title: Autologous versus reduced-intensity allogeneic hematopoietic cell transplantation for patients with chemosensitive follicular non-Hodgkin lymphoma beyond first complete response or first partial response.
abstract: Patients with follicular lymphoma (FL) typically experience an indolent course; however, the disease is rarely curable with conventional chemotherapy. Autologous hematopoietic cell transplantation (HCT) can extend progression-free survival (PFS) and overall survival (OS), but relapse is the primary cause of failure. Allogeneic HCT confers lower relapse rates due to a graft-versus-lymphoma effect. Reduced-intensity conditioning (RIC) allows the performance of allogeneic HCT with lower toxicity. The Blood and Marrow Transplant Clinical Trials Network conducted a prospective multicenter trial comparing these two strategies in patients with relapsed, chemotherapy-sensitive FL. Patients were assigned to a treatment arm based on the availability of an HLA-matched sibling donor (MSD). Those with an MSD underwent allogeneic HCT (n = 8) with the FCR preparative regimen (fludarabine, cyclophosphamide [Cy], rituximab [RTX]) and received tacrolimus and methotrexate for graft-versus-host disease (GVHD) prophylaxis. Those without an MSD (n = 22) underwent mobilization with Cy, RTX, and filgrastim and received a conditioning regimen of either CBV (Cy, carmustine, Etoposide [VP16]) or total body irradiation with Cy and VP16. Patients undergoing autologous HCT received 4 doses of weekly maintenance RTX (375 mg/m²) starting on day +42 post-HCT. Sixteen patients were in complete remission, 10 patients were in partial remission, and 1 patient had stable disease after salvage therapy and before HCT. Median follow-up was 36 months (range, 1-51 months). OS was 73% in autologous HCT versus 100% in allogeneic HCT, and PFS was 63% in autologous HCT versus 86% in allogeneic HCT. No patient had grade II-IV acute GVHD; two patients developed extensive chronic GVHD. Three autologous recipients died from nonrelapse causes. This trial closed early because of slow accrual. We show that the FCR regimen is well tolerated, and that both allogeneic and autologous HCT result in promising 3-year OS and PFS in patients with relapsed FL.
authors.affiliation: Blood and Marrow Transplant Program, H. Lee Moffitt Cancer and Research Center, Tampa, Florida, USA.
authors.forename: Marcie R
authors.initials: MR
authors.lastname: Tomblyn
authors.forename: Marian
authors.initials: M
authors.lastname: Ewell
authors.forename: Christopher
authors.initials: C
authors.lastname: Bredeson
authors.forename: Brad S
authors.initials: BS
authors.lastname: Kahl
authors.forename: Stacey A
authors.initials: SA
authors.lastname: Goodman
authors.forename: Mary M
authors.initials: MM
authors.lastname: Horowitz
authors.forename: Julie M
authors.initials: JM
authors.lastname: Vose
authors.forename: Robert S
authors.initials: RS
authors.lastname: Negrin
authors.forename: Ginna G
authors.initials: GG
authors.lastname: Laport
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control; D020350:Graft vs Tumor Effect; D006680:HLA Antigens / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000706:statistics & numerical data; D006648:Histocompatibility; D006801:Humans; D019520:Living Donors; D008224:Lymphoma, Follicular / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D012074:Remission Induction; D000069283:Rituximab; D016879:Salvage Therapy; D035781:Siblings; D016559:Tacrolimus / Q000627:therapeutic use; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods*; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D014916:Whole-Body Irradiation
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D006680:HLA Antigens; D000069283:Rituximab; D005047:Etoposide; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine; D016559:Tacrolimus; D008727:Methotrexate