TREATMENT OF REFRACTORY CHRONIC GVHD WITH RITUXIMAB I. Vicuña (1), R TREATMENT OF REFRACTORY CHRONIC GVHD WITH RITUXIMAB I. Vicuña (1), R. Forés (1), D. Caballero (2), J. García-Marco (1), M. J. Pascual (3), J. De la Serna (4), R. Duarte (5), C. Barrenetxea (6), A. Martinez (7), M.A. Diaz (8), J.M. Ribera (9), G. Bravo (1), J. Cartier (1), A. Sebrango (1), B. Navarro (1) y J.R. Cabrera (1) on behalf of the GETH (Grupo Español de Trasplante Hematopoyético) Spanish Cooperative Group. (1) H. Puerta de Hierro; (2).H C. Salamanca , (3) H. Carlos Haya, (4) H. Doce de Octubre, (5) H. Duran i Reynals, (6) H. Vall d’’Hebron, (7) H. La Paz, (8) H. Niño Jesús, (9) H. Germans Trias i Pujol Replace with logo Introduction Rituximab was given IV at a weekly dose of 375 mg/m2 with 94% of patients receiving 4 doses. Four patients (12%) had mild adverse effects during infusion: fever (2), bronchospasm (1), pharyngeal symptoms (1), hypotension (1). - Time (months) from transplantation to diagnosis of cGVHD (median) : 7 (range 3 -156). - All cases were refractory to several treatment lines, median 2 (range 1-5). Twenty four patients had cutaneous involvement. Other sites of organ involvement frecuently were mouth, eyes and liver. cGVHD: “de novo” 3 Quiescent 16 Progresive 10 Post-DLI 2 Lim./extensive 6/26 Interm./High (Akpek): 64% NIH skin grade (Fig.2) - Results could be evaluated in 30 patients: overall response rate was 80% (10% complete response, 70% partial response). (Fig.4) - The best response rates were observed in cases with skin ( 70%), oral (80%) or liver (70%) involvement and in patients with peripheral cytopenias. (Fig3). - Response was transitory in 16 of the responsive patients with a median of 8 months. - Seven patients (23%) developed bronchiolitis obliterans (BO) after treatment. (Fig 5). - Clinical relapse was only observed in 2 cases of Hodgkin´s lymphoma. There is no standard therapy for patients with chronic graft-versus-host disease (cGVHD) who do not respond to first-line therapy with steroids. Rituximab has been shown to induce clinical response in a proportion of patients with refractory cGVHD. OVERALL RESPONSE (30 patients) Fig. 2 Results Methods DISEASE FREE SURVIVAL: 68% at 5 years - LIVE (23): 4 without treatment. - DEATHS (8): - Pneumonia (2) - Myocardial infarction (1) - Multiorgan system failure (1) - Bronchiolitis obliterans (2) - Infection (1) - Necrotic epidermolysis+ aGVHD (1) Retrospective study (nine hospitals from Spain). Patientes (n.) 31 Age (years) 37 (13 – 65) Male/female 19/12 Disease: - AML 10 - ALL/LL 4 - NHL 5 - CML 4 - HD 3 - Other 5 Stem cell transplant: - HLA-identical sibling/other 23/8 - PB/BM/Cord blood 24/6/1 - Myeloablative/RIC 15/16 - aGVHD proph. CyA+MTX/Other 26/5 - Acute GVHD (grade) Fig. 4 Days Fig. 6 Adverse effects: Progressive Multifocal Leucoencephalopathy: No cases (0%). Others: Acute myocardial infarction (1). Pulmonary infiltrates (BOOP) (1). Psoriasis (1). Hepatitis (1). Bronchiolitis obliterans (BO): 7 patients (23%). Conclusions 1- Rituximab treatment represents a therapeutic option for patients with refractory cGVHD. 2- Overall response rate is high but transient in many cases. 3- We have observed a high percentage of patients who had developed bronchiolitis obliterans after treatment. Fig. 5 Fig. 3 Fig. 1 Printed by