Jiaxin Wu
Hongxiang Wang*- The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Objective: To explore the clinical characteristics, diagnosis and treatment process of a case initially diagnosed with primary immune thrombocytopenia (ITP) and finally diagnosed as chronic myeloid-monocytic leukemia (CMML).
Methods: The clinical manifestations, laboratory tests, bone marrow morphology, molecular genetic test results and treatment history of a CMML patient with thrombocytopenia as the first symptom were retrospectively analyzed.
Results: One patient was initially diagnosed with immune thrombocytopenia (ITP). After receiving immunosuppressive treatment, the platelets temporarily rebounded, but subsequently the white blood cells increased, the proportion of monocytes increased, and typical CMML-related mutations were found in bone marrow morphology and NGS testing, and he was finally diagnosed as CMML. His condition stabilized after treatment with decitabine chemotherapy.
Conclusion: CMML can manifest as atypical thrombocytopenia in the early stage, which is delayed by the progression of ITP. Clinical attention should be paid to potential clonal bone marrow diseases in ITP patients who are refractory or have poor response to treatment. Early bone marrow morphological and molecular detection can help to clarify the diagnosis, guide treatment, and improve prognosis.
1 Introduction
Primary immune thrombocytopenia (ITP) is an acquired autoimmune bleeding disorder characterized by reduced platelet counts, with or without skin and mucosal bleeding. ITP can occur at all ages, with women of childbearing age and the elderly over 60 years old being the most susceptible groups (1). The annual incidence of ITP in adults has been reported to range from 2 to 10 per 100,000 population in Western countries; however accurate epidemiological data in China are still lacking (2, 3). The main goals of ITP treatment are to control and prevent bleeding and maintain platelet counts at safe levels (4). Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disease with characteristics of both myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN) (5). According to the 5th edition of the World Health Organization classification, CMML is diagnosed using the following criteria. Based on white blood cell count, CMML is subdivided into myelodysplastic type (MD-CMML) if the count is ≤13x10^9/L and myeloproliferative type (MP-CMML) if the count is >13x10^9/L. Because of the cytopenias observed in MDS-CMML, the disease often presents with a range of nonspecific clinical features, including fatigue secondary to anemia, increased susceptibility to infections due to neutropenia, and a tendency toward bruising or bleeding as a result of thrombocytopenia. In contrast, MPN-CMML is more commonly associated with systemic symptoms such as fever, weight loss, night sweats, and pruritus (6). Both ITP and CMML can have thrombocytopenia as the first or only symptom. The bone marrow morphology and clinical symptoms of CMML are often atypical, causing patients to be misdiagnosed as ITP. Immune thrombocytopenia (ITP) may represent an early manifestation of an underlying myeloid malignancy. We report an elderly patient who initially presented with ITP and was subsequently diagnosed with chronic myelomonocytic leukemia (CMML). This case highlights the atypical clinical presentation of CMML and discusses the diagnostic approach, aiming to raise awareness of early recognition and appropriate management of such conditions.
2 Patient information
2.1 Basic information
A64-year-old male patient was admitted to the Department of Hematology at Wuhan Central Hospital on January 16, 2023, with a 2-day history of spontaneous nasal bleeding. The bleeding occurred without an obvious trigger. The patient denied fever, bone pain, gingival bleeding, cough, sputum production, hematemesis, or melena. No other specific discomfort was reported. A routine blood examination performed at presentation revealed a white blood cell count of 8.17 × 109/L, a hemoglobin level of 128 g/L, and a platelet count of 15 × 109/L, with a monocyte percentage of 14.60%. Given the presence of severe thrombocytopenia, the patient was admitted for further evaluation and management. The patient had a 2-year history of autoimmune hemolytic anemia and connective tissue disease and systemic lupus erythematosus, which was considered to be of moderate disease activity at the time of admission, and had been receiving long-term oral glucocorticoids and cyclosporine. He denied a history of chronic conditions such as diabetes mellitus or hypertension, as well as infectious diseases including hepatitis and tuberculosis. There was no reported family history of malignancy.
2.2 Physical examination and laboratory examination on admission
On admission, the patient was 178 cm in height and weighed 79 kg. His body temperature was within the normal range. He was conscious, alert, and in good general condition. Physical examination revealed no petechiae or ecchymoses on the skin or mucous membranes. No superficial lymphadenopathy was detected. The liver and spleen were not palpable, and sternal tenderness was absent. Cardiopulmonary auscultation revealed no remarkable abnormalities.
