Dasatinib-Induced Pulmonary Arterial Hypertension Treated with Upfront Combination Therapy

Nishimori, Makoto; Honjo, Tomoyuki; Kaihotsu, Kenji; Sone, Naohiko; Yoshikawa, Sachiko; Imanishi, Junichi; Nakayama, Keiichi I.; Emoto, Noriaki; Iwahashi, Masanori

doi:10.1155/2018/3895197

Cited by 6 publications

(5 citation statements)

References 10 publications

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“…Of note, the efficacy of and need for PAH-specific therapy for dasatinib-induced PAH remains inconclusive. Some reports have suggested that dasatinib-induced PAH is alleviated by PAH-specific therapy, and others have mentioned that the hemodynamics improved with discontinuation of dasatinib alone, without using a pulmonary vasodilator (19,20). When the case 1 patient was hospitalized, there were no data showing that PAH-specific treatments were effective for dasatinib-induced PAH; therefore, we simply discontinued dasatinib.…”

Section: Discussionmentioning

confidence: 98%

Relationship between Dasatinib-induced Pulmonary Hypertension and Drug Dose

Kubota

Imai

et al. 2022

Intern. Med.

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Objective Dasatinib, a second-generation tyrosine kinase inhibitor, is used for chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). It reportedly causes pulmonary arterial hypertension (PAH) and the dose-dependent induction of apoptosis in pulmonary endothelial cells. However, no report has yet discussed the relationship between dasatinib-induced PAH and drug dose. We therefore investigated the incidence of dasatinib-induced PAH and the relationship between dasatinib-PAH and drug dose in consecutive patients with CML and Ph+ ALL who took dasatinib. Methods The clinical data of 128 patients with CML (94 patients) and Ph+ ALL (34 patients) were retrospectively analyzed. Patients All patients (>17 years old) who received dasatinib from January 2009 to March 2020 at Jichi Medical University (Tochigi, Japan) were included. Patients who transferred within one month of starting dasatinib administration were excluded. Results Four (4.3%) and three (8.8%) patients developed pulmonary hypertension (PH), which was considered present when the transtricuspid pressure gradient was ! 40 mmHg, in the CML and ALL groups, respectively. No significant difference was observed between the PH onset and the administration period, cumulative dose, or daily dose of dasatinib. PH occurred in seven patients (5.5%), and the period from the start of dasatinib administration to the PH onset ranged from 7 to 39 (median: 28) months. No patients died from PH in either group. Conclusion Dasatinib-induced PAH does not occur time-or dose-dependently. When administering dasatinib, cardiovascular diagnostic modalities should be routinely checked, and PAH occurrence should be promptly detected.

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Section: Discussionmentioning

confidence: 98%

Relationship between Dasatinib-induced Pulmonary Hypertension and Drug Dose

Kubota

Imai

et al. 2022

Intern. Med.

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“…Sildenafil was also evaluated in combination with bosentan (20 mg TDS and 62.5 mg BD, respectively) in a patient with mPAP of 37 mmHg, WHO functional class 2 and BNP 685 pg mL -1 . All variables improved after 6 months of treatment [ 86 ]. In another case, right ventricle systolic pressure (RVSP) was reduced from 71 mmHg to 55 mmHg after treatment with 25 mg once daily sildenafil.…”

Section: Managementmentioning

confidence: 99%

A narrative review on adverse effects of dasatinib with a focus on pharmacotherapy of dasatinib-induced pulmonary toxicities

2021

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Chronic myeloid leukemia (CML), a myeloproliferative disorder caused by the over activity of BCR-ABL1 (breakpoint cluster region-Abelson), has been successfully treated by Tyrosine kinase inhibitors (TKIs). While imatinib is known as the first-line treatment of CML, in some cases other TKIs including dasatinib, nilotinib, bosutinib, and ponatinib may be preferred. Dasatinib, a second-generation TKI, inhibits multiple family kinases including BCR-ABL, SRC family kinases, receptor kinases, and TEC family kinases. It is effective against most imatinib-resistant cases except T315I mutation. Despite the superiority of dasatinib in its hematologic and cytogenetic responses in CML compared to imatinib, its potentially harmful pulmonary complications including pleural effusion (PE) and pulmonary arterial hypertension (PAH) may limit its use. Appropriate management of these serious adverse reactions is critical in both improving the quality of life and the outcome of the patient. In this narrative review, we will scrutinize the pulmonary complications of dasatinib and focus on the management of these toxicities.

