{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T07:59:10Z","timestamp":1781078350597,"version":"3.54.1"},"reference-count":13,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Thrombocytopenia in chronic lymphocytic leukemia (CLL) is a heterogeneous and multifactorial complication that often reflects the combined effects of immune dysregulation, impaired megakaryopoiesis, bone marrow microenvironmental disruption, and disease-related factors. In patients with high-risk molecular features, particularly TP53 abnormalities, management becomes increasingly challenging and frequently refractory to conventional therapies. Methods: We report a 57-year-old male with long-standing CLL characterized by a highly aggressive and treatment-refractory course. The patient developed persistent severe thrombocytopenia despite multiple lines of therapy, including corticosteroids, intravenous immunoglobulin, rituximab, splenectomy, and thrombopoietin receptor agonists. Subsequent treatments with ibrutinib and a venetoclax-based regimen failed to improve platelet counts and were discontinued due to worsening cytopenia. Bone marrow evaluation, molecular\/cytogenetic analyses, and subsequent treatment responses were thoroughly evaluated. Results: Bone marrow evaluation revealed hypercellularity with significant CLL infiltration, dysplastic megakaryopoiesis, and reticulin fibrosis, indicating impaired platelet production in addition to immune-mediated destruction. Molecular and cytogenetic analyses demonstrated high-risk disease with deletion of 17p and dual TP53 mutations (p.His179Tyr and p.Arg282Trp), consistent with biallelic TP53 disruption. Romiplostim monotherapy did not result in a meaningful hematologic response. However, following the addition of idelalisib, a rapid and sustained increase in platelet counts was observed, allowing tapering of romiplostim and stabilization of hematologic parameters. Conclusions: This case highlights the complex and dynamic pathophysiology of thrombocytopenia in CLL, where immune-mediated destruction and defective thrombopoiesis coexist within a profoundly altered marrow microenvironment. TP53 disruption appears to play a central role not only in driving treatment resistance but also in promoting immune dysregulation and disease aggressiveness. Although a delayed therapeutic effect of romiplostim cannot be entirely excluded, the distinct temporal association following idelalisib initiation suggests a potential collaborative interaction or disease-directed clearance that may facilitate platelet recovery in this setting. Refractory thrombocytopenia in CLL should be approached as a manifestation of complex disease biology rather than an isolated complication. This single observation indicates that in TP53 aberrant cases with multi-mechanism thrombocytopenia, disease-directed targeted therapy may contribute significantly to platelet recovery.<\/jats:p>","DOI":"10.3390\/jcm15124483","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T06:33:44Z","timestamp":1781073224000},"page":"4483","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Refractory Thrombocytopenia in TP53\u2014Aberrant Chronic Lymphocytic Leukemia: A Multimechanistic Case with Response to Idelalisib and Romiplostim"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8933-1081","authenticated-orcid":false,"given":"Serkan","family":"Guven","sequence":"first","affiliation":[{"name":"Department of Hematology, Canakkale Mehmet Akif Ersoy State Hospital, Ministry of Health, 17000 Canakkale, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5353-0564","authenticated-orcid":false,"given":"Hulya","family":"Kacar","sequence":"additional","affiliation":[{"name":"Department of Pathology, Canakkale Mehmet Akif Ersoy State Hospital, Ministry of Health, 17000 Canakkale, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omer","family":"Seker","sequence":"additional","affiliation":[{"name":"Department of Hematology, Sirnak State Hospital, Ministry of Health, 73000 Sirnak, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatih","family":"Demirkan","sequence":"additional","affiliation":[{"name":"Department of Hematology, Medstar Antalya Hospital, 07000 Antalya, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1016\/j.hoc.2025.05.002","article-title":"Autoimmune Cytopenias in Chronic Lymphocytic Leukemia","volume":"39","author":"Vitale","year":"2025","journal-title":"Hematol. 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