Chronic myeloid Leukemia is a myeloproliferative neoplasm characterized by the BCR- ABL1 fusion gene resulting from the Philadelphia chromosome translocation. Tyrosine kinase inhibitors have dramatically improved outcomes in CML. Dasatinib, a second-generation TKI has shown superior responses compared to imatinib. However, dasatinib is associated with unique adverse effects, most notably pleural effusion, which can occur at any time during therapy and may impact treatment continuity. This case highlights the importance of vigilance for pulmonary adverse effects during dasatinib therapy and discusses the possible mechanisms, risk factors, and management strategies.
Case report
A 56-year-old male, a known case of chronic myeloid Leukemia in chronic phase, was receiving dasatinib therapy since January 2024. He was initiated on dasatinib 70 mg once daily and remained compliant with treatment.
Routine molecular monitoring showed:
BCR-ABL1 QPCR:
| April 2024 | 5.6143 |
| September 2024 | 0.7158 |
| February 2025 | 1.2612 |
| October 2025 | 0.2853 |
Based on response and tolerability, the dasatinib dose was reduced to 50 mg once daily.
During routine follow-up, the patient reported gradually progressive breathlessness on
exertion, particularly while climbing stairs. There was no associated chest pain, cough, fever, orthopnea, paroxysmal nocturnal dyspnea, or lower limb edema. There was no prior history of cardiac disease, pulmonary disease, tuberculosis, or smoking.
On examination, vital parameters were stable with normal oxygen saturation on room air. Respiratory examination revealed mildly reduced breath sounds at bilateral lung bases.
Cardiovascular examination was unremarkable.
Investigations revealed:
- Chest X-ray: Mild bilateral pleural effusion
- Echocardiography: Normal cardiac structure and function, no pulmonary hypertension
- Complete blood count: Stable hematologic parameters
- Renal and liver function tests: Within normal limits
In the absence of cardiac or infectious causes, and given the temporal association with dasatinib therapy, a diagnosis of dasatinib-induced pleural effusion was considered.
Dasatinib was temporarily withheld, and the patient was managed with oral diuretics and a short course of systemic corticosteroids, resulting in significant symptomatic improvement. A plan was made for cautious reintroduction of dasatinib at a lower dose with close monitoring.
Discussion
Chronic myeloid Leukemia is a clonal myeloproliferative neoplasm characterized by constitutive activation of the BCR-ABL1 tyrosine kinase, leading to unchecked myeloid proliferation and reduced apoptosis. The advent of tyrosine kinase inhibitors has
fundamentally altered the natural history of CML, transforming it from a fatal disease into a chronic condition with near-normal life expectancy for most patients. Long-term TKI therapy, however, has brought increasing recognition of drug-related toxicities that may affect
treatment adherence and quality of life.
Tyrosine kinase inhibitors act by selectively inhibiting the ATP-binding site of the BCR-
ABL1 oncoprotein, thereby suppressing downstream signalling pathways involved in
leukemogenesis. Second-generation agents including dasatinib offer greater potency and efficacy against resistant mutations but are associated with distinct off-target effects. These
adverse effects are increasingly relevant as patients remain on therapy for prolonged periods.
Dasatinib-related pleural effusion represents one of the most characteristic non-hematological toxicities of this agent. The effusion is often bilateral and may occur at any time during therapy, even in the absence of traditional cardiopulmonary risk factors.
The exact pathophysiology remains unclear; however, several mechanisms have been proposed:
- Src family kinase inhibitionDasatinib inhibits Src kinases, which play a role in maintaining endothelial integrity. Their inhibition may increase vascular permeability, facilitating pleural fluid accumulation.
- Immune-mediated mechanismMany pleural effusions associated with dasatinib are lymphocyte-predominant exudates, suggesting an immune-mediated process.
- Altered pulmonary endothelial function
Dasatinib may cause endothelial dysfunction, leading to capillary leak and pleural fluid formation.
Risk factors include advanced age, longer treatment duration, prior cardiac or pulmonary disease, and hypertension. Management strategies include temporary drug interruption, diuretics, corticosteroids, and dose modification or switching to alternative TKIs in recurrent cases.
In the present case, the temporal association with dasatinib use, exclusion of alternative
etiologies, and clinical improvement following drug interruption strongly support a causal relationship.
Recognition of this adverse effect is clinically important, particularly in patients presenting with unexplained breathlessness, as misattribution to infection, cardiac failure, or disease progression can lead to unnecessary investigations and inappropriate management. Early identification allows timely intervention through dose modification or drug interruption, ensuring symptom resolution while maintaining optimal control of CML.
References
- Hughes P, Laneuville P, Rousselo P, et Incidence, outcomes, and management of pleural effusion in patients receiving dasatinib therapy.
https://pmc.ncbi.nlm.nih.gov/articles/PMC6312029/[1] - Bergeron A, Réa D, Levy V, Picard C, Meignin V, Tamburini J, et Lung abnormalities after dasatinib treatment for chronic myeloid leukemia: a case series.https://pubmed.ncbi.nlm.nih.gov/17600277/[2]
Dr. Madhumitha R M, MBBS
(DNB General Medicine Resident),
Kauvery Hospital, Chennai.[3]
Dr. Arshad Raja, MBBS, M.D.(Transfusion Medicine)
Fellowship in Clinical Haematology, Consultant Haematology,
Kauvery Hospital, Chennai.[3]