Myelodysplastic/myeloproliferative neoplasms with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T): Mayo-Moffitt collaborative study of 158 patients.

Abhishek A Mangaonkar,Rhett P Ketterling,Rami Komrokji,Kebede H Begna,Chetasi Talati,Najla H Al Ali,Mrinal M Patnaik,Animesh Pardanani,David Sallman,Eric Padron,Aref Al-Kali,Kaaren K Reichard,Naseema Gangat,Ayalew Tefferi,Terra L Lasho

doi:10.1038/s41408-022-00622-8

Abhishek A Mangaonkar, Rhett P Ketterling + Show 13 more

Open Access

https://doi.org/10.1038/s41408-022-00622-8

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Abstract

The current World Health Organization (WHO) classification of myeloid malignancies includes myelodysplastic/myeloproliferative neoplasms with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) as a distinct entity. Previous literature on predictors of survival was based on the provisional category of refractory anemia with ring sideroblast and thrombocytosis (RARS-T), which was not subject to MDS/MPN-RS-T exclusionary criteria such as PB blast% ≥1, BM blast% ≥5 or cytogenetic abnormalities such as t(3;3)(q21.2;q26.2), inv(3)(q21.23q26.2) or isolated del(5q). We examined overall (OS) and leukemia-free (LFS) survival and its predictors, among 158 patients with WHO-defined MDS/MPN-RS-T. In univariate analysis, age ≥70 years (P = 0.006), hemoglobin (Hb) ≤10 g/dL (P = 0.03) and abnormal karyotype (excluding -Y, P = 0.008) were associated with shortened OS, which was otherwise not affected by either ASXL1 (P = 0.7), SF3B1 (P = 0.4) or JAK2 V617F (P = 0.7) mutations; in multivariable analysis, Hb ≤ 10 g/dL (P = 0.03) and abnormal karyotype (P = 0.001) remained significant, and thus allowed the development of an operational survival model with low (0 risk factors, median OS 10.5 years), intermediate (1 risk factor, median OS 4.8 years) and high risk (2 risk factors, median OS 1.4 years) categories (P = 0.0009). Comparison of MDS/MPN-RS-T (n = 158) and MDS/MPN-U with BM RS ≥ 15% (MDS/MPN-U-RS; n = 25) did not reveal significant differences in frequency of thrombosis, OS, or LFS, although SF3B1 mutation frequency was higher in the former (93% versus 59%; P = 0.0005). These data suggest limited survival impact for molecular abnormalities and the morphological distinction between MDS/MPN-RS-T and MDS/MPN-U-RS.

Highlights

The 2016 World Health Organization (WHO) revision of myeloid malignancies and its recent iteration included patients with myelodysplastic/myeloproliferative neoplasms with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) as a distinct entity, under the MDS/MPN category [1, 2]. These patients were included under the provisional MDS/MPN category of refractory anemia with ring sideroblasts and thrombocytosis (RARS-T) [3, 4]
MDS/MPN-RS-T is distinguished from myelodysplastic syndrome with ring sideroblasts (MDS-RS) by the presence of thrombocytosis and bone marrow (BM) megakaryocyte morphology similar to that seen in MPN
We have previously reported data from a large cohort of patients (n = 135) with MDS/MPN-U and found that patients with BM RS ≥ 15% (n = 13) had better outcomes than those with BM RS < 15% (n = 103), but similar outcomes when compared to patients with MDS/MPN-RS-T patients (n = 72) [12]

Summary

Introduction

The 2016 World Health Organization (WHO) revision of myeloid malignancies and its recent iteration included patients with myelodysplastic/myeloproliferative neoplasms with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) as a distinct entity, under the MDS/MPN category [1, 2]. These patients were included under the provisional MDS/MPN category of refractory anemia with ring sideroblasts and thrombocytosis (RARS-T) [3, 4]. MDS/MPN-RS-T is distinguished from myelodysplastic syndrome with ring sideroblasts (MDS-RS) by the presence of thrombocytosis (platelet count ≥450 × 109/L) and bone marrow (BM) megakaryocyte morphology similar to that seen in MPN.

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