Laboratory evaluation showed a reticulocyte count of 1.61%. Epstein–Barr virus (EBV) DNA was detected at a level of 3.57 × 104 copies/L. High-sensitivity C-reactive protein was 0.19 mg/L, and the erythrocyte sedimentation rate was 18 mm/h. Immunological testing revealed complement levels of C3 0.93 g/L, C4 0.24 g/L, and C1q 32.90 mg/L. Antinuclear antibody (ANA) profile showed weakly positive anti-histone IgG antibodies. ANA testing demonstrated a granular nuclear pattern (1:100) and a nuclear membrane pattern (1:100). Anti–double-stranded DNA antibodies and antiphospholipid antibody profile were negative. Coagulation parameters as well as liver and renal function tests were within normal limits.
2.3 Diagnosis and treatment process
Based on the patient’s clinical manifestations and laboratory findings, a diagnosis of immune thrombocytopenia (ITP) was initially considered. On the day following admission, the patient developed fresh blood per rectum after defecation, without other accompanying discomfort. He was treated with oral rupatadine fumarate (20 mg/day), prednisone acetate (60 mg/day), and cyclosporine (50 mg/day), along with intravenous recombinant human thrombopoietin (15,000 units/day). One unit of platelet concentrate was transfused on the same day for symptomatic management.
Owing to the patient’s personal preference, no adjustment of medications was made, and bone marrow aspiration and biopsy were performed on the third day after admission, at which time the platelet count remained 15 × 109/L. On day 5, bone marrow cytological examination revealed markedly active hematopoiesis with a decreased granulocyte-to-erythroid ratio (Figure 1). Platelets were occasionally observed, and megakaryocytes were increased with evidence of maturation disorder.
Figure 1. Routine bone marrow examination for diagnosing ITP.
Immunophenotypic analysis showed that blasts accounted for 0.3% of nucleated cells, lymphocytes for 3.7% (predominantly T lymphocytes), neutrophils for 62.4%, and monocytes for 6.1%. No obvious immunophenotypic abnormalities were identified. Taken together, these findings were consistent with a diagnosis of ITP.
The platelet count remained low at 16 × 109/L, and high-dose dexamethasone pulse therapy (20 mg/day for 4 consecutive days) was subsequently initiated. On day 9, repeat blood testing showed an increase in platelet count to 31 × 109/L. The patient’s hemorrhoidal bleeding improved, and no additional symptoms were reported. Treatment was then continued with oral prednisone at the initial dose in combination with recombinant thrombopoietin to further increase platelet levels.
On day 11, follow-up complete blood counts revealed a white blood cell count of 14.79 × 109/L, a hemoglobin level of 124 g/L, and a platelet count of 52 × 109/L. Given the significant improvement in thrombocytopenia, the patient was discharged. After discharge, he continued oral prednisone (60 mg/day) and hetrombopag (2.5 mg/day) and was followed up on an outpatient basis.
On September 4, 2024, the patient returned to our hospital for follow-up evaluation. A complete blood count showed a platelet count of 192 × 109/L, with a monocyte percentage of 25.8%. Bone marrow examination demonstrated markedly to extremely active hematopoiesis. Bone marrow cytological analysis revealed a granulocyte-to-erythroid ratio of 2.72:1, with granulocytic proliferation accounting for 62.5% of nucleated cells, including 1.0% promyelocytes; monocytes accounted for 11.5% of nucleated cells, including 1.0% immature forms (Figure 2). Serum tumor markers were within normal ranges, including carbohydrate antigen 19-9 (3.49 U/mL), alpha-fetoprotein (3.18 ng/mL), and carcinoembryonic antigen (1.10 ng/mL). To further clarify the etiology and exclude MPN and CMML, additional molecular testing, including BCR/ABL, myeloproliferative neoplasm–related genes, Chromosomal analysis, and next-generation sequencing (NGS) of hematologic malignancy–associated genes, was recommended.
Figure 2. Routine bone marrow examination for diagnosing CMML.
The patient subsequently underwent these investigations at another institution. The results showed negative BCR/ABL p190 and p210 transcripts. Cytogenetic karyotype analysis revealed a normal karyotype (Figure 3). NGS of hematologic malignancy–associated genes detected mutations in ASXL1, NRAS, EZH2, and TET2. Specifically, the following variants were identified: NRAS NM_002524:c.35G>A (p.G12D) with a variant allele frequency (VAF) of 41.1%; ASXL1 NM_015338:c.1888_1910del (p.E635Rfs*15) with a VAF of 45.4%; EZH2 NM_004456:c.836A>G (p.H279R) with a VAF of 43.7%; and TET2 NM_001127208:c.973C>T (p.Q325X) with a VAF of 45.8%. Based on these findings, a diagnosis of chronic myelomonocytic leukemia was established.
