title: Comparison of outcomes after two standards-of-care reduced-intensity conditioning regimens and two different graft sources for allogeneic stem cell transplantation in adults with hematologic diseases: a single-center analysis.
abstract: Recent advances in allogeneic stem cell transplantation (allo-HSCT) have included the advent of reduced-intensity conditioning (RIC) regimens to decrease the toxicity of myeloablative allo-SCT and the use of double umbilical cord blood (dUCB) units as a graft source in adults lacking a suitable donor. The FB2A2 regimen (fludarabine 30 mg/kg/day for 5-6 days + i.v. busulfan 3.6 mg/kg/day for 2 days + rabbit antithymocyte globulin 2.5 mg/kg/day for 2 days) supported by peripheral blood stem cells (PBSCs) and the TCF regimen (fludarabine 200 mg/m² for 5 days + cyclophosphamide 50 mg/kg for 1 day + low-dose [2 Gy] total body irradiation) supported by dUCB units are currently the most widely used RIC regimens in many centers and could be considered standard of care in adults eligible for an RIC allo-SCT. Here we compared, retrospectively, the outcomes of adults patients who received the FB2A2-PBSC RIC regimen (n = 52; median age, 59 years; median follow-up, 19 months) and those who received the dUCB-TCF RIC regimen (n = 39; median age, 56 years; median follow-up, 20 months) for allo-SCT between January 2007 and November 2010. There were no significant between-group differences in patient and disease characteristics. Cumulative incidences of engraftment, acute grade II-IV and chronic graft-versus-host disease were similar in the 2 groups. The median time to platelet recovery, incidence of early death (before day +100), and 2-year nonrelapse mortality were significantly higher in the dUCB-TCF group (38 days versus 0 days [P <.0001]; 20.5% versus 4% [P = .05], and 26.5% versus 6% [P = .02], respectively). The groups did not differ in terms of 2-year overall survival (62% for FB2A2-PBSC versus 61% for dUCB-TCF), disease-free survival (59% versus 50.5%), or relapse incidence (35.5% versus 23%). In multivariate analysis, the presence of a lymphoid disorder was associated with a significantly higher 2-year overall survival (hazard ratio, 0.42; 95% confidence interval, 0.20-0.87; P = .02), whereas patients receiving a FB2A2-PBSC allo-SCT had a significantly lower 2-year nonrelapse mortality (hazard ratio, 0.24; 95% confidence interval, 0.1-0.7; P = .01). There were no factors associated with higher 2-year disease-free survival or lower relapse incidence. This study suggests that the dUCB-TCF regimen provides a valid alternative in adults lacking a suitable donor and eligible for RIC allo-SCT. Prospective and randomized studies are warranted to establish the definitive role of dUCB RIC allo-SCT in adults. In addition, strategies for decreasing nonrelapse mortality after dUCB RIC allo-SCT are urgently needed.
authors.affiliation: Department and CIC, CHU Hotel Dieu, Nantes, France.
authors.forename: Amandine
authors.initials: A
authors.lastname: Le Bourgeois
authors.forename: Catherine
authors.initials: C
authors.lastname: Mohr
authors.forename: Thierry
authors.initials: T
authors.lastname: Guillaume
authors.forename: Jacques
authors.initials: J
authors.lastname: Delaunay
authors.forename: Florent
authors.initials: F
authors.lastname: Malard
authors.forename: Marion
authors.initials: M
authors.lastname: Loirat
authors.forename: Pierre
authors.initials: P
authors.lastname: Peterlin
authors.forename: Nicolas
authors.initials: N
authors.lastname: Blin
authors.forename: Viviane
authors.initials: V
authors.lastname: Dubruille
authors.forename: Beatrice
authors.initials: B
authors.lastname: Mahe
authors.forename: Thomas
authors.initials: T
authors.lastname: Gastinne
authors.forename: Steven
authors.initials: S
authors.lastname: Le Gouill
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreau
authors.forename: Mohamad
authors.initials: M
authors.lastname: Mohty
authors.forename: Lucie
authors.initials: L
authors.lastname: Planche
authors.forename: Laurence
authors.initials: L
authors.lastname: Lode
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Bene
authors.forename: Patrice
authors.initials: P
authors.lastname: Chevallier
mesh_terms: D000328:Adult; D000368:Aged; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D002066:Busulfan / Q000627:therapeutic use; D036101:Cord Blood Stem Cell Transplantation; D003520:Cyclophosphamide / Q000627:therapeutic use; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D019337:Hematologic Neoplasms / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use*; D036102:Peripheral Blood Stem Cell Transplantation; D012008:Recurrence; D012189:Retrospective Studies; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D000961:Antilymphocyte Serum; D019653:Myeloablative Agonists; D003520:Cyclophosphamide; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine