title: Stratification of de novo adult acute myelogenous leukemia with adverse-risk karyotype: can we overcome the worse prognosis of adverse-risk group acute myelogenous leukemia with hematopoietic stem cell transplantation?
abstract: Karyotype is a powerful prognostic factor for complete remission (CR) and overall survival (OS) in acute myelogenous leukemia (AML). Adverse-risk karyotype AML is now treated with intensive chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) to overcome relapse. We attempted to stratify patients with this disease using a combination of known factors. We evaluated clinical correlates in 211 adults with AML and adverse-risk karyotypes. We divided the patients into several subgroups based on the number of chromosomal aberrations (NCAs), normal karyotype (NK) mosaicism, and monosomal karyotype (MK) status. CR rates and survival outcomes were compared among the subgroups, and the relapse rate was calculated in the allo-HSCT subgroup. The cutoff of NCA ≥ 5 showed the worst OS (P < .001) compared with NCA ≥ 3 or NCA ≥ 4 even after allo-HSCT. NK mosaicism significantly improved OS in both the NCA <5 (P = .024) and NCA ≥ 5 (P = .030) subgroups, but after allo-HSCT, it showed a favorable effect only in the NCA <5 subgroup. MK showed worse OS (P = .041), but there was no significantly worse effect after allo-HSCT compared with non-MK. Finally, we stratified patients into 4 subgroups, NCA ≥ 5 and NCA <5 with and without NK mosaicism. The most favorable OS and lower relapse rate after allo-HSCT were achieved by the NCA <5 with NK mosaicism subgroup, and the NCA ≥ 5 without NK mosaicism subgroup showed the worst prognosis in both entire group and allo-HSCT subgroup analysis. This study reveals that the combination of NCA and NK mosaicism may predict survival outcomes accurately, and suggests that novel treatment strategies for highly adverse-risk group AML should be tailored in the future.
authors.affiliation: Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, Catholic University of Korea, Seoul, Korea.
authors.forename: Jae-Ho
authors.initials: JH
authors.lastname: Yoon
authors.affiliation: Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, Catholic University of Korea, Seoul, Korea. Electronic address: cumckim@catholic.ac.kr.
authors.forename: Hee-Je
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, Catholic University of Korea, Seoul, Korea.
authors.forename: Seung-Hwan
authors.initials: SH
authors.lastname: Shin
authors.affiliation: Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, Catholic University of Korea, Seoul, Korea.
authors.forename: Sung-Eun
authors.initials: SE
authors.lastname: Lee
authors.affiliation: Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, Catholic University of Korea, Seoul, Korea.
authors.forename: Byung-Sik
authors.initials: BS
authors.lastname: Cho
authors.affiliation: Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, Catholic University of Korea, Seoul, Korea.
authors.forename: Ki-Seong
authors.initials: KS
authors.lastname: Eom
authors.affiliation: Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, Catholic University of Korea, Seoul, Korea.
authors.forename: Yoo-Jin
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, Catholic University of Korea, Seoul, Korea.
authors.forename: Seok
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, Catholic University of Korea, Seoul, Korea.
authors.forename: Chang-Ki
authors.initials: CK
authors.lastname: Min
authors.affiliation: Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, Catholic University of Korea, Seoul, Korea.
authors.forename: Seok-Goo
authors.initials: SG
authors.lastname: Cho
authors.affiliation: Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, Catholic University of Korea, Seoul, Korea.
authors.forename: Dong-Wook
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, Catholic University of Korea, Seoul, Korea.
authors.forename: Jong-Wook
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, Catholic University of Korea, Seoul, Korea.
authors.forename: Woo-Sung
authors.initials: WS
authors.lastname: Min
authors.affiliation: Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, Catholic University of Korea, Seoul, Korea.
authors.forename: Chong-Won
authors.initials: CW
authors.lastname: Park
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002869:Chromosome Aberrations; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D059785:Karyotype; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012107:Research Design; D012306:Risk; D055502:Secondary Prevention; D012720:Severity of Illness Index; D016019:Survival Analysis; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents
keywords: Acute myelogenous leukemia; Adverse risk; Chromosomal aberration; Monosomal karyotype; Mosaicism