Figure 3. Chromosome analysis.
On October 16, 2024, routine blood testing at our hospital revealed a white blood cell count of 57.26 × 109/L and a platelet count of 122.0 × 109/L. The first course of hypomethylating therapy with azacitidine was initiated on October 20, 2024. Supportive care, including antiemetics, acid suppression, hepatoprotective treatment, hydration, and urine alkalinization, was provided concurrently. During chemotherapy, the patient developed urinary urgency and dysuria, which resolved following anti-infective treatment. The patient was discharged after completion of the treatment course, with a platelet count of 127 × 109/L at discharge.
After discharge, the patient continued oral hetrombopag (25 mg every other day) and prednisone (5 mg once daily). Subsequently, the second, third, and fourth courses of chemotherapy with decitabine (25 mg/day for 5 consecutive days) were administered on November 20, 2024, December 22, 2024, and January 19, 2025, respectively. During these treatment cycles, supportive measures including platelet support, antiemetics, acid suppression, hepatoprotection, hydration, and urine alkalinization were provided. The treatment courses were well tolerated. A clinical timeline summarizing the patient’s diagnostic course from initial presentation to the final diagnosis and treatment is shown in Table 1.
Table 1. Clinical timeline from initial presentation to diagnosis and treatment.
At present, the patient remains clinically stable and is undergoing regular outpatient follow-up. Serial complete blood counts have remained within normal ranges, with no recurrence of thrombocytopenia, and no transfusion requirement has been observed.
3 Discussion
Recent studies have shown that immune thrombocytopenia is not always an isolated benign immune disease (7). In some patients, it may be associated with underlying clonal myeloid disorders and serve a prodromal or revealing manifestation (8). Autoimmune cytopenias, including immune thrombocytopenia, have been described as immune manifestations of myeloid neoplasms in clinical practice (9). This case reflects this clinical scenario, where immune thrombocytopenia was the initial presentation, and presence of an underlying myeloproliferative disorder became evident during follow-up.
Immune thrombocytopenia can appear in patients with a confirmed diagnosis of a myeloid neoplasm, especially in elderly individuals or those unresponsive to treatment, and may indicate an underlying risk of clonal hematopoietic abnormalities. A single-center retrospective cohort study by Wang et al. found that clonal hematopoiesis was detected in approximately 10–11% of the included ITP patients, and the incidence of CH was significantly increased in ITP patients ≥65 years of age (10). Moreover, it was shown that CH-positive patients had a lower initial response rate to glucocorticoids, requiring more intervention to increase platelet count. A multicenter, retrospective cohort study conducted by Fattizzo et al. further demonstrated that clonal hematopoiesis was identified in a substantial proportion of ITP patients, particularly among those aged 60–65 years and older (11). Collectively, these findings suggest that a subset of patients initially diagnosed with ITP may harbor underlying clonal hematopoietic abnormalities, and that refractory ITP may mask concomitant clonal myeloid disorders.
Myeloid neoplasms, including chronic myelomonocytic leukemia, are characterized by significant immune imbalance and chronic inflammation. Recurrent mutations in CMML, such as TET2, ASXL1, and SRSF2, not only affect hematopoiesis but are also deeply involved in immune regulation and inflammatory responses; these alterations are associated with aberrant monocyte behavior and dysregulated inflammatory mediator production, which may contribute to immune microenvironment disruption and the development of autoimmune phenomena (12). In addition, Sato et al. reported an increased prevalence of ASXL1 mutations in elderly individuals with chronic inflammatory conditions and, based on animal models, proposed a bidirectional model distinct from traditional linear views. In this model, ASXL1 mutations contribute to chronic inflammation through altered immune cell function, while chronic inflammatory states, in turn, provide a selective advantage for ASXL1-mutant clones, promoting their clonal expansion and forming a self-perpetuating cycle (13). Similar findings were reported in a population-based retrospective cohort study, in which approximately 33.6% of patients with CMML had autoimmune diseases or other inflammatory conditions; however, the presence of autoimmune manifestations did not significantly affect overall survival (OS) (14).In this context, in patients with refractory immune thrombocytopenia, comprehensive molecular evaluation and close longitudinal follow-up may be warranted.
Immune thrombocytopenia (ITP) is a heterogeneous immune-mediated disorder characterized by thrombocytopenia resulting from immune-mediated platelet destruction in the peripheral blood, spleen, and liver, superimposed on impaired megakaryocyte production in the bone marrow, ultimately leading to autoimmune responses directed against both megakaryocytes and circulating platelets (15).
