Exudative pleural effusion during sunitinib treatment.

Drug-induced pleural effusion is one of the rare causes of exudative pleural effusion and a high index of suspicion is necessary to lead to early diagnosis. We hereby present the case of a young male in his late 30s, known case of metastatic gastrointestinal stromal tumour on sunitinib therapy, who presented with right-sided mild pleural effusion. Diagnostic thoracentesis showed the effusion to be a monomorphic exudate with low adenosine deaminase, which was negative for malignant cells on cytopathology. A contrast-enhanced CT chest revealed an enlarged lymph node (LN) at the 4R station, cytological analysis of which was suggestive of reactive lymphoid hyperplasia. Infective workup of the LN aspirate and bronchoalveolar lavage taken from the right middle lobe was negative. After systematically excluding the usual causes of exudative pleural effusion, sunitinib was considered to be a possible cause and was, therefore, withheld. A repeat chest X-ray after 3 weeks of stopping the drug showed resolution of the pleural effusion.

An association between Dasatinib, elevated left atrial pressure and pleural effusion.

BACKGROUND: Tyrosine kinase inhibitors (TKI), such as Dasatinib, are effective in the treatment of chronic myeloid leukemia (CML) but associated with development of pleural effusions (PE). The relationship between haemodynamic parameters identified on transthoracic echocardiogram (TTE) such as elevated estimated left atrial pressure (LAP), and PE development is unknown. This study aims to describe associations between Dasatinib, elevated LAP and PE. METHODS: This was a retrospective study of 71 CML patients who underwent TTE during treatment with various TKIs. Descriptive analysis was performed to identify associations between TKI use, PE and elevated LAP on TTE. Multivariate logistic regression was performed to identify predictors of elevated LAP. RESULTS: There were 36 patients treated with Dasatinib, 15 Nilotinib, and 20 Imatinib. Those treated with Dasatinib had higher rates of elevated LAP (44% vs 7% Nilotinib vs 10% Imatinib, p < 0.01) and PE (39% vs 7% vs 0%, p < 0.01). In the 15 patients who developed PE, 14 (93%) patients were treated with Dasatinib. Patients with PE had higher rates of elevated LAP (67% vs 16%, p < 0.01). Nineteen (26.8%) patients in the entire cohort had elevated LAP. After multivariate adjustment, Dasatinib (OR 33.50, 95% CI = 4.99-224.73, p < 0.01) and age (OR 1.12, 95% CI = 1.04-1.20, p < 0.01) were associated with elevated LAP. CONCLUSIONS: Among patients with CML, there was an association between Dasatinib use, PE and elevated LAP on TTE. These findings are hypothesis generating and further studies are required to evaluate the utility of elevated LAP on TTE as a novel marker for prediction and surveillance of PE.

Analysis of invasive diagnostic techniques for pathological confirmation of pleural mesothelioma.

BACKGROUND AND OBJECTIVES: Mesothelioma is an infrequent neoplasm with a poor prognosis that is related to exposure to asbestos and whose peak incidence in Europe is estimated from 2020. Its diagnosis is complex; imaging techniques and the performance of invasive pleural techniques being essential for pathological confirmation. The different diagnostic yields of these invasive techniques are collected in the medical literature. The present work consisted of reviewing how the definitive diagnosis of mesothelioma cases in our centre was reached to check if there was concordance with the data in the bibliography. MATERIALS AND METHODS: Retrospective review of patients with a diagnosis of pleural mesothelioma in the period 2019-2021, analysing demographic data and exposure to asbestos, the semiology of the radiological findings and the invasive techniques performed to reach the diagnosis. RESULTS: Twenty-six mesothelioma cases were reviewed. 22 men and 4 women. Median age 74 years. 9 patients had a history of asbestos exposure. Moderate-severe pleural effusion was the most frequent radiological finding (23/26). The sensitivity of the invasive techniques was as follows: Cytology 13%, biopsy without image guidance 11%, image-guided biopsy 93%, surgical biopsy 67%. CONCLUSIONS: In our review, pleural biopsy performed with image guidance was the test that had the highest diagnostic yield, so it should be considered as the initial invasive test for the study of mesothelioma.

Incidence of pleural effusion with dasatinib and the effect of switching therapy to a different TKI in patients with chronic phase CML.

