Addition of ATG reduces incidence of chronic GVHD in patients with acute leukemia

The inclusion of antihuman T-lymphocyte immune globulin in a myeloablative conditioning regimen for patients with acute leukemia significantly reduced the rate of chronic graft-versus-host disease following allogeneic stem cell transplantation, according to findings from a prospective, randomized phase 3 study.

Graft-versus-host disease (GVHD) — a major complication of allogeneic stem cell transplantation — leads to poorer quality of life, later illness or death in patients with acute leukemia. Efforts to prevent acute GVHD have improved in the past 2 decades, but efforts to make considerable improvements to prevent chronic GVHD have not been as successful, according to study background.

Prior studies suggested antihuman T-lymphocyte immune globulin (ATG) can reduce incidence of chronic GVHD following stem cell transplantation from an unrelated donor. Smaller retrospective studies also have shown ATG can reduce chronic GVHD after human leukocyte antigen (HLA)-identical transplantation.

Nicolaus Kröger, MD, professor and medical director of the department of stem cell transplantation at University Hospital Hamburg-Eppendorf in Germany, and colleagues conducted a multicenter, open-label, randomized study to evaluate whether the inclusion of ATG in a myeloablative conditioning regimen reduced the risk for chronic GVHD in patients who were in complete remission from acute leukemia and who received peripheral blood stem cells from an HLA-matched sibling.

Researchers enrolled 168 patients treated at 27 centers. Investigators randomly assigned patients 1:1 to ATG or no ATG, and they stratified patients by treatment center and disease risk.

Cumulative incidence of chronic GVHD at 2 years served as the primary endpoint. Secondary endpoints included incidence of acute GVHD, engraftment, nonrelapse-related death, RFS and OS at 2 years, and a composite endpoint of chronic GVHD-free survival and RFS at 2 years.

The final analysis included 155 patients enrolled between December 2006 and February 2012. Of these, 83 (63.9% men) received ATG and 72 (55.6% men) did not. Median age (39 years vs. 43.5 years) was comparable between groups.

After a median follow-up of 24 months, researchers determined the addition of ATG reduced cumulative incidence of chronic GVHD by 53%.

Researchers reported chronic GVHD in 32.2% (95% CI, 22.1-46.7) of patients in the ATG group and 68.7% (95% CI, 58.4-80.7) of those in the non-ATG group (P < .001).

“More important, the between-group difference in the rate of chronic GVHD was seen mainly in patients with the clinical extensive form of chronic GVHD,” Kröger and colleagues wrote.

Among those patients, incidence of chronic GVHD was 7.6% among those assigned ATG and 52.4% among those who did not receive ATG.

Kröger and colleagues reported no significant differences in 2-year RFS (59.4% vs. 64.6%) and OS (74.1% vs. 77.9%) between the ATG and control groups. The researchers observed no significant differences in rates of relapse, infections, acute GVHD or other adverse events.

However, the rate of combined chronic GVHD-free survival and RFS at 2 years was significantly higher among patients assigned ATG (36.6% vs. 16.8%; P = .005). – by Anthony SanFilippo

Disclosure: The study was funded in part by a research grant from Neovii Biotech. Kröger reports research funding from Neovii Biotech. The other researchers report research funding or honoraria from, consultant/advisory roles with, or other financial relationships with Amgen, Celgene, Fresenius Biotech, Neovii Biotech, Novartis and Pfizer.