Dasatinib, an oral second-generation BCR-ABL tyrosine kinase inhibitor (TKI), received approval from the U.S. Food and Drug Administration in 2006 for patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) or acute lymphoblastic leukemia (ALL) who were resistant or intolerant to prior therapy, and was subsequently approved in 2010 for newly diagnosed chronic-phase CML (Foà et al., 2024; Advani et al., 2023). Compared with the first-generation TKI imatinib, dasatinib exhibits greater potency and broader kinase inhibition, targeting not only BCR-ABL but also a spectrum of kinases including Src-family kinases (SFKs), KIT proto-oncogene receptor tyrosine kinase (c-KIT), platelet-derived growth factor receptor beta (PDGFR-β), and ephrin type-A receptor 2 (EPHA2) (Keating, 2017). This expanded inhibitory profile underlies its superior therapeutic efficacy while also accounting for distinct adverse-event patterns. While adverse events are generally infrequent, pleural effusion has emerged as a notable complication, and in rare instances, this may evolve into chylothorax—an accumulation of chyle in the pleural space, typically presenting with milky effusion rich in triglycerides and lymphocytes (Huang et al., 2023). The underlying pathophysiology of dasatinib-induced chylothorax is not fully understood, but it is thought to involve off-target effects on lymphatic vessels and alterations in vascular permeability (Molina et al., 2020). To date, available data on dasatinib-induced chylothorax are primarily from case reports and small series, providing limited guidance for clinicians in terms of diagnosis and management. Understanding the clinical features, diagnostic strategies, and treatment options is crucial for improving patient outcomes. This study aims to retrospectively analyze the clinical characteristics, management approaches, and outcomes of patients with dasatinib-induced chylothorax, offering insights that may aid in the early recognition and effective management of this rare complication.

A standardized form was used to extract relevant information from each eligible article. The following data were collected: patient characteristics (age, sex), underlying disease (CML, Ph + ALL, etc.), dasatinib dosage and treatment duration, time to onset of chylothorax, presenting symptoms, imaging findings, pleural fluid characteristics (triglycerides, lymphocytes, albumin, lactate dehydrogenase), management strategies (discontinuation of dasatinib, use of alternative TKIs, supportive treatments), and patient outcomes (recovery, recurrence, or mortality).

Chylothorax primarily occurs following disruption of the thoracic duct, which may result from traumatic injury such as cardiac surgery, or from non-traumatic causes including lymphatic obstruction associated with sarcoidosis, lymphoma, or superior vena cava syndrome (Armas-Villalba and Jimenez, 2025). In contrast, pleural effusion is a far more common non-hematologic toxicity of dasatinib, occurring in 20%–30% of CML patients, often within the first year of therapy, and is associated with immune-mediated mechanisms, endothelial permeability changes, and fluid retention (Breccia et al., 2011; Jain et al., 2024). Chylothorax, however, is exceedingly rare and generally develops after prolonged exposure. Eskazan et al. reported that dasatinib-related pleural effusion may be accompanied by pericardial effusion but rarely by ascites, suggesting selective serosal involvement (Küçükyurt et al., 2024). These findings highlight chylothorax as a rare and distinct complication of dasatinib, with timing, mechanisms, and clinical implications differing from pleural effusion. In clinical practice, diagnostic confirmation of chylothorax is based on pleural fluid characteristics, which often present as a milky effusion with elevated triglycerides and predominance of lymphocytes. Widely accepted criteria include triglyceride levels >110 mg/dL (>1.24 mmol/L) or the presence of chylomicrons, with nucleated cell counts showing >70% lymphocytes further supporting a chylous etiology (Armas-Villalba and Jimenez, 2025; Riley and Ataya, 2019). While medication-induced chylothorax is rare, dasatinib is recognized as an uncommon pharmacological cause, representing one of the few drug-related etiologies identified to date (Agrawal et al., 2022). As noted in our analysis, the majority of patients developed chylothorax after prolonged exposure to dasatinib, with the median time to symptom onset being 41 months. This finding indicating that chylothorax typically arises in the later stages of anti-myeloid leukemia treatment following extended drug exposure. Noteworthy, reported cases span a broad age range, from pediatric to elderly patients, underscoring the need for vigilance across age groups. Given the limited pediatric evidence, decisions regarding dose adjustment, switching to alternative TKIs, and the appropriateness of rechallenge should be individualized and carefully balanced against the risk of recurrence. Although the exact pathophysiological mechanisms remain unclear, they are thought to involve dasatinib-induced disruption of lymphatic function and vascular integrity, potentially through the inhibition of PDGFR-β and SFKs, both of which are crucial for maintaining lymphatic drainage and vascular stability (Huang et al., 2015; Bergers et al., 2003). Mechanistically, PDGFR-β regulates lymphangiogenesis, and its inhibition leads to the formation of abnormal lymphatic vessels, resulting in leakage into the pleural space (Zhang et al., 2024). Similarly, SFKs inhibition can modulate endothelial barrier function and increase vascular permeability, potentially destabilizing the pleural microvasculature and favoring effusion formation (Cai et al., 2020). However, the specific reasons behind dasatinib’s heightened affinity for the vasculature and lymphatics remain unclear.

