Bronwen E Shaw1, Antonio Martin Jimenez-Jimenez2, Linda J Burns1, Brent R Logan1, Farhad Khimani3, Brian C Shaffer4, Nirav N Shah5, Alisha Mussetter6, Xiao-Ying Tang1, John M McCarty7, Asif Alavi8, Nosha Farhadfar9, Katarzyna Jamieson10, Nancy M Hardy11, Hannah Choe12, Richard F Ambinder13, Claudio Anasetti3, Miguel-Angel Perales4, Stephen R Spellman6, Alan Howard6, Krishna V Komanduri2, Leo Luznik13, Maxim Norkin14, Joseph A Pidala3, Voravit Ratanatharathorn8, Dennis L Confer6, Steven M Devine6, Mary M Horowitz1, Javier Bolaños-Meade13. 1. Center for International Blood and Marrow Transplant Research/Medical College of Wisconsin, Milwaukee, WI. 2. Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL. 3. H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL. 4. Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY. 5. Department of Medicine, Medical College of Wisconsin, Milwaukee, WI. 6. Center for International Blood and Marrow Transplant Research/National Marrow Donor Program, Minneapolis, MN. 7. Massey Cancer Center Bone Marrow Transplant Program, Virginia Commonwealth University, Richmond, VA. 8. Department of Oncology, Blood and Marrow Stem Cell Transplant Program, Karmanos Cancer Institute/Wayne State University, Detroit, MI. 9. Division of Hematology/Oncology, University of Florida College of Medicine, Gainesville, FL. 10. University of North Carolina Hospitals - Chapel Hill, Chapel Hill, NC. 11. Greenebaum Cancer Center, University of Maryland, Baltimore, MD. 12. James Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH. 13. The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD. 14. LifeSouth Community Blood Centers, Baptist MD Anderson Cancer Center, Jacksonville, FL.
Abstract
PURPOSE: Hematopoietic cell transplantation (HCT) is curative for hematologic disorders, but outcomes are historically inferior when using HLA-mismatched donors. Despite unrelated donor registries listing > 38 million volunteers, 25%-80% of US patients lack an HLA-matched unrelated donor, with significant disparity across ethnic groups. We hypothesized that HCT with a mismatched unrelated donor (MMUD) using post-transplant cyclophosphamide (PTCy), a novel strategy successful in overcoming genetic disparity using mismatched related donors, would be feasible and increase access to HCT. PATIENTS AND METHODS: We performed a prospective phase II study of MMUD bone marrow HCT with PTCy for patients with hematologic malignancies. The primary end point was 1-year overall survival (OS), hypothesized to be 65% or better. 80 patients enrolled at 11 US transplant centers (December 2016-March 2019). Following myeloablative or reduced-intensity conditioning-based HCT, patients received PTCy on days +3, +4, with sirolimus and mycophenolate mofetil starting on day +5. We compared outcomes to Center for International Blood and Marrow Transplant Research contemporary controls receiving PTCy. RESULTS: Notably, 48% of patients enrolled were ethnic minorities. 39% of pairs were matched for 4-6 out of 8 HLA alleles. The primary end point was met, with 1-year OS of 76% (90% CI, 67.3 to 83.3) in the entire cohort, and 72% and 79% in the myeloablative and reduced-intensity conditioning strata, respectively. Secondary end points related to engraftment and graft-versus-host-disease were reached. Multivariate analysis comparing the study group with other mismatched HCT controls found no significant differences in OS. CONCLUSION: Our prospective study demonstrates the feasibility and effectiveness of HCT with an MMUD in the setting of PTCy. Remarkably, nearly half of the study participants belonged to an ethnic minority population, suggesting this approach may significantly expand access to HCT.
PURPOSE: Hematopoietic cell transplantation (HCT) is curative for hematologic disorders, but outcomes are historically inferior when using HLA-mismatched donors. Despite unrelated donor registries listing > 38 million volunteers, 25%-80% of US patients lack an HLA-matched unrelated donor, with significant disparity across ethnic groups. We hypothesized that HCT with a mismatched unrelated donor (MMUD) using post-transplant cyclophosphamide (PTCy), a novel strategy successful in overcoming genetic disparity using mismatched related donors, would be feasible and increase access to HCT. PATIENTS AND METHODS: We performed a prospective phase II study of MMUD bone marrow HCT with PTCy for patients with hematologic malignancies. The primary end point was 1-year overall survival (OS), hypothesized to be 65% or better. 80 patients enrolled at 11 US transplant centers (December 2016-March 2019). Following myeloablative or reduced-intensity conditioning-based HCT, patients received PTCy on days +3, +4, with sirolimus and mycophenolate mofetil starting on day +5. We compared outcomes to Center for International Blood and Marrow Transplant Research contemporary controls receiving PTCy. RESULTS: Notably, 48% of patients enrolled were ethnic minorities. 39% of pairs were matched for 4-6 out of 8 HLA alleles. The primary end point was met, with 1-year OS of 76% (90% CI, 67.3 to 83.3) in the entire cohort, and 72% and 79% in the myeloablative and reduced-intensity conditioning strata, respectively. Secondary end points related to engraftment and graft-versus-host-disease were reached. Multivariate analysis comparing the study group with other mismatched HCT controls found no significant differences in OS. CONCLUSION: Our prospective study demonstrates the feasibility and effectiveness of HCT with an MMUD in the setting of PTCy. Remarkably, nearly half of the study participants belonged to an ethnic minority population, suggesting this approach may significantly expand access to HCT.
