Benoît Ranchoux, Sven Günther, Rozenn Quarck, Marie-Camille Chaumais, Peter Dorfmüller, FabriceAntigny, Sébastien J. Dumas, Nicolas Raymond, Edmund Lau, Laurent Savale, Xavier Jaïs, Olivier Sitbon, Gérald Simonneau, Kurt Stenmark, Sylvia Cohen-Kaminsky, Marc Humbert, David Montani, Frédéric Perros
Université Paris-Sud and Hôpital de Bicêtre. Centre Chirurgical Marie Lannelongue. Assistance Publique des Hôpitaux de Paris. KU Leuven. University of Colorado at Denver.
France, Belgium and United States
American Journal of Pathology
Am J Pathol 2015; 185: 356-371
DOI: 10.1016/j.ajpath.2014.10.021
Abstract
Pulmonary veno-occlusive disease (PVOD) is an uncommon form of pulmonary hypertension (PH) characterized by progressive obstruction of small pulmonary veins and a dismal prognosis. Limited case series have reported a possible association between different chemotherapeutic agents and PVOD. We evaluated the relationship between chemotherapeutic agents and PVOD. Cases of chemotherapy-induced PVOD from the French PH network and literature were reviewed. Consequences of chemotherapy exposure on the pulmonary vasculature and hemodynamics were investigated in three different animal models (mouse, rat, and rabbit). Thirty-seven cases of chemotherapy-associated PVOD were identified in the French PH network and systematic literature analysis. Exposure to alkylating agents was observed in 83.8% of cases, mostly represented by cyclophosphamide (43.2%). In three different animal models, cyclophosphamide was able to induce PH on the basis of hemodynamic, morphological, and biological parameters. In these models, histopathological assessment confirmed significant pulmonary venous involvement highly suggestive of PVOD. Together, clinical data and animal models demonstrated a plausible cause-effect relationship between alkylating agents and PVOD. Clinicians should be aware of this uncommon, but severe, pulmonary vascular complication of alkylating agents.
Category
Class I. Pulmonary Veno-occlusive Disease and Pulmonary Capillary Hemangiomatosis
Environmental Factors Associated with Pulmonary Vascular Disease
Animal Models of Pulmonary Vascular Disease and Therapy
Age Focus: Adult Pulmonary Vascular Disease
Fresh or Filed Publication: Filed (PHiled). Greater than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes