Everolimus-Related Chylothorax: A Rare Case Report.

Everolimus is an orally administered mechanistic target of rapamycin inhibitor in solid-organ transplant patients. In addition to the common adverse side effects of this treatment, such as hyperlipidemia, rash, stomatitis, anorexia, diarrhea, anemia, thrombocytopenia, and leukopenia, pulmonary toxicity is also an important adverse side effect. Although pulmonary toxicity due to everolimus has been reported mostly as pneumonitis, cases of pleural effusion due to everolimus have also been reported rarely. Chylothorax is defined as the accumulation of lymphatic fluid in the pleural space. It may develop secondary to trauma or malignancy. In this case report, we present a patient with chylothorax after everolimus treatment.

Drug-induced chylothorax as a rare pleural complication in dasatinib therapy for chronic myeloid leukaemia.

Chylothorax is a lymphatic chylous pleural effusion typically associated with traumatic (iatrogenic, non-iatrogenic) and non-traumatic (infections, malignancy, lymphatic disorders) aetiologies. Drug-induced chylothorax is uncommon and mostly reported in association with BCR-ABL tyrosine kinase inhibitor therapy.

Fluid retention-associated adverse events in patients treated with BCR::ABL1 inhibitors based on FDA Adverse Event Reporting System (FAERS): a retrospective pharmacovigilance study.

OBJECTIVES: This study aimed to conduct a thorough analysis of fluid retention-associated adverse events (AEs) associated with BCR::ABL inhibitors. DESIGN: A retrospective pharmacovigilance study. SETTING: Food and Drug Administration Adverse Event Reporting System (FAERS) database for BCR::ABL inhibitors was searched from 1 January 2004 to 30 September 2021. MAIN OUTCOME MEASURES: Reporting OR (ROR) and 95% CI were used to detect the signals. ROR was calculated by dividing the odds of fluid retention event reporting for the target drug by the odds of fluid retention event reporting for all other drugs. The signal was considered positive if the lower limit of 95% CI of ROR was >1. The analysis was run only considering coupled fluid retention events/BCR::ABL inhibitors with at least three cases. RESULTS: A total of 97 823 reports were identified in FAERS. Imatinib had the most fluid retention signals, followed by dasatinib and nilotinib, while bosutinib and ponatinib had fewer signals. Periorbital oedema (ROR=24.931, 95% CI 22.404 to 27.743), chylothorax (ROR=161.427, 95% CI 125.835 to 207.085), nipple swelling (ROR=48.796, 95% CI 26.270 to 90.636), chylothorax (ROR=35.798, 95% CI 14.791 to 86.642) and gallbladder oedema (ROR=77.996, 95% CI 38.286 to 158.893) were the strongest signals detected for imatinib, dasatinib, nilotinib, bosutinib and ponatinib, respectively. Pleural effusion, pericardial effusion and pulmonary oedema were detected for all BCR::ABL inhibitors, with dasatinib having the highest RORs for pleural effusion (ROR=37.424, 95% CI 35.715 to 39.216), pericardial effusion (ROR=14.146, 95% CI 12.649 to 15.819) and pulmonary oedema (ROR=11.217, 95% CI 10.303 to 12.213). Patients aged ≥65 years using dasatinib, imatinib, nilotinib or bosutinib had higher RORs for pleural effusion, pericardial effusion and pulmonary oedema. Patients aged ≥65 years and females using imatinib had higher RORs for periorbital oedema, generalised oedema and face oedema. CONCLUSIONS: This pharmacovigilance study serves as a clinical reminder to physicians to be more vigilant for fluid retention-associated AEs with BCR::ABL inhibitors.

Dasatinib-induced Chylothorax in Chronic Myeloid Leukemia.

