Dasatinib therapy can result in significant pulmonary toxicity

Abstract

thromboembolism (VTE) in SCD, with a higher mortality observed in patients with VTE compared to those without this complication [5].There are few studies specifically addressing treatment of PHT in SCD. Current strategies include optimizing SCD therapy and identifying potentially modifiable etiologies such as obstructive sleep apnea, pulmonary thrombosis, and left ventricular dysfunction. Hydroxyurea, approved for treatment of severe anemia and frequent vaso-occlusive episodes, has the potential benefit of being an NO donor. Endothelin receptor antagonists and prostaglandin therapy are approved for treatment of pulmonary arterial hypertension and have been recommended for select SCD patients with marked elevation of pulmonary vascular resistance and normal pulmonary artery occlusion pressure on RHC, and related symptoms [1]. Phosphodiesterase-5 inhibitor therapy is presently not recommended as first-line treatment for RHC-confirmed PHT due to the association of sildenafil with increased hospitalizations for pain crises. Riociguat, a soluble guanylate cyclase stimulator, is a vasodilator that bypasses the NO pathway. It has shown promise in CTEPH and PAH, but has not yet been studied in SCD. Although a study of the low molecular weight heparin, tinzaparin showed a reduction in the duration of pain crisis and hospitalization [6], most studies of anticoagulants in SCD have been small and poorly controlled. Treatment with the factor Xa inhibitor, rivaroxaban, as well as PAR-2 or IL-6 deficiency have been reported to attenuate PHT in animal models [7]. A study of rivaroxaban in SCD is ongoing to assess its pharmacodynamics effects (www.clinical trials.gov. identifier NCT02072668). Finally, pulmonary endarterectomy is standard for non-SCD patients with CTEPH, but the experience in SCD is limited, possibly due to concerns for a high risk of perioperative complications. Pulmonary endarterectomy requires cardiopulmonary bypass, hypothermia, and periods of circulatory arrest, which will likely increase the risk of sickling. These two cases, along with the previously published reports of four patients who underwent pulmonary endarterectomy [8][9][10], demonstrate that patients can undergo this procedure safely, with symptomatic and hemodynamic benefit. In summary, SCD patients with CTEPH, should be considered for pulmonary endarterectomy. AcknowledgmentAuthors thank Ertan Pamuklar, MD for help with the figure.

Pneumocystis jirovecii-associated immune reconstitution inflammatory syndrome-like phenomenon in a child with leukaemia: a case report and literature review

“…Though there is no previous report showing that G-CSF can induce IRIS, in this case, we consider G-CSF as a promoter of IRIS-like reaction by increasing the number and function of neutrophils [ 13 ], which in turn enhances the neutrophil-mediated inflammatory response. Furthermore, the use of chemotherapeutic agents which had pulmonary toxicity could also lead to lung injuries, such as dasatinib and cyclophosphamide [ 14 , 15 ], although they were not regarded as the main reason in this case.…”

The incidence and natural history of dasatinib complications in the treatment of chronic myeloid leukemia

“…We concur with recently published suggestions that a baseline transthoracic echocardiogram, particularly in the elderly and those with risk factors for PHTN (age .60, smoking history, diabetes mellitus, hypertension, known cardiovascular disease), should be considered when initiating dasatinib therapy to exclude preexisting PHTN. 24,25 In view of the association between PHTN and pleural effusion, a transthoracic echocardiogram should also be performed in patients presenting with pleural effusion.…”

Chronic myeloid leukaemia and tyrosine kinase inhibitor therapy: assessment and management of cardiovascular risk factors

“…Reported rates of PAH during dasatinib treatment vary between 0.45% in a French registry up to 25% in a small retrospective study . These cases of PAH were clinically significant events, requiring medical intervention and cessation of dasatinib.…”

“…Reported rates of PAH during dasatinib treatment vary between 0.45% in a French registry up to 25% in a small retrospective study. 13,14 These cases of PAH were clinically significant events, requiring medical intervention and cessation of dasatinib. Clinical and haemodynamic improvement was seen in most patients within 9 months of discontinuing dasatinib in the registry data.…”