MARKER CHROMOSOME IS A STRONG POOR PROGNOSIS FACTOR AFTER ALLOGENEIC HSCT FOR AML PATIENTS
Author(s): ,
Kyoko Fuse
Affiliations:
Department of Hematology, Endocrinology and Metabolism,Niigata University Faculty of Medicine,Niigata,Japan
,
Tomoyuki Tanaka
Affiliations:
Department of Hematology,Nagaoka Red Cross Hospital,Nagaoka,Japan
,
Shun Uemura
Affiliations:
Department of Hematology, Endocrinology and Metabolism,Niigata University Faculty of Medicine,Niigata,Japan
,
Suguru Tamura
Affiliations:
Department of Hematology, Endocrinology and Metabolism,Niigata University Faculty of Medicine,Niigata,Japan
,
Tatsuya Suwabe
Affiliations:
Department of Hematology, Endocrinology and Metabolism,Niigata University Faculty of Medicine,Niigata,Japan
,
Takayuki Katagiri
Affiliations:
Department of Hematology, Endocrinology and Metabolism,Niigata University Faculty of Medicine,Niigata,Japan
,
Takashi Ushiki
Affiliations:
Department of Hematology, Endocrinology and Metabolism,Niigata University Faculty of Medicine,Niigata,Japan
,
Yasuhiko Shibasaki
Affiliations:
Department of Hematopoietic Cell Transplantation,Niigata University Medical and Dental Hospital,Niigata,Japan
,
Naoko Satou
Affiliations:
Department of Hematology,Nagaoka Red Cross Hospital,Nagaoka,Japan
,
Toshio Yano
Affiliations:
Department of Hematology,Nagaoka Red Cross Hospital,Nagaoka,Japan
,
Takashi Kuroha
Affiliations:
Department of Hematology,Nagaoka Red Cross Hospital,Nagaoka,Japan
,
Shigeo Hashimoto
Affiliations:
Department of Hematology,Nagaoka Red Cross Hospital,Nagaoka,Japan
,
Tastuo Furukawa
Affiliations:
Department of Hematology,Nagaoka Red Cross Hospital,Nagaoka,Japan
,
Miwako Narita
Affiliations:
Laboratory of Hematology and Oncology, Graduate School of Health Sciences, Niigata University,Niigata,Japan
,
Hirohito Sone
Affiliations:
Department of Hematology, Endocrinology and Metabolism,Niigata University Faculty of Medicine,Niigata,Japan
Masayoshi Masuko
Affiliations:
Department of Hematopoietic Cell Transplantation,Niigata University Medical and Dental Hospital,Niigata,Japan
EHA Library. Fuse K. Jun 15, 2019; 266667; PS1050
Dr. Kyok Fuse
Dr. Kyok Fuse
Contributions
Abstract

Abstract: PS1050

Type: Poster Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 17:30 - 19:00

Location: Poster area

Background
A marker chromosome (MC) is a fragmented chromosome whose origin cannot be identified from an existing autosomal or sex chromosome. Recently, MC was found to result from chromothripsis. Chromothripsis is a catastrophic phenomenon by which chromosomes are shattered into tens to hundreds of fragments, and half of the cases are related to TP53 gene mutation. MC is a relatively common abnormality and its incidence in acute myeloid leukemia (AML) is approximately 15%. Although AML with MC was reported to have a poor prognosis after intensive chemotherapy, the influence of MC on the outcome after allo-HSCT for AML is unclear.

Aims

We evaluated the outcomes of AML patients with MC after allo-HSCT in comparison with other chromosomal abnormalities such as monosomal karyotype (MK), complex karyotype (CK) and existing sub-clone (SC).

Methods
This retrospective analysis included 166 AML patients who received allo-HCT in our study group between 1990 and 2017. The median age of the patients at allo-HCT was 38 years old. The median follow-up period was 2.0 y.According to the revised Medical Research Council (rMRC) criteria for cytogenetic risk categories, 26 (15.7%), 104 (62.7%) and 36 (21.7%) patients were categorized as favorable-, intermediate- and adverse-risk, respectively.

Results

MC was detected in 14 (8.4%) of 166 patients. Eleven (78.6%) had adverse-risk karyotypes. CK, MK and SC were observed in 26 (16.3%), 20 (12.0%) and 23 (13.9%) patients, respectively. The median age of AML with MC (AML/MC+, n=14) and AML without MC (AML/MC-, n=152) patients was similar (38.5 y vs 38 y, P=0.812). Twelve AML/MC+ patients (85.7%) received allo-HCT at an advanced stage and 10 (71.4%) demonstrated primary induction failure. Compared with AML/MC- patients, AML/MC+ patients had a higher coexistence rate of CK (85.7% vs. 9.9%, p<0.001), MK (78.6% vs. 5.9%, p<0.001) and sub-clone (64.3% vs. 9.2%, p<0.001). On univariate analysis, the 2-y overall survival (OS) and median survival period of AML/MC+ patients were poorer than those of AML/MC- patients (26.8% vs. 61.3% and 0.78 y vs. 4.9 y, p=0.0126). The 2-y cumulated incidence of relapse (CIR) in AML/MC+ patients was higher than that in AML/MC- patients (80.4% vs. 37.2%, p<0.01).

To further investigate the impact of MC on the outcome after allo-HSCT, we compared AML patients with/without MC among those with an adverse-risk karyotype. The 2-y OS of adverse-risk AML/MC+ patients (n=11) was lower than that of adverse-risk AML/MC- patients (n=25) (9.1% vs 58.3%, p=0.003). The median survival periods were 0.58 y and 4.0 y, and the 2-y CIR was 89.6% and 44.7% (p=0.002), respectively. On the other hand, the 2-y OS of CK, MK and SC in adverse-risk AML patients was 33.2%, 26.9% and 34.7%, respectively.

Based on our results, MC is the poorest factor after allo-HSCT, and we performed multivariate analysis for confirmation. In the multivariate analysis adjusted for donor, conditioning, disease stage before allo-HCT, CK, MK and SC, only MC was an independent poor risk factor for OS (HR 3.547, 95%CI: 1.46-8.63, p=0.005) and CIR (HR 3.90, 95%CI: 1.47-10.33, p=0.006) in adverse-risk AML patients.

Conclusion
MC frequently coexists with other cytogenetic abnormalities. AML with MC has a poor outcome even after allo-HSCT compared with other chromosomal abnormalities.

Session topic: 4. Acute myeloid leukemia - Clinical

Keyword(s): Acute myeloid leukemia, Allogeneic hematopoietic stem cell transplant, Chromosomal abnormality, Prognostic factor

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