Dasatinib is a potent second-generation tyrosine kinase inhibitor (TKI) used in the first- and second-line treatment of chronic myeloid leukemia (CML). Chylothorax is a rare presentation that results in chyle leakage from the lymphatic system into the pleural space as a consequence of thoracic duct damage. Pleural effusion has been reported frequently in patients treated with Dasatinib however chylothorax has been rarely reported. Here we report an 18year old female presenting with chylothorax after 63 months of Dasatinib intake along with a review of the relevant literature. Currently there are no standard guidelines regarding the approach to chylothorax management after the initial discontinuation of Dasatinib. Since the TKI options after stopping Dasatinib are limited, and most patients would have already failed the trial of first generation TKI, we suggest implementing a complete treatment strategy for this patient population. Key words: chronic myeloid leukemia, Dasatinib, Pleural effusion, Chylothorax.

Diagnostic Pitfalls of Chylothorax After Dasatinib Treatment of Chronic Myeloid Leukemia.

BACKGROUND Chronic myeloid leukemia (CML) is a myeloproliferative malignancy generally treated with Dasatinib, a tyrosin-kinase inhibitor. Pleural effusions are a known adverse effect, but only 0.8% of patients develop pleural effusions after 6 years of use. Recent case reports have implicated Dasatinib as a rare cause of chylothorax. CASE REPORT We describe a woman in her 30's with a history of chronic myeloid leukemia, who had been taking Dasatinib for 10 years and presented to the Emergency Department after a chest X-ray revealed bilateral pleural effusions in the setting of worsening dyspnea on exertion for 6 months. She had previously received radiotherapy at age 11 prior to an allogenic bone marrow transplant nearly 30 years prior. Thoracentesis removed 900 cc of chylous fluid, and flow cytometry and cultures found no evidence of infection or malignancy. Dasatinib was discontinued, and she was treated with diuretics, steroids, and a low-fat diet. The effusions reaccumulated twice in the following month and required 2 additional thoracenteses and courses of steroids. Months later, the bilateral chylous effusions recurred, and MR lymphangiogram demonstrated 2 thoracic duct tears. CONCLUSIONS While previous reports have indicated that Dasatinib can rarely cause chylous pleural effusions, it is unlikely after 5 years of use, and other etiologies must be considered by clinicians. Initial misattribution to Dasatinib alone can delay further necessary investigations, including lymphangiography. In our patient, it is more likely that other factors contributed to her chylothorax, including her previous radiotherapy 30 years prior, given her recurrence of chylous effusions following cessation of the medication.

Pazopanib-induced chylothorax in a patient with renal cell carcinoma.

Pazopanib is an oral multi-kinase inhibitor approved for the treatment of advanced renal cell carcinoma (RCC). It is an anti-angiogenic agent, which blocks the activation signaling pathways of tyrosine kinases and prevents the activities of primarily vascular endothelial growth factor receptors (VEGFR)-2 and VEGFR-3, which are important in lymphangiogenesis. Herein, we report a patient with advanced RCC who developed asymptomatic left-sided chylothorax under pazopanib therapy. Chylothorax developed in the 16th month and gradually increased until it was diagnosed by thoracentesis in the 22nd month. The development of chylothorax was attributed to pazopanib therapy after ruling out all possible traumatic and nontraumatic etiologies. The 'Adverse Drug Reaction Probability Scale' revealed a total score of 6, which fell into 'probable' category. Chylothorax regressed significantly 5 weeks after the discontinuation of pazopanib therapy.

Quilotórax espontáneo secundario a dasatinib / Chylothorax Secondary to Dasatinib

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Dasatinib-induced chylothorax: report of a case and review of the literature.

