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A Strange Cause of Chylothorax– Dasatinib Induced

By September 4, 2018volume1-issue1
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Natraj.M et al.: A Strange Cause of Chylothorax– Dasatinib Induced

Case Report

A Strange Cause of Chylothorax– Dasatinib Induced

Natraj.M1, Dhanasekar2, Irfan Ismail Ayub3, Abdul Majeed Arshad4, Rajagopalan5, Chandrasekar6
1Senior Resident, 2Professor, 3Associate Professor, 4Assistant Professor, 5Professor, 6Prof. & HOD
Department of Chest & TB, SRMC & RI, Porur, Chennai

ABSTRACT:

Dasatinib is a potent second-generati on tyrosine kinase inhibitor for the treatment of chronic myeloid leukemia. Pulmonary side effects like pleural effusion due fluid retention are common. But dasatinib, causing chylothorax is very rarely reported. Exact mechanism along with clinical manifestations is very poorly understood. Here we report 35-year-old man presenting with chylothorax following with dasatinib use.

Keywords: Dasatinib, chylothorax, chronic myeloid leukemia
Corresponding Author: Dr. Natraj. M, Department of Chest & TB, Sri Ramachandra University, Porur, Chennai. Email: dr.natrajm@gmail.com

INTRODUCTION

Dasatinib is a highly potent small-molecule inhibitor of BCR-ABL and Src family tyrosine kinases, which is indicated for the treatment of adults with newly diagnosed chronic-phase chronic myeloid leukemia (CML), resistance or intolerance to prior CML therapy, or Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). Pleural effusion was a common complication in 14%-32% of all patients in clinical trials1 chylothorax have rarely been reported. The pathophysiology and management of chylothorax remain unclear

CASE REPORT

35 year old male patient who is a known case of chronic myeloid leukemia presented to our emergency department with complaints of dyspnea which was progressive for one month and cough which was non productive. He had no history of fever, chest pain, expectoration, loss of weight or loss appetite. Patient was started 11 months prior to the development of chylothorax, on Dasatinib (140mg/day), after the failure of using Imatinib for chronic myeloid leukemia.

Base line blood investigations including complete blood count, liver function test, renal function test, serum electrolytes were found to be normal. Peripheral smear did not show any blast cells. Chest X ray done showed features of right-sided massive effusion [FIG.1].

A pleural tap was done which showed chylous pleural effusion [FIG.2] containing Triglycerides – 1280mg/dl, Amylase- 48, cholesterol – 71, sugar 132, protein – 5.4, LDH – 1184, ADA – 11.30 and Ether clearance test was done and showed no clearance. There was no bacterial growth and no malignant cells on cytological examination. Flowing which dasatinib was stopped for a period of 2 months. Repeat chest x ray showed good radiological clearance with no reoccurrence.

Following pleural fluid aspiration and obtaining the analysis, Dasatinib was stopped and patient was reviewed with repeat chest X ray that showed good clearance [FIG.3].

After getting medical oncology patient was started on low dosage of Dasatinib, repeat chest radiograph after 1year [FIG.4] showed no recurrence of chylothorax.

DISCUSSION

Chronic Myeloid Leukemia is a type of cancer that involves the hematopoietic stem cells and results in an increase in both myeloid and erythoid cells and platelets in peripheral blood and marked hyperplasia in bone marrow. The basic pathogenesis is unregulated signal transduction by a tyrosine kinase. Imatinib is the drug of choice for CML; but with the observed rise in resistance, Dasatinib is used. 1, 2, 3 Dasatinib, an ABL-kinase inhibitor has the benefit of binding to both active and inactive conformations of ABL kinase receptor site. 4, 5, 6 Dasatinib induced pleural effusions are reported in 14% to 30 % of patients in the accelerated phase and 28% in myeloid phase. 7, 8

Dasatinib induced pleural effusions are attributed to multiple causes, the most common cause being off target kinase inhibition. This potently inhibits platelet derived growth factor receptor beta, which is expressed in pericytes and responsible for angiogenesis. 9 Another explanation is that Dasatinib inhibits tyrosine kinase overexpression in capillaries of pulmonary vasculature and pleural epithelium. 10 In a multivariate analysis study done earlier, it was shown that Dasatinib induced pleural effusion depends on the dose schedules. 11, 12

Dasatinib induced pleural effusion is common; but the development of chylothorax is not very common and the mechanism behind the fact is a lymphatic obstruction. 13 Management of Dasatinib induced chylothorax is thoracentesis, Dasatinib should be discontinued and a short course of diuretics may be used.

REFERENCES

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  11. Hochhaus A, Kim, DW, Rousselot, P, et al: Dasatinib (SPRYCEL) 50mg or 70mg BID versus 100mg or 140mg QD in patients with chronic myeloid leukemia in chronic phase (CML- CP) resistant or intolerant to imatinib: Results of the CA180-034 study. Blood 108, 2006 (abstr 166)
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