sildenafil-citrate and Leukemia--Myelogenous--Chronic--BCR-ABL-Positive

We describe two cases of pulmonary arterial hypertension (PAH) that occurred under dasatinib treatment and were resolved after dasatinib discontinuation. Two patients with chronic phase chronic myeloid leukemia (CML) were switched to dasatinib therapy because of hematological progress while receiving imatinib. These patients had New York Heart Association (NYHA) functional class II dyspnea with elevated right ventricular systolic pressure (RVSP), which progressed under dasatinib treatment. After dasatinib treatment was discontinued, subjective symptoms were improved to NYHA functional class I and the follow-up transthoracic Doppler echocardiography showed improved RVSP. Treatment with an alternate tyrosine kinase inhibitor was initiated and had been continued without development of dyspnea or elevation of RVSP. This report suggests that dasatinib can cause the reversible PAH, therefore, routine cardiopulmonary evaluation before and during treatment with dasatinib may be needed in CML patients with clinical manifestations.

Topics: Adult; Antihypertensive Agents; Antineoplastic Agents; Calcium Channel Blockers; Dasatinib; Diuretics; Humans; Hypertension, Pulmonary; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Middle Aged; Sildenafil Citrate; Vasodilator Agents

Pulmonary arterial hypertension and secondary pleural effusion have been reported in association with long-term therapy with the multi-tyrosine kinase inhibitor dasatinib, approved for the treatment of chronic myeloid leukemia. Here, we present the case of a 50-year-old man, diagnosed with chronic myeloid leukemia in August 2003, who developed pulmonary arterial hypertension after > 4 years of treatment with dasatinib. The complete remission of pulmonary arterial hypertension following dasatinib discontinuation suggests an etiological role of the drug in its development, although the administration of sildenafil may have played a therapeutic role.

Topics: Dasatinib; Humans; Hypertension, Pulmonary; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Middle Aged; Phosphodiesterase 5 Inhibitors; Piperazines; Protein Kinase Inhibitors; Purines; Pyrimidines; Sildenafil Citrate; Sulfones; Thiazoles

We present a case of pulmonary arterial hypertension (PAH), which is potentially related to treatment with dasatinib (Sprycel(®)). A 61-year-old woman, who had been treated with dasatinib for 27 months for chronic myeloid leukemia (CML), visited our hospital complaining of dyspnea. In right heart catheterization, her mean pulmonary arterial pressure was 35 mmHg. After other possible etiologies to cause PAH were excluded, the patient was diagnosed as a dasatinib-related PAH. As notified by U.S. Food and Drug Administration (FDA) in October 2011, we recommend routine cardiopulmonary evaluation before and during treatment with dasatinib in CML patients in terms of the adverse effects of PAH.

Topics: Dasatinib; Echocardiography; Electrocardiography; Familial Primary Pulmonary Hypertension; Female; Humans; Hypertension, Pulmonary; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Middle Aged; Piperazines; Protein Kinase Inhibitors; Purines; Pyrimidines; Sildenafil Citrate; Sulfones; Thiazoles; Treatment Outcome; Vasodilator Agents; Withholding Treatment