Gleevec for graft versus host disease – pro

Chronic graft-vs-host disease (GVHD) is the most common complication of allogeneic hematopoietic stem cell transplantation (HSCT). Patients with chronic GVHD can have infections and a variety of complications due to multiple abnormalities of their reconstructed immune systems. Infection is the most common cause of death in patients with chronic GVHD. Chronic GHVD may also compromise a patient’s quality of life as a result of long-term immunosuppressive therapy and the symptoms of GVHD itself. Chronic GVHD is the major determinant in the survival and quality of life of patients after allogeneic HSCT.

The primary strategy to prevent GVHD is the use of cyclosporine and tacrolimus in combination with other immunosuppressants. Despite these prophylactic therapies, GVHD still develops in 30%-80% of patients. One of the newer potentially promising agents is Gleevec. It is especially attractive for patients transplanted for CML or Philadelphia chromosome positive ALL, where Gleevec has an anti leukemia effect as well.

There are two small phase II studies and a restrospective review as well as case series and reports. In the consensus paper published by the Consensus Conference of Clinical Practice in Chronic GVHD wrote:“Use in greater than second-line treatment justified” based upon “Evidence from opinions of respected authorities based on clinical experience, descriptive studies or reports from expert committees”. A 2012 guideline (Dinghan et al) recommends it for second line treatment.

DDignan FL, Amrolia P, Clark A, Cornish J, Jackson G, Mahendra P, Scarisbrick JJ, Taylor PC, Shaw BE, Potter MN, on behalf of the Haemato-oncology Task Force of the British Committee [trunc]. Diagnosis and management of chronic graft-versus-host disease. Br J Haematol 2012 Jul;158(1):46-61. [125 references]

Wolff D. Schleuning M. von Harsdorf S. Bacher U. Gerbitz A. Stadler M. Ayuk F. Kiani A. Schwerdtfeger R. Vogelsang GB. Kobbe G. Gramatzki M. Lawitschka A. Mohty M. Pavletic SZ. Greinix H. Holler E. Consensus Conference on Clinical Practice in Chronic GVHD: Second-Line Treatment of Chronic Graft-versus-Host Disease. Biology of Blood & Marrow Transplantation. 17(1):1-17, 2011.

Magro L. Mohty M. Catteau B. Coiteux V. Chevallier P. Terriou L. Jouet JP. Yakoub-Agha I. Imatinib mesylate as salvage therapy for refractory sclerotic chronic graft-versushost disease. Blood. 114(3):719-22, 2009.

Magro L, Catteau B, Coiteux V, Bruno B, Jouet JP, Yakoub-Agha I. Efficacy of imatinib mesylate in the treatment of refractory sclerodermatous chronic GVHD.Bone Marrow Transplant. 2008 Dec;42(11):757-60.

IJuan A. Moreno-Romero, MD; Francesc Fernández-Avilés, MD; Enric Carreras, MD; Montserrat Rovira, MD; Carmen Martínez, MD; José M. Mascaró Jr, MD Imatinib as a Potential Treatment for Sclerodermatous Chronic Graft-vs-Host Disease Arch Dermatol. 2008;144(9):1106-1109.

Attilio Olivieri et al, Imatinib for refractory chronic graft-versus-host disease with fibrotic features, Blood July 16, 2009 vol. 114 no. 3 709-718

Leonardo Magro et al, Imatinib mesylate as salvage therapy for refractory sclerotic chronic graft-versus-host disease Blood July 16, 2009 vol. 114 no. 3 719-722

Olivieri A. Locatelli F. Zecca M. Sanna A. Cimminiello M. Raimondi R. Gini G. Mordini N. Balduzzi A. Leoni P. Gabrielli A. Bacigalupo A. Imatinib for refractory chronic graftversus-host disease with fibrotic features. Blood. 114(3):709-18, 2009.

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