title: Effectiveness of subcutaneous low-dose alemtuzumab and rituximab combination therapy for steroid-resistant chronic graft-versus-host disease.
abstract: BACKGROUND
  Chronic graft-versus-host disease is a common late complication of allogeneic hematopoietic stem cell transplantation. Corticosteroids are the standard initial treatment. Second-line treatment has not been well defined. We evaluated the effectiveness and safety of low doses of alemtuzumab plus low doses of rituximab in the treatment of steroid-refractory chronic graft-versus-host disease.
  
  
  METHODS
  Ten men and 5 women were prospectively included in the study. All patients received one cycle of subcutaneous alemtuzumab 10 mg/day/3 days and intravenous rituximab 100 mg on Days +4, +11, +18 and +25. The therapeutic response was measured on Days +30, +90 and +365 of the protocol.
  
  
  RESULTS
  Median age was 41 years. The main site involved was the oral mucosa (86.7%) followed by the eyes (66.7%), liver (60%), skin (53%), lungs (13.3%) and intestinal tract (6.7%). The overall response was 100% at Day +30 evaluation: 10 patients (67%) had partial remission, 5 (33%) had complete remission. At Day +90 evaluation, 7 (50%) patients had partial remission, 4 (28%) had complete remission; 3 (21%) had relapsed chronic graft-versus-host disease and one patient did not reach the evaluation time point. So far, 5 patients have reached the Day +365 follow-up evaluation; 2 (40%) had partial remission, 2 had complete remission and one experienced chronic graft-versus-host disease progression. Adverse effects were mainly infections in 67% of patients; these were all quickly solved, except for one patient who died from pneumonia.
  
  
  CONCLUSIONS
  This combination therapy appears to be an efficacious and safe treatment for steroid-refractory chronic graft-versus-host disease. Longer follow up to determine the durability of response and survival is required (ClinicalTrials.gov: NCT01042509).
authors: Service of Hematology, Hospital Universitario Dr José E González Universidad Autónoma de Nuevo León, Monterrey, NL, México.
authors: Cesar Homero
authors: CH
authors: Gutiérrez-Aguirre
authors: Olga Graciela
authors: OG
authors: Cantú-Rodríguez
authors: Omar David
authors: OD
authors: Borjas-Almaguer
authors: Oscar
authors: O
authors: González-Llano
authors: José Carlos
authors: JC
authors: Jaime-Pérez
authors: Manuel
authors: M
authors: Solano-Genesta
authors: Miguel
authors: M
authors: Gómez-Guijosa
authors: Consuelo
authors: C
authors: Mancias-Guerra
authors: Luz
authors: L
authors: Tarin
authors: David
authors: D
authors: Gómez-Almaguer
mesh_terms: D000328:Adult; D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012074:Remission Induction; D000069283:Rituximab; D013256:Steroids / Q000494:pharmacology*; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D013256:Steroids; D000074323:Alemtuzumab; D000069283:Rituximab