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Items 1-46 of 46 (Display the 46 citations in PubMed)

 

 

2.

Dasatinib-Induced Pulmonary Arterial Hypertension

Can J Cardiol. 2019 Nov;35(11):1604.e1-1604.e3. doi: 10.1016/j.cjca.2019.08.002. Epub 2019 Aug 8.

Authors

Abstract

A 73-year-old woman with chronic myeloid leukemia developed severe pulmonary arterial hypertension (PAH) and pleural effusions after treatment with dasatinib. During workup, partial anomalous pulmonary venous connection and a sinus venosus atrial septal defect were found; these anomalies may have predisposed her to developing this rare and life-threatening condition. Fortunately, her PAH was completely reversible by discontinuation of dasatinib. This case highlights dasatinib’s ability to cause PAH in patients predisposed to pulmonary vascular disease.

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Elsevier Science
3.

Dasatinib-induced pulmonary arterial hypertension – A rare late complication

J Oncol Pharm Pract. 2019 Apr;25(3):727-730. doi: 10.1177/1078155217753740. Epub 2018 Jan 17.

Authors

Uroosa Ibrahim  1 Amina Saqib  2 Vidhya Dhar  3 Marcel Odaimi  1

Affiliations

  • 1 1 Department of Hematology/Oncology, Staten Island University Hospital, Staten Island, New York, USA.
  • 2 2 Department of Pulmonary/Critical Care, Staten Island University Hospital, Staten Island, New York, USA.
  • 3 3 Department of Medicine, Staten Island University Hospital, Staten Island, New York, USA.

Abstract

Dasatinib is a dual Src/Abl tyrosine kinase inhibitor approved for frontline and second line treatment of chronic phase chronic myelogenous leukemia. Pulmonary arterial hypertension is defined by an increase in mean pulmonary arterial pressure >25 mmHg at rest. Dasatinib-induced pulmonary hypertension has been reported in less than 1% of patients on chronic dasatinib treatment for chronic myelogenous leukemia. The pulmonary arterial hypertension from dasatinib may be categorized as either group 1 (drug-induced) or group 5 based on various mechanisms that may be involved including the pathogenesis of the disease process of chronic myelogenous leukemia. There have been reports of dasatinib-induced pulmonary arterial hypertension being reversible. We report a case of pulmonary arterial hypertension in a 46-year-old female patient with chronic phase chronic myelogenous leukemia on dasatinib treatment for over 10 years. She had significant improvement in symptoms after discontinuation of dasatinib and initiation of vasodilators. Several clinical questions arise once patients experience significant adverse effects as discussed in our case.

Keywords: CML; Chronic myeloid leukemia; dasatinib; pulmonary arterial hypertension; tyrosine kinase inhibitor.

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Atypon
4.

[Reversible dasatinib-related pulmonary arterial hypertension in a CML patient]

Rinsho Ketsueki. 2016 May;57(5):618-23. doi: 10.11406/rinketsu.57.618.
[Article in Japanese]

Affiliation

  • 1 Department of Hematology, Seichokai Fuchu Hospital.

Abstract

A 59-year-old man diagnosed with the chronic phase of chronic myeloid leukemia (CML) in June 2011 was started on dasatinib (100 mg/day). He had no signs of pleural effusion (PE) or right heart failure before treatment, but symptoms of PE and dyspnea (New York Heart Association class III) appeared in January 2013 and May 2014, respectively. Doppler transthoracic echocardiography and right heart catheterization revealed pulmonary arterial hypertension (PAH) with an estimated pulmonary artery systolic pressure (PASP) of 80 mmHg and estimated mean pulmonary artery pressure of 29 mmHg. Rheumatoid factor, antinuclear antibody, dsDNA antibody, and SCL70 were not elevated, and computed tomography confirmed the absence of a pulmonary embolism. Therefore, dasatinib-related PAH was diagnosed and treatment with this agent was discontinued. The PASP had decreased to 51 and 40 mmHg at one month and one year, respectively, after dasatinib discontinuation. This patient developed PAH while receiving dasatinib administration and only discontinuation of this agent improved his symptoms. The possibility that dasatinib can cause PAH must be considered before administering this agent to patients with CML.

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5.

Beneficial Effects of Imatinib in a Patient with Suspected Pulmonary Veno-Occlusive Disease

Tohoku J Exp Med. 2019 Feb;247(2):69-73. doi: 10.1620/tjem.247.69.

Authors

Haruka Sato  1 Koichiro Sugimura  1 Masanobu Miura  1 Ryo Konno  1 Katsuya Kozu  1 Nobuhiro Yaoita  1 Toru Shimizu  1 Saori Yamamoto  1 Tatsuo Aoki  1 Shunsuke Tatebe  1 Kimio Satoh  1 Hiroaki Shimokawa  1

Affiliation

  • 1 Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine.

