Jean-Yves Cahn; Hannah Choe; Rabi Hanna; Peiman Hematti; Rammurti T Kamble; Carrie L Kitko; Mary Laughlin; Lazaros Lekakis; Margaret L MacMillan; Rodrigo Martino; Parinda A Mehta; Taiga Nishihori; Sagar S Patel; Miguel-Angel Perales; Hemalatha G Rangarajan; Olov Ringdén; Joseph Rosenthal; Bipin N Savani; Kirk R Schultz; Sachiko Seo; Takanori Teshima; Marjolein van der Poel; Leo F Verdonck; Daniel Weisdorf; Baldeep Wirk; Jean A Yared; Jeffrey Schriber; Richard E Champlin; Stefan O Ciurea

doi:10.1016/j.jtct.2022.07.013

Characteristics of Graft-Versus-Host Disease (GvHD) After Post-Transplantation Cyclophosphamide Versus Conventional GvHD Prophylaxis

Transplant Cell Ther. 2022 Oct;28(10):681-693. doi: 10.1016/j.jtct.2022.07.013. Epub 2022 Jul 16.

Authors

Rima M Saliba¹, Amin M Alousi², Joseph Pidala³, Mukta Arora⁴, Stephen R Spellman⁵, Michael T Hemmer⁶, Tao Wang⁷, Camille Abboud⁸, Sairah Ahmed⁹, Joseph H Antin¹⁰, Amer Beitinjaneh¹¹, David Buchbinder¹², Michael Byrne¹³, Jean-Yves Cahn¹⁴, Hannah Choe¹⁵, Rabi Hanna¹⁶, Peiman Hematti¹⁷, Rammurti T Kamble¹⁸, Carrie L Kitko¹⁹, Mary Laughlin²⁰, Lazaros Lekakis¹¹, Margaret L MacMillan²¹, Rodrigo Martino²², Parinda A Mehta²³, Taiga Nishihori²⁴, Sagar S Patel²⁵, Miguel-Angel Perales²⁶, Hemalatha G Rangarajan²⁷, Olov Ringdén²⁸, Joseph Rosenthal²⁹, Bipin N Savani³⁰, Kirk R Schultz³¹, Sachiko Seo³², Takanori Teshima³³, Marjolein van der Poel³⁴, Leo F Verdonck³⁵, Daniel Weisdorf³⁶, Baldeep Wirk³⁷, Jean A Yared³⁸, Jeffrey Schriber³⁹, Richard E Champlin², Stefan O Ciurea⁴⁰

