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Marker chromosome is a strong poor prognosis factor after allogeneic HSCT for adverse-risk AML patients

Kyoko Fuse¹, Tomoyuki Tanaka¹, Yasuhiko Shibasaki²

¹Department of Hematology, Endocrinology and Metabolism, Faculty of Medicine Graduate School of Medical and Dental Science, Niigata University, Niigata, Japan.

European Journal of Haematology

|July 25, 2020

Abstract

Introduction:

Chromosome analysis is necessary for the risk classification of acute myeloid leukemia (AML). Marker chromosome (MC) is a fragmented chromosome whose origin cannot be identified from other chromosomes and originates from marked genomic instability. Although AML with MC (MC+) has a poor prognosis even after intensive chemotherapy, its influence on the outcome after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is unclear.

Objective And Methods:

We retrospectively analyzed 162 AML patients after allo-HSCT. To evaluate the significance of MC, we compared it with other chromosomal abnormalities.

Result:

Marker chromosome was detected in 14 (8.6%, MC+) patients (vs MC-, n = 158). The 2-year overall survival (OS) in MC+ vs MC- was 26.8% vs 62.2% (P = .0098). The 2-year cumulative incidence of relapse (CIR) in MC+ vs MC- was 80.4% vs 35.5% (P = .0004). Among adverse-risk AML (AD-AML, n = 36), AD-AML/MC+ (n = 11) demonstrated a poorer 2-year OS (9.1%, vs AD-AML/MC- n = 25, 58.3%, P = .0031) and higher 2-year CIR (89.6%, vs AD-AML/MC- 44.7%, P = .002). In multivariate analysis, MC (HR 3.08, 95% CI; 1.02-9.29, P = .046) and HCT-CI (HR 3.23, 95% CI; 1.00-10.4, P = .049) were independent risk factors for CIR among AD-AML.

Conclusion:

Our study suggests MC as a new independent factor for chromosome risk classification to further classify AD-AML.

Insights

Marker chromosome (MC) presence in acute myeloid leukemia (AML) patients significantly worsens outcomes after allogeneic hematopoietic stem cell transplantation (allo-HSCT), increasing relapse risk. MC is identified as a new independent factor for classifying adverse-risk AML.

Area of Science:

Hematology
Cancer Genetics
Transplantation Immunology

Background:

Chromosome analysis is crucial for acute myeloid leukemia (AML) risk stratification.
Marker chromosomes (MC) indicate genomic instability and are associated with poor prognosis in AML.
The impact of MC on outcomes following allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear.

Purpose of the Study:

To evaluate the prognostic significance of marker chromosomes (MC) in AML patients undergoing allo-HSCT.
To compare the outcomes of MC-positive (MC+) AML patients with MC-negative (MC-) patients post-transplant.
To determine if MC is an independent risk factor for adverse outcomes in AML after allo-HSCT.

Main Methods:

Retrospective analysis of 162 AML patients who underwent allo-HSCT.
Categorization of patients into MC-positive (MC+) and MC-negative (MC-) groups.
Comparison of overall survival (OS) and cumulative incidence of relapse (CIR) between groups, including subgroup analysis for adverse-risk AML (AD-AML).

Main Results:

Marker chromosomes (MC) were detected in 14 (8.6%) of AML patients.
MC-positive (MC+) patients exhibited significantly lower 2-year overall survival (OS) (26.8% vs. 62.2%) and higher 2-year cumulative incidence of relapse (CIR) (80.4% vs. 35.5%) compared to MC-negative (MC-) patients.
In the adverse-risk AML (AD-AML) subgroup, MC-positive patients had poorer OS (9.1% vs. 58.3%) and higher CIR (89.6% vs. 44.7%).
Multivariate analysis identified MC as an independent risk factor for CIR in AD-AML.

Conclusions:

Marker chromosome (MC) is a significant adverse prognostic factor in AML patients undergoing allo-HSCT.
MC should be considered as a new independent factor for refining chromosome-based risk classification in AML.
Further classification of adverse-risk AML (AD-AML) by MC status can improve risk stratification and treatment strategies.

Read full analysis

Keywords:

acute myeloid leukemia clinical trials transplantation

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