Free article

Abstract

Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary hypertension (PH). The prognosis of PVOD patients remains poor, since no effective medical therapy is yet available. Imatinib is a tyrosine kinase inhibitor specific for platelet-derived growth factor receptor and is expected as a treatment option for pulmonary arterial hypertension (PAH). Recently, it has been reported that imatinib improved functional capacity of a patient with PVOD. We here report a patient with suspected PVOD who has been successfully treated with imatinib and is alive for 6 years after diagnosis. A 57-year-old woman was admitted to a hospital for severe dyspnea. Echocardiography suggested the presence of PH, because tricuspid regurgitation pressure gradient was elevated. The patient was then transferred to our hospital by an ambulance ahead of schedule due to fever and worsening dyspnea. Because the patient had no left heart disease, we diagnosed that she had PAH associated with severe right heart failure. We immediately started treatment with nitric oxide (NO) for her severe hypoxia; however, it caused pulmonary edema. We suspected PVOD from CT characteristics and pulmonary edema after PAH-targeted vasodilator therapy, and then started oral imatinib treatment. In response to imatinib, her pulmonary edema gradually improved. Since then, the patient has been alive for 6 years with imatinib and pulmonary vasodilators. At present, lung transplantation is the only effective therapy for PVOD with limited availability. We therefore propose that imatinib may be a treatment option for PVOD and a bridge to lung transplantation.

Keywords: imatinib; pulmonary arterial hypertension; pulmonary hypertension; pulmonary veno-occlusive disease; transplantation.

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6.

Dasatinib-Induced Pulmonary Arterial Hypertension Treated with Upfront Combination Therapy

Case Rep Cardiol. 2018 May 20;2018:3895197. doi: 10.1155/2018/3895197. eCollection 2018.

Authors

Makoto Nishimori  1 Tomoyuki Honjo  1 Kenji Kaihotsu  1 Naohiko Sone  1 Sachiko Yoshikawa  1 Junichi Imanishi  1 Kazuhiko Nakayama  2 Noriaki Emoto  2   3 Masanori Iwahashi  1

Affiliations

  • 1 Division of Cardiology, Department of Internal Medicine, Shinko Hospital, Kobe, Japan.
  • 2 Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
  • 3 Department of Clinical Pharmacy, Kobe Pharmaceutical University, Kobe, Japan.

Free PMC article

Abstract

Pulmonary arterial hypertension (PAH) is a rare complication of dasatinib that was approved as a first-line therapy for chronic myelocytic leukemia (CML). A 24-year-old man presenting dyspnea at rest and leg edema was admitted to our hospital. He had been diagnosed with CML and prescribed dasatinib for 4 years. Chest X-ray showed significant bilateral pleural effusion and heart enlargement. Echocardiography revealed interventricular septal compression and elevated peak tricuspid regurgitation pressure gradient of 66.7 mmHg indicating severe pulmonary hypertension. After the other specific diseases to provoke PAH were excluded, he was diagnosed with dasatinib-induced PAH. Despite discontinuation of dasatinib and intravenous administration of diuretic for two weeks, World Health Organization (WHO) functional class was still II and mean pulmonary arterial pressure (PAP) was high at 37 mmHg. Therefore, we administered sildenafil and bosentan together as an upfront combination therapy three weeks after dasatinib discontinuation. Six months later, his symptoms improved to WHO functional class I and mean PAP was decreased to 31 mmHg. Although PAH is a rare complication of dasatinib, symptomatic patients prescribed with dasatinib should have an echocardiogram for PAH screening. Moreover, the upfront combination therapy would be a useful option for symptomatic patients after discontinuation of dasatinib.

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7.

Dasatinib-induced pulmonary arterial hypertension complicated with scleroderma: a case report

Eur Heart J Case Rep. 2019 Mar 15;3(1):ytz025. doi: 10.1093/ehjcr/ytz025. eCollection 2019 Mar.

Authors

Takumi Toya  1 Yuji Nagatomo  1 Kazuki Kagami  1 Takeshi Adachi  1

Affiliation

  • 1 Department of Cardiology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Japan.

Free PMC article

Abstract

Background: Although the BCR-ABL tyrosine kinase inhibitor dasatinib is a potent treatment for chronic myeloid leukaemia, it is associated with the risk of dasatinib-induced pulmonary arterial hypertension (DASA-PAH), for which predisposing factors have yet to be elucidated. However, animal studies have shown that dasatinib exacerbates pulmonary hypertension (PH) in rodent models of PH but not in controls, providing support for a two-hit theory of DASA-PAH pathophysiology.

Case summary: A 63-year-old man with worsening dyspnoea was diagnosed with severe DASA-PAH and concomitant scleroderma. He was successfully treated with discontinuation of dasatinib and administration of pulmonary vasodilators.

Discussion: Our case suggests that scleroderma may be a predisposing factor for the development of DASA-PAH, providing new insight into its pathophysiology.

Keywords: BCR-ABL tyrosine kinase inhibitor; Case report; Dasatinib; Pulmonary arterial hypertension; Scleroderma.

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8.

[Repeated partially reversible pulmonary arterial hypertension related to dasatinib: a case report and literature review]

Zhonghua Jie He He Hu Xi Za Zhi. 2016 Feb;39(2):83-7. doi: 10.3760/cma.j.issn.1001-0939.2016.02.002.
[Article in Chinese]

Authors

J Jin  1 X M XuC Wang

Affiliation

  • 1 National Clinical Research Center for Respiratory Diseases, Department of Respiratory and Critical Care Medicine, Beijing Hospital, Beijing 100730, China.

Abstract

Objective: To study the clinical features and prognosis of pulmonary arterial hypertension related to dasatinib.

Methods: A case of pulmonary arterial hypertension(PAH) during dasatinib therapy was retrospectively analyzed and the related literature was reviewed.

