P135 | CLONAL EVOLUTION IN IMMUNE THROMBOCYTOPENIA (ITP): THREE CASES OF CHRONIC MYELOMONOCYTIC LEUKEMIA DURING TREATMENT WITH THROMBOPOIETIN RECEPTOR AGONISTS FOR ITP

Introduction: Immune thrombocytopenia (ITP) is an acquired autoimmune cytopenia generally benign, though its long-term outcomes remain uncertain. While no clear evidence links ITP to increased risk of myeloid neoplasms (myelodysplastic syndromes or chronic myelomonocytic leukemia, CMML), rare co-occurrences suggest possible clonal hematopoiesis. We report three cases of long-standing ITP evolving into CMML during thrombopoietin receptor agonist (TPO-RA) therapy. Patients and Methods: Three patients (pts) (2 females, 1 male) were diagnosed with ITP at ages 52, 50, and 57, with disease durations of 23, 4, and 15 years, respectively. Initial bone marrow evaluations confirmed ITP. All received corticosteroids as first-line therapy. Second-line treatments included rituximab (n=2) and azacitidine with prednisone (n=1). Due to refractoriness, third-line TPO-RAs were introduced: romiplostim (n=2) and eltrombopag (n=1), with partial responses. Sequential switches followed, and all pts eventually received avatrombopag (Ava). During this therapy, progressive monocytosis and anemia developed, despite partial (n=2) or complete (n=1) platelet responses. In the male patient, monocytosis and leukocytosis had previously occurred under eltrombopag and romiplostim but regressed after their discontinuation. One patient developed an ischemic stroke due to aortic arch thrombosis and middle cerebral artery stenosis, requiring Ava withdrawal. All pts underwent repeat bone marrow evaluations including histology, cytogenetics, and next-generation sequencing (NGS). Results: Bone marrow histology confirmed CMML in all cases, with grade 1–2 reticulin fibrosis and 2–10% myeloid blasts. Cytogenetic analysis was normal. NGS for AML-related mutations was negative. Two patients carried TET2 and ASXL1 mutations, one also had SRSF2. The third patient had SRSF2, NRAS, and RUNX1 mutations. No other pathogenic variants were detected. All patients discontinued TPO-RA therapy. Two remain under follow-up with intermittent corticosteroids or IVIG for persistent thrombocytopenia. The oldest patient died at 76 from cardiovascular complications during SARS-CoV-2 infection (Tab. 1 ). Conclusions: These cases suggest that long-standing ITP may evolve into CMML, particularly during TPO-RA therapy. Early bone marrow evaluation and NGS at diagnosis may help detect clonal hematopoiesis before TPO-RA initiation, especially in patients with additional cytopenias or morphologic/numeric abnormalities.