Randomized study of 2 reduced‐intensity conditioning strategies for human leukocyte antigen‐matched, related allogeneic peripheral blood stem cell transplantation

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 ¼ 69) or total body irradiation (TBI) (n ¼ 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 ¼ .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 ¼ .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 ¼ .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. Cancer 2013;119:602-11.

Impact of rabbit ATG-containing myeloablative conditioning regimens on the outcome of patients undergoing unrelated single-unit cord blood transplantation for hematological malignancies

“…In agreement with other reports, [18][19][20][21][22] we observed that the myeloablative conditioning regimen lacking ATG resulted in a higher incidence of aGVHD development. One may ask why the beneficial effect of ATG in reducing aGVHD does not translate into benefits in patient survival.…”

Reduced-intensity conditioned allogeneic SCT in adults with AML

“…Despite their limitations, a limited number of comparative studies suggest that regimen intensity is directly associated with non-relapse mortality (NRM) and inversely associated with relapse, leading to equivalent survival rates regardless of regimen intensity. 17,23,24 One commonly used regimen is Flu/TBI2. Mature results show that almost half of the recipients completed transplant as outpatients and only 4% encountered graft rejection.…”

Results from a clofarabine-busulfan-containing, reduced-toxicity conditioning regimen prior to allogeneic stem cell transplantation: the phase 2 prospective CLORIC trial

“…The combination of fludarabine, an intermediate dose of intravenous busulfan and lowdose antithymocyte globulins is among the most popular RIC regimens used in Europe, particularly in France. [6][7][8][9] Nevertheless, relapse remains challenging after such regimens. [6][7][8][9][10][11] Therefore, attempts to intensify the RIC regimen without increasing nonrelapse mortality might be an attractive option in order to obtain better disease control while waiting for the immune graft-versus-leukemia effect.…”