Authors: Jun Zou; Stefan O Ciurea; Piyanuch Kongtim; Min Yi; Yudith Carmazzi; Gabriela Rondon; Samer Srour; David Partlow; Richard E Champlin; Kai Cao Journal: Blood Adv Date: 2020-08-11
Authors: Stephanie Williams; Amy A Ayers; Michelle T Hildebrandt; Lorna H McNeill; Christopher R Flowers Journal: Oncology (Williston Park) Date: 2020-06-10 Impact factor: 2.990
Authors: Christopher G Kanakry; Sudipto Ganguly; Marianna Zahurak; Javier Bolaños-Meade; Christopher Thoburn; Brandy Perkins; Ephraim J Fuchs; Richard J Jones; Allan D Hess; Leo Luznik Journal: Sci Transl Med Date: 2013-11-13 Impact factor: 17.956
Authors: Anita D'Souza; Caitrin Fretham; Stephanie J Lee; Mukta Arora; Janet Brunner; Saurabh Chhabra; Steven Devine; Mary Eapen; Mehdi Hamadani; Parameswaran Hari; Marcelo C Pasquini; Waleska Perez; Rachel A Phelan; Marcie L Riches; J Douglas Rizzo; Wael Saber; Bronwen E Shaw; Stephen R Spellman; Patricia Steinert; Daniel J Weisdorf; Mary M Horowitz Journal: Biol Blood Marrow Transplant Date: 2020-05-11 Impact factor: 5.609
Authors: Hemant S Murthy; Kwang Woo Ahn; Noel Estrada-Merly; Hassan B Alkhateeb; Susan Bal; Mohamed A Kharfan-Dabaja; Bhagirathbhai Dholaria; Francine Foss; Lohith Gowda; Deepa Jagadeesh; Craig Sauter; Muhammad Bilal Abid; Mahmoud Aljurf; Farrukh T Awan; Ulrike Bacher; Sherif M Badawy; Minoo Battiwalla; Chris Bredeson; Jan Cerny; Saurabh Chhabra; Abhinav Deol; Miguel Angel Diaz; Nosha Farhadfar; César Freytes; James Gajewski; Manish J Gandhi; Siddhartha Ganguly; Michael R Grunwald; Joerg Halter; Shahrukh Hashmi; Gerhard C Hildebrandt; Yoshihiro Inamoto; Antonio Martin Jimenez-Jimenez; Matt Kalaycio; Rammurti Kamble; Maxwell M Krem; Hillard M Lazarus; Aleksandr Lazaryan; Joseph Maakaron; Pashna N Munshi; Reinhold Munker; Aziz Nazha; Taiga Nishihori; Olalekan O Oluwole; Guillermo Ortí; Dorothy C Pan; Sagar S Patel; Attaphol Pawarode; David Rizzieri; Nakhle S Saba; Bipin Savani; Sachiko Seo; Celalettin Ustun; Marjolein van der Poel; Leo F Verdonck; John L Wagner; Baldeep Wirk; Betul Oran; Ryotaro Nakamura; Bart Scott; Wael Saber Journal: Transplant Cell Ther Date: 2022-01-23
Authors: Muna Qayed; Benjamin Watkins; Scott Gillespie; Brandi Bratrude; Kayla Betz; Sung W Choi; Jeffrey Davis; Christine Duncan; Roger Giller; Michael Grimley; Andrew C Harris; David Jacobsohn; Nahal Lalefar; Maxim Norkin; Nosha Farhadfar; Michael A Pulsipher; Shalini Shenoy; Aleksandra Petrovic; Kirk R Schultz; Gregory A Yanik; Edmund K Waller; Amelia Langston; Leslie S Kean; John T Horan Journal: Blood Adv Date: 2022-02-08