title: Ibritumomab tiuxetan (Zevalin) combined with reduced-intensity conditioning and allogeneic stem-cell transplantation (SCT) in patients with chemorefractory non-Hodgkin's lymphoma.
abstract: Allogeneic SCT is an effective therapy for lymphoma. Reduced-intensity conditioning (RIC) reduces non-relapse mortality (NRM) associated with myeloablative conditioning but relapse rates are high when performed in active disease. This study was designed to explore the safety and outcome of ibritumomab tiuxetan (Zevalin) combined with RIC in patients with advanced lymphoma. The study included 12 patients, median age 54 years (37-62), with a median of four prior treatments (2-6) and active disease documented on PET-CT. Zevalin 0.4 mCi/kg was given on day -14 and fludarabine combined with BU (n=6) or melphalan (n=6) was started on day -6. GVHD prevention was tapered 3 months after SCT to augment the graft-versus-lymphoma effect. All patients engrafted, a median of 14 days after SCT. Eighty-three percent achieved CR/PR. With a median follow-up of 21 months (12-37), 2-year PFS is 33%. Only three patients relapsed; cumulative incidence 25%. NRM was 42%, predominantly due to acute GVHD. Zevalin-RIC is feasible with consistent engraftment, acceptable organ toxicity, but high rates of acute GVHD. The low incidence of relapse suggests augmented anti-lymphoma effect. Zevalin-RIC merits further study. Better results may be achieved in patients earlier in disease course and with longer duration of immune-suppression.
authors.affiliation: The Division of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel-Hashomer, Israel. ashimoni@sheba.health.gov.il
authors.forename: A
authors.initials: A
authors.lastname: Shimoni
authors.forename: S T
authors.initials: ST
authors.lastname: Zwas
authors.forename: Y
authors.initials: Y
authors.lastname: Oksman
authors.forename: I
authors.initials: I
authors.lastname: Hardan
authors.forename: N
authors.initials: N
authors.lastname: Shem-Tov
authors.forename: A
authors.initials: A
authors.lastname: Rand
authors.forename: R
authors.initials: R
authors.lastname: Yerushalmi
authors.forename: A
authors.initials: A
authors.lastname: Avigdor
authors.forename: I
authors.initials: I
authors.lastname: Ben-Bassat
authors.forename: A
authors.initials: A
authors.lastname: Nagler
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use*; D016499:Radioimmunotherapy / Q000379:methods; D012074:Remission Induction; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D020866:omega-Conotoxin GVIA
chemical_list: D000911:Antibodies, Monoclonal; D019653:Myeloablative Agonists; C422802:ibritumomab tiuxetan; D020866:omega-Conotoxin GVIA