Results: A 55-year-old male with chronic myelogenous leukemia was treated with dasatinib at a dosage of 100 mg/d.After 36 months of initiating the therapy, he presented with chest distress, fatigue and general edema. His heart function was graded as NHYA Ⅳ. Transthoracic Doppler echocardiography documented right ventricle enlargement, right ventricular wall thickening, reduction of right ventricular systolic function, widening of the main pulmonary artery and branches , and an estimated systolic pulmonary arterial pressure(SPAP) of 115 mmHg(1 mmHg=0.133 kPa), with pericardial effusion and normal systolic left ventricular function.Chest ultrasound documented bilateral pleural effusion.The patient had taken and withdrew dasatinib 5 times by himself.The symptom had improved after stopping the drug, with SPAP decreasing to 37-82 mmHg measured by echocardiography at the first 3 times, and the pleural effusion and the pericardial effusion had disappeared. But 1 year after the 4(th) withdrawal of the drug, his pulmonary arterial pressure had failed to decrease, and he had taken the drug again by himself. Other causes of pulmonary arterial hypertension such as lung parenchymal diseases, pulmonary thromboembolism, connective tissue diseases, other drug induced PAH, were excluded by extensive examinations. The patient refused to receive right-sided heart catheterization. The patient was followed until now.

Conclusions: Dasatinib can cause partially reversible PAH. But after repeated use of the drug, PAH may become irreversible. Monitoring SPAP by transthoracic Doppler echocardiography is necessary during dasatinib therapy.

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Chinese Medical Association Publishing House Ltd.
9.

Pulmonary arterial hypertension in a patient treated with dasatinib: a case report

J Med Case Rep. 2017 Dec 29;11(1):362. doi: 10.1186/s13256-017-1515-9.

Authors

Andris Skride  1   2 Matiss Sablinskis  1 Kristaps Sablinskis  1 Krista Lesina  1   3 Aivars Lejnieks  1   3 Sandra Lejniece  4   5

Affiliations

  • 1 Riga Stradins University, Riga, Latvia.
  • 2 Pauls Stradins Clinical University Hospital, Riga, Latvia.
  • 3 Riga East University Hospital, Riga, Latvia.
  • 4 Riga Stradins University, Riga, Latvia. lejniece@latnet.lv.
  • 5 Riga East University Hospital, Riga, Latvia. lejniece@latnet.lv.

Free PMC article

Abstract

Background: There have been several reports on dasatinib-induced reversible pulmonary hypertension. This is the first reported case in Latvia; the patient did not discontinue the drug after the first adverse effects in the form of pleural effusions, which we speculate led only to partial reversion of the disease.

Case presentation: A 67-year-old white man with chronic myelogenous leukemia was treated with the dual Src and BCR-ABL tyrosine kinase inhibitor dasatinib. After treatment with dasatinib he had multiple pleural effusions which were suspected to be caused by congestive heart failure. Later a transthoracic Doppler echocardiography and right-sided heart catheterization revealed severe pulmonary hypertension with pulmonary vascular resistance of 12 Wood units and mean pulmonary artery pressure of 53 mmHg. Computed tomography ruled out a possible pulmonary embolism; laboratory specific tests for human immunodeficiency virus, rheumatoid factor, and anti-nuclear antibodies were negative, and dasatinib-induced pulmonary arterial hypertension was diagnosed. A follow-up right-sided heart catheterization and 6-minute walk test done a month after the discontinuation of dasatinib showed significant improvement: mean pulmonary artery pressure of 34 mmHg and pulmonary vascular resistance of 4 Wood units.

Conclusions: Patients should always be closely monitored when using dasatinib for a prolonged time. Dasatinib-induced pulmonary hypertension may be fully reversible after the therapy is suspended, but the key factors involved are still unclear and need to be further studied.

Keywords: Chronic myelogenous leukemia; Dasatinib; Pleural effusion; Pulmonary arterial hypertension.

Conflict of interest statement

Ethics approval and consent to participate

Not applicable.

Consent for publication

Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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10.

Incident pulmonary arterial hypertension associated with Bosutinib

Pulm Circ. 2020 Aug 21;10(3):2045894020936913. doi: 10.1177/2045894020936913. eCollection Jul-Sep 2020.

Authors

Shaun Yo  1 John Thenganatt  1 Jeffrey Lipton  2 John Granton  1

Affiliations

  • 1 Division of Respirology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
  • 2 Princess Margaret Cancer Centre, Toronto, Ontario, Canada.

Free PMC article

Abstract

Pulmonary arterial hypertension is associated with tyrosine kinase inhibitors used in the treatment of chronic myeloid leukemia. Dasatinib is a known cause of drug-induced pulmonary arterial hypertension. There have been case reports linking Bosutinib with deterioration of pre-existing pulmonary arterial hypertension. Here, we present a case of a 37-year-old woman with chronic myeloid leukemia treated with Bosutinib who was diagnosed with pulmonary arterial hypertension. Prior to Bosutinib, she had received Dasatinib without documented cardiopulmonary toxicity. Withdrawal of Bosutinib led to partial reversal of pulmonary arterial hypertension, and with the addition of pulmonary arterial hypertension-targeted treatment, there was near normalization of hemodynamics.

Keywords: Macitentan; chronic myeloid leukemia; drug-induced pulmonary hypertension; tyrosine kinase inhibitors.

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11.

Lupus-like symptoms with anti-RNP/Sm and anti-nuclear antibodies positivity: An extremely rare adverse event of dasatinib

J Oncol Pharm Pract. 2020 Apr;26(3):738-741. doi: 10.1177/1078155219863469. Epub 2019 Jul 30.

