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Blood, 16 July 2009, Vol. 114, No. 3, pp. 709-718.
Prepublished online as a Blood First Edition Paper on April 29, 2009; DOI 10.1182/blood-2009-02-204156.
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Submitted February 10, 2009
Accepted April 13, 2009
Imatinib for refractory chronic graft-versus-host-disease with fibrotic features
Attilio Olivieri*, Franco Locatelli, Marco Zecca, Adele Sanna, Michele Cimminiello, Roberto Raimondi, Guido Gini, Nicola Mordini, Adriana Balduzzi, Pietro Leoni, Armando Gabrielli, and Andrea Bacigalupo
Department of Hematology, San Carlo Hospital, Potenza, Italy
Pediatric Hematology/Oncology, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
Unit of Bone Marrow Transplantation, Ospedale Regionale per le Microcitemie, Cagliari, Italy
Department of Hematology, St Bortolo Hospital, Vicenza, Italy
Department of Hematology, Universita Politecnica delle Marche-Ancona, Ancona, Italy
Department of Hematology, Santa Croce e Carle Hospital, Cuneo, Italy
Department of Pediatric Hematology, San Gerardo Hospital, Monza, Italy
Department of Internal Medicine, Universita Politecnica delle Marche-Ancona, Ancona, Italy
Hematology Unit and Stem Cell Transplant Unit, San Martino Hospital, Genova, Italy
* Corresponding author; email: attilio.olivieri{at}ospedalesancarlo.it.
We previously reported that patients with fibrotic, chronic graft-versus-host disease (cGvHD) have antibodies activating the platelet-derived growth factor receptor (PDGF-R) pathway. As this pathway can be inhibited by Imatinib, we carried out a pilot study including 19 patients with refractory cGvHD, given Imatinib at a starting dose of 100 mg/day. All patients had active cGvHD with measurable involvement of skin or other districts and had previously failed at least 2 treatment lines. Patient median age was 29 years (range 10-62), while median duration of cGVHD was 37 months (range 4-107). The organs involved were: skin (n=17), lung (n=11) and bowel (n=5); 15 patients had sicca syndrome. Imatinib-related, grade 3-4 toxicity included fluid retention, infections and anemia. Imatinib was discontinued in 8 patients: in 3 because of toxicity and in 5 due to lack of response (3) or relapse of malignancy(2). The overall response rate at 6 months was 79%, with 7 complete remissions (CR) and 8 partial remissions (PR). With a median follow up of 17 months, 16 patients are alive, 14 still in CR or PR. The 18-month probability of overall survival is 84%. This study suggests that Imatinib is a promising treatment for patients with refractory fibrotic cGvHD.
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