Dasatinib has a half-life of approximately 3–5 h and is primarily metabolized by the liver via the CYP3A4 enzyme, with excretion occurring through bile and urine (Advani et al., 2023). The typical dosage of dasatinib is administered once daily, usually at doses of 50 mg or 100 mg, adjusted based on the patient’s specific condition and tolerance (Pontarollo and Reinhardt, 2023). Notably, dasatinib is associated with a broad adverse-event profile that includes hematologic toxicities (e.g., neutropenia, anemia, thrombocytopenia), cardiopulmonary events (e.g., pleural effusion, pulmonary arterial hypertension, arrhythmias), hepatic dysfunction, cutaneous reactions, and fluid-retention syndromes, as well as systemic symptoms such as headache and fatigue (Pontarollo and Reinhardt, 2023). In our analysis of 24 patients, the most commonly reported clinical manifestations were dyspnea (62.5%), followed by fever (25.0%), cough (16.7%), and abdominal pain and hypoxia. The diagnosis of dasatinib-induced chylothorax is confirmed through pleural fluid analysis, which typically shows a characteristic milky appearance and elevated triglyceride levels, findings that were observed in the majority of our cases. The pleural fluid analysis also showed a predominance of lymphocytes, which is consistent with the typical presentation of chylothorax. This highlights the critical role of pleural fluid analysis in differentiating dasatinib-induced chylothorax from other potential causes of pleural effusion, such as malignancy or infection. Given that this complication is relatively rare, clinicians must maintain a high degree of suspicion when faced with patients on dasatinib therapy presenting with pleural effusion.

Management of dasatinib-induced chylothorax primarily involves discontinuing the drug, which was associated with clinical improvement in the majority of patients in our analysis. Alternative TKIs such as nilotinib, imatinib, and bosutinib were frequently used in place of dasatinib, with no recurrence of chylothorax in most cases. Nilotinib is generally considered a suitable alternative owing to its efficacy and lower incidence of pleural effusion compared with dasatinib (Jain et al., 2024). Imatinib, although less potent, remains a well-tolerated option, particularly in patients with stable disease or those intolerant to other second-generation TKIs (Jain et al., 2024; Cortes et al., 2016; Paydas, 2014). Bosutinib, another second-generation TKI, has been associated with gastrointestinal toxicities but rarely with pleural or chylous effusions, making it a reasonable alternative in selected cases (Cortes et al., 2018). Clinicians should individualize the choice of an alternative TKI based on prior therapy, comorbidities, and overall risk-benefit assessment. In addition to drug discontinuation, supportive treatments, including corticosteroids, diuretics, and thoracentesis, were employed and were effective in most patients. These interventions contributed significantly to symptom resolution, with the median recovery time being 12.2 weeks. Although most patients recovered within 10 weeks, some required a prolonged treatment course, with recovery extending up to 52 weeks in a few isolated cases. Of particular concern is the high rate of recurrence of chylothorax upon rechallenge with dasatinib. Notably, three out of four patients who were rechallenged with dasatinib experienced a recurrence of symptoms, highlighting the high risk of relapse with re-exposure to the drug. This finding underscores the high risk of relapse with rechallenge and suggests that rechallenging with dasatinib should be avoided once chylothorax has developed. In refractory cases, additional therapeutic approaches have been described. For instance, a single case report documented the use of Goreisan combined with diuretics, which achieved control of dasatinib-induced chylothorax (Sasaki et al., 2019). Nevertheless, because of the concomitant treatment, the independent efficacy of Goreisan remains uncertain and warrants further evaluation.

In conclusion, dasatinib-induced chylothorax is a rare but serious complication that requires early recognition and prompt management. Discontinuation of dasatinib, combined with appropriate supportive therapies, remains the cornerstone of treatment. The high risk of recurrence upon rechallenge underscores the need for caution when considering re-exposure to the drug. Further research is needed to explore alternative treatment options and to understand the underlying mechanisms of this complication.