Cancer Research and Treatment

Case Report

Reversible Pulmonary Arterial Hypertension Associated with Dasatinib for Chronic Myeloid Leukemia: Ji Hyung Hong, Sung-Eun Lee, Soo Young Choi, Soo-Hyun Kim, Eun-Jung Jang, Ju-Hee Bang, Jin Eok Park, Hye-Rim Jeon, Yun Jeong Oh, Jeong-Eun Yi, Hae Ok Jung, Ho Joong Youn, Dong-Wook Kim; Cancer Res Treat. 2015;47(4):937-942. Published online November 17, 2014; DOI: https://doi.org/10.4143/crt.2013.155

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.

Citations

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Original Article

Coexisting with Clonal Evolution and BCR-ABL Mutant in CML Patients Treated with Second-generation Tyrosine Kinase Inhibitors Predict the Discrepancy of in vitro Drug Sensitivity: Jae-Sook Ahn, Yeo-Kyeoung Kim, Se Ryeon Lee, Li Yu, Deok-Hwan Yang, Sang-Hee Cho, Hyun Jeong Shim, Woo Kyun Bae, Je-Jung Lee, Ik-Joo Chung, Myung Gun Shin, Hyeoung-Joon Kim; Cancer Res Treat. 2010;42(1):37-41. Published online March 31, 2010; DOI: https://doi.org/10.4143/crt.2010.42.1.37

Abstract PDF PubReader ePub

Purpose

Second-generation tyrosine kinase inhibitors (second TKIs) such as nilotinib and dasatinib control the activity of most ABL kinase domain mutations observed in patients with imatinib resistance. Although in vitro data show that both agents can inhibit all mutations except T315I, some discrepancies have been observed in a small subset of mutation clones. Cytogenetic clonal evolution is the important resistance mechanism of chronic myeloid leukemia (CML). Accordingly, we observed the clinical significance of coexisting with clonal evolution and BCR-ABL mutant in CML patients treated with second TKIs.

Materials and Methods

We monitored BCR-ABL transcript kinetics, interrelationship of clones expressing non-mutated and mutant transcripts and clonal aberrations within Philadelphia (Ph) positive and negative clones, respectively, in eight patients with CML receiving dasatinib or nilotinib for 3~41 months.

Results

Clinical responses were correlated with in vitro sensitivity of the BCR-ABL mutants to the second TKIs in four patients. Four patients showed resistance to the second TKIs as compared to in vitro observations; three of them developed chromosomal abnormalities in the Ph chromosome positive or negative metaphases. Another patient lost the original mutation but acquired a more resistant new mutation and became resistant to the second TKI.

Conclusion

Cytogenetic clonal evolution is an independent poor prognostic factor in CML, which could explain the onset of mechanisms for second TKIs resistance to ABL kinase domain mutations. The results indicate that an additional evaluation of chromosomal abnormalities is warranted when BCR-ABL mutants are more resistant than indicated by in vitro data.

Citations

Citations to this article as recorded by

T315I – a gatekeeper point mutation and its impact on the prognosis of chronic myeloid leukemia
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Impacto de la mutación T315I en el pronóstico de la leucemia mieloide crónica
Bushra Kaleem, Sadaf Shahab, Tahir Sultan Shamsi
Advances in Laboratory Medicine / Avances en Medicina de Laboratorio.2024; 5(4): 418. CrossRef
BCR-ABL1 mutation development during first-line treatment with dasatinib or imatinib for chronic myeloid leukemia in chronic phase
T P Hughes, G Saglio, A Quintás-Cardama, M J Mauro, D-W Kim, J H Lipton, M B Bradley-Garelik, J Ukropec, A Hochhaus
Leukemia.2015; 29(9): 1832. CrossRef

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