Affiliations

¹ Department of Stem Cell Transplantation and Cellular Therapy, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas. Electronic address: rsaliba@mdanderson.org.
² Department of Stem Cell Transplantation and Cellular Therapy, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
³ H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
⁴ CIBMTR® (Center for International Blood and Marrow Transplant Research), National Marrow Donor Program/Be the Match, Minneapolis, Minnesota; Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota Medical Center, Minneapolis, Minnesota.
⁵ CIBMTR® (Center for International Blood and Marrow Transplant Research), National Marrow Donor Program/Be the Match, Minneapolis, Minnesota.
⁶ CIBMTR® (Center for International Blood and Marrow Transplant Research), Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
⁷ CIBMTR® (Center for International Blood and Marrow Transplant Research), Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin; Divsion of Biostatistics, Institute for Health and Equity, Medical College of Wisconsin, Milwaukee, Wisconsin.
⁸ Washington University in St. Louis School of Medicine, Division of Oncology, Section of BMT and Leukemia, St. Louis, Missouri.
⁹ Department of Lymphoma-Myeloma, The University of Texas, MD Anderson Cancer Center, Houston, Texas.
¹⁰ Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
¹¹ Division of Transplantation and Cellular Therapy, University of Miami Hospital and Clinics, Sylvester Comprehensive Cancer Center, Miami, Florida.
¹² Division of Pediatric Hematology, Children's Hospital of Orange County, Orange, California.
¹³ Vanderbilt University Medical Center, Nashville, Tennessee.
¹⁴ Department of Hematology, CHU Grenoble Alpes, Université Grenoble Alpes, Grenoble, France.
¹⁵ The Ohio State University Wexner Medical Center, James Comprehensive Cancer Center, Columbus, Ohio.
¹⁶ Cleveland Clinic, Cleveland, Ohio.
¹⁷ Division of Hematology/Oncology/Bone Marrow Transplantation, Department of Medicine, University of Wisconsin, Madison, Wisconsin.
¹⁸ Division of Hematology and Oncology, Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas.
¹⁹ Division of Pediatric Hematology/Oncology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee.
²⁰ Medical Director, Cleveland Cord Blood Center, Cleveland, Ohio.
²¹ Blood and Marrow Transplant Program, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota.
²² Division of Clinical Hematology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
²³ Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
²⁴ Department of Blood & Marrow Transplant and Cellular Immunotherapy (BMT CI), Moffitt Cancer Center, Tampa, Florida.
²⁵ Blood and Marrow Transplant Program, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.
²⁶ Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
²⁷ Department of Pediatric Hematology, Oncology, Blood and Marrow Transplantation, Nationwide Children's Hospital, Columbus, Ohio.
²⁸ Translational Cell Therapy Group, CLINTEC (Clinical Science, Intervention and Technology), Karolinska Institutet, Stockholm, Sweden.
²⁹ City of Hope, Duarte, California.
³⁰ Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
³¹ Department of Pediatric Hematology, Oncology and Bone Marrow Transplant, British Columbia's Children's Hospital, The University of British Columbia, Vancouver, British Columbia, Canada.
³² Department of Hematology and Oncology, Dokkyo Medical University, Tochigi, Japan.
³³ Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan.
³⁴ Department of Internal Medicine, Division of Hematology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands.
³⁵ Department of Hematology/Oncology, Isala Clinic, Zwolle, The Netherlands.
³⁶ Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minnesota.
³⁷ Bone Marrow Transplant Program, Penn State Cancer Institute, Hershey, Pennsylvania.
³⁸ Transplantation & Cellular Therapy Program, Division of Hematology/Oncology, Department of Medicine, Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, Maryland.
³⁹ Cancer Treatment Centers of America Comprehensive Care and Research Center, Phoenix, Arizona.
⁴⁰ Hematopoietic Stem Cell Transplantation and Cellular Therapy Program, University of California, Irvine, Orange, California.

Abstract

Post-transplantation cyclophosphamide (PTCy) has been shown to effectively control graft-versus-host disease (GvHD) in haploidentical (Haplo) transplantations. In this retrospective registry study, we compared GvHD organ distribution, severity, and outcomes in patients with GvHD occurring after Haplo transplantation with PTCy GvHD prophylaxis (Haplo/PTCy) versus HLA-matched unrelated donor transplantation with conventional prophylaxis (MUD/conventional). We evaluated 2 cohorts: patients with grade 2 to 4 acute GvHD (aGvHD) including 264 and 1163 recipients of Haplo and MUD transplants; and patients with any chronic GvHD (cGvHD) including 206 and 1018 recipients of Haplo and MUD transplants, respectively. In comparison with MUD/conventional transplantation ± antithymocyte globulin (ATG), grade 3-4 aGvHD (28% versus 39%, P = .001), stage 3-4 lower gastrointestinal (GI) tract aGvHD (14% versus 21%, P = .01), and chronic GI GvHD (21% versus 31%, P = .006) were less common after Haplo/PTCy transplantation. In patients with grade 2-4 aGvHD, cGvHD rate after Haplo/PTCY was also lower (hazard ratio [HR] = .4, P < .001) in comparison with MUD/conventional transplantation without ATG in the nonmyeloablative conditioning setting. Irrespective of the use of ATG, non-relapse mortality rate was lower (HR = .6, P = .01) after Haplo/PTCy transplantation, except for transplants that were from a female donor into a male recipient. In patients with cGvHD, irrespective of ATG use, Haplo/PTCy transplantation had lower non-relapse mortality rates (HR = .6, P = .04). Mortality rate was higher (HR = 1.6, P = .03) during, but not after (HR = .9, P = .6) the first 6 months after cGvHD diagnosis. Our results suggest that PTCy-based GvHD prophylaxis mitigates the development of GI GvHD and may translate into lower GvHD-related non-relapse mortality rate.

Keywords: Graft-versus-host disease; Non-relapse mortality; Post-transplantation cyclophosphamide; Prophylaxis.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Antilymphocyte Serum / therapeutic use
Cyclophosphamide / therapeutic use
Female
Graft vs Host Disease* / prevention & control
Hematopoietic Stem Cell Transplantation* / adverse effects
Humans
Male
Retrospective Studies

Substances

Antilymphocyte Serum
Cyclophosphamide

Abstract

Publication types

MeSH terms

Substances

Grants and funding