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.

Abstract

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.

• Authors: Didier Blaise, Reza Tabrizi, Jean-Marie Boher, Anne-Gaëlle Le Corroller-Soriano, Jacques-Olivier Bay, Nathalie Fegueux, Jean-Michel Boiron, Sabine Fürst, Luca Castagna, Christian Chabannon, Agnes Boyer-Chammard, Noël Milpied, Hélène Labussière-Wallet, Catherine Faucher, Valerie-Jeanne Bardou, Mohamad Mohty, Mauricette Michallet
• Journal: Cancer (Cancer) Vol. 119 Issue 3 Pg. 602-11 (Feb 01 2013) ISSN: 1097-0142 [Electronic] United States
• PMID: 22893313 (Publication Type: Clinical Trial, Phase II, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 American Cancer Society.

Chemical References

• HLA Antigens

Topics

• Adult
• Aged
• Blood Grouping and Crossmatching
• Female
• Graft vs Host Disease (epidemiology, mortality)
• HLA Antigens (immunology)
• Hematologic Neoplasms (diagnosis, mortality, therapy)
• Humans
• Male
• Middle Aged
• Peripheral Blood Stem Cell Transplantation (adverse effects, methods)
• Siblings
• Socioeconomic Factors
• Survival Analysis
• Transplantation Conditioning (adverse effects, methods)
• Transplantation, Homologous
• Young Adult