SYMPTOMATIC RECURRENT BILATERAL PLEURAL EFFUSIONS REQUIRING REPEATED THERAPEUTIC THORACENTESIS IN ESRD ON MAINTENANCE HEMODIALYSIS: IS THIS PULMONARY HYPERTESNION, HYPERVOLEMIA OR IS IT DASATINIB-ASSOCIATED ADVERSE REACTION?

Dasatinib, a second-generation tyrosine kinase inhibitor (TKI), has proven to be effective for the long-term treatment of chronic myeloid leukemia (CML), both as initial and subsequent lines of therapy. Pleural effusion is an adverse event that has been reported more commonly with Dasatinib than with other TKIs in patients with leukemia. Dasatinib use can result in pleural effusion in some patients, occurring at any time during treatment and commonly characterized as mild to moderate in severity. Early identification of symptoms is essential in the proper management of pleural effusion. Prompt confirmation of diagnosis and management of pleural effusion can minimize morbidity and maximize the ability to preserve long-term clinical benefits with Dasatinib. We encountered an 87-yo male with ESRD on maintenance hemodialysis since 2016, who in the past 8 months had required repeated bilateral therapeutic paracentesis for recurrent symptomatic bilateral pleural effusions despite regular thrice weekly hemodialysis with ultrafiltration, and without concurrent excessive inter-dialytic weight gains. The question arose whether these recurrent pleural effusions were secondary to ESRD-associated hypervolemia, newly evident pulmonary hypertension, or Dasatinib-associated adverse reaction even though he had been on the TKI, Dasatninib, since 2015. 

Case Report.

An 87-yo male patient with oligo-anuric ESRD on maintenance hemodialysis since February 2016, with additional medical history for atrial fibrillation and heart failure with preserved ejection fraction, was diagnosed in November 2007 with chronic myeloid leukemia (CML) with initial WBC count of 373.60 (4.0 – 10.4) K/cmm. He had responded to imatinib, a TKI, and was in remission while on Imatinib through 2016-2017. He experienced a recurrence in early 2017 while on Imatinib and was started on Dasatinib, 20 mg daily, a second generation TKI. He had done generally well on hemodialysis and in the last few years had to dialyze via a left thigh AV graft. In late 2021, he started intra-dialytic parenteral nutrition (IDPN) for malnutrition with hypoalbuminemia. In March 2022, he was diagnosed with right-sided community-acquired pneumonia that was complicated by right pleural effusion that required therapeutic thoracentesis of 1.5 liters of serosanguinous fluid with 3.4 g/dL of total protein. This was regarded as a para-pneumonic pleural effusion. Over the next 32 months, he continued to do well on maintenance thrice weekly hemodialysis + thrice weekly IDPN supplementation, without any respiratory problems. Then in November 2024, he developed progressive dyspnea and was shown to have bilateral pleural effusions. 

He required bilateral ultrasound-guided bilateral therapeutic thoracentesis with 1.4 liters of yellow clear fluid removed from the right pleural space and 600 cc of yellow clear fluid removed from the left pleural space, with symptomatic relief (FIGURE 1). 

A subsequent echocardiogram in March 2025 revealed LVEF 55%-60%, normal sized right atrium, normal sized IVC with normal right atrial pressure of 0-5 mm Hg but with pulmonary hypertension, pulmonary artery pressure of ≥ 50 mm Hg. There was no pericardial effusion. He subsequently since then has required repeated ultrasound-guided bilateral therapeutic thoracenteses for recurring symptomatic bilateral pleural effusions in May 2025, again in early July 2025, and again in the last week of July 2025. Of note, NT Pro BNP levels had increased to 47,500 pg/mL in May 2025 and was 91,300 pg/mL in July 2025. Efforts were increased to achieve higher net ultrafiltration goals during hemodialysis to mitigate these recurrences. At each of these times, chest radiographs were confirmatory for the recurring bilateral effusions (FIGURE 2). The volumes of pleural fluid removed at all four procedures appear in Table 1. 

