title: Long-term outcome and prospective validation of NIH response criteria in 39 patients receiving imatinib for steroid-refractory chronic GVHD.
abstract: 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.
authors.affiliation: Clinica di Ematologia, Università Politecnica delle Marche, Ancona, Italy;
authors.forename: Attilio
authors.initials: A
authors.lastname: Olivieri
authors.forename: Michele
authors.initials: M
authors.lastname: Cimminiello
authors.forename: Paolo
authors.initials: P
authors.lastname: Corradini
authors.forename: Nicola
authors.initials: N
authors.lastname: Mordini
authors.forename: Roberta
authors.initials: R
authors.lastname: Fedele
authors.forename: Carmine
authors.initials: C
authors.lastname: Selleri
authors.forename: Francesco
authors.initials: F
authors.lastname: Onida
authors.forename: Francesca
authors.initials: F
authors.lastname: Patriarca
authors.forename: Enzo
authors.initials: E
authors.lastname: Pavone
authors.forename: Silvia
authors.initials: S
authors.lastname: Svegliati
authors.forename: Armando
authors.initials: A
authors.lastname: Gabrielli
authors.forename: Paola
authors.initials: P
authors.lastname: Bresciani
authors.forename: Roberta
authors.initials: R
authors.lastname: Nuccorini
authors.forename: Sara
authors.initials: S
authors.lastname: Pascale
authors.forename: Sabrina
authors.initials: S
authors.lastname: Coluzzi
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Pane
authors.forename: Antonella
authors.initials: A
authors.lastname: Poloni
authors.forename: Jacopo
authors.initials: J
authors.lastname: Olivieri
authors.forename: Pietro
authors.initials: P
authors.lastname: Leoni
authors.forename: Andrea
authors.initials: A
authors.lastname: Bacigalupo
mesh_terms: D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000009:adverse effects; D001323:Autoantibodies / Q000097:blood; D001549:Benzamides / Q000008:administration & dosage* / Q000009:adverse effects; D002908:Chronic Disease; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000097:blood / Q000188:drug therapy* / Q000401:mortality*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D000068877:Imatinib Mesylate; D008232:Lymphoproliferative Disorders; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic / Q000379:methods; D009196:Myeloproliferative Disorders / Q000401:mortality / Q000628:therapy; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D011239:Prednisolone / Q000008:administration & dosage / Q000009:adverse effects; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D017479:Receptors, Platelet-Derived Growth Factor / Q000097:blood; D012720:Severity of Illness Index; D015996:Survival Rate; D013997:Time Factors
chemical_list: D018931:Antineoplastic Agents, Hormonal; D001323:Autoantibodies; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011239:Prednisolone; D017479:Receptors, Platelet-Derived Growth Factor