An international learning collaborative phase 2 trial for haploidentical bone marrow transplant in sickle cell disease.

Autor:	Kassim AA; Division of Hematology/Oncology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN.; Vanderbilt-Meharry Sickle Cell Disease Center of Excellence, Vanderbilt University School of Medicine, Nashville, TN., de la Fuente J; Department of Paediatrics, St. Mary's Hospital, Imperial College, London, United Kingdom., Nur E; Department of Hematology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.; Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Amsterdam, The Netherlands., Wilkerson KL; Division of Hematology/Oncology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN.; Vanderbilt-Meharry Sickle Cell Disease Center of Excellence, Vanderbilt University School of Medicine, Nashville, TN., Alahmari AD; Adult Hematology and Stem Cell Therapy and Cellular Therapy Program, King Faisal Specialist Hospital, Riyadh, Saudi Arabia., Seber A; Pediatric Hematopoietic Stem Cell Transplantation Program, Pediatric Hematopoietic Cell Transplantation, Hospital Samaritano Higienopolis-Americas, São Paulo, Brazil.; Pediatric Hematopoietic Stem Cell Transplantation Program, Pediatric Hematopoietic Cell Transplantation, Instituto de Oncologia Pediatrica-Graacc/Unifesp, São Paulo, Brazil., Bonfim C; Pediatric Bone Marrow Transplantation Program, Hospital Pequeno Príncipe/Instituto de Pesquisa Pele Pequeno Principe, Curitiba, Brazil., Simões BP; Department of Medicine, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.; Department of Hematology, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.; Department of Clinical Oncology, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil., Alzahrani M; Department of Pediatric Hematology/Oncology, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia., Eckrich MJ; Department of Pediatrics, Pediatric Transplant and Cellular Therapy, Wake Forest University School of Medicine, Atrium Health Levine Children's Hospital, Charlotte, NC., Horn B; Department of Pediatrics, Pediatric Bone Marrow Transplant and Cell Therapy Program, University of Florida, Gainesville, FL., Hanna R; Department of Pediatric Hematology/Oncology, Pediatric Hematology Oncology and Blood and Marrow Transplantation, Cleveland Clinic, Cleveland, OH., Dhedin N; Department of Hematology, Hematology Adolescents and Young Adults, Saint-Louis Hospital, Paris, France., Rangarajan HG; Department of Pediatric Hematology, Oncology, Blood and Marrow Transplant, Nationwide Children's Hospital, Columbus, OH., Gouveia RV; Pediatric Hematopoietic Stem Cell Transplantation Program, Pediatric Hematopoietic Cell Transplantation, Hospital Samaritano Higienopolis-Americas, São Paulo, Brazil.; Pediatric Hematopoietic Stem Cell Transplantation Program, Pediatric Hematopoietic Cell Transplantation, Instituto de Oncologia Pediatrica-Graacc/Unifesp, São Paulo, Brazil., Almohareb F; Adult Hematology and Stem Cell Therapy and Cellular Therapy Program, King Faisal Specialist Hospital, Riyadh, Saudi Arabia., Aljurf M; Adult Hematology and Stem Cell Therapy and Cellular Therapy Program, King Faisal Specialist Hospital, Riyadh, Saudi Arabia., Essa M; Department of Pediatric Hematology/Oncology, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia., Alahmari B; Department of Pediatric Hematology/Oncology, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia., Gatwood K; Department of Pharmaceutical Services, Vanderbilt University Medical Center, Nashville, TN., Connelly JA; Department of Pediatrics, Hematology/Oncology, Vanderbilt University School of Medicine, Nashville, TN., Dovern E; Department of Hematology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands., Rodeghier M; Rodeghier Consultants, Chicago, IL., DeBaun MR; Vanderbilt-Meharry Sickle Cell Disease Center of Excellence, Vanderbilt University School of Medicine, Nashville, TN.; Department of Pediatrics, Hematology/Oncology, Vanderbilt University School of Medicine, Nashville, TN.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2024 Jun 20; Vol. 143 (25), pp. 2654-2665.
DOI:	10.1182/blood.2023023301
Abstrakt:	Abstract: In the setting of a learning collaborative, we conducted an international multicenter phase 2 clinical trial testing the hypothesis that nonmyeloablative-related haploidentical bone marrow transplant (BMT) with thiotepa and posttransplant cyclophosphamide (PTCy) will result in 2-year event-free survival (no graft failure or death) of at least 80%. A total of 70 participants were evaluable based on the conditioning protocol. Graft failure occurred in 8 of 70 (11.4%) and only in participants aged <18 years; all had autologous reconstitution. After a median follow-up of 2.4 years, the 2-year Kaplan-Meier-based probability of event-free survival was 82.6%. The 2-year overall survival was 94.1%, with no difference between children and adult participants. After excluding participants with graft failure (n = 8), participants with engraftment had median whole blood donor chimerism values at days +180 and +365 after transplant of 100% (n = 58), respectively, and 96.6% (57/59) were off immunosuppression 1 year after transplant. The 1-year grade 3 to 4 acute graft-versus-host disease (GVHD) rate was 10%, and the 2-year moderate-severe chronic GVHD rate was 10%. Five participants (7.1%) died from infectious complications. We demonstrate that nonmyeloablative haploidentical BMT with thiotepa and PTCy is a readily available curative therapy for most adults, even those with organ damage, compared to the more expensive myeloablative gene therapy and gene editing. Additional strategies are required for children to decrease graft failure rates. The trial was registered at www.clinicaltrials.gov as #NCT01850108. (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)
Databáze:	MEDLINE
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