title: Multicenter biologic assignment trial comparing reduced-intensity allogeneic hematopoietic cell transplant to hypomethylating therapy or best supportive care in patients aged 50 to 75 with intermediate-2 and high-risk myelodysplastic syndrome: Blood and Marrow Transplant Clinical Trials Network #1102 study rationale, design, and methods.
abstract: The introduction of reduced-intensity conditioning (RIC) regimens made it possible to offer allogeneic hematopoietic cell transplantation (alloHCT) to older patients with myelodysplastic syndromes (MDS). However, the relative risks and benefits of alloHCT compared with novel nontransplant therapies continue to be the source of considerable uncertainty. We will perform a prospective biologic assignment trial to compare RIC alloHCT with nontransplant therapies based on donor availability. Primary outcome is 3-year overall survival. Secondary outcomes include leukemia-free survival, quality of life, and cost-effectiveness. Four hundred patients will be enrolled over roughly 3 years. Planned subgroup analyses will evaluate key biologic questions, such as the impact of age and response to hypomethylating agents on treatment effects. Findings from this study potentially may set a new standard of care for older MDS patients who are considered candidates for alloHCT.
authors: Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, Wisconsin. Electronic address: wsaber@mcw.edu.
authors: Wael
authors: W
authors: Saber
authors: Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors: Jennifer
authors: J
authors: Le Rademacher
authors: Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio.
authors: Mikkael
authors: M
authors: Sekeres
authors: Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors: Brent
authors: B
authors: Logan
authors: The EMMES Corporation, Rockville, Maryland.
authors: Moira
authors: M
authors: Lewis
authors: The EMMES Corporation, Rockville, Maryland.
authors: Adam
authors: A
authors: Mendizabal
authors: National Heart, Lung, and Blood Institute, Bethesda, Maryland.
authors: Eric
authors: E
authors: Leifer
authors: Fred Hutchinson Cancer Research Center, University of Washington School of Medicine, Seattle, Washington.
authors: Frederick R
authors: FR
authors: Appelbaum
authors: Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors: Mary M
authors: MM
authors: Horowitz
authors: City of Hope National Medical Center, Duarte, California.
authors: Ryotaro
authors: R
authors: Nakamura
authors: Dana Farber Cancer Institute, Boston, Massachusetts.
authors: Corey S
authors: CS
authors: Cutler
mesh_terms: D000367:Age Factors; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D003362:Cost-Benefit Analysis; D019175:DNA Methylation / Q000187:drug effects; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D057194:Intention to Treat Analysis; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use; D009190:Myelodysplastic Syndromes / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D011379:Prognosis; D011446:Prospective Studies; D011788:Quality of Life; D012307:Risk Factors; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D061349:Unrelated Donors
chemical_list: D000964:Antimetabolites, Antineoplastic; D019653:Myeloablative Agonists
keywords: Biologic assignment; MDS; Transplantation