Dasatinib is a tyrosine kinase inhibitor for the treatment of BCR-ABL-positive chronic myeloid leukaemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukaemia (ALL). Although fluid retention is a common adverse event associated with dasatinib, chylothorax is exceptionally rare. The pathological mechanism, clinical manifestation and management of dasatinib-induced chylothorax are completely unclear. A 71-year-old man treated with dasatinib for CML was admitted for progressive dyspnea. Computed tomography (CT) showed a pleural effusion that was more prominent on the right thoracic cavity. Thoracentesis showed thick milky pleural fluid, which was then confirmed as chylothorax by chylum qualitative tests and triglyceride measurements. Radionuclide lymphoscintigraphy yielded an obstruction at the end segment of the thoracic duct, but no leakage points were found. After excluding common causes, drug-induced chylothorax was presumed. Then, dasatinib was withdrawn, and 1 week later, chylothorax resolved. To further elucidate the relationship between the medication and chylothorax, dasatinib was resumed tentatively for 2 days. As expected, pleural effusion recurred soon. Based on these clinical manifestations, the diagnosis of dasatinib-induced chylothorax was identified. The patient was suggested to stop dasatinib and use an alternative drug as recommended by the haematologist. Pleural effusion is the common adverse reaction of dasatinib, but chylothorax is rare. Only six cases of dasatinib-induced chylothorax have been reported, and our patient is the seventh case. Once a patient with dasatinib treatment develops chylothorax, dasatinib should be considered one of the possible causes. If no other definitive aetiological factor is identified, dasatinib discontinuation might be the optimum scheme.

Dasatinib-induced Chylothorax in Chronic Myelogenous Leukemia in Pediatric Patient: Report of a Case and Review of Literature.

Dasatinib is a second-generation potent and efficacious oral tyrosine kinase inhibitor frequently used for imatinib-resistant or intolerant BCR-ABL-positive chronic myeloid leukemia and for Philadelphia chromosome-positive acute lymphocytic leukemia. Dasatinib is known to cause adverse pulmonary events such as chylothorax and has been described in the adult literature but not pediatric literature. The authors present a pediatric case of dasatinib-related chylothorax, subsequent management, and a review of the literature of adult cases with dasatinib-related chylothorax.

Chylothorax: complication attributed to dasatinib use.

A 63-year-old woman with a medical history of chronic myelogenous leukaemia treated with dasatinib, chronic obstructive pulmonary disease and heart failure with preserved ejection fraction presented with difficulty in breathing. Chest X-ray showed large right-sided pleural effusion, which was confirmed on a CT angiogram of the chest. Echocardiogram showed an ejection fraction of 61% with moderate to severely dilated right ventricle and right ventricular systolic pressure of 60 mm Hg. Diagnostic and therapeutic thoracentesis was performed, and 2.2 L of pleural fluid was removed. Pleural fluid analysis was consistent with chylothorax. Significant symptomatic improvement was noted after thoracentesis. In the absence of an alternate explanation, chylothorax was attributed to dasatinib, which was switched to nilotinib. This resulted in resolution of her pleural effusions.

Successful Control of Dasatinib-related Chylothorax by the Japanese Herbal Medicine "Goreisan".

Dasatinib-related chylothorax is a rare adverse event, and the mechanism underlying its occurrence is still not fully understood. We herein report the case of a 73-year-old woman with chronic myeloid leukemia (CML) who developed dasatinib-related chylothorax refractory to conventional treatments, except for steroids. To the best of our knowledge, this is the first case of dasatinib-related chylothorax which was successfully controlled by combining diuretics with the Japanese herbal medicine "Goreisan." "Goreisan" is known to inhibit aquaporin channels and regulate the water flow. Our findings showed that "Goreisan" is an effective treatment option for uncontrollable dasatinib-related chylothorax.

[Chylothorax Related with Dasatinib in the Treatment of Chronic Myeloid Leukemia: Report of 3 Cases].

OBJECTIVE: To study the clinical features and prognosis of chylothorax related with dasatinib in treatment of chronic myeloid leukemia(CML). METHODS: The clinical data from 3 cases of CML with chylothorax after the treatment with dasatinib were collected. The clinical characteristics were analyzed and compared in the light of published literatures. RESULTS: They were treated with imatinib 400 mg once daily after diagnosing the illness as CML. The patients achieved optimal response after switching to dasatinib 100 mg once daily when didn't resisted or endured to imatinib. However, the symptom of dyspnea occurred in the patient after dasatinib treatment for 8,19, and 24 months. The CT examination all showed pleural effusion. According to the results of the pleural effusion test, dasatinib-related chylothorax was diagnosed. Among them 1 case did not stop for dasatinib, only received the support treatment, up to now, the patient still in CMR. The effect of another case was not obvious after giving half dose of dasatinb. The symptoms was disappeared after stopping dasatinb, but there was still a small amount of pleural effusion. Currently, he was been given imatinib 400 mg once a day. The third case stopped taking dasatinib for 48 days, fasting for 35 days, supporting parenteral nutrition and basic therapy. Ligation of thoracic duct was also used to reduce pleural effusion. At present, the patient continued to dasatinib and the symptoms of chest distress disappeared, promising review to the hospital in 3 months. CONCLUSION: The second-generation TKI dasatinib can lead to serious chylothorax in treatment of CML, timely and appropriate intervention are necessary when finding early detection of lung symptoms.

