title: Nonablative allogeneic hematopoietic transplantation as adoptive immunotherapy for indolent lymphoma: low incidence of toxicity, acute graft-versus-host disease, and treatment-related mortality.
abstract: This study investigated the use of a nonablative conditioning regimen to decrease toxicity and achieve engraftment of an allogeneic blood stem cell transplant, allowing a graft-versus-malignancy effect to occur. All patients had follicular or small cell lymphocytic lymphoma after relapse from a prior response to conventional chemotherapy. Patients received a preparative regimen of fludarabine (25 mg/m(2) given daily for 5 days or 30 mg/m(2) daily for 3 days) and intravenous cyclophosphamide (1 g/m(2) given daily for 2 days or 750 mg/m(2) daily for 3 days). Nine patients received rituximab in addition to the chemotherapy. Tacrolimus and methotrexate were used for graft-versus-host disease (GVHD) prophylaxis. Twenty patients were studied; their median age was 51 years. Twelve were in complete remission (CR) at transplantation. All patients achieved engraftment of donor cells. The median number of days with severe neutropenia was 6. Only 2 patients required more than one platelet transfusion. The cumulative incidence of acute grade II to IV GVHD was 20%. Only one patient developed acute GVHD of greater than grade II. All patients achieved CR. None have had a relapse of disease, with a median follow-up period of 21 months. The actuarial probability of being alive and in remission at 2 years was 84% (95% confidence interval, 57%-94%). Nonablative chemotherapy with fludarabine/cyclophosphamide followed by allogeneic stem cell transplantation is a promising therapy for indolent lymphoma with minimal toxicity and myelosuppression. Further studies are warranted to compare nonablative allogeneic hematopoietic transplantation with alternative treatment strategies.
authors.affiliation: Department of Blood and Marrow Transplantation, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. ikhouri@notes.mdacc.tmc.edu
authors.forename: I F
authors.initials: IF
authors.lastname: Khouri
authors.forename: R M
authors.initials: RM
authors.lastname: Saliba
authors.forename: S A
authors.initials: SA
authors.lastname: Giralt
authors.forename: M S
authors.initials: MS
authors.lastname: Lee
authors.forename: G J
authors.initials: GJ
authors.lastname: Okoroji
authors.forename: F B
authors.initials: FB
authors.lastname: Hagemeister
authors.forename: M
authors.initials: M
authors.lastname: Korbling
authors.forename: A
authors.initials: A
authors.lastname: Younes
authors.forename: C
authors.initials: C
authors.lastname: Ippoliti
authors.forename: J L
authors.initials: JL
authors.lastname: Gajewski
authors.forename: P
authors.initials: P
authors.lastname: McLaughlin
authors.forename: P
authors.initials: P
authors.lastname: Anderlini
authors.forename: M L
authors.initials: ML
authors.lastname: Donato
authors.forename: F F
authors.initials: FF
authors.lastname: Cabanillas
authors.forename: R E
authors.initials: RE
authors.lastname: Champlin
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D058846:Antibodies, Monoclonal, Murine-Derived; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000453:epidemiology* / Q000517:prevention & control; D020350:Graft vs Tumor Effect; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D016219:Immunotherapy, Adoptive; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000401:mortality / Q000628:therapy*; D008224:Lymphoma, Follicular / Q000401:mortality / Q000628:therapy; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D017713:Platelet Transfusion; D012008:Recurrence; D012074:Remission Induction; D000069283:Rituximab; D016559:Tacrolimus / Q000627:therapeutic use; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D007166:Immunosuppressive Agents; D000069283:Rituximab; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine; D016559:Tacrolimus; D008727:Methotrexate