Dasatinib is one of the second generation tyrosine kinase inhibitors (TKI) which is approved for the treatment of patients with chronic phase CML (CP-CML) both in the front line and in the second line setting. Pleural effusion (PE) is a unique toxicity associated with dasatinib use. Our aim was to study the incidence of pleural effusion in our cohort of patients who were treated with dasatinib for CP-CML and the safety upon TKI switch. A total of 390 patients were treated with dasatinib during their course of treatment for CP-CML. A total of 69 patients (17.6%) developed any grade of PE. About 33 (48%) patients developed CTCAE grade 2 PE, 34 (49%) grade 3 and only 1 patient developed grade 4 PE. Recurrence of PE was observed in 34 (49%) patients. While only 12 patients (17.3%) continued using dasatinib after development of PE, dasatinib was discontinued in the other 57 patients. Therapy was switched to bosutinib in 13 patients out of which 6 (46%) patients re-developed PE. While only 12.5% patients developed re-accumulation of pleural fluid in patients switched to imatinib, none of the patients switched to nilotinib re-developed PE. A change in TKI to bosutinib was associated with a 46% risk of recurrence of PE in patients who develop PE on dasatinib for the treatment of CP-CML. The incidence of recurrent PE was markedly lower in patient switched to imatinib or nilotinib.

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.

Clinical impact of pleural fluid carcinoembryonic antigen on therapeutic strategy and efficacy in lung adenocarcinoma patients with malignant pleural effusion.

BACKGROUND/AIMS: Epidermal growth factor receptor (EGFR) mutation is important in determining the treatment strategy for advanced lung cancer patients with malignant pleural effusion (MPE). Contrary to serum carcinoembryonic antigen (S-CEA) levels, the associations between pleural fluid CEA (PF-CEA) levels and EGFR mutation status as well as between PF-CEA levels and treatment efficacy have rarely been investigated in lung adenocarcinoma patients with MPE. METHODS: This retrospective study enrolled lung adenocarcinoma patients with MPE and available PF-CEA levels and EGFR mutation results. The patients were categorized based on PF-CEA levels: < 10 ng/mL, 10-100 ng/mL, 100-500 ng/mL, and ≥ 500 ng/mL. The association between PF-CEA levels and EGFR mutation status as well as their therapeutic impact on overall survival was compared among the four groups. RESULTS: This study included 188 patients. PF-CEA level was found to be an independent predictor of EGFR mutation but not S-CEA level. The EGFR mutation rates were higher as the PF-CEA levels increased, regardless of cytology results or sample types. Among EGFR-mutant lung adenocarcinoma patients receiving EGFR-tyrosine kinase inhibitor (TKI) treatment, those with high PF-CEA levels had significantly better survival outcomes than those with low PF-CEA levels. CONCLUSION: High PF-CEA levels were associated with high EGFR mutation rate and may lead to a favorable clinical outcome of EGFR-TKI treatment in EGFR-mutant lung adenocarcinoma patients with MPE. These findings highlight the importance of actively investigating EGFR mutation detection in patients with suspected MPE and elevated PF-CEA levels despite negative cytology results.

Disseminated Cryptococcus neoformans presenting with an isolated pleural effusion in a patient receiving temozolomide and long-term steroids.

Cryptococcus neoformans is a ubiquitous environmental organism found worldwide. Infection with this organism occurs predominantly in immunocompromised hosts, including persons living with HIV or those with impaired cellular immunity. Cryptococcal pleural effusions have been described in cases with extensive pulmonary involvement. Here we present the case of a woman receiving temozolomide and steroids for glioblastoma multiforme, who developed cough and dyspnoea and was found to have an uncomplicated pleural effusion. Pleural fluid culture grew Cryptococcus neoformans with negative culture on bronchoalveolar lavage. High serum cryptococcal antigen titre of 1:64 prompted lumbar puncture which demonstrated positive cerebrospinal fluid for Cryptococcus neoformans She was treated with liposomal amphotericin B and flucytosine, followed by consolidation and maintenance therapy with fluconazole. Pleural involvement in the absence of pulmonary involvement has rarely been reported. We review pulmonary and radiographic manifestations of cryptococcal infection, when to assess for disseminated infection, and management principles.

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.

Recurrent pleural effusion as a rare manifestation after prolonged PD1 inhibitor (camrelizumab)-based immunotherapy: A case report.

