Blood, 2013-12-12, Vol.122 (25), p.4111-4118
Forty adults aged 28 to 73 years were entered into a prospective trial of imatinib for the treatment of steroid-refractory chronic graft-versus-host disease (SR-cGVHD). After 6 months, intention-to-treat (ITT) analysis of 39 patients who received the drug, regardless of the duration of treatment, revealed 14 partial responses (PR), 4 minor responses (MR) with relevant steroid sparing (46%) according to Couriel criteria, and 20 ≥ PR (51.3%), as per the National Institutes of Health (NIH) criteria and NIH severity score changes. The best responses were seen in the lungs, gut, and skin (35%, 50%, and 32%, respectively). After a median follow-up of 40 months, 28 patients were alive, with a 3-year overall survival (OS) and event-free survival of 72% and 46%, respectively. The 3-year OS was 94% for patients responding at 6 months and 58% for nonresponders according to NIH response, suggesting that these criteria represent a reliable tool for predicting OS after second-line treatment. Monitoring of anti-platelet-derived growth factor receptor (PDGF-R) antibodies showed a significant decrease in PDGF-R stimulatory activity in 7 responders, whereas it remained high in 4 nonresponders. This study confirms the efficacy of imatinib against SR-cGVHD and suggests that the response at 6 months significantly predicts long-term survival.
Piperazines - administration & dosage ; Prednisolone - adverse effects ; Prednisolone - administration & dosage ; Prospective Studies ; Follow-Up Studies ; Lymphoproliferative Disorders ; Autoantibodies - blood ; Humans ; Middle Aged ; Male ; Protein Kinase Inhibitors - adverse effects ; Antineoplastic Agents, Hormonal - adverse effects ; Benzamides - administration & dosage ; Graft vs Host Disease - mortality ; Time Factors ; Receptors, Platelet-Derived Growth Factor - blood ; Adult ; Female ; Benzamides - adverse effects ; Severity of Illness Index ; Myeloproliferative Disorders - therapy ; Pyrimidines - administration & dosage ; Antineoplastic Agents, Hormonal - administration & dosage ; Hematopoietic Stem Cell Transplantation ; Survival Rate ; Graft vs Host Disease - blood ; Imatinib Mesylate ; Piperazines - adverse effects ; Disease-Free Survival ; Protein Kinase Inhibitors - administration & dosage ; Graft vs Host Disease - drug therapy ; Pyrimidines - adverse effects ; Monitoring, Physiologic - methods ; Aged ; Chronic Disease ; Myeloproliferative Disorders - mortality ; Index Medicus ; Abridged Index Medicus
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