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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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TRANSPLANTATION
Imatinib for refractory chronic graft-versus-host disease with fibrotic features
Attilio Olivieri1,
Franco Locatelli2,*,
Marco Zecca2,
Adele Sanna3,
Michele Cimminiello1,
Roberto Raimondi4,
Guido Gini5,
Nicola Mordini6,
Adriana Balduzzi7,
Pietro Leoni5,
Armando Gabrielli8, and
Andrea Bacigalupo9,*
1 Department of Hematology, San Carlo Hospital, Potenza;
2 Pediatric Hematology/Oncology, Fondazione Instituto Di Ricerca e Cura a Caratiere Scientifica, Policlinico San Matteo, University of Pavia, Pavia;
3 Unit of Bone Marrow Transplantation, Ospedale Regionale per le Microcitemie, Cagliari;
4 Department of Hematology, St Bortolo Hospital, Vicenza;
5 Department of Hematology, Università Politecnica delle Marche, Ancona;
6 Department of Hematology, Santa Croce e Carle Hospital, Cuneo;
7 Department of Pediatric Hematology, San Gerardo Hospital, Monza;
8 Department of Internal Medicine, Università Politecnica delle Marche, Ancona; and
9 Hematology Unit and Stem Cell Transplant Unit San Martino Hospital, Genova, Italy
We previously reported that patients with fibrotic, chronic graft-versus-host disease (cGVHD) have antibodies activating the platelet-derived growth factor receptor pathway. Because this pathway can be inhibited by imatinib, we performed a pilot study including 19 patients with refractory cGVHD, given imatinib at a starting dose of 100 mg per 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 years), and median duration of cGvHD was 37 months (range, 4-107 months). The organs involved were skin (n = 17), lung (n = 11), and bowel (n = 5); 15 patients had sicca syndrome. Imatinib-related, grade 3 to 4 toxicity included fluid retention, infections, and anemia. Imatinib was discontinued in 8 patients: in 3 because of toxicity and in 5 because of lack of response (n = 3) or relapse of malignancy (n = 2). Overall response rate at 6 months was 79%, with 7 complete remissions (CRs) and 8 partial remissions (PRs). 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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