Transplantationstechnologien und Forschung

Decreased Risk of Acute Graft-versus-Host Disease Using Reduced Intensity Conditioning Compared to Myeloablative Conditioning is Independent of Donor-Recipient T-cell Chimerism

Abstract

Olle Ringdén, Behnam Sadeghi, Mehmet Uzunel, Martin Solders, Michael Uhlin, Jonas Mattsson and Mats Remberger

Background: It is not known if the reduced risk of graft-versus-host disease (GVHD) among patients receiving reduced intensity conditioning (RIC) as opposed to myeloablative conditioning (MAC) is due to differences in mixed donor-recipients chimerism, or to the intensity of the regimen.
Methods: We compared patients with acute myeloid leukemia (AML) selected for RIC (n=47) to 46 patients selected for MAC before allogeneic hematopoietic stem cell transplantation (HSCT).
Results: Time to neutrophils >0.5 x 109/L was median 15 days in the MAC group, which was faster than 17 days in the RIC group (p=0.001). MAC patients required more erythrocytes (p=0.001) and platelet transfusions (p=0.003). At four weeks, mixed donor-recipient T-cell chimerism was seen in 29% of the MAC patients and 46% of the RIC patients. Acute GVHD grades II-IV was 55% and 17% in the two groups, respectively (p<0.001). In multivariate analysis, acute GVHD was reduced using RIC (hazards ratio (HR) 0.23, p<0.001), for year of HSCT (HR 1.27, p=0.01), but not for mixed donor-recipient T-cell chimerism (HR 1.11, p=0.80). Transplant-related mortality (TRM) at three years was 15% versus 13%. Chronic GVHD and relapse were similar. Overall mortality was not affected by conditioning (HR 1.39, p=0.36).
Discussion: To conclude, patients treated with RIC had an increased risk of acute GVHD as opposed to recipients of MAC, which was due to less intense conditioning and not due to mixed donor T-cell chimerism.