NEW YORK (Reuters Health) – Reduced-intensity conditioning that includes two daily 2.5-mg/kg doses of antithymocyte globulin before allogeneic stem-cell transplantation for hematologic malignancy significantly reduces graft-versus-host disease (GvHD) without loss of disease control, according to a team based in Marseille, France.
“The current data indicate that 5 mg/kg of ATG (antithymocyte globulin) provides satisfactory T-cell depletion in this type of RIC (reduced-intensity conditioning) transplantation,” they conclude in their paper in Cancer online October 23.
Dr. Roberto Crocchiolo, at the Institut Paoli-Calmettes, and colleagues explain that reduced-intensity conditioning with fludarabine, busulfan and ATG before allogeneic stem-cell transplantation is an option when patients are not fit enough to withstand myeloablative procedures. ATG prevents GvHD but titration of the dose is “crucial,” to balance the reduced risk of GvHD against increased risks of relapse and infection.
In the current retrospective analysis, the team compared outcomes in 229 adult patients treated at their institution with fludarabine and busulfan along with ATG at 2.5 mg/kg/d for either 1 day (FBA1) or 2 days (FBA2) before undergoing stem-cell transplantation.
Median follow-up was 38 months. Comparing the FBA1 cohort to the FBA2 cohort, the cumulative incidence of grade 2-4 acute GvHD was 42% vs 23%, respectively, and corresponding rates of chronic GvHD were 69% vs 35%.
“This is particularly notable because the FBA2 cohort was both older and had a higher proportion of unrelated donors,” Dr. Crocchiolo and colleagues point out.
Furthermore, they found no significant difference in the FBA1 and FBA2 groups at 2-years in terms of overall survival (67% vs 65%; p=0.9) or in relapse/progression rates (30% versus 19%; p=0.09).
Given these results, the authors conclude that ATG 5 mg/kg combined with fludarabine and busulfan “may be a platform for the development of strategies aimed at improving disease control, such as intensification of the busulfan dose in the conditioning regimen and/or the addition of post-transplantation therapeutics in high-risk patients.”