In late July 2025, he was admitted for chills, feeling unwell and altered mental status, a day following the last thoracentesis procedure. Dasatinib administration was suspended. At the same time, Oxybutynin, which was started about 6 weeks earlier for painful dysuria was discontinued as the suspected cause of the confused mental state. He has since been doing well, not confused and not short of breath, and is back to his thrice weekly in-center outpatient maintenance hemodialysis.

With the advent of BCR-ABL1 tyrosine kinase inhibitors (TKIs), chronic myeloid leukemia (CML) is now a manageable disease with the possibility of near-normal life expectancy. Dasatinib, a second-generation TKI, has proven to be effective for the long-term treatment of CML, both as initial and subsequent lines of therapy. Pleural effusion is an adverse event that has been reported more commonly with Dasatinib than with other TKIs in patients with leukemia. Dasatinib use can result in pleural effusion in some patients, occurring any time during treatment and commonly characterized as mild to moderate in severity. With adequate clinical management (including dose interruptions, dose reductions, and pharmacologic interventions), discontinuation of Dasatinib owing to the related pleural effusions was necessary in a minority of patients with chronic myeloid leukemia in chronic phase (CML-CP) in both the DASatinib versus Imatinib Study In treatment-Naïve CML patients (DASISION) trial and the CA180-034 study, a phase III dose-optimization trial that evaluated 4 Dasatinib dosing regimens in imatinib-resistant or -intolerant patients with CML in chronic phase. Medium to large pleural effusions will require therapeutic paracentesis and other etiologic processes must be ruled out as the cause of the pleural effusions. If thoracentesis is performed, then measurements of total protein, lactate dehydrogenase, cell count with differential, cytology, and microbiology can and should be obtained, to determine the origin of the effusion. During the 5-year follow-up period in DASISION, 6% of Dasatinib-treated patients discontinued therapy owing to drug-related pleural effusion of any grade. Although the mechanism of Dasatinib-related pleural effusion is not clearly understood, it has been speculated that this adverse event may be immune-mediated, based on reports of high lymphocyte counts, often of a natural killer cell phenotype, in pleural fluid and tissue. The role of diuretics and steroids in the management of Dasatinib-related pleural effusions, although commonly used for this purpose, is unclear, and studies to elucidate their clinical benefit are needed.

Very importantly, it must be acknowledged that pleural effusion can occur at any time during treatment with Dasatinib. For example, in DASISION, the median time to first grade 1/2 pleural effusion was 114 weeks (range, 4-299 weeks). Therefore, for all patients on Dasatnib, there must remain a watchful observation for the occurrence of pleural effusions and when they occur, to be promptly managed. Given the rapid recurrence of symptomatic bilateral effusions in our patient in 2025, with no evidence for significant volume overload (weight + physical exam), and although there may be some contribution from pulmonary hypertension as manifested by the cardiac echo data, we submit that our patient’s recurrent bilateral pleural effusions are more likely secondary to Dasatinib, even after several years of being on the drug for CML. Following the latest admission to the hospital in late July 2025, Dasatinib was withheld, pending further review.

There was no evidence supporting severe decompensated RV failure such as worsening symptomatic right heart failure from pulmonary hypertension and he exhibited no hepatomegaly, a pulsatile or tender liver, new peripheral edema or ascites. His inter-dialytic weight gains did not change, and he had continued to tolerate the thrice weekly IDPN infusions for nutrition support. While awaiting follow up results following the discontinuation of Dasatinib in late July 2025, we strongly posit that our patient’s recurrent symptomatic bilateral pleural effusions despite repeated monthly bilateral therapeutic thoracentesis where upwards of 0.5 – 1.5 liters of pleural fluid were repeatedly removed from each lung respectively, were secondary to Dasatininb adverse reactions. As shown in previous Phase 3 drug trials, such pleural effusions could occur after several years on Dasatininb. Our patient started Dasatinib for CML in early 2017 and only started exhibiting such recurrent pleural effusions in November 2024, over 7 years later. Coincidentally, the altered mental status had occurred about 6 weeks after starting Oxybutynin and this has since resolved since the drug was also discontinued at the last admission in late July 2025. As at last review in early August 2025, the patient is feeling better, much improved, not short of breath, and no longer confused. This is a lesson for providers when considering adverse drug reactions and the timing of drug initiation.