Authors

Affiliations

  • 1 Department of Hematology, Dıskapı Yıldırım Beyazıt Research and Training Hospital, Ankara, Turkey.
  • 2 Department of Hematology, Ataturk Research and Training Hospital, Ankara, Turkey.
  • 3 Department of Rheumatology, Ataturk Research and Training Hospital, Ankara, Turkey.

Abstract

Introduction: Dasatinib is a potent tyrosine-kinase inhibitor which is used for chronic myeloid leukemia treatment. Pleural effusion is a frequent side effect in patients during dasatinib treatment. Pulmonary arterial hypertension is a rare and life-threatening adverse event of dasatinib. The relationship between dasatinib and autoimmune disorders is unclear, but there are reports of possible mechanisms that have triggered autoimmunity by dasatinib.

Case report: A 53-year-old male was diagnosed with chronic myeloid leukemia and initiated imatinib mesylate as a treatment. Imatinib was changed to dasatinib as the patient was unresponsive in the first year of treatment. In the fourth year of dasatinib when chronic myeloid leukemia was in both hematological and cytogenetical remission, the patient presented with bilateral massive exudative pleural effusion. Echocardiography was consistent with pericardial effusion with right ventricle enlargement and normal left-side cardiac function. Pulmonary arterial hypertension was diagnosed with high systolic pulmonary arterial pressure. When he had fever and arthralgia, further investigation showed positivity of anti-nuclear antibodies (1/160 titer) and anti-RNP/Sm, which have high specificity for the diagnosis of Systemic Lupus Erythematosus (SLE).

Management and outcome: Dasatinib was discontinued and nilotinib was initiated. As the pleural effusion persisted despite diuretics and methylprednisolone, mycophenolate mofetil was initiated as a steroid-sparing immune-suppressive agent. The lupus-like symptoms disappeared, and antibodies became undetectable after dasatinib discontinuation. Pericardial effusion improved and pleural effusion did not relapse.

Discussion: Screening for auto-antibodies may be recommended for patients with a history or symptoms of autoimmune disease before starting dasatinib. All patients who develop pleural effusion while on dasatinib treatment should be investigated for antibodies for lupus.

Keywords: Dasatinib; lupus; pleural effusion; pulmonary arterial hypertension.

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Atypon
12.

[Development of pulmonary arterial hypertension during oral dasatinib therapy for chronic myelogenous leukemia]

Rinsho Ketsueki. 2016 Aug;57(8):999-1003. doi: 10.11406/rinketsu.57.999.
[Article in Japanese]

Affiliation

  • 1 Department of Hematology, Yokohama City University Medical Center.

Abstract

We present a 36-year-old woman who had been taking oral dasatinib for 3 years for the treatment of chronic myelogenous leukemia (CML). Although adverse events such as thrombocytopenia and pleural effusion developed, she showed a major molecular response (MMR) 22 months after the initiation of oral dasatinib administration, and the therapy was thus continued. Approximately 34 months after oral dasatinib initiation, she developed severe exertional dyspnea and had to be urgently hospitalized. There was no apparent pleural effusion increase, and neither imaging nor blood test results suggested pneumonia or other infections. Pulmonary arterial hypertension (PAH) was suspected on the basis of transthoracic echocardiography. PAH was then confirmed by right heart catheterization. Though dasatinib was discontinued on the day of hospitalization, pulmonary hypertension and heart failure progressed, and she did not respond to catecholamines or PDE5 (phosphodiesterase type 5) inhibitors. On the 4(th) hospital day, she experienced cardiopulmonary arrest and died 1 week later. Cases with PAH due to oral administration of dasatinib have been reported previously. However, cases showing the rapid progression documented in our patient are rare and we advocate that PAH be considered a potential adverse event associated with dasatinib therapy.

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J-STAGE, Japan Science and Technology Information Aggregator, Electronic
13.

Combination targeted pulmonary hypertension therapy in the resolution of Dasatinib-associated pulmonary arterial hypertension

Pulm Circ. Oct-Dec 2017;7(4):803-807. doi: 10.1177/2045893217716659. Epub 2017 Jul 5.

Authors

Arun Jose  1 Hind Rafei  2 Jalil Ahari  1

Affiliations

  • 1 1 Pulmonary, Critical Care, and Sleep Medicine Division, The George Washington University, Washington DC, USA.
  • 2 2 Department of Medicine, The George Washington University, Washington DC, USA.

Free PMC article

Abstract

Dasatinib is a small-molecule tyrosine kinase inhibitor used in the treatment of hematological malignancies. Pulmonary arterial hypertension (PAH) is a rare but known complication. The mainstay of treatment is cessation of Dasatinib, and while clinical improvement is rapid, complete hemodynamic resolution of pulmonary hypertension (PH) still remains exceedingly uncommon. We present a case of Dasatinib-induced PAH in a woman with chronic myeloid leukemia, who demonstrated rapid and complete clinical and hemodynamic resolution following treatment with combination pulmonary vasodilator therapy using an endothelin receptor antagonist and a phosphodiesterase-5 inhibitor. This case suggests there may be an association between the use of targeted PH medication in combination and the complete resolution of dasatinib-associated PAH, but further investigation is required.

Keywords: Ambrisentan; Tadalafil; right heart catheterization; tyrosine kinase inhibitor.

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14.

Imatinib Dramatically Improved Pulmonary Hypertension Caused by Pulmonary Tumor Thrombotic Microangiopathy (PTTM) Associated with Metastatic Breast Cancer

Int Heart J. 2020 May 30;61(3):624-628. doi: 10.1536/ihj.19-556. Epub 2020 Apr 29.

Authors

Affiliation

  • 1 Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine.

Free article

Abstract

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare malignancy-related respiratory complication, showing rapid progression of respiratory dysfunction and pulmonary hypertension (PH). Accumulating evidence suggests that imatinib, a platelet-derived growth factor (PDGF) receptor-tyrosine kinase inhibitor, might be effective and improve severe PH in patients with PTTM associated with gastric cancer. However, its efficacy in PTTM with breast cancer is generally believed as very limited. We experienced a rare case of PTTM associated with metastatic breast cancer, a rare case who were treated with imatinib, exhibiting significant improvement of respiratory dysfunction and PH.

Keywords: Cardio-oncology; Heart failure; Malignancy.

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J-STAGE, Japan Science and Technology Information Aggregator, Electronic
15.

Imatinib for the treatment of pulmonary arterial hypertension and pulmonary capillary hemangiomatosis

Pulm Circ. 2014 Jun;4(2):342-5. doi: 10.1086/675996.

Authors

Affiliations

  • 1 St. Vincent’s Hospital, Sydney, Australia ; University of New South Wales, Kensington, Australia.
  • 2 St. Vincent’s Hospital, Sydney, Australia.

Free PMC article

Abstract

Despite currently available treatments, the prognoses of pulmonary arterial hypertension (PAH) and pulmonary capillary hemangiomatosis (PCH) remain poor. Platelet-derived growth factor and its receptor (PDGFR) have been implicated in the pathogenesis of pulmonary hypertension in PAH and PCH. Imatinib, a PDGFR antagonist, may be beneficial in the treatment of both conditions because of its potent antiproliferative effect. We report two cases that demonstrate the potential for safe and efficacious use of imatinib in PAH and PCH.

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16.

[Reversible pulmonary arterial hypertension related to dasatinib in the treatment for chronic myelogenous leukemia: a case report and literature review]

Zhonghua Xue Ye Xue Za Zhi. 2014 Jul;35(7):581-6. doi: 10.3760/cma.j.issn.0253-2727.2014.07.002.
[Article in Chinese]

Authors

Bingcheng Liu  1 Ying Wang  1 Yingchang Mi  1 Jianxiang Wang  1

Affiliation

  • 1 Institute of Hematology & Blood Diseases Hospital, CAMS & PUMC, Tianjin 300020, China.

Abstract

Objective: To study the clinical features and prognosis of pulmonary arterial hypertension associated with dasatinib.

Methods: To present a case of pulmonary arterial hypertension (PAH) associated with long-term exposure to dasatinib and review the related literatures.

Results: A 23-year-old female with chronic myelogenous leukemia was treated with dasatinib at a dosage of 140 mg/d after failure of imatinib treatment and achieved complete cytogenetic response. The patient was presented with exertional dyspnea after 35 months of administration with dasatinib. The electrocardiogram showed right ventricular hypertrophy and right axis deviation; transthoracic Doppler echocardiography documented a reduction in diameters of left heart chambers with normal systolic left ventricular function, right heart chambers and pulmonary trunk dilatation, an estimated pulmonary arterial pressure of 114 mmHg; Computed tomography showed thickened pulmonary artery. PAH related to dasatinib was diagnosed and dasatinib was permanently discontinued. The symptom of dyspnea disappeared quickly after withdrawal of dasatinib. The heart structure and pulmonary arterial pressure completely recovered after 7 months of dasatinib discontinuation.

Conclusion: PAH is a rare adverse effect of dasatinib treatment. Echocardiograhpy, as a non-invasive screening test for PAH, should be performed before starting dasatinib treatment and repeated during the administration with dasatinib. Dasatinib should be withdrawn permanently in patients with PAH.

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Chinese Medical Association Publishing House Ltd.
17.

Dasatinib-induced pulmonary hypertension in acute lymphoblastic leukemia: case report

Turk Kardiyol Dern Ars. 2015 Jan;43(1):78-81. doi: 10.5543/tkda.2015.41763.

Authors

Affiliations

  • 1 Department of Cardiology, Gazi University Faculty of Medicine, Ankara, Turkey. gtacoy@yahoo.com.
  • 2 Department of Cardiology, Gazi University Faculty of Medicine, Ankara, Turkey.
  • 3 Department of Oncology, Gazi University Faculty of Medicine, Ankara, Turkey.

Free article

Abstract

Pulmonary hypertension (PHT) is a pathological condition determined as an increase in mean pulmonary arterial pressure ≥25 mmHg. Pulmonary arterial hypertension (PAH) is precapillary PHT and a life-threatening disease group which consists of different etiologies with the same pathological and clinical findings, and which is characterized by elevated pulmonary vascular resistance. Dasatinib is a dual Src/Abl kinase inhibitor associated with higher affinity for BCR/ABL kinase than imatinib, and is used in the treatment of chronic myelocytic leukemia and Philadelphia chromosome positive acute lymphoblastic leukemia (ALL). We describe a case with ALL, in whom dasatinib treatment induced PAH, and who recovered with bosentan treatment.

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Kare Publishing
18.

