Deciphering clinical features and treatment patterns of thrombocytopenic myelodysplastic syndromes

Here we studied 260 patients with myelodysplastic neoplasms (MDS) focusing on thrombocytopenic patients with PLT < 50 × 10⁹/L. Clinical and laboratory features, bone marrow data, therapies and outcomes were compared with MDS without thrombocytopenia. Thirty-five subjects (13.5%) had moderate to severe thrombocytopenia (median PLT 38 × 10⁹/L, range: 9-50 × 10⁹/L) and 20% displayed signs of bleeding, mostly grade 1-2. At diagnosis, thrombocytopenic MDS were mostly low- or very low- risk IPSS-R, a higher frequency of 40% belonged to intermediate IPSS-R group. Bone marrow evaluation showed hypocellularity (26% vs. 8.4%) and abnormal karyotype (46% vs. 27%), with trisomy 8 and complex karyotype as the most frequent alterations. Eighteen patients (51%) underwent NGS for genes commonly mutated in myeloid neoplasms, detecting at least a mutation in 11 (61%), with TP53 and STAG2 as most frequent. In a subgroup analysis immune-histochemistry on bone marrow biopsies highlighted deposits of IgG, IgM, and complement fractions C3 and C4d in most cases. AML transformation and mortality rates were superior in thrombocytopenic versus non-thrombocytopenic patients. Two distinct phenotypes of thrombocytopenic MDS could be hypothesized, one closer to immune thrombocytopenia marked by trisomy 8 and STAG2 mutation, responsive to immunosuppressive treatment and the other more similar to higher-risk MDS with complex karyotypes and TP53 mutations showing a worsen outcome.