title: Phase II Trial of Tandem High-Dose Chemotherapy with Autologous Stem Cell Transplantation Followed by Reduced-Intensity Allogeneic Stem Cell Transplantation for Patients with High-Risk Lymphoma.
abstract: Many patients with lymphoma relapse after autologous stem cell transplantation (AutoSCT). These patients are often considered for allogeneic stem cell transplantation (AlloSCT) if remission can be achieved. If a tandem approach was organized, some cases of relapse might be prevented. We conducted a phase II trial of tandem AutoSCT followed by reduced-intensity conditioning (RIC) AlloSCT for patients with high-risk lymphoma. High-dose chemotherapy was given with busulfan, cyclophosphamide, and etoposide. AlloSCT was composed of RIC with busulfan/fludarabine and tacrolimus, sirolimus, and methotrexate as graft-versus-host disease (GVHD) prophylaxis. Donors were fully matched related or unrelated donors. AlloSCT was performed any time between 40 days and 6 months after AutoSCT. Forty-two patients were enrolled, and all patients underwent AutoSCT. RIC AlloSCT was performed in 29 patients. In the 29 patients who underwent tandem transplant, median time from AutoSCT to AlloSCT was 96 days (range, 48 to 169). The 6-month cumulative incidence of grades II to IV acute GVHD was 13.8% (90% confidence interval [CI], 5.3% to 26.3%). Cumulative incidence of chronic GVHD at 1 year was 37.9% (90% CI, 23.1% to 52.7%). Nonrelapse mortality at 2 years after AlloSCT was 11.1% (90% CI, 3.5% to 23.6%). At a median follow-up of 30 months (range, 17.1 to 51.5) for the entire group, the 2-year progression-free survival rate was 64% (90% CI, 50% to 75%) and the 2-year overall survival rate was 69% (90% CI, 43% to 85%). For the 29 patients who underwent tandem SCT, the 2-year progression-free survival rate was 72% (90% CI, 55% to 83%) and the 2-year OS rate was 89% (90% CI, 74% to 96%). Tandem AutoSCT-RIC AlloSCT appears to be safe and effective in patients with high-risk lymphoma. Prospective trials using such an approach in specific lymphoma subtypes are warranted.
authors.affiliation: Division of Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts. Electronic address: ychen6@partners.org.
authors.forename: Yi-Bin
authors.initials: YB
authors.lastname: Chen
authors.affiliation: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Shuli
authors.initials: S
authors.lastname: Li
authors.affiliation: Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: David C
authors.initials: DC
authors.lastname: Fisher
authors.affiliation: Division of Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Jessica
authors.initials: J
authors.lastname: Driscoll
authors.affiliation: Division of Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Candice
authors.initials: C
authors.lastname: Del Rio
authors.affiliation: Division of Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Abramson
authors.affiliation: Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Philippe
authors.initials: P
authors.lastname: Armand
authors.affiliation: Division of Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Barnes
authors.affiliation: Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Brown
authors.affiliation: Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Corey
authors.initials: C
authors.lastname: Cutler
authors.affiliation: Division of Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Areej
authors.initials: A
authors.lastname: El-Jawahri
authors.affiliation: Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Vincent T
authors.initials: VT
authors.lastname: Ho
authors.affiliation: Division of Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Ephraim
authors.initials: E
authors.lastname: Hochberg
authors.affiliation: Division of Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Steven
authors.initials: S
authors.lastname: McAfee
authors.affiliation: Division of Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Ronald
authors.initials: R
authors.lastname: Takvorian
authors.affiliation: Division of Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Spitzer
authors.affiliation: Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Antin
authors.affiliation: Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Robert
authors.initials: R
authors.lastname: Soiffer
authors.affiliation: Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Eric
authors.initials: E
authors.lastname: Jacobsen
mesh_terms: D000328:Adult; D000368:Aged; D064591:Allografts; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D064592:Autografts; D002066:Busulfan / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000401:mortality / Q000517:prevention & control; D006801:Humans; D008223:Lymphoma / Q000401:mortality* / Q000628:therapy*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D020123:Sirolimus / Q000008:administration & dosage; D033581:Stem Cell Transplantation; D015996:Survival Rate; D016559:Tacrolimus / Q000008:administration & dosage; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine; D020123:Sirolimus; D016559:Tacrolimus; D008727:Methotrexate
keywords: Auto-allo; Lymphoma; Reduced-intensity conditioning; Tandem transplant