Immune-related adverse events (irAEs) pose a significant challenge for the widespread adoption of immuno-oncology therapies, but their symptoms can vary widely. In particular, the relationship between irAEs and pleural effusion (PE) in patients with advanced non-small cell lung cancer (NSCLC) remains unclear. In this report, we present the case of an advanced NSCLC patient who developed persistent PE despite receiving camrelizumab (an anti-programmed death receptor 1 [PD-1] antibody) and chemotherapy as first-line treatment. While the patient's tumor biomarkers decreased after multiple cycles of treatment, the PE persisted despite negative findings on cytology and pleural biopsy. Additionally, the use of anti-angiogenic drugs failed to alleviate the PE. Screening for rheumatic connective tissue markers and tuberculosis yielded negative results, but intrathoracic dexamethasone injections in two doses resulted in a significant reduction of the PE. This case suggests that PE may represent a rare type of irAE that should be monitored for during prolonged immuno-oncology therapy.

An Analysis of Dasatinib Treatment Patterns in Patients with Chronic Myeloid Leukemia after Experiencing Pleural Effusion during Dasatinib Therapy.

INTRODUCTION: Treatment with dasatinib for chronic myeloid leukemia (CML) has been associated with development of pleural effusion; however, data regarding its optimal management are limited. We examined treatment patterns and healthcare resource utilization (HCRU) and costs among patients with CML treated with dasatinib who experienced a subsequent pleural effusion. METHODS: Adults with CML and ≥1 pharmacy claim for dasatinib in 2015-2018 who experienced pleural effusion after dasatinib were identified using data from claims databases. RESULTS: Overall, 123 patients were eligible. After 1 year, of the 38.2% of patients with a dose modification, 72.3% did not switch treatment; among these patients, 70.6% continued treatment. Among patients with a stable dose after pleural effusion (61.8%), 57.9% later switched to another TKI. The mean (SD) duration of dasatinib treatment after pleural effusion was 262.0 (124.0) days for patients with a dose modification versus 149.1 (155.2) days for those with a stable dose (p < 0.001). HCRU and costs were similar between groups. CONCLUSION: Dasatinib dose modification after pleural effusion was not always required; however, patients with dose modifications continued therapy for a longer duration with a lower rate of switching to another TKI versus patients who remained on a stable dose.

Management and Risk Factors for Pleural Effusion in Japanese Patients with Chronic Myeloid Leukemia Treated with First-line Dasatinib in Real-world Clinical Practice.

Objective Pleural effusion (PE) is a common adverse event that occurs during dasatinib therapy for chronic myeloid leukemia (CML). However, the pathomechanism of PE and appropriate management of Asian patients with CML have not been elucidated. This study investigated the incidence rate, risk, and appropriate management of PE in Asian patients with CML treated with dasatinib. Methods We retrospectively collected data on patients in the chronic phase of CML who received first-line dasatinib therapy and were registered in the CML-Cooperative Study Group database. Patients We identified 44 cases of PE in a series of 89 patients and analyzed previously reported risk factors and effective management of PE. Results A univariate analysis revealed that age, diabetes mellitus, chronic renal failure, hypertension, the history of cardiovascular events, and dasatinib dose were significantly associated with PE. A multivariate analysis revealed that age ≥65 years old was the only independent risk factor for PE. Dasatinib dose reduction and switching to a tyrosine kinase inhibitor showed a statistically significant difference in effectively reducing PE volume compared to single diuretic use. Conclusion Although further studies are warranted, our observations showed that advanced age is a significant risk factor for PE, and tyrosine kinase inhibitor dose reduction or replacement of dasatinib may be an effective management strategy for PE in Asian CML patients who received first-line treatment with dasatinib in real-world clinical practice.

Development of a human herpesvirus 8-negative effusion-based lymphoma during treatment with dasatinib for chronic myeloid leukemia.

We present the case of an 85-year-old male patient diagnosed with human herpesvirus 8 (HHV8)-negative effusion-based lymphoma (EBL) that developed from long-lasting pleural effusion (PE) induced by dasatinib treatment for chronic myeloid leukemia (CML). After the onset of this disorder, dasatinib treatment was discontinued and drainage was performed to regress the effusion. The major molecular response (MMR) was thus lost. The patient did not tolerate nilotinib treatment, but bosutinib was successful in restoring MMR. During these clinical courses, the patient suffered from a recurrence of EBL, which was treated with rituximab-based chemotherapy. The PE sample just before the 3rd cycle of chemotherapy revealed the proliferation of CD57-positive T cells, along with the disappearance of lymphoma cells. Anti-tumor immunity may have been activated following the immunochemotherapy in the undisturbed immunological environment when both EBL and CML almost regressed. After four cycles of R-CVP therapy, the patient has been in remission for 16 months and no longer requires drainage.

