Skip to Content
MilliporeSigma

Chemotherapy-induced pulmonary hypertension: role of alkylating agents.

The American journal of pathology (2014-12-17)
Benoît Ranchoux, Sven Günther, Rozenn Quarck, Marie-Camille Chaumais, Peter Dorfmüller, Fabrice Antigny, 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
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Glycerol solution, 83.5-89.5% (T)
Sigma-Aldrich
Glycerol solution, puriss., meets analytical specification of Ph. Eur., BP, 84-88%
Supelco
Glycerin, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Ethylenediaminetetraacetic acid, 99.995% trace metals basis
Sigma-Aldrich
Ethylenediaminetetraacetic acid disodium salt solution, BioUltra, for molecular biology, pH 8.0, ~0.5 M in H2O
Sigma-Aldrich
Ethylenediaminetetraacetic acid, BioUltra, ≥99.0% (KT)
Sigma-Aldrich
Glycerin, meets USP testing specifications
Sigma-Aldrich
Glycerol, FCC, FG
Sigma-Aldrich
Ethylenediaminetetraacetic acid, ≥98.0% (KT)
Sigma-Aldrich
Glycerol, BioUltra, for molecular biology, anhydrous, ≥99.5% (GC)
Sigma-Aldrich
Glycerol, for molecular biology, ≥99.0%
Sigma-Aldrich
Glycerol, BioReagent, suitable for cell culture, suitable for insect cell culture, suitable for electrophoresis, ≥99% (GC)
Sigma-Aldrich
Ethylenediaminetetraacetic acid solution, 0.02% in DPBS (0.5 mM), sterile-filtered, BioReagent, suitable for cell culture
Sigma-Aldrich
Ethylenediaminetetraacetic acid, ACS reagent, 99.4-100.6%, powder
Sigma-Aldrich
Ethylenediaminetetraacetic acid, anhydrous, crystalline, BioReagent, suitable for cell culture
Sigma-Aldrich
Ethylenediaminetetraacetic acid, purified grade, ≥98.5%, powder
Sigma-Aldrich
Ethylenediaminetetraacetic acid, anhydrous, BioUltra, ≥99% (titration)
Sigma-Aldrich
Glycerol, BioXtra, ≥99% (GC)
Sigma-Aldrich
Glycerol, ≥99.5%
USP
Glycerin, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Glycerol, tested according to Ph. Eur., anhydrous
Supelco
Glycerol, analytical standard
Sigma-Aldrich
Glycerol, puriss., anhydrous, 99.0-101.0% (alkalimetric)
Sigma-Aldrich
Glycerol, ACS reagent, ≥99.5%
Sigma-Aldrich
Glycerol, ReagentPlus®, ≥99.0% (GC)
Sigma-Aldrich
Glycerol, puriss. p.a., ACS reagent, anhydrous, dist., ≥99.5% (GC)