Page 143 - Haematologica Vol. 109 - July 2024

ARTICLE - Myelodysplastic Syndromes
Patterns of lower risk myelodysplastic syndrome progression: factors predicting progression to high-risk myelodysplastic syndrome and acute myeloid leukemia
Akriti G. Jain,1 Somedeb Ball,2 Luis Aguirre,3 Najla Al Ali,4 David Kaldas,5 Sara Tinsley-Vance,4 Andrew Kuykendall,4 Onyee Chan,4 Kendra Sweet,4 Jeffrey E. Lancet,4 Eric Padron,4 David A. Sallman4 and Rami Komrokji4
1Leukemia Division, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH; 2Vanderbilt- Ingram Cancer Center, Nashville, TN; 3Dana-Farber Cancer Institute, Boston, MA; 4Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL and 5Department of Internal Medicine, University of South Florida, Tampa, FL, USA
Abstract
The patterns of low-risk myelodysplastic syndrome (MDS) progression and the clinical and molecular features of those patterns have not been well described. We divided our low-risk (LR) MDS patients (N=1,914) into 4 cohorts: 1) patients who remained LR-MDS (LR-LR; N=1,300; 68%), 2) patients who progressed from LR to high-risk (HR) MDS (LR-HR) without trans- formation into acute myeloid leukemia (AML) (N=317; 16.5%), 3) patients who progressed from LR to HR MDS and then AML (LR-HR-AML; N=124; 6.5%), and 4) patients who progressed from LR MDS directly to AML (LR-AML; N=173; 9%). Risk factors for progression included: male gender, low absolute neutrophil count (ANC), low platelet count, high bone marrow (BM) blasts, ferritin >1000 mcg/L, albumin <3.5 g/dL, multi-lineage dysplasia (MLD), and lack of ring sideroblasts. Among patients with marked BM fibrosis (N=49), 18% progressed directly to AML. Somatic mutations (SM) associated with an increased risk of direct or indirect AML progression included SRSF2 and NRAS. SM in IDH1, IDH2 and NPM1 were more common in patients with direct AML transformation. SM associated with progression to higher risk disease only, without AML transformation, were ASXL1, TP53, RUNX1, and CBL. SF3B1 mutation was associated with less progression. About 171 patients (13.1% of all LR-LR patients) died within two years of diagnosis of LR-MDS without disease progression. Among the 61 cases with doc- umented cause of death, 18 patients (29.5%) died from cytopenia and MDS-related complications. Identifying patterns of disease progression of LR MDS patients and their predictive factors will be crucial to be able to tailor therapy accordingly.
Correspondence: R. Komrokji Rami.Komrokji@moffitt.org
A.G. Jain
Jaina9@ccf.org
Received: Accepted: Early view:
June 1, 2023. January 22, 2024. February 1, 2024.
https://doi.org/10.3324/haematol.2023.283661
©2024 Ferrata Storti Foundation Published under a CC BY-NC license
Introduction
Myelodysplastic syndromes (MDS) are heterogeneous stem cell neoplasms that primarily affect the elderly population. The approach to treatment of MDS includes management of symptoms or cytopenias, and treatments to alter the nat- ural history of the disease in order to prevent progression to acute myeloid leukemia (AML).
Management is largely risk-adapted based on various prog- nostic scoring systems. The International Prognostic Scoring System (IPSS) was introduced in 1997 and was an important standard to assess prognosis in patients with MDS at initial diagnosis.1 The IPSS divides patients into 4 risk categories: low, intermediate-1, intermediate-2, and high risk.1 Bone marrow (BM) blasts, karyotype and number of cytopenias
are the only 3 variables comprising the IPSS. The Revised International Prognostic Scoring System (IPSS-R) was intro- duced in 2012. This added a refined cytogenetic classification, degree of cytopenia, and improved BM blast percentage as categories, and introduced 5 subgroups of MDS: very low (VL) risk, low risk (LR), intermediate, high, and very high risk.2 Some other tools that have been developed and widely used for risk stratification include the Global MD Anderson Model, the lower risk MD Anderson model (LR-MDAS), and the WHO-based prognostic scoring system (WPSS).3-5
In low-risk disease (LR MDS), the aim of therapy is to im- prove cytopenias in patients with anemia, neutropenia and/ or thrombocytopenia in order to improve quality of life and prevent complications from cytopenias in an attempt to pro- long overall survival (OS). Cytopenia-related complications
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