Long-Term Assessment of Dasatinib-Induced Pulmonary Arterial Hypertension in Chronic Myeloid Leukemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5535-5535 ◽  
Author(s):  
Jee Hyun Kong ◽  
Young-Woo Jeon ◽  
Sung-Eun Lee ◽  
Soo Young Choi ◽  
Soo-Hyun Kim ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Pleural Effusion ◽  
Chronic Myeloid Leukemia ◽  
Arterial Hypertension ◽  
Doppler Echocardiography ◽  
Myeloid Leukemia ◽  
Treatment Duration ◽  
Pulmonary Arterial ◽  
Dasatinib Treatment

Abstract Background: To explore a real incidence of dasatinib-induced pulmonary arterial hypertension (D-PAH) in clinical practice, we investigated 82 imatinib or other 2G tyrosine kinase inhibitor (TKI)-failed chronic myeloid leukemia (CML) patients who received dasatinib as a second-line therapy. Methods: Routine chest X-ray and Doppler echocardiography were regularly evaluated in all patients and additional tests were performed if dyspnea developed on treatment. Results: Median age at the time of starting dasatinib was 48 (16-82) years. Of 82 patients, 8 patients (9.8%) showed an elevation of right ventricular systolic pressure (RVSP>35mmHg) by Doppler echocardiography. Among them, 7 patients (8.5%) were considered D-PAH with a median dasatinib treatment duration of 32.6 (10.3-108.7) months. They underwent follow-up Doppler echocardiography median 5 (2-9) times. Five patients showed severe D-PAH (RVSP >70mmHg), 1 was moderate (RVSP 46mmHg), and 1 was mild (RVSP 41mmHg). Advanced studies such as pulmonary angiographic catheterization (patient 1 and 2) or pulmonary arterial computed tomography (patient 3 and 4) were performed for confirming D-PAH or ruling out PAH due to pulmonary vascular abnormality. Six patients had bilateral pleural effusion and 1 had unilateral pleural effusion. With sildenafil (n=5) + dose reduction (n=1) + switch to other TKI (n=6), all of patients improved dyspnea, and RVSP level was completely resolved in 3 patients. In addition, previous nilotinib therapy and concomitant pleural effusion were significant contributing factors for D-PAH. Conclusion: Regardless of complete resolution of pleural effusion, a patient with sustained dyspnea on dasatinib treatment should be carefully evaluated by Doppler echocardiography and a regular monitoring will be needed for early intervention. Abstract 5535. Table 1. Characteristics of patients with dasatinib-induced PAH Cohort Age at PAH diagnosis (year) Sex Treatment duration before dasatinib (month) Previous therapy for CML Duration between initiation of dasatinib and diagnosis of PAH (month) Daily mean dose of dasatinib (mg/d) Duration between diagnosis of D-PAH and last follow up (month) Treatment of D-PAH Switch to other TKI Outcome 1 53 M 54.4 Interferon, Hydroxyurea, Imatinib, nilotinib 26.4 123 73.5 Sildenafil nilotinib and ponatinib partial 2 50 M 36.6 Interferon, Hydroxyurea, Imatinib, dasatinib, nilotinib 50.3 112 55.2 Sildenafil nilotinib and radotinib partial 3 37 F 31.7 Imatinib, nilotinib 21.7 88 39.7 SildenafilDose de-escalation radotinib partial 4 45 M 70.9 Hydroxyurea, Imatinib 69.8 101 35.2 SildenafilDose de-escalation ponatinib complete 5 59 F 107.4 Interferon, Hydroxyurea, Imatinib 83.6 92 14.3 none radotinib partial 6 46 F 12.6 Imatinib 29.1 76 13.0 Steroid, Sildenafil radotinib complete 7 38 F 30.2 Imatinib 33.1 98 10.2 Dose reduction NA complete Disclosures No relevant conflicts of interest to declare.

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

2019 ◽  
Vol 26 (3) ◽  
pp. 738-741 ◽  
Author(s):  
Senem Maral ◽  
Sule Mine Bakanay ◽  
Orhan Kucuksahin ◽  
Imdat Dilek
Keyword(s):  
Adverse Event ◽  
Pulmonary Arterial Hypertension ◽  
Pleural Effusion ◽  
Chronic Myeloid Leukemia ◽  
Pericardial Effusion ◽  
Arterial Hypertension ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Pulmonary Arterial ◽  
Dasatinib Treatment

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.

