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1535 Significance of Marker Chromosome on the Outcome of Allogeneic Hematopoietic Stem Cell Transplantation for AML

Program: Oral and Poster Abstracts
Session: 732. Clinical Allogeneic Transplantation: Results: Poster I
Hematology Disease Topics & Pathways:
AML, Adult, Diseases, Study Population, Myeloid Malignancies, Clinically relevant
Saturday, December 5, 2020, 7:00 AM-3:30 PM

Kyoko Fuse, MD, Ph.D1*, Masayoshi Masuko, MD, Ph.D2, Shohei Mizuno, MD, PhD3*, Kaito Harada, MD4*, Naoyuki Uchida, MD, PhD5, Noriko Doki, MD, PhD6*, Takahiro Fukuda7*, Masatsugu Tanaka, MD8*, Yukiyasu Ozawa, MD, PhD9*, Kazuhiro Ikegame, MD, PhD10*, Tetsuya Eto, MD, PhD11*, Yoshinobu Kanda, MD, PhD12, Tatsuo Ichinohe13, Yoshiko Atsuta, MD, PhD14* and Masamitsu Yanada, MD, PhD15*

1Division of Transplantation Medicine, Niigata University Faculty of Medicine, Niigata City, Japan
2Division of Transplantation Medicine, Niigata University Medical and Dental Hospital, Niigata, Japan
3Department of Hematology, Aichi Medical University School of Medicine, Nagakute, AIC, Japan
4Department of Hematology and Oncology, Tokai University School of Medicine, Kanagawa, Japan
5Department of Hematology, Federation of National Public Service Personnel Mutual Aid Associations, Toranomon Hospital, Tokyo, Japan
6Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
7Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan
8Department of Hematology, Kanagawa Cancer Center, Yokohama, KAN, Japan
9Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan
10Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
11Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan
12Jichi Medical Univ., Saitama, Japan
13Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan
14Japanese Data Center for Hematopoietic Cell Transplantation, Nagoya, Japan
15Aichi Cancer Center, Nagoya, Japan


A marker chromosome (MAR) is a structurally abnormal chromosome that cannot be unambiguously identified or characterized by conventional chromosome analysis. MAR is considered to reflect genomic instability and is observed in 5% of acute myeloid leukemia (AML) patients. Although AML with MAR (AML/MAR+) was previously reported as refractory to chemotherapy, MAR is currently not considered associated with any specific cytogenetic risk category. Furthermore, the influence of MAR on the outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is unclear. Thus, to understand the characteristics of AML/MAR+ and the influence on prognosis in patients with AML, we reviewed national survey data from Japan.

[Patients and Methods]

This retrospective study included 14,099 adult patients with AML evaluable for cytogenetic risk who received their first allo-HSCT between January 1986 and December 2017. All data were sourced from the registry of the Japanese Society for Hematopoietic Cell Transplantation. The median age at allo-HSCT was 48 y (range, 16–85 y). The median follow-up period was 1.4 y (range, 0–30 y). The definition of chromosomal abnormalities adhered to the International System for Human Cytogenetic Nomenclature guidelines; chromosomal gains and structural abnormalities had to be detected in at least two metaphases, and chromosomal losses in at least three metaphases to be acknowledged as clonal. Three or more chromosomal abnormalities were defined as “complex karyotype” (CK). Cytogenetic risk was classified as favorable (n = 2,246), intermediate (n = 9,236), or poor (n = 2,617) in accordance with the criteria provided by the National Comprehensive Cancer Network Guidelines (Version 1, 2016). We defined 1st/2nd/3rd remission (n = 8,039) as “remission” and underlying disease or primary induction failure (n = 5,960) as “non-remission”. Some patients (n = 100) lacked disease stage data of pre-transplantation. For MAR evaluation, clinical phenotypes were compared, and overall survival (OS) and cumulated incidence of relapse (CIR) were calculated. These variables were validated using multivariate analysis.


