Randomized study of 2 reduced-intensity conditioning strategies for human leukocyte antigen-matched, related allogeneic peripheral blood stem cell transplantation: prospective clinical and socioeconomic evaluation.
BACKGROUND
The optimal intensity of reduced-intensity conditioning (RIC) before allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains uncertain.


METHODS
In this centrally randomized phase 2 study, the authors compared 2 different strategies of RIC. In total, 139 patients (median age, 54 years; range, 21-65 years) with hematologic malignancies underwent allo-HSCT from a human leukocyte antigen-identical sibling after conditioning combining fludarabine with either busulfan and rabbit antithymocyte-globulin (BU-rATG) (n = 69) or total body irradiation (TBI) (n = 70). Postgraft immunosuppression consisted of cyclosporin A in all patients with the addition of mycophenolate-mophetil after TBI.


RESULTS
The median follow-up was 54 months (range, 26-88 months). One-year overall survival rate was identical in both groups. Four patients experienced graft-failure after TBI. The incidence of grade 2 through 4 acute graft-versus-host-disease was greater after BU-rATG than after TBI (47% vs 27%; P = .01), whereas no difference was observed with chronic graft-versus-host-disease. The BU-rATG group had a higher objective response rate (65% vs 46%; P = .05) and a lower relapse rate (27% vs 54%; P < .01). However, the nonrelapse mortality rate was higher after BU-rATG than after TBI (38% vs 22%; P = .027). At 5 years, the overall and progression-free survival rates were 41% and 29%, respectively, and did not differ statistically between groups. A detrimental effect on some parameters of quality of life was more pronounced after BU-rATG, but recovery was identical in both groups. The mean total cost per patient, including the cost to treat disease progression post-transplantation, did not differ statistically between groups.


CONCLUSIONS
Five years after transplantation, the BU-rATG regimen was associated with greater disease control. However, because of the higher nonrelapse mortality rate, this did not translate into better overall or progression-free survival.
Transplant Program, Hematology Department, Paoli Calmettes Institute, Marseille, France. blaised@ipc.unicancer.fr
Didier
D
Blaise
Reza
R
Tabrizi
Jean-Marie
JM
Boher
Anne-Gaëlle
AG
Le Corroller-Soriano
Jacques-Olivier
JO
Bay
Nathalie
N
Fegueux
Jean-Michel
JM
Boiron
Sabine
S
Fürst
Luca
L
Castagna
Christian
C
Chabannon
Agnes
A
Boyer-Chammard
Noël
N
Milpied
Hélène
H
Labussière-Wallet
Catherine
C
Faucher
Valerie-Jeanne
VJ
Bardou
Mohamad
M
Mohty
Mauricette
M
Michallet
D000328:Adult; D000368:Aged; D001788:Blood Grouping and Crossmatching; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000401:mortality; D006680:HLA Antigens / Q000276:immunology*; D019337:Hematologic Neoplasms / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods; D035781:Siblings; D012959:Socioeconomic Factors; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods*; D014184:Transplantation, Homologous; D055815:Young Adult
D006680:HLA Antigens