Impact of Conditioning Intensity of Allogeneic Transplantation for Acute Myeloid Leukemia With Genomic Evidence of Residual Disease.

Autor:	Hourigan CS; National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD., Dillon LW; National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD., Gui G; National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD., Logan BR; Medical College of Wisconsin, Milwaukee, WI., Fei M; Medical College of Wisconsin, Milwaukee, WI., Ghannam J; National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD., Li Y; National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD., Licon A; ArcherDX, Boulder, CO., Alyea EP; Dana-Farber Cancer Institute, Boston, MA., Bashey A; Blood and Marrow Transplant Program at Northside Hospital, Atlanta, GA., Deeg HJ; Fred Hutchinson Cancer Research Center, Seattle, WA., Devine SM; National Marrow Donor Program and Center for International Blood and Marrow Transplant Research, Minneapolis, MN., Fernandez HF; Moffitt Cancer Center and Research Institute, Tampa, FL., Giralt S; Memorial Sloan Kettering Cancer Center, New York, NY., Hamadani M; West Virginia University Medicine, Morgantown, WV., Howard A; National Marrow Donor Program and Center for International Blood and Marrow Transplant Research, Minneapolis, MN., Maziarz RT; Knight Cancer Institute, Oregon Health & Science University, Portland, OR., Porter DL; University of Pennsylvania, Philadelphia, PA., Scott BL; Fred Hutchinson Cancer Research Center, Seattle, WA., Warlick ED; University of Minnesota, Minneapolis, MN., Pasquini MC; Medical College of Wisconsin, Milwaukee, WI., Horwitz ME; Duke University, Durham, NC.
Jazyk:	angličtina
Zdroj:	Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2020 Apr 20; Vol. 38 (12), pp. 1273-1283. Date of Electronic Publication: 2019 Dec 20.
DOI:	10.1200/JCO.19.03011
Abstrakt:	Purpose: Patients with acute myeloid leukemia (AML) in remission remain at risk for relapse even after allogeneic hematopoietic cell transplantation (alloHCT). AML measurable residual disease (MRD) status before alloHCT has been shown to be prognostic. Whether modulation of the intensity of the alloHCT conditioning regimen in patients with AML who test positive for MRD can prevent relapse and improve survival is unknown. Methods: Ultra-deep, error-corrected sequencing for 13 commonly mutated genes in AML was performed on preconditioning blood from patients treated in a phase III clinical trial that randomly assigned adult patients with myeloid malignancy in morphologic complete remission to myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC). Results: No mutations were detected in 32% of MAC and 37% of RIC recipients; these groups had similar survival (3-year overall survival [OS], 56% v 63%; P = .96). In patients with a detectable mutation (next-generation sequencing [NGS] positive), relapse (3-year cumulative incidence, 19% v 67%; P < .001) and survival (3-year OS, 61% v 43%; P = .02) was significantly different between the MAC and RIC arms, respectively. In multivariable analysis for NGS-positive patients, adjusting for disease risk and donor group, RIC was significantly associated with increased relapse (hazard ratio [HR], 6.38; 95% CI, 3.37 to 12.10; P < .001), decreased relapse-free survival (HR, 2.94; 95% CI, 1.84 to 4.69; P < .001), and decreased OS (HR, 1.97; 95% CI, 1.17 to 3.30; P = .01) compared with MAC. Models of AML MRD also showed benefit for MAC over RIC for those who tested positive. Conclusion: This study provides evidence that MAC rather than RIC in patients with AML with genomic evidence of MRD before alloHCT can result in improved survival.
Databáze:	MEDLINE
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