Pathophysiology

Chronic Myeloid Leukemia is driven by the reciprocal chromosomal translocation t(9;22), (q34;q11), which generates the BCR‑ABL1 oncogene encoding a constitutively active tyrosine kinase. This abnormal kinase promotes uncontrolled proliferation of the myeloid cells through persistent activation of downstream signaling pathways. Additionally, apoptosis is inhibited, and genomic instability occurs. This facilitates disease progression from chronic phase to accelerated and blast phases when the disease is left untreated.

Symptoms

Patients typically present with insidious constitutional symptoms, which include fatigue, weight loss, low‑grade fever, and night sweats. Abdominal fullness resulting from splenomegaly is also common. Nigerian studies consistently report severe anemia and massive splenomegaly at presentation, reflecting late health‑seeking behavior and diagnostic delays.

Clinical Findings

Physical examination often reveals pallor, marked splenomegaly, and occasionally hepatomegaly. Hematologic evaluation commonly demonstrates pronounced leukocytosis with a left shift, normocytic normochromic anemia, and variable thrombocytosis or thrombocytopenia depending on disease phase.

Relevant Investigations

Diagnostic evaluation includes a full blood count, with a peripheral blood film, which shows a complete spectrum of the myeloid series. Bone marrow examination demonstrates myeloid hyperplasia. A definitive diagnosis requires cytogenetic detection of the Philadelphia chromosome or molecular identification of BCR‑ABL1 transcripts through the use of reverse‑transcription polymerase chain reaction. In Nigeria, limited access to molecular diagnostics remains a significant barrier to optimal disease monitoring.

Differential Diagnoses

The differential diagnosis includes leukemoid reaction, polycythemia vera, essential thrombocythemia, acute myeloid leukemia, and other chronic myeloproliferative neoplasms. Molecular testing is essential in distinguishing CML from these conditions.

Treatment

Tyrosine kinase inhibitors (TKIs) constitute the cornerstone of CML management. Imatinib mesylate has significantly improved survival outcomes among Nigerian patients since its introduction, transforming CML into a chronic, manageable condition. Second‑generation TKIs are indicated in cases of resistance or intolerance. Hematopoietic stem cell transplantation, although potentially curative, remains largely inaccessible due to financial and infrastructural constraints.

Follow‑Up

Long‑term follow‑up involves serial hematologic and molecular monitoring to assess treatment response and detect resistance. Quantitative BCR‑ABL1 monitoring is recommended where available. Adherence assessment, toxicity surveillance, and supportive care are integral to sustained disease control.

Prevention and Control

Given its genetic etiology, primary prevention of CML is not currently feasible. Control strategies focus on early diagnosis, expansion of diagnostic capacity, improved access to TKIs, and strengthening of healthcare systems to facilitate long‑term patient follow‑up.

Conclusion

Chronic myeloid leukemia has evolved into a highly treatable malignancy in Nigeria with the advent of targeted therapy. Nevertheless, late presentation and limited diagnostic infrastructures continue to adversely affect the disease outcome. Therefore, addressing these challenges through health system strengthening and facilitating equitable access to treatment is essential for better outcomes.

Reflections

Based on my professional experience in managing CML in Nigeria, treatment of the disease can be made more effective by increasing the coverage of the health insurance scheme and establishing molecular testing centres in public hospitals. Most patients cannot afford to pay for BCR-ABL analysis out-of-pocket. Furthermore, patients who can afford to pay for the test have to deal with a delayed turnaround time of at least 14 working days.

Imatinib is made accessible to CML patients through sponsorship by Max Access Solutions, a non-governmental organization in the southern and northern parts of the country. This current limited access can be improved by establishing more standard diagnostic centers with efficient communication systems in more regions of the country.

Despite these challenges, managing CML has been quite successful with hydroxyurea and partial exchange transfusions as temporary remedial measures before initiation of targeted therapy.