Six-Year Follow-Up Of Dasatinib-Related Pulmonary Arterial Hypertension (PAH) For Chronic Myeloid Leukemia In Single Center

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4017-4017 ◽  
Author(s):  
Young-Woo Jeon ◽  
Sung-Eun Lee ◽  
Soo-Hyun Kim ◽  
Soo-Young Choi ◽  
Jin-Eok Park ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Pulmonary Arterial Hypertension ◽  
Chronic Myeloid Leukemia ◽  
Arterial Hypertension ◽  
Myeloid Leukemia ◽  
Systolic Pressure ◽  
Ventricular Systolic Pressure ◽  
Pulmonary Arterial ◽  
Dasatinib Treatment

Abstract Introduction Recent randomized trial (DASISION trial), compared clinical outcomes between dasatinib and imatinib in newly diagnosed (chronic myeloid leukemia) CML patients. Results showed that dasatinib had faster and deeper responses compared with imatinib, and thus dasatinib became to be considered as a first-line therapy in CML patients. However, the long-term administration of dasatinib has been reported to have a risk of pleural effusion and dasatinib-related (pulmonary arterial hypertension) PAH. So, we have prospectively evaluated for emergence of PAH in all CML patients treated with dasatinib in our institute. Materials and methods Between May 2005 and July 2013, a total of 89 CP CML patients on dasatinib treatment were tested with laboratory studies, Brain natriuretic peptide (BNP), echocardiography (echo) in the Catholic University of Korea, Seoul, and baseline functional capacity (NYHA or WHO functional class) was assessed. PAH was defined as mean pulmonary artery pressure (mPAP) of >25mmHg at rest, with wedge pressure < 15mmHg, or Rt. Ventricular systolic pressure (RVSP) of 40 mmHg on echocardiography. And patients who had abnormal RVSP and/or symptoms (New York heart association-NYHA class 3, 4) were performed with additional studies such as pulmonary angiographic catheterization or pulmonary arterial computed tomography. Results So far, 62 patients (70%) of total 89 were evaluated with echocardiography (46 male, 16 female). The median age was 48 year old (range, 22∼72). The median duration of disease was 8.5 years (range, 0.8∼16.1). The median mean daily dosage of dasatinib was 102mg (range, 73∼140mg). The duration of dasatinib treatment was 34.6 months (range, 0.5∼99.6). 8 of 66 patients (12.1%) showed abnormal echocardiographic findings as increased right ventricular systolic pressure or symptom. All of 8 patients had treated with dasatinib as second line, and had exertional dyspnea (2 patients on class 2, and 5 patients on class 3 of NYHA). 5 patients of these showed abnormal BNP levels. The mean RVSP in screened patients was 65.2 mmHg (range, 40∼108mmHg), 2 of 8 patients were confirmed diagnosis with overt PAH on as pulmonary angiographic catheterization, and right ventricular hypertrophy on pulmonary angiographic computed tomography. Clinical, functional, or hemodynamic improvements were observed within 5 months of dasatinib discontinuation and then, in 5 patients the treatment was switched to radotinib, and another 3 patients received reduced dosage of dasatinib. Conclusion Although the lowest estimate of incident PAH occurring in patients exposed to dasatinib was 0.45% in France group. our preliminary data show more higher incidence rates (8 of 66 patients, 12.1%) in Korea. So, we suggest that the long-term dasatinib treatment for CML requires careful attention to cardiopulmonary adverse effects. and routine cardiovascular and pulmonary evaluation on regular basis is strongly recommended before and during treatment with dasatinib. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Pulmonary Arterial Hypertension Caused by Treatment with Dasatinib for Chronic Myeloid Leukemia -Critical Alert-

2012 ◽  
Vol 51 (17) ◽  
pp. 2337-2340 ◽  
Author(s):  
Makoto Sano ◽  
Masao Saotome ◽  
Tsuyoshi Urushida ◽  
Hideki Katoh ◽  
Hiroshi Satoh ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Chronic Myeloid Leukemia ◽  
Arterial Hypertension ◽  
Myeloid Leukemia ◽  
Pulmonary Arterial

scholarly journals Incident pulmonary arterial hypertension associated with Bosutinib

2020 ◽  
Vol 10 (3) ◽  
pp. 204589402093691 ◽  
Author(s):  
Shaun Yo ◽  
John Thenganatt ◽  
Jeffrey Lipton ◽  
John Granton
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Arterial Hypertension ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Case Reports ◽  
Drug Induced ◽  
Pulmonary Arterial ◽  
Partial Reversal

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.

scholarly journals Reversible Pulmonary Arterial Hypertension Induced by Dasatinib in a Patient With Chronic Myeloid Leukemia