Bosutinib-induced massive pleural effusion: Cross-intolerance with all tyrosine kinase inhibitors.

BACKGROUND: The discovery of tyrosine kinase inhibitors provided a breakthrough in the treatment of chronic myeloid leukemia. Nowadays, the management of tyrosine kinase inhibitor-related side effects is one of the important problems in chronic myeloid leukemia treatment. Grades 3-4 pulmonary toxicity; especially pleural effusion is mostly seen with dasatinib treatment but rarely seen with nilotinib and bosutinib. Development of cross-intolerance due to pleural effusion is not an expected situation. Pleural effusion related to tyrosine kinase inhibitors is mostly exudative in nature with abundant lymphocytes. CASE REPORT: Massive pleural effusion developed in a 59-year-old male patient with chronic myeloid leukemia, who was being treated with bosutinib. In the past, the patient had experienced massive pleural effusion also with dasatinib and nilotinib. The evaluation for differential diagnosis of pleural effusion did not reveal any additional malignancy. MANAGEMENT AND OUTCOME: After discontinuation of bosutinib and initiation of prednisolone, pleural effusion was totally resolved. Prednisolone was gradually discontinued and third-generation tyrosine kinase inhibitor ponatinib was started. After 12 months of follow-up, massive pleural effusion occurred again, leading to discontinuation of ponatinib. DISCUSSION: Cross-intolerance is an important problem in the tyrosine kinase inhibitor era. The significance of this case is the development of cross-intolerance to all second-generation tyrosine kinase inhibitors and furthermore to a third-generation tyrosine kinase inhibitor. Management strategies for pleural effusion and close follow-up are important.

Spontaneous regression of dasatinib-related primary effusion lymphoma-like lymphoma.

Primary effusion lymphoma-like lymphoma (PEL-LL) shows a unique clinical presentation, characterized by lymphomatous effusions in the body cavities. PEL-LL may be associated with hepatitis C virus infections and fluid overload states; and owing to its rarity, no standard therapies have been established. We report a case of a 55-year-old woman who developed PEL-LL during treatment with dasatinib, for chronic myeloid leukemia (CML). She presented to our hospital with dyspnea lasting for approximately a month and showed pericardial and bilateral pleural effusions. The pericardial effusion was exudative, and cytopathological and immunophenotypic examinations showed numerous CD 20-positive, large atypical lymphoid cells, which were also positive for the Epstein-Barr virus gene. No evidence of lymphadenopathy or bone marrow infiltration was found. We diagnosed PEL-LL, immediately discontinued dasatinib, and performed continuous drainage of the pericardial effusions. Complete response was achieved, and remission was maintained for 15 months. Two months after discontinuation of dasatinib, she was administered imatinib and a deep molecular response for the CML was maintained. PEL-LL occurring during dasatinib treatment is rare. We compared the results of previous reports with this case, and found that early diagnosis of PEL-LL, discontinuation of dasatinib, and sufficient drainage can improve the prognosis of PEL-LL.

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.

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.

A Case Report of Clozapine-induced Pleural Effusion in a 28-Year-Old Chinese Male.

Increasing reports have appeared of pleural effusion and peripheral eosinophilia associated with clozapine treatment. These reports describe the onset of pleural effusion from 2 to 5 weeks after initiation of clozapine. Here, we describe a case of a 28-year-old Chinese male who presented with pleural effusion and peripheral eosinophilia ∼17 weeks after initiation of clozapine. We discuss this delayed presentation and examine the potential significance of the patient's East Asian ethnicity. We recommend clinicians consider ethnicity and other factors that can affect the metabolism of clozapine when choosing a clozapine titration schedule and when monitoring during clozapine treatment.

Eosinophilic Pleural Effusion Induced by Paliperidone Palmitate: Case Report and Literature Review.

BACKGROUND: Eosinophilic pleural effusions are defined by an eosinophil count ≥ 10% in pleural fluid and represent approximately 10% of exudative pleural effusions. They are associated with a large spectrum of etiologies, both benign and malignant. Drug-induced eosinophilic pleural effusions remain rarely described. OBJECTIVE AND METHODS: After ruling out other causes with a careful diagnostic assessment, we retain paliperidone as the etiology, given the disappearance of the pleural effusion after drug discontinuation. RESULTS: We report the first case of eosinophilic pleural effusion induced by paliperidone palmitate treatment. CONCLUSION: After considering other etiologies, drug-induced eosinophilic pleural effusion should be sought.