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Title: Chemotherapy-Induced Pulmonary Hypertension: Role of Alkylating Agents
Authors: Ranchoux, Benoît ×
Günther, Sven
Quarck, Rozenn
Chaumais, Marie-Camille
Dorfmüller, Peter
Antigny, Fabrice
Dumas, Sébastien J
Raymond, Nicolas
Lau, Edmund
Savale, Laurent
Jaïs, Xavier
Sitbon, Olivier
Simonneau, Gérald
Stenmark, Kurt
Cohen-Kaminsky, Sylvia
Humbert, Marc
Montani, David
Perros, Frédéric #
Issue Date: Feb-2015
Series Title: American Journal of Pathology vol:185 issue:2 pages:356-71
Article number: S0002-9440(14)00654-3
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.
URI: 
ISSN: 0002-9440
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Pneumology
× corresponding author
# (joint) last author

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