[Mixed connective tissue disease with pulmonary hypertension developing in a chronic myeloid leukemia patient on dasatinib treatment]

Rinsho Ketsueki. 2018;59(2):174-177. doi: 10.11406/rinketsu.59.174.
[Article in Japanese]

Authors

Affiliations

  • 1 Division of Hematology, Department of Medicine, Keio University School of Medicine.
  • 2 Division of Rheumatology, Department of Medicine, Keio University School of Medicine.
  • 3 Division of Cardiology, Department of Medicine, Keio University School of Medicine.

Abstract

A 37-year-old woman was diagnosed with chronic phase chronic myeloid leukemia. Nilotinib treatment was initiated; however, it had to be discontinued due to an allergic reaction one month later, and dasatinib treatment was provided. Although favorable response was obtained, she started complaining of shortness of breath 7 months after initiating dasatinib treatment. Chest X-ray and echocardiography indicated pulmonary congestion and hypertension. Further, she was diagnosed with mixed connective tissue disease (MCTD) based on Raynaud phenomenon, swollen fingers, sclerodactyly, pancytopenia, hypocomplementemia, and positive anti-U1-RNP antibody. Consequently, dasatinib treatment was discontinued, and she was administered prednisolone (1 mg/kg/day), which was effective and successfully tapered with concomitant administration of cyclophosphamide. This is the first case of MCTD that developed during dasatinib treatment. However, because the present case was a young woman, the development of MCTD could probably be attributed to autoimmune diatheses or it may be a coincidence. However, the possibility of patients receiving dasatinib treatment developing autoimmune diseases needs to be assessed.

Keywords: Chronic myeloid leukemia; Dasatinib; Mixed connective tissue disease; Pulmonary hypertension.

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J-STAGE, Japan Science and Technology Information Aggregator, Electronic
19.

[Pulmonary arterial hypertension and chronic heart failure as dasatinib cardiotoxicity. A case report]

Kardiologiia. 2017 Apr;57(S4):53-60. doi: 10.18087/cardio.2428.
[Article in Russian]

Authors

L M Makeeva  1 E I Emelina  1 G E Gendlin  1 I G Nikitin  1 Y A Vasyuk  2 V V Nesvetov  2

Affiliations

  • 1 Federal State Budgetary Educational Institution of Higher Education, “Pirogov Russian National Research Medical University” of the Ministry of Health of the Russian Federation.
  • 2 Federal State Budgetary Educational Institution of Higher Education, “A. I. Evdokimov Moscow State University for Medicine and Dentistry” of the Ministry of Health of the Russian Federation.

Abstract

Modern treatment of patients with oncohematological diseases has allowed to achieve remission or even convalescence in many cases. One of ambitious aims put forward by the hematological society is 100% survival and preservation of quality of life in patients with chronic myeloid leukemia (CML). This hope is related with the emergence of targeted therapy for CML. The second-generation tyrosine kinase inhibitor, dasatinib, which is used for treatment of CML, can occasionally induce severe pulmonary hypertension (PH). We presented here a case report of such cardiotoxicity, which was evident as PH and heart failure in a young female patient with CML treated with dasatinib. Information from published reports about this type of cardiotoxicity is provided. At present time, dasatinib is beginning to be extensively used also in other oncological diseases. For this reason, cardiologists and physicians should be aware of this cardiotoxicity, which can cause heart failure in dasatinib-treated patients.

Keywords: oncohematological diseases, cardiotoxicity, dasatinib, pulmonary arterial hypertension.

20.

Reversible Pulmonary Arterial Hypertension Associated with Dasatinib for Chronic Myeloid Leukemia

Cancer Res Treat. 2015 Oct;47(4):937-42. doi: 10.4143/crt.2013.155. Epub 2014 Nov 17.

Authors

Ji Hyung Hong  1   2 Sung-Eun Lee  2   3 Soo Young Choi  2 Soo-Hyun Kim  2 Eun-Jung Jang  2 Ju-Hee Bang  2 Jin Eok Park  2 Hye-Rim Jeon  2 Yun Jeong Oh  2 Jeong-Eun Yi  4 Hae Ok Jung  4 Ho Joong Youn  4 Dong-Wook Kim  2   3

Free PMC article

Abstract

我々は,ダサチニブ投与下で発症し,ダサチニブ投与中止後に治癒した肺動脈性肺高血圧症(PAH)の2例を報告した.慢性期の慢性骨髄性白血病(CML)の患者2名は、イマチニブ投与中に血液学的な経過が見られたため、ダサチニブ治療に切り替えられました。これらの患者は、ニューヨーク心臓協会 (NYHA) 機能クラス II の呼吸困難と右心室収縮圧 (RVSP) の上昇を呈していましたが、ダサチニブ治療で進行しました。ダサチニブ治療を中止したところ、自覚症状はNYHA機能クラスIに改善し、経過観察の経胸壁ドップラー心エコー検査ではRVSPの改善が認められました。その後、他のチロシンキナーゼ阻害剤による治療が開始され、呼吸困難やRVSPの上昇を伴うことなく治療が継続されています。今回の報告では,ダサチニブが可逆的なPAHを引き起こす可能性が示唆されたため,臨床症状のあるCML患者に対しては,ダサチニブの投与前および投与中に定期的な心肺機能の評価が必要であると考えられます。(イマチニブだった良かったけど、ダサチニブに変更してPHになった。ダサやめたら良くなった

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

Conflict of interest statement

Conflict of interest relevant to this article was not reported.

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21.

A 59-Year-Old Woman With Shortness of Breath and Chest Pain

Chest. 2020 Aug;158(2):e65-e69. doi: 10.1016/j.chest.2020.02.059.

