Effect Of Antithymocyte Globulins (Atg) As Part Of The Myeloablative Conditioning (Mac) Regimen On The Risk Of Severe Graft-Versus-Host Disease (Gvhd) After Allogeneic Stem Cell Transplantation (Allo-Sct) From Matched-Unrelated Donors (Mud)

JOURNAL OF CLINICAL ONCOLOGY(2009)

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摘要
7025 Here, we report the results of a multicenter retrospective study analyzing the effect of ATG, incorporated within the MAC regimen for MUD-transplants in leukemic patients. The purpose of the study was to compare the incidence and severity of acute and chronic GVHD as well as overall outcome. 171 adult patients with acute leukemia and MDS, for whom detailed allelic HLA typing (4 digits) was available, were included. 81% of patients were transplanted from 10/10 allelic MUD, and 19% from a MUD with at least one allelic difference. 120 patients (70%) did not receive ATG (no-ATG group), while 51 patients received ATG (ATG group; thymoglobuline* in all cases) as part of the MAC regimen. Except for a significantly higher number of allelic differences between recipient and donor (33% vs. 13%; p = 0.002), the no-ATG and ATG groups were strictly comparable. With a median follow-up of 30.3 (range, 2.6–68.1) months, grade 0–1 and 2–4 acute GVHD occurred in 74 (46%) and 88 patients (54%) respectively, with grade 3–4 acute GVHD being significantly lower in the ATG group (18% vs. 32%; p = 0.04). Extensive chronic GVHD was significantly lower in the ATG group (5% vs. 33%; p = 0.001). Patients from the ATG group had a higher incidence of limited chronic GVHD (33% vs. 18%; p = 0.06). Moreover, infection-related mortality was comparable between both groups (23% vs. 27%, p = NS). Also, NRM was comparable between both groups (30% vs. 29%; p = NS). In multivariate analysis, an HLA allelic mismatch and the non-use of ATG were associated with an increased risk of grade 3–4 acute GVHD (RR = 2.80, 95% CI, 1.5–5.3, p = 0.001; and RR = 2.4, 95% CI, 1.1–5.0, p = 0.02 respectively). Similarly, multivariate analysis showed that the absence of use of ATG was the unique parameter associated with an increased risk of extensive chronic GVHD (RR = 6.9; 95% CI, 1.7–29.0, p = 0.008). Finally, LFS and OS at 2 years were not significantly different between the no-ATG and ATG group (48.8% vs. 41.3%, p = NS; and 53.6% vs. 54.3%, p = NS; respectively). These results suggest a global long-term beneficial effect of ATG when used as part of the MAC regimen prior to allo-SCT from MUD (especially in the HLA mismatch setting). No significant financial relationships to disclose.
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关键词
allogeneic stem cell transplantation,antithymocyte globulins,myeloablative conditioning,graft-versus-host,allo-sct,matched-unrelated
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