A case of everolimus-associated chylothorax in a cardiac transplant recipient.

We herein report a case of putative everolimus-associated chylothorax in a cardiac transplant recipient. A 17-year-old Japanese boy with dilated cardiomyopathy and severe cardiac failure requiring left ventricular assist support was determined to be a cardiac transplant candidate in 1992. He underwent overseas heart transplantation in Houston, Texas in October 1992. He was subsequently treated with immunosuppression therapy: Cyclosporine (CSA), azathioprine, and prednisolone (PRD). After several acute rejection episodes requiring steroid therapy, intravascular ultrasonography revealed a moderate degree of transplant coronary arterial vasculopathy (TCAV) with 50% stenosis in 2003. He underwent coronary stenting twice; the immunosuppressive regimen was converted to CSA, mycophenolate mofetil, everolimus (EVL), and PRD in 2006. TCAV has not progressed since then. In October 2008, chest x-ray showed bilateral pleural effusion. As we thought that the pleural effusion was caused by cardiac dysfunction due to moderate mitral regurgitation and TCAV as well as renal impairment, he was treated with diuretics and digoxin. However, the pleural effusion progressed gradually associated with exertional dyspnea and moderate edema of his lower legs. Chest computed tomography showed massive bilateral pleural effusions without evidence of malignancy in 2011. A pleural tap in 2011 revealed chylothorax. Although mammalian target of rapamycin inhibitors were major drugs for lymphoangioleimyomatosis, we believed that the chylothorax was associated with EVL. EVL was discontinued in March 2011: the chylothorax spontaneously resolved in November 2011.

Ergotamine-associated valvulopathy with recurrent chylous pleural effusion.

We report a rare case of ergotamine-associated mitral stenosis in a 55-year-old woman who presented with recurrent chylous pleural effusion. Echocardiographic, gross, and microscopic features of the mitral valve were consistent with chronic ergotamine-induced valvulopathy. We conclude that medication-induced valvulopathy should be included in the differential diagnosis of valvular heart disease. In addition, cardiac function should be monitored before and during long-term therapy with ergotamine or ergotamine-derived dopamine agonists.

Acute sirolimus pulmonary toxicity in an infant heart transplant recipient: case report and literature review.

Sirolimus-associated pulmonary disease should be considered in the differential diagnosis of acute respiratory distress syndrome in transplant recipients receiving this drug. It represents a rare, potentially lethal, and yet reversible adverse effect. We report the case an infant who presented with acute respiratory distress 57 days after heart transplantation 3 days after starting sirolimus. The acute presentation and prompt resolution after discontinuation of this drug suggest a direct toxic effect to the lungs. To our knowledge, this is the first published pediatric description of this syndrome after heart transplantation.

[Analysis of patients of psoriasis coexisting with chylothorax].

Six patients diagnosed as Psoriasis with complication of chylothorax (3 of chylothorax, 3 of both chylothorax and chyloperitoneum, age from 21 to 50, male 4, female 2) were reported. All patients have a history of taking a chinese medicine named "complex Wulong powder" for treating psoriasis. All patients have not the history of trauma, operation, and the history of living in epidemic focus of filariasis. Their X-ray exam and CT exam of chest did not show lung lesion but pleural effusion. Chylothorax coexisting with psoriasis was not found in literature. This result suggests that using complex WuLong powder might be the cause of chylothorax. The mechanism was unknown.