Authors

Abstract

59歳の女性が失神で救急外来を受診しました。症状発現の1カ月前から、わずかな活動でも進行性の息切れがあり、前胸部に安静時の胸痛があった。また、10年前にDVTと肺塞栓症の既往があり、ワルファリンを服用していました。患者は慢性骨髄性白血病の慢性期にあり、当初はイマチニブによる治療を受けていましたが、発表の約4.5年前にダサチニブに変更されました。この患者は、ダサチニブ140mgを1日1回投与することで、分子レベルの主要な寛解を達成しました。家族歴は、肺高血圧症と心不全を認めませんでした。喫煙歴(50パック年)がありましたが、23年前に禁煙しました。(イマチニブだったら良かったけどダサチニブに変更してPHになった感じ

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Elsevier Science
22.

[Reversible pulmonary hypertension as a consequence of dasatinib treatment in a patient with chronic myeloid leukemia and scleroderma]

Pol Merkur Lekarski. 2013 Jun;34(204):342-4.
[Article in Polish]

Abstract

肺高血圧症は,結合組織病をはじめとする多くの臨床疾患と関連している可能性がある。今回,強皮症と慢性骨髄性白血病を合併し,重篤な肺高血圧症を発症した患者の一例を紹介する。肺高血圧症の症状が完全に寛解し,血行動態も改善するという非典型的な臨床経過を示したことから,肺高血圧症の病因に批判的なアプローチがなされた。ダサチニブ(チロシンキナーゼ阻害剤)の使用と時間的に一致していることや、文献にあるいくつかの症例報告を考慮すると、この患者の可逆性肺高血圧症はダサチニブの使用と関連していると思われます。肺高血圧症の危険因子として認められている既往歴の強皮症が、当初は正しい診断を遅らせていました。再分類されたことで、この特定の症例では肺高血圧症の臨床的予後が変わり、肺高血圧症の特定の治療を終了することができ、良い結果が得られました

24.

Reversible pre-capillary pulmonary hypertension due to dasatinib

Respir Care. 2014 May;59(5):e77-80. doi: 10.4187/respcare.02692. Epub 2013 Oct 22.

Free article

Abstract

慢性骨髄性白血病の治療薬として承認されているマルチチロシンキナーゼ阻害剤であるダサチニブの長期投与に関連して、肺動脈性肺高血圧症と二次性胸水が報告されている。ここでは、2003年8月に慢性骨髄性白血病と診断された50歳の男性が、ダサチニブによる4年以上の治療後に肺動脈性肺高血圧症を発症した症例を紹介します。ダサチニブ中止後に肺動脈性肺高血圧症が完全に寛解したことから,シルデナフィルの投与が治療的役割を果たした可能性はあるものの,肺動脈性肺高血圧症の発症に本剤が病因的に関与していることが示唆された

Keywords: chronic myeloid leukemia; drug-induced; long-term therapy; pulmonary hypertension.

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HighWire
25.

A case of worsening pulmonary arterial hypertension and pleural effusions by bosutinib after prior treatment with dasatinib

Pulm Circ. Oct-Dec 2017;7(4):808-812. doi: 10.1177/2045893217733444. Epub 2017 Oct 24.

Authors

Karan Seegobin  1 Amit Babbar  2 Jason Ferreira  2 Brittany Lyons  1 James Cury  2 Vandana Seeram  2

Free PMC article

Abstract

慢性骨髄性白血病(CML)の既往歴を持つ52歳の男性が,2カ月間にわたって進行性の息切れを発症した.当初,ダサチニブによる治療を4年間受けていたが,胸水を伴う肺動脈性肺高血圧症(PAH)を発症した.ダサチニブの投与を中止したところ、症状が改善しました。その後、ボスチニブに変更して約1年間治療を受けましたが、入院前に息切れが悪化したため中止しました。初診時の検査では、重症のPAHと肺気腫を伴う両側の胸水が認められました。ボスチニブを中止した後、PAHに特化した治療で症状が改善しました。チロシンキナーゼ阻害薬(TKI)の時代になってCML患者の余命が延び、TKIの有害事象(AE)の管理やQOLの向上が重要になっているという。肺高血圧症(PH)と胸水は、ボスチニブのAEとしてはまれにしか報告されていません。ダサチニブの前治療歴のある患者さんで、ボスチニブの使用後に肺高血圧症や胸水が発生したという報告が増えていることは、さらに気になるところです。新しい化学療法剤が登場した今、医師はこれらの化学療法剤が患者の生活に大きな影響を与えることに注意しなければなりません」

Keywords: bosutinib; dasatinib; pleural effusions; pulmonary arterial hypertension.

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28.

Cardiovascular care of patients with chronic myeloid leukemia (CML) on tyrosine kinase inhibitor (TKI) therapy

Hematology Am Soc Hematol Educ Program. 2017 Dec 8;2017(1):110-114. doi: 10.1182/asheducation-2017.1.110.

Authors

Mary C Barber  1   2   3 Michael J Mauro  4 Javid Moslehi  1   2   3

Affiliations

  • 1 Cardiovascular Division.
  • 2 Cardio-Oncology Program, and.
  • 3 Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN; and.
  • 4 Memorial Sloan-Kettering Cancer Center, New York, NY.

