Complete Resolution of Life-Threatening Bleomycin-Induced Pneumonitis After Treatment With Imatinib Mesylate in a Patient With Hodgkin's Lymphoma: Hope for Severe Chemotherapy-Induced Toxicity?

Carnevale-Schianca, Fabrizio; Gallo, Susanna; Rota–Scalabrini, Delia; Sangiolo, Dario; Fizzotti, Marco; Caravelli, Daniela; Capaldi, Antonio; Anselmetti, G; Palesandro, Erica; D’Ambrosio, Lorenzo; Coha, Valentina; Obert, R; Aglietta, Massimo; Grignani, Giovanni

doi:10.1200/jco.2011.35.6733

Cited by 39 publications

(50 citation statements)

References 12 publications

(5 reference statements)

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“…As noted before, this study elucidates previous clinical observations favoring imatinib treatment in edema. 5,11 Combining our study with these clinical observations provides bench-to-bedside evidence for a protective effect of imatinib on endothelial barrier dysfunction and supports clinical development of imatinib as therapeutic approach to edema.…”

Section: Discussionmentioning

confidence: 79%

“…The protective effect of imatinib on brain edema was mainly attributed to PDGFR-␣ inhibition on perivascular astrocytes, 12,13 which is unlikely to explain the protective effects of imatinib observed in pulmonary edema. Otherwise, the descriptive character of mentioned case reports 5,11 limited mechanistic interpretation, although an effect of imatinib on endothelial barrier function was suggested. 5 Little is known about the direct effects of imatinib on the endothelial barrier as main regulator of fluid exchange.…”

Section: Editorial See P 2677 Clinical Perspective On P 2738mentioning

confidence: 99%

“…Yet, increas-ing evidence indicates that imatinib may protect against edema. [11][12][13] A second case report revealed clinical improvement of acute lung injury on initiation of imatinib, 11 whereas two experimental studies demonstrated that imatinib protects against brain edema after stroke. 12,13 The mechanism by which imatinib may protect against edema remains largely unclear.…”

Section: Editorial See P 2677 Clinical Perspective On P 2738mentioning

confidence: 99%

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Effective Treatment of Edema and Endothelial Barrier Dysfunction With Imatinib

et al. 2012

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Background-Tissue edema and endothelial barrier dysfunction as observed in sepsis and acute lung injury carry high morbidity and mortality, but currently lack specific therapy. In a recent case report, we described fast resolution of pulmonary edema on treatment with the tyrosine kinase inhibitor imatinib through an unknown mechanism. Here, we explored the effect of imatinib on endothelial barrier dysfunction and edema formation. Methods and Results-We evaluated the effect of imatinib on endothelial barrier function in vitro and in vivo. In human macro-and microvascular endothelial monolayers, imatinib attenuated endothelial barrier dysfunction induced by thrombin and histamine. Small interfering RNA knock-downs of the imatinib-sensitive kinases revealed that imatinib attenuates endothelial barrier dysfunction via inhibition of Abl-related gene kinase (Arg/Abl2), a previously unknown mediator of endothelial barrier dysfunction. Indeed, Arg was activated by endothelial stimulation with thrombin, histamine, and vascular endothelial growth factor. Imatinib limited Arg-mediated endothelial barrier dysfunction by enhancing Rac1 activity and enforcing adhesion of endothelial cells to the extracellular matrix. Using mouse models of vascular leakage as proof-of-concept, we found that pretreatment with imatinib protected against vascular endothelial growth factor-induced vascular leakage in the skin, and effectively prevented edema formation in the lungs. In a murine model of sepsis, imatinib treatment (6 hours and 18 hours after induction of sepsis) attenuated vascular leakage in the kidneys and the lungs (24 hours after induction of sepsis). Conclusions-Thus, imatinib prevents endothelial barrier dysfunction and edema formation via inhibition of Arg. These findings identify imatinib as a promising approach to permeability edema and indicate Arg as novel target for edema treatment. (Circulation. 2012;126:2728-2738.)

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Section: Discussionmentioning

confidence: 79%

Section: Editorial See P 2677 Clinical Perspective On P 2738mentioning

confidence: 99%

Section: Editorial See P 2677 Clinical Perspective On P 2738mentioning

confidence: 99%

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Effective Treatment of Edema and Endothelial Barrier Dysfunction With Imatinib

et al. 2012

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“…Bleomycin induced pneumonitis occurs in nearly 20% of cancer patients who are administered regimens containing bleomycin (29). With predisposing factors like pulmonary a disorders renal disorders and old bleomycin toxicity can be fatal (30,31).…”

Section: Bleomycin Toxicitymentioning

confidence: 99%

Bleomycin Chemotherapy for Oral Leukoplakia

2017

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“…Bleomycin has long track of being used in experimental studies to induce idiopathic pulmonary fibrosis and pulmonary hypertension [65][66][67][68]. Management usually directed toward supportive treatment, steroids and azathioprine with a possible role for imatinib and bosentan [69][70][71].…”

Section: Bleomycinmentioning

confidence: 99%

Insights into etiological factors of pulmonary hypertension in cancer patients

Al-Mansouri

AL-Obaidi²

2017

Nowotwory. Journal of Oncology

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Pulmonary hypertension is a rare vascular disease that can affect patients with or surviving malignancy resulting in significant morbidity and high mortality. Malignant diseases can lead to elevated pulmonary artery pressure through different mechanisms, either directly by structural obstruction of pulmonary vessels or indirectly through hypercoagulable state or treatment toxicity culminating in high pulmonary vascular resistance. The most common causes of cancer-related pulmonary hypertension are thromboembolic diseases, tumour emboli and treatment toxicity and less commonly intravascular tumours and malignant extrinsic compression. NOWOTWORY J Oncol 2017; 67, 4: 236-242

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Complete Resolution of Life-Threatening Bleomycin-Induced Pneumonitis After Treatment With Imatinib Mesylate in a Patient With Hodgkin's Lymphoma: Hope for Severe Chemotherapy-Induced Toxicity?

Cited by 39 publications

References 12 publications

Effective Treatment of Edema and Endothelial Barrier Dysfunction With Imatinib

Effective Treatment of Edema and Endothelial Barrier Dysfunction With Imatinib

Bleomycin Chemotherapy for Oral Leukoplakia

Insights into etiological factors of pulmonary hypertension in cancer patients

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