2017 ◽  
Vol 33 (4) ◽  
pp. 284-289 ◽  
Author(s):  
Atai Watanabe ◽  
Kazuaki Yokoyama ◽  
Nobuhiro Ohno ◽  
Kaoru Uchimaru ◽  
Naohide Yamashita ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Chronic Myeloid Leukemia ◽  
Arterial Hypertension ◽  
Transthoracic Echocardiography ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Heart Function ◽  
Drug Discontinuation ◽  
Right Heart ◽  
Pulmonary Arterial

A case study is provided of dasatinib-induced pulmonary arterial hypertension (PAH) in a patient with chronic myeloid leukemia. This condition resolved completely within 2 months of drug discontinuation. Transthoracic echocardiography (TTE) data were obtained throughout the recovery process. After 30 months of dasatinib treatment, a woman in her 30s developed orthopnea and signs of right heart failure (leg edema, hepatomegaly, and weight gain). Transthoracic echocardiography indicated elevated mean pulmonary artery pressure, severely impaired systolic and diastolic right ventricular functions, and dilation of the right ventricle and atrium. Once dasatinib was discontinued, clinical symptoms improved rapidly, and follow-up TTE 2 months later showed normal right heart function. Treatment with an alternative tyrosine kinase inhibitor was initiated and has continued without recurrence of PAH. This case suggests that dasatinib, which inhibits a broad spectrum of tyrosine kinases, could cause reversible PAH; therefore, careful cardiopulmonary evaluation by TTE is necessary.

scholarly journals Reversible Pulmonary Arterial Hypertension Associated with Dasatinib for Chronic Myeloid Leukemia

2014 ◽  
Vol 47 (4) ◽  
pp. 937-942 ◽  
Author(s):  
Ji Hyung Hong ◽  
Sung-Eun Lee ◽  
Soo Young Choi ◽  
Soo-Hyun Kim ◽  
Eun-Jung Jang ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Chronic Myeloid Leukemia ◽  
Arterial Hypertension ◽  
Myeloid Leukemia ◽  
Pulmonary Arterial

Change of myocardial fluorodeoxyglucose uptake distribution after specific therapy of pulmonary arterial hypertension patients

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
R Kazimierczyk ◽  
P Szumowski ◽  
L.M Malek ◽  
P Blaszczak ◽  
D Jurgilewicz ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Glucose Uptake ◽  
Funding Source ◽  
Hemodynamic Parameters ◽  
Fdg Uptake ◽  
Baseline Visit ◽  
Pulmonary Arterial ◽  
Rv Function

Abstract Background Right ventricular (RV) function is a major determinant of survival in patients with pulmonary arterial hypertension (PAH). In our previous study, we confirmed that increased RV fluorodeoxyglucose (FDG) uptake in positron emission tomography (PET) (presented as higher ratio of FDG uptake of RV to LV) was associated with progressive RV dysfunction and preceded hemodynamic and clinical deterioration in PAH patients. Now, we obtained second PET/MRI assessments of the study group after 2-years of PAH-targeted treatment. Aim The aim of the study was to obtain change of cardiac FDG uptake in PAH patients after follow-up period and to indicate factors mainly affecting this change. Methods Twenty-eight PAH patients (51.32±15.91 years) had simultaneous PET/MRI scans performed during baseline visit. FDG was used and its uptake was quantified as mean standardized uptake value (SUV) for both left (LV) and RV. Second PET/MRI assessments were done after 2 years in the group of twenty patients (four deaths, four patients did not agree to perform additional scans). Results After follow-up period, we observed significant change of MRI-derived RV ejection fraction (45±10% to 51.2±12.7%, p=0.03), and improvement in hemodynamic parameters obtained from right heart catheterization (RHC) e.g. mean pulmonary artery pressure, mPAP (48.5±17.2 to 41.8±17.1 mmHg, p=0.01) and pulmonary vascular resistance, PVR (8.7±5.3 to 7.0±4.2 WU, p=0.04). Follow-up SUVRV/SUVLV ratio significantly correlated with follow-up RV hemodynamic parameters confirming relationship between RV function and cardiac metabolic alterations (Table 1). Interestingly, patients who had improvement in SUVRV/SUVLV (lower follow-up value than baseline, n=11) had significantly higher mPAP at baseline visit (58.9±18.7 vs 40.3±11.8 mmHg, p=0.02), suggesting that RV FDG accumulation in advanced PAH may decrease after the PAH-specific treatment in accordance with the degree of reduction in the pulmonary vascular resistance. Conclusion Impaired RV function is associated with increased glucose uptake of RV myocytes estimated by FDG PET in PAH patients. Targeted treatment may improve RV function and thus affect previously altered cardiac glucose uptake. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Polish National Science Centre

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