Dasatinib-induced pulmonary arterial hypertension – A rare late complication

2018 ◽  
Vol 25 (3) ◽  
pp. 727-730 ◽  
Author(s):  
Uroosa Ibrahim ◽  
Amina Saqib ◽  
Vidhya Dhar ◽  
Marcel Odaimi
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Chronic Myelogenous Leukemia ◽  
Kinase Inhibitor ◽  
Late Complication ◽  
Disease Process ◽  
Chronic Phase ◽  
Myelogenous Leukemia ◽  
Pulmonary Arterial ◽  
Dasatinib Treatment

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.

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.

Pulmonary Hypertension

2013 ◽  
Author(s):  
George K Istaphanous ◽  
Andreas W Loepke
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Pulmonary Artery ◽  
Arterial Hypertension ◽  
Pulmonary Artery Pressure ◽  
Disease Process ◽  
Underlying Disease ◽  
Artery Pressure ◽  
Pulmonary Arterial ◽  
Made In

Pediatric pulmonary arterial hypertension (PAH) is characterized by a pathologically elevated pulmonary artery pressure in children. The etiology of PAH is multifactorial, and while its prognosis is closely related to the reversibility of the underlying disease process, much progress has recently been made in its diagnosis and treatment, significantly decreasing the associated morbidity and mortality.

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.

scholarly journals Hypoxia-inducible factors in human pulmonary arterial hypertension: a link to the intrinsic myeloid abnormalities

Blood ◽  
2011 ◽  
Vol 117 (13) ◽  
pp. 3485-3493 ◽  
Author(s):  
Samar Farha ◽  
Kewal Asosingh ◽  
Weiling Xu ◽  
Jacqueline Sharp ◽  
Deepa George ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Endothelial Cells ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Hypoxia Inducible Factor ◽  
Pulmonary Arteries ◽  
Disease Process ◽  
Pulmonary Vasculature ◽  
Normal Numbers ◽  
Pulmonary Arterial

AbstractPulmonary arterial hypertension (PAH) is a proliferative vasculopathy characterized by high circulating CD34+CD133+ proangiogenic progenitors, and endothelial cells that have pathologic expression of hypoxia-inducible factor 1 α (HIF-1α). Here, CD34+CD133+ progenitor cell numbers are shown to be higher in PAH bone marrow, blood, and pulmonary arteries than in healthy controls. The HIF-inducible myeloid-activating factors erythropoietin, stem cell factor (SCF), and hepatocyte growth factor (HGF) are also present at higher than normal levels in PAH blood, and related to disease severity. Primary endothelial cells harvested from human PAH lungs produce greater HGF and progenitor recruitment factor stromal-derived factor 1 α (SDF-1α) than control lung endothelial cells, and thus may contribute to bone marrow activation. Even though PAH patients had normal numbers of circulating blood elements, hematopoietic alterations in myeloid and erythroid lineages and reticulin fibrosis identified a subclinical myeloproliferative process. Unexpectedly, evaluation of bone marrow progenitors and reticulin in nonaffected family members of patients with familial PAH revealed similar myeloid abnormalities. Altogether, the results show that PAH is linked to myeloid abnormalities, some of which may be related to increased production of HIF-inducible factors by diseased pulmonary vasculature, but findings in nonaffected family suggest myeloid abnormalities may be intrinsic to the disease process.

scholarly journals Double-Blind, Placebo-Controlled Clinical Trial With a Rho-Kinase Inhibitor in Pulmonary Arterial Hypertension

2013 ◽  
Vol 77 (10) ◽  
pp. 2619-2625 ◽  
Author(s):  
Yoshihiro Fukumoto ◽  
Norikazu Yamada ◽  
Hiromi Matsubara ◽  
Minori Mizoguchi ◽  
Kazuaki Uchino ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Kinase Inhibitor ◽  
Rho Kinase ◽  
Controlled Clinical Trial ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Rho Kinase Inhibitor ◽  
Pulmonary Arterial

scholarly journals Novel Treatment Pathways in Pulmonary Arterial Hypertension

2021 ◽  
Vol 17 (2) ◽  
pp. 106-114
Author(s):  
Kanza N Qaiser ◽  
Adriano R Tonelli
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Disease Process ◽  
Ongoing Research ◽  
Treatment Pathways ◽  
Pulmonary Vascular Remodeling ◽  
Pulmonary Arterial ◽  
Long Term Prognosis ◽  
New Treatments

Pulmonary arterial hypertension (PAH) is a severe and progressive vascular disease characterized by pulmonary vascular remodeling, proliferation, and inflammation. Despite the availability of effective treatments, PAH may culminate in right ventricular failure and death. Currently approved medications act through three well-characterized pathways: the nitric oxide, endothelin, and prostacyclin pathways. Ongoing research efforts continue to expand our understanding of the molecular pathogenesis of this complex and multifactorial disease. Based on recent discoveries in the pathobiology of PAH, several new treatments are being developed and tested with the goal of modifying the disease process and ultimately improving the long-term prognosis.

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

2017 ◽  
Vol 7 (4) ◽  
pp. 803-807 ◽  
Author(s):  
Arun Jose ◽  
Hind Rafei ◽  
Jalil Ahari
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Vasodilator Therapy ◽  
Pulmonary Vasodilator ◽  
Hypertension Therapy ◽  
Pulmonary Arterial ◽  
Phosphodiesterase 5

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.

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