Deciphering clinical features and treatment patterns of thrombocytopenic myelodysplastic syndromes

• Published in: Annals of hematology Vol. 104; no. 6; pp. 3261 - 3269
• Main Authors: Galli, Nicole, Pettine, Loredana, Croci, Giorgio, Passamonti, Francesco, Barcellini, Wilma, Fattizzo, Bruno
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.06.2025; Springer Nature B.V
• Subjects: Adult; Aged; Aged, 80 and over; Blood platelets; Bone marrow; Bone Marrow - pathology; Chromosomes, Human, Pair 8; Cloning; Female; Hematology; Humans; Immunoglobulins; Immunohistochemistry; Leukemia; Male; Medicine; Medicine & Public Health; Middle Aged; Mutation; Myelodysplastic syndromes; Myelodysplastic Syndromes - blood; Myelodysplastic Syndromes - complications; Myelodysplastic Syndromes - diagnosis; Myelodysplastic Syndromes - genetics; Myelodysplastic Syndromes - mortality; Myelodysplastic Syndromes - pathology; Myelodysplastic Syndromes - therapy; Oncology; Retrospective Studies; Thrombocytopenia; Thrombocytopenia - blood; Thrombocytopenia - diagnosis; Thrombocytopenia - genetics; Thrombocytopenia - therapy; Trisomy; Thrombocytopenia; Autoimmunity; NGS; Trephine biopsy; Myelodysplastic syndromes
• ISSN: 0939-5555; 1432-0584; 1432-0584
• DOI: 10.1007/s00277-025-06421-y

Here we studied 260 patients with myelodysplastic neoplasms (MDS) focusing on thrombocytopenic patients with PLT < 50 × 10 9 /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 × 10 9 /L, range: 9-50 × 10 9 /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. Key Points Thirty-five MDS subjects (13.5%) had thrombocytopenia < 50 × 10^9/L, had more frequent anti-PLT antibodies, bone marrow hypocellularity, karyotype aberrations, and deposits of IgG, IgM, and complement fractions. Trisomy 8 and STAG2 mutations associated with a better response to immunosuppressive therapy, while complex karyotype and TP53 predicted higher AML transformation.