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“…As dasatinib can lead to fluid retention along with pleural effusion and pericardial effusion, in patients with pleural effusion or with a high risk of pleural effusion occurrence, prescribing another inhibitor would be better. Dasatinib may also lead to pulmonary arterial hypertension, in the treatment of which stopping dasatinib induction can help improve hemodynamic parameters, as vasodilator agents do not exhibit clinical advantages [26,27]. For the side effect of bone marrow suppression, which occurs due to dasatinib induction, particularly in advanced cases of CML, adjusting the doses can help reverse the side effect.…”

Section: Which Tki Is the Best Methods As The Frontline Treatment Of Cmentioning

confidence: 99%

Current perspectives for the treatment of chronic myeloid leukemia

Aladağ¹,

Haznedaroğlu²

2019

Turk J Med Sci

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Background: With an annual incidence of 1-2 in a million, Ph*(+) chronic myeloid leukemia (CML) is a clonal hematopoietic stem cell disease that makes myeloid neoplastic cells breed out of control. This BCR-ABL (+) myeloproliferative disease makes up about 15-20% of all leukemia cases in adults. CML is seen more in males than females, with a rate of three to two. However, it does not show difference in prevalence in terms of age. CML consists of three clinical phases. The first one is the chronic phase, defined by rising white blood cell levels and also by myeloid proliferation and bone marrow maturation. While this phase does not exhibit complications, in diagnosis, it composes most of the patients. The second phase is the accelerated phase, which the disease progresses onto if it is not treated or does not respond to treatment. This time usually takes about three years. The third phase is the blastic phase. The chronic phase can still progress onto the next two phases within the first 2 years, with a rate of 10%. In the following years, the possibility increases by a 15-20% each year. Tyrosine kinase inhibitors (TKI) are the revolutionary drugs for the management of disease course in CML. Methods: The aim of this review is to assess current approaches to CML patient’s follow-up and treatment with TKI. The CML and TKI literature search was made in PubMed, Web of Science, Scopus with particular focus on the randomized clinical trials, recommendations, guidelines and expert opinions. Results: In managing CML, various treatment methods have been utilized for many decades. Prior to the development of tyrosine kinase inhibitors (TKI), interferon alpha was the primary tool, which was then complemented by allogeneic hematopoietic stem cell transplantation (HSCT). HSCT was actually successful in slowing the disease down in the long term and curing up to a 50% of the patients. Then the coming of imatinib era opened up different treatment perspectives. For the patients resistant or intolerant to the imatinib, second and third generation TKIs are successfully used in distinct CML disease states. Conclusion: The survival benefits of TKI including imatinib, nilotinib, dasatinib, bosutinib, and ponatinib for the CML patients are outstanding. TKI-related adverse events could impact on the clinical course especially in long-term drug administrations. Current aim for the CML disease management in TKI era is to provide age- and sex-matched normal life duration to the CML patients. Keywords: Chronic, myeloid, leukemia, tyrosine, kinase, inhibitors

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Dasatinib-Induced Pulmonary Arterial Hypertension Treated with Upfront Combination Therapy

Cited by 6 publications

References 10 publications

Relationship between Dasatinib-induced Pulmonary Hypertension and Drug Dose

Relationship between Dasatinib-induced Pulmonary Hypertension and Drug Dose

A narrative review on adverse effects of dasatinib with a focus on pharmacotherapy of dasatinib-induced pulmonary toxicities

Current perspectives for the treatment of chronic myeloid leukemia

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