Literature DB >> 35402127

Effective collaboration between hematologists and cardiologists facilitated successful control of reversible dasatinib-related pulmonary arterial hypertension and treatment-free remission of chronic myeloid leukemia: a case report.

Zhensheng Hua1, Takuya Oyakawa2, Aya Ebihara3, Yasuhito Terui4, Taro Shiga5.   

Abstract

The BCR-ABL1 tyrosine kinase inhibitor dasatinib is effective in chronic myeloid leukemia (CML) treatment. The major known adverse effects of dasatinib include pleural effusion and pulmonary arterial hypertension (PAH); however, the underlying mechanisms remain unclear. This case report describes a two-step dasatinib dose reduction decided by multi-disciplinary collaboration between cardiologists and hematologists for the management of PAH that led to treatment-free remission (TFR), suggesting an important improvement in the field. Herein, a 43-year-old woman with CML was administered 100 mg of dasatinib daily as a first-line therapy from May 2014. There were no evident abnormalities on her electrocardiogram and transthoracic echocardiography (TTE) charts before she started taking dasatinib. She developed leg edema in June 2015, and the TTE showed a high transtricuspid pressure gradient value. Based on these findings, we diagnosed PAH and right-sided heart failure due to dasatinib. However, since it was confirmed that the molecular response (MR4.5) (International Scale: BCR-ABL1IS ≤ 0.0032%) was sustained, the hematologist decided to reduce the dasatinib dose to 70 mg after thorough deliberations with the cardiologists. After the dose reduction, the PAH improved immediately; however, it was observed again in 2017, which improved with a second dose reduction to 50 mg. Additionally, cardiovascular drug therapy was initiated. The PAH was exacerbated again in 2018 with sustained MR4.5. Hence, we decided to discontinue dasatinib as the MR4.5 had been sustained over 4 years. After the discontinuation of dasatinib, PAH improved again, and near MR4.0 (BCR-ABL1IS ≤ 0.01%) level has been sustained for several years now. Thereafter, no apparent deterioration in PAH was observed. We present a case of reversible dasatinib-induced PAH. Successful management of recurrent PAH was possible with several dose reductions, and TFR was achieved. This was partly due to effective collaboration between the hematologists and cardiologists. If needed, dose reduction as a treatment strategy may be considered before discontinuing dasatinib.
© The Author(s) under exclusive licence to The Japan Society of Clinical Oncology 2022.

Entities:  

Keywords:  Chronic myeloid leukemia; Dasatinib; Multi-disciplinary collaboration; Pulmonary arterial hypertension; Treatment-free remission; Tyrosine kinase inhibitor

Year:  2022        PMID: 35402127      PMCID: PMC8938585          DOI: 10.1007/s13691-022-00537-y

Source DB:  PubMed          Journal:  Int Cancer Conf J        ISSN: 2192-3183


  10 in total

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Authors:  Lawrence G Rudski; Wyman W Lai; Jonathan Afilalo; Lanqi Hua; Mark D Handschumacher; Krishnaswamy Chandrasekaran; Scott D Solomon; Eric K Louie; Nelson B Schiller
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Review 2.  Pulmonary arterial hypertension induced by tyrosine kinase inhibitors.

Authors:  Jason Weatherald; Marie-Camille Chaumais; David Montani
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3.  Reversible pre-capillary pulmonary hypertension due to dasatinib.

Authors:  Herminia L Buchelli Ramirez; Celso M Álvarez Álvarez; José J Rodríguez Reguero; Marta M García Clemente; Pere Casan Clarà
Journal:  Respir Care       Date:  2013-10-22       Impact factor: 2.258

4.  CARE guidelines for case reports: explanation and elaboration document.

Authors:  David S Riley; Melissa S Barber; Gunver S Kienle; Jeffrey K Aronson; Tido von Schoen-Angerer; Peter Tugwell; Helmut Kiene; Mark Helfand; Douglas G Altman; Harold Sox; Paul G Werthmann; David Moher; Richard A Rison; Larissa Shamseer; Christian A Koch; Gordon H Sun; Patrick Hanaway; Nancy L Sudak; Marietta Kaszkin-Bettag; James E Carpenter; Joel J Gagnier
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5.  Dasatinib induces lung vascular toxicity and predisposes to pulmonary hypertension.

Authors:  Christophe Guignabert; Carole Phan; Andrei Seferian; Alice Huertas; Ly Tu; Raphaël Thuillet; Caroline Sattler; Morane Le Hiress; Yuichi Tamura; Etienne-Marie Jutant; Marie-Camille Chaumais; Stéphane Bouchet; Benjamin Manéglier; Mathieu Molimard; Philippe Rousselot; Olivier Sitbon; Gérald Simonneau; David Montani; Marc Humbert
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Review 6.  Dasatinib-induced pulmonary arterial hypertension.

Authors:  Nurgül Özgür Yurttaş; Ahmet Emre Eşkazan
Journal:  Br J Clin Pharmacol       Date:  2018-03-06       Impact factor: 4.335

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Authors:  David Montani; Emmanuel Bergot; Sven Günther; Laurent Savale; Anne Bergeron; Arnaud Bourdin; Helene Bouvaist; Matthieu Canuet; Christophe Pison; Margareth Macro; Patrice Poubeau; Barbara Girerd; Delphine Natali; Christophe Guignabert; Frédéric Perros; Dermot S O'Callaghan; Xavier Jaïs; Pascale Tubert-Bitter; Gérard Zalcman; Olivier Sitbon; Gérald Simonneau; Marc Humbert
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8.  2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines:  The Task Force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC).

Authors:  Jose Luis Zamorano; Patrizio Lancellotti; Daniel Rodriguez Muñoz; Victor Aboyans; Riccardo Asteggiano; Maurizio Galderisi; Gilbert Habib; Daniel J Lenihan; Gregory Y H Lip; Alexander R Lyon; Teresa Lopez Fernandez; Dania Mohty; Massimo F Piepoli; Juan Tamargo; Adam Torbicki; Thomas M Suter
Journal:  Eur Heart J       Date:  2016-08-26       Impact factor: 29.983

9.  Dasatinib in imatinib-resistant or -intolerant chronic-phase, chronic myeloid leukemia patients: 7-year follow-up of study CA180-034.

Authors:  Neil P Shah; Philippe Rousselot; Charles Schiffer; Delphine Rea; Jorge E Cortes; Jorge Milone; Hesham Mohamed; Diane Healey; Hagop Kantarjian; Andreas Hochhaus; Giuseppe Saglio
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Review 10.  Treatment-free remission with first- and second-generation tyrosine kinase inhibitors.

Authors:  Jorge Cortes; Delphine Rea; Jeffrey H Lipton
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  10 in total

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