Free PMC article

Abstract

慢性骨髄性白血病(CML)患者にとって、心血管の健康は、予後を改善するための重要な検討事項として浮上しています。実際、BCR-ABL1チロシンキナーゼ阻害剤(TKI)の成功により、腫瘍治療における生存率と晩期毒性への関心が高まっています。癌患者のサバイバーシップの問題には、一般の人々に広く見られるCV疾患の予防も含まれます。BCR-ABL1 TKIの導入は、無期限のがん治療というユニークな概念を表していましたが、つい最近になって「無治療寛解」を含むようになりました。重要なのは、後続のBCR-ABL1 TKIが心臓病の合併症と関連していることです。ダサチニブは胸水、心嚢水、肺高血圧症と関連しており、ニロチニブとポナチニブは血管閉塞性イベントの発生と関連しています。現在、CML患者における薬物毒性のメカニズム、リスクのある患者のサブセット、およびCV合併症を軽減するための予防・治療戦略に関するデータは十分ではありません。とはいえ、患者の最適なCVリスク評価は、CML患者の治療において、より中心的な考え方となる必要があります。私たちは、CML患者、特に慢性的なTKI治療を受けている患者のCVの健康に関して、実践的な腫瘍医のためにいくつかの実用的な検討事項を提案します。(具体的に何が書かれているのかわからないような抄録、けしからんですな

Conflict of interest statement

Conflict-of-interest disclosure: M.C.B. declares no competing financial interests. M.J.M. has received research funding and has consulted for Bristol-Myers Squibb, Novartis Oncology, Pfizer, Takeda, and ARIAD Pharmaceuticals, Inc. J.M. has received research funding and has consulted for Novartis, Pfizer, Bristol-Myers Squibb, Takeda, ARIAD Pharmaceuticals, Inc., Acceleron Pharma, Pharmacyclics, Daiichi Sankyo, and Regeneron Pharmaceuticals.

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30.

Multi tyrosine kinase inhibitor dasatinib as novel cause of severe pre-capillary pulmonary hypertension?

BMC Pulm Med. 2011 May 23;11:30. doi: 10.1186/1471-2466-11-30.

Free PMC article

Abstract

背景 肺高血圧症(PH)は生命を脅かす疾患であり、予後も悪い。肺高血圧症の主要な血管増殖因子を標的とした治療法が開発されている。イマチニブをはじめとするチロシンキナーゼ阻害剤は、新たな治療法として期待されている。

症例報告。 慢性骨髄性白血病 (CML) およびフィラデルフィア染色体陽性の急性リンパ性白血病の治療薬として承認されているマルチチロシンキナーゼ阻害剤ダサチニブの長期投与下で前毛細血管性PHを発症した、特徴的な患者を追加しました (全患者のダサチニブ投与期間の平均は 26 ヶ月)。現時点では、 ダサチニブによる PH の真の発生率は不明瞭で、 血行動態に関する系統的なデータもありません。

結論 現在、 ダサチニブによる肺高血圧症の真の発生率は不明であり、 血行動態に関する体系的なデータも不足しています。(症例はダサチニブによるPAHらしいが、ロジックがおかしな文献

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32.

Pulmonary arterial hypertension after childhood cancer therapy and bone marrow transplantation

Cardiology. 2006;105(3):188-94. doi: 10.1159/000091638. Epub 2006 Feb 21.

Abstract

肺動脈性肺高血圧症(PAH)に関する第3回世界シンポジウムによると、化学療法はPAHを発症する患者のリスク要因の1つと考えられている。しかし、これまでに、この疾患のリスク、自然史、効果的な治療法について十分に言及した文献はない。我々は、早期診断、詳細な経過観察、適切な治療の適用により、がん治療後の小児期のPAH管理を成功に導いた経験を報告する。この報告は、PAHが白血病の化学療法や骨髄移植の合併症として認識されていることを再確認させた。肺血管拡張薬の併用療法は、初期の急性肺血管拡張薬検査で示唆されたように、患者の状態と機能的状態の改善に有益な効果がある。(アブストラクトでは具体的な例示が有るのかわからないので本文確認要

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S. Karger AG, Basel, Switzerland
34.

Pulmonary arterial hypertension caused by treatment with dasatinib for chronic myeloid leukemia -critical alert-

Intern Med. 2012;51(17):2337-40. doi: 10.2169/internalmedicine.51.7472. Epub 2012 Sep 1.

Free article

Abstract

今回,ダサチニブ(Sprycel(®))による治療との関連が考えられる肺動脈性肺高血圧症(PAH)の1例を紹介する.慢性骨髄性白血病(CML)に対して27ヵ月間ダサチニブを投与していた61歳の女性が,呼吸困難を訴えて当院を受診した.右心カテーテル検査では,平均肺動脈圧は35mmHgであった.PAHの原因となる他の病因を除外した結果、この患者はダサチニブ関連PAHと診断されました。2011 年 10 月に米国食品医薬品局 (FDA) が通達したように、 PAH の副作用の観点から、 CML 患者のダサチニブ投与前および投与中に、 定期的な心肺機能の評価を行うことを推奨します。

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J-STAGE, Japan Science and Technology Information Aggregator, Electronic
45.

Elevation of pulmonary artery pressure as a complication of nilotinib therapy for chronic myeloid leukemia

Int J Hematol. 2012 Jul;96(1):132-5. doi: 10.1007/s12185-012-1103-0. Epub 2012 May 26.

Abstract

We present the case of a 72-year-old male with chronic phase myeloid leukemia. Elevation of the pulmonary artery pressure due to nilotinib therapy was noted. This effect on pulmonary artery pressure was nilotinib dose dependent.

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Springer

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