Biologic Assignment Trial of Reduced-Intensity Hematopoietic Cell Transplantation Based on Donor Availability in Patients 50-75 Years of Age With Advanced Myelodysplastic Syndrome.

TitleBiologic Assignment Trial of Reduced-Intensity Hematopoietic Cell Transplantation Based on Donor Availability in Patients 50-75 Years of Age With Advanced Myelodysplastic Syndrome.
Publication TypeJournal Article
Year of Publication2021
AuthorsNakamura, R, Saber, W, Martens, MJ, Ramirez, A, Scott, B, Oran, B, Leifer, E, Tamari, R, Mishra, A, Maziarz, RT, McGuirk, J, Westervelt, P, Vasu, S, Patnaik, M, Kamble, R, Forman, SJ, Sekeres, MA, Appelbaum, F, Mendizabal, A, Logan, B, Horowitz, M, Cutler, C
JournalJ Clin Oncol
Volume39
Issue30
Pagination3328-3339
Date Published2021 10 20
ISSN1527-7755
KeywordsAged, Female, Follow-Up Studies, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Histocompatibility Testing, Humans, Intention to Treat Analysis, Leukemia, Male, Middle Aged, Myelodysplastic Syndromes, Quality of Life, Survival Rate, Tissue Donors, Transplantation Conditioning, Transplantation, Homologous, Treatment Outcome
Abstract

PURPOSE: Allogeneic hematopoietic cell transplantation (HCT) is the only potentially curative therapy for myelodysplastic syndromes (MDS), although it is infrequently offered to older patients. The relative benefits of HCT over non-HCT therapy in older patients with higher-risk MDS have not been defined.

METHODS: We conducted a multicenter biologic assignment trial comparing reduced-intensity HCT to hypomethylating therapy or best supportive care in subjects 50-75 years of age with intermediate-2 or high-risk de novo MDS. The primary outcome was overall survival probability at 3 years. Between January 2014 and November 2018, we enrolled 384 subjects at 34 centers. Subjects were assigned to the Donor or No-Donor arms according to the availability of a matched donor within 90 days of study registration.

RESULTS: The median follow-up time for surviving subjects was 34.2 months (range: 2.3-38 months) in the Donor arm and 26.9 months (range: 2.4-37.2 months) in the No-Donor arm. In an intention-to-treat analysis, the adjusted overall survival rate at 3 years in the Donor arm was 47.9% (95% CI, 41.3 to 54.1) compared with 26.6% (95% CI, 18.4 to 35.6) in the No-Donor arm ( = .0001) with an absolute difference of 21.3% (95% CI, 10.2 to 31.8). Leukemia-free survival at 3 years was greater in the Donor arm (35.8%; 95% CI, 29.8 to 41.8) compared with the No-Donor arm (20.6%; 95% CI, 13.3 to 29.1; = .003). The survival benefit was seen across all subgroups examined.

CONCLUSION: We observed a significant survival advantage in older subjects with higher-risk MDS who have a matched donor identified and underwent reduced-intensity HCT, when compared with those without a donor. HCT should be included as an integral part of MDS management plans in fit older adults with higher-risk MDS.

DOI10.1200/JCO.20.03380
Alternate JournalJ Clin Oncol
PubMed ID34106753
PubMed Central IDPMC8791814
Grant ListU10 HL069294 / HL / NHLBI NIH HHS / United States
U24 HL138660 / HL / NHLBI NIH HHS / United States
UG1 HL108945 / HL / NHLBI NIH HHS / United States