title: Clinical outcome after failure of hypomethylating therapy for myelodysplastic syndrome.
abstract: Around half of patients with myelodysplastic syndrome (MDS) fail to respond to hypomethylating therapy (HMT) and most responders progress within 2 yr. Retrospective studies report poor outcomes after HMT failure. Here, we analyzed the outcomes of patients suffering HMT failure. Of 149 patients with MDS treated with either azacitidine or decitabine, 91 who experienced HMT failure were included in the study. Median overall survival (OS) was 12.1 months: 16.2 months for lower-risk MDS and 9.3 months for higher-risk MDS. Disease status and progression to acute myeloid leukemia (AML) at the time of HMT failure were independent prognostic factors for OS. Fifty-four patients received one or more treatment modalities, and 23 received allogeneic hematopoietic cell transplantation (HCT). The objective response to non-transplant treatments was poor (11-17%), whereas 17 transplanted patients showed a complete response. OS probability at 2 yr post-HCT was 60.9%: 78.6% for patients receiving HCT during MDS and 33.3% for those receiving HCT after developing AML. In conclusion, the clinical outcome of patients after HMT failure was poor. Long-term disease-free survival was observed in approximately 50% of patients who received allogeneic HCT. Therefore, allogeneic HCT should be performed early in appropriate patients, and particularly before progression to AML.
authors.affiliation: Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Je-Hwan
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Yunsuk
authors.initials: Y
authors.lastname: Choi
authors.affiliation: Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Sung-Doo
authors.initials: SD
authors.lastname: Kim
authors.affiliation: Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Dae-Young
authors.initials: DY
authors.lastname: Kim
authors.affiliation: Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Jung-Hee
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Kyoo-Hyung
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Busan Paik Hospital, Inje University College of Medicine, Busan, Korea.
authors.forename: Sang-Min
authors.initials: SM
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Busan Paik Hospital, Inje University College of Medicine, Busan, Korea.
authors.forename: Won-Sik
authors.initials: WS
authors.lastname: Lee
authors.affiliation: Department of Hematology, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea.
authors.forename: Young-Don
authors.initials: YD
authors.lastname: Joo
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use*; D001374:Azacitidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors*; D000077209:Decitabine; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000401:mortality* / Q000628:therapy*; D063868:Patient Outcome Assessment; D016879:Salvage Therapy; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D000964:Antimetabolites, Antineoplastic; D000077209:Decitabine; D015254:DNA Modification Methylases; D001374:Azacitidine
keywords: azacitidine; decitabine; hematopoietic stem cell transplantation; hypomethylating therapy failure; myelodysplastic syndrome