Clinical spectrum, outcome and management of immune thrombocytopenia associated with myelodysplastic syndromes and chronic myelomonocytic leukemia

Abstract

Myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) are associated with systemic inflammatory or autoimmune diseases in 10-20 % of cases. Among them, immune thrombocytopenia (ITP) has been reported but large studies assessing this association are missing. Whether such patients have a particular phenotype and require particular management is unclear. This study analyzes the clinical spectrum, outcome and therapeutic management of patients with ITP associated with MDS or CMML, in comparison (i) to patients with primary ITP without MDS/CMML and (ii) to patients with MDS/CMML without ITP. Forty-one MDS/CMML-associated ITP patients were included, with chronic ITP in 26 (63%) patients, low-risk myelodysplasia in 30 (73%) patients and CMML in 24 (59%) patients. An associated autoimmune disease was noted in 10 (24%) patients. In comparison to primary ITP patients, MDS/CMML-associated ITP patients had a higher occurrence of severe bleeding despite similar platelet counts at diagnosis. First-line treatment consisted of glucocorticoids (98%) and intravenous immunoglobulin (IVIg) (56%). Response achievement with IVIg was more frequent in primary ITP than in MDS/CMML-associated ITP patients. Response rates to second-line therapies were not statistically different between primary ITP and MDS/CMMLassociated ITP patients. Ten percent (n=4) of patients with MDS/CMML-associated ITP had multirefractory ITP versus none in primary ITP controls. After a median follow-up of 60 months, there was no difference in overall survival between MDS/CMML-associated ITP and primary ITP patients. Leukemia-free-survival was significantly better in MDS/CMMLassociated ITP patients than in MDS/CMML without ITP MDS/CMML-associated ITP have a particular outcome with more severe bleeding and multirefractory profile than primary ITP, similar response profile to primary ITP therapy except for IVIg, and less progression toward acute myeloid leukemia than MDS/CMML without ITP.

Prospective validation of a biomarker-driven response prediction model to romiplostim in lower-risk myelodysplastic neoplasms – results of the EUROPE trial by EMSCO

“…One cerebrovascular accident (CTCAE grade 3) in a responder 22 weeks after starting ROM, one pulmonary embolism (CTCAE grade 4) in a non-responder at seven weeks of ROM and one case of asthenia (CTCAE grade 3) were reported as serious adverse events CTCAE ≥ grade 3 possibly attributed to ROM. This is in line with literature reporting a slightly higher rate of thromboembolic events in patients during TPO-RA treatment compared to patients without TPO-RA [4,16,19,37,38].…”

“…Romiplostim (ROM) and Eltrombopag (EPAG) are thrombopoietin receptor agonists (TPO-RA) [15][16][17], which both have already demonstrated clinical efficacy in treating MDS patients with thrombocytopenia [18][19][20][21][22]. Both ROM and EPAG stimulate megakaryocyte differentiation and proliferation [23,24].…”

“…While the oral small molecule EPAG binds to a transmembrane site of the TPO-receptor [17,25,26] the peptide mimetic ROM binds directly at the extracellular TPO-receptor binding site where also native TPO binds [27][28][29][30]. Until now, both TPO-RA are not approved for the treatment of MDS patients with thrombocytopenia, thus regular platelet transfusions still represent the only supportive treatment option for these patients [16,17]. ROM has shown safety and clinical efficacy in prospective randomized trials in LR-MDS [4,12,20,31,32].…”

Inflammatory and Immune Disorders Associated with Myelodysplastic Syndromes

“…In a cohort of 41 MDS/CMML patients with immune thrombocytopenia (ITP), defined by response to steroids, including chronic ITP in 63%, low-risk myelodysplasia in 73% and CMML in 59%, it was recently reported that MDS/CMML-associated ITP have a particular outcome with more severe bleeding and multi-refractory profile than primary ITP, a similar response profile to primary ITP therapy except for intravenous immunoglobulin, and less progression toward acute myeloid leukemia than MDS/CMML without ITP [105].…”

Chronic Myeloid Leukemia in a Patient with Previous Idiopathic Thrombocytopenic Purpura: How to Manage Imatinib Together with Eltrombopag

“…In particular, recent papers studied patho-biological mechanisms linking ITP and clonal disorders, and their temporal association. Many published experiences focused on ITP and myelodysplastic syndrome (MDS)/chronic myelomonocytic leukemia (CMML), but when analyzing the temporal association, it was evident that, in the majority of cases, ITP followed the diagnosis of MDS/CMML and only very few cases were diagnosed as MDS/CMML after ITP [2][3][4].…”