Reversible Pulmonary Arterial Hypertension Associated with Dasatinib for Chronic Myeloid Leukemia

Abstract

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.

Keywords: Chronic myeloid leukemia; Dasatinib; Pulmonary arterial hypertension.

Fig. 1.

(A) The changes in clinical courses, cardiopulmonary parameters and treatment history in patient in case 1 are depicted over time. (B) The changes in parameters of in patient in case 2 are depicted over time. (C) Patient in case 1 had an elevated tricuspid regurgitation velocity (4.4 m/sec), consistent with pulmonary arterial hypertension (left). Four months after dasatinib discontinuation (right), there was an improvement of tricuspid regurgitation velocity (3.6 m/sec) in patient 1. NYHA, New York Heart Association; RVSP, right ventricular systolic pressure; G, grade; SF, sildenafil; TKI, thyrosine kinase inhibitor; HUR, hydroxyurea; IM, imatinib; Das, dasatinib; Pon, ponatinib; HR, hematologic response; CP, chronic phase; CHR, complete hematologic response; IS, international scale; Nil, nilitinib.