Clinically, the diagnosis of ITP remains one of exclusion. At initial presentation, this patient exhibited isolated thrombocytopenia without hepatosplenomegaly or sternal tenderness. Bone marrow cytology and immunophenotyping revealed no evidence of dysplastic hematopoiesis or abnormal differentiation, and despite weakly positive anti-histone IgG antibodies with granular (1:100) and nuclear membrane (1:100) ANA patterns, anti–double-stranded DNA and anti-Sm antibodies were negative, complement C3 and C4 levels were not persistently decreased, and no evidence of antiphospholipid syndrome was present, supporting a diagnosis of ITP.
According to current guidelines (16), observation is recommended for asymptomatic patients with mild to moderate thrombocytopenia, whereas treatment is recommended for patients with higher bleeding risk or platelet counts below 30 × 109/L. High-dose dexamethasone pulse therapy is preferentially recommended in this setting. In the present case, the patient presented with a platelet count of 15 × 109/L and was therefore treated with high-dose corticosteroids, without severe bleeding events or the need for additional interventions.
Following the initial diagnosis of immune thrombocytopenia, repeat bone marrow examination combined with molecular testing subsequently enabled a timely diagnosis of chronic myelomonocytic leukemia, and hypomethylating agent therapy was initiated accordingly, resulting in a favorable clinical outcome.
This case also highlights certain limitations in the initial diagnostic approach. Although immune thrombocytopenia could be reasonably diagnosed at presentation, the evaluation was initially limited to morphological assessment, without immediate cytogenetic and molecular analyses. Earlier incorporation of these investigations might have facilitated more comprehensive risk assessment and earlier recognition of the underlying clonal myeloid disorder.
Although immune thrombocytopenia patients harboring chromosome 20q deletion have been reported to carry an increased risk of subsequent MDS or CMML, currently available cytogenetic and molecular studies remain insufficient to reliably identify which ITP patients are at risk of progression (7). The lack of large-scale clinicopathological studies integrating autoimmune manifestations with clonal hematopoiesis has limited our understanding of the mechanistic link between ITP and MDS/CMML (6).
Therefore, in patients with refractory or relapsing immune thrombocytopenia—particularly among the elderly—heightened vigilance for an underlying myeloid neoplasm is warranted. Close longitudinal monitoring should be undertaken, and comprehensive bone marrow and molecular evaluations considered when clinically indicated, to facilitate earlier recognition of clonal myeloid disorders.
In summary, the clinical manifestations and bone marrow findings at the initial presentation of this patient were consistent with immune thrombocytopenia, while repeat bone marrow examination and molecular testing after approximately 20 months of follow-up led to a revised diagnosis of chronic myelomonocytic leukemia. These findings suggest that in patients with long-standing or recurrent thrombocytopenia initially diagnosed as ITP, the possibility of an underlying clonal myeloid disorder should be carefully considered. Distinguishing primary ITP from thrombocytopenia related to myelodysplastic or myeloproliferative neoplasms remains clinically challenging but critically important. Therefore, during outpatient follow-up, even in patients with an established diagnosis of ITP, persistent or relapsing thrombocytopenia should prompt continued evaluation beyond serial bone marrow morphology. Comprehensive cytogenetic and molecular analyses, particularly targeting genes frequently mutated in MDS and related myeloid neoplasms, should be considered to facilitate earlier recognition of underlying clonal disease and to avoid delayed diagnosis.
Data availability statement
The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.
Ethics statement
The studies involving humans were approved by The Ethics Committee of Wuhan Central Hospital. The studies were conducted in accordance with the local legislation and institutional requirements. The human samples used in this study were acquired from a by- product of routine care or industry. Written informed consent for participation was not required from the participants or the participants’ legal guardians/next of kin in accordance with the national legislation and institutional requirements. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.
Author contributions
JW: Writing – original draft, Writing – review & editing. HW: Writing – review & editing, Writing – original draft.
Funding
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Keywords: chronic myelomonocytic leukemia, immune thrombocytopenia, prodromal manifestation, clonal hematopoiesis, thrombocytopenia
Citation: Wu J and Wang H (2026) Case Report: Chronic myelomonocytic leukemia initially diagnosed as immune thrombocytopenia. Front. Hematol. 5:1748301. doi: 10.3389/frhem.2026.1748301
Received: 17 November 2025; Accepted: 19 January 2026; Revised: 11 January 2026;
Published: 04 February 2026.
Edited by:
Prashant Ramesh Tembhare, Research and Education in Cancer (ACTREC), IndiaReviewed by:
JiaPei Gao, Yangzhou University, ChinaRim Rakez, University Hospital of Martinique, Martinique
Copyright © 2026 Wu and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Hongxiang Wang, d2hpdGVseTE5NzJAc2luYS5jb20=