Atypical Presentations of Chronic Myeloid Leukemia with Isolated Thrombocytosis: A Systematic Review

Background

Chronic myeloid leukemia (CML) typically presents with leucocytosis and may also show elevated platelet counts. However, isolated thrombocytosis with normal leukocyte count is an atypical presentation. This systematic review aims to summarize and analyze case reports of such atypical presentations to enhance understanding and awareness among Haematologists and emphasize the need for a new risk assessment tool for these patients.

Methods:

A comprehensive search was conducted in PubMed and Google Scholar databases for case reports published in English without restriction on age or publication year. The inclusion criteria were cases diagnosed with CML diagnostic criteria) presenting with isolated thrombocytopenia and normal leukocyte counts. Data on patient demographics, clinical presentation, diagnostic methodology, treatment, and outcomes were extracted and analyzed.

Results:

We reviewed 29 articles from the available published literature from 1987 to 2023. Data from 33 patients were collected, with ages ranging from 5 to 77 and a median age of 42.6 years. A female predominance was observed, with a ratio of approximately 4 to 1. In about 60% of cases, no spleen enlargement was observed, while only 20% of patients displayed splenomegaly as detected through clinical examination or ultrasound. All cases reported isolated thrombocytosis as the initial hematologic abnormality, with platelet counts ranging from 500,000 to over 8 million/µL. Leukocyte counts were within normal limits. The absence of leukocytosis often leads to initial misdiagnosis, commonly essential thrombocythemia. The definitive diagnosis was obtained by detecting the BCR-ABL1 fusion gene via Cytogenetic and/or molecular analysis. Of the patients tested for the JAK2 mutation, 26% were found to have a positive co-mutation. For patients with enough data to assess with the Sokal score, 46.5% were categorized as high risk, 32% as intermediate risk, and 19% as low risk. In contrast, all patients evaluated using the EUTOS score were classified as low risk. There were 18 patients initially treated with hydroxyurea: 5 had no response, 6 had undocumented responses, and 7 achieved a complete hematological response. Twelve patients started on tyrosine kinase inhibitors (TKIs) (8 on imatinib and 3 on dasatinib): all but one attained at least a complete hematological response.

Discussion:

This systematic review of CML cases with isolated thrombocytosis highlighted key findings. The wide age range (5-77 years) indicates that this atypical presentation can occur across all ages. The notable female predominance (4:1 ratio) suggests a potential gender-related factor, warranting further study. The absence of splenomegaly in 60% of cases challenges traditional CML presentations, urging physicians to remain vigilant. The presence of JAK2 mutations in 26% of patients suggests potential co-mutations and the need to check for BCR-ABL even if JAK2 is found in isolated thrombocytosis. Risk assessment showed disparities between the Sokal and EUTOS scores, with the former identifying patients more as high-risk and the latter predominantly low risk, highlighting the need for updated assessment models tailored to atypical presentations. Treatment outcomes varied with hydroxyurea, while TKIs generally led to positive responses.

Conclusion

Patients with CML may present with isolated thrombocytosis. These patients exhibit different clinical characteristics and genetic profiles than classic CML cases. Further prospective studies are needed to gain a better understanding of this unique and rare condition.

No relevant conflicts of interest to declare.