MAR was detected in 668 (4.6%) of the 14,099 patients. The median age of patients with AML/MAR+ was 55 y (range, 16–77 y), and so these patients were older than AML/MAR– patients (n = 13,431; age, 48 y; range, 16–85 y; P < 0.001). AML/MAR+ included more secondary AML than AML/MAR- (10.9% vs. 6.5%, P < 0.001). The frequency of MAR in poor-risk AML patients (n = 580, 22.2%) was significantly higher than in favorable- (n = 13, 0.6%) and intermediate-risk (n = 75, 0.8%) AML patients (P < 0.001). When the analysis was limited to poor-risk AML patients with CK (CK+AML, n = 1,368), the frequency of MAR was 42.1% (n = 576). Most cases of AML/MAR+ (n = 580, 86.8%) were categorized as poor-risk cases (vs. AML/MAR-, n = 2,037, 15.2%; P < 0.001). Moreover, almost all cases of poor-risk MAR (n = 576/580, 99.3%) reflected adjuncts of CK.

Since AML/MAR+ has usually been considered poor-risk AML, especially CK+AML, we performed an evaluation focusing on these patients. First, among poor-risk AML patients, MAR was an independent risk factor of OS (hazard ratio [HR], 1.37; 95% confidence interval [CI], 1.20–1.56; P < 0.001) and CIR (HR, 1.41; 95% CI, 1.15–1.72; P < 0.001), based on the multivariable analysis adjusting for age, time of transplantation, performance status, disease stage, graft source, conditioning regimen, type of AML, and with/without CK. Next, in CK+AML, the 2-y-OS of CK+AML/MAR+ patients (n = 576) was 20.0% and thereby worse than that of CK+AML/ MAR– patients (n = 792, 33.2%; P < 0.001). The 2-y-CIR of CK+AML/MAR+ patients was 61.4% (vs. 48.2% in CK+AML/MAR– patients, P < 0.001). Furthermore, CK+AML/MAR+ patients who underwent transplant even in remission (n = 160) showed worse 2-y-OS (39.2%) and CIR (55.8%), than CK+AML/MAR– patients (n = 286, 54.5% [P = 0.004] and 37.8% [P=0.0011], respectively). In multivariable analysis adjusted for other prognosis factors, MAR was an independent risk factor of OS in CK+AML patients (HR, 1.40; 95% CI, 1.23–1.61; P < 0.001) and for CIR (HR, 1.44; 95% CI, 1.17–1.77; P < 0.001).


Cases of MAR almost exclusively reflected adjuncts of CK. MAR can be used to further stratify AML with CK after allo-HSCT.

Disclosures: Uchida: Sumitomo Dainippon Pharma: Honoraria; Astellas Pharma Inc.: Honoraria; Otsuka: Honoraria; Chugai Pharma: Honoraria; Novartis Pharma KK: Honoraria. Ozawa: Novartis Co., Ltd.: Honoraria. Kanda: Shionogi: Research Funding; Meiji Seika Kaisha: Honoraria; Sanofi: Honoraria, Research Funding; Mundipharma: Honoraria; Mochida Pharmaceutical: Honoraria; Nippon Shinyaku: Honoraria, Research Funding; Ono Pharmaceutical: Honoraria; Daiichi Sankyo: Honoraria; Shire: Honoraria; Alexion Pharmaceuticals: Honoraria; Takeda Pharmaceuticals: Honoraria; Bristol-Myers Squibb: Honoraria; Kyowa Kirin: Honoraria, Research Funding; Novartis: Honoraria; Eisai: Honoraria, Research Funding; Sumitomo Dainippon Pharma: Honoraria; Celgene: Honoraria; Otsuka: Honoraria, Research Funding; Chugai Pharma: Honoraria, Research Funding; Janssen: Honoraria; Astellas Pharma: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Merck Sharp & Dohme: Honoraria. Ichinohe: Chugai Pharmaceutical Co., Ltd.: Research Funding; Zenyaku Kogyo Company, Limited: Research Funding; Bristol-Myers Squibb: Honoraria; Celgene Corporation: Honoraria; Repertoire Genesis: Research Funding; FUJIFILM Wako Pure Chemical Corporation: Research Funding; Takara Bio Inc.: Research Funding; Takeda Pharmaceutical Company Limited: Research Funding; Nippon Shinyaku Co., Ltd.: Research Funding; ONO PHARMACEUTICAL CO., LTD.: Research Funding; Kyowa Kirin: Honoraria, Research Funding; Janssen: Honoraria; Pfizer: Research Funding.

*signifies non-member of ASH