Catherine Lister, Mercer University College of Pharmacy
Chronic graft-versus-host disease is the leading cause of long-term morbidity and mortality in allogeneic hematopoietic stem cell transplant patients. 
It is estimated that within the first two years post transplant the cumulative incidence of chronic graft-versus-host disease (GVHD) is 30% to 40%. Studies have shown that antihuman lymphocyte immune globulin can reduce the risk of chronic GVHD when used in the conditioning regimen. 
A recent, published study in The New England Journal of Medicine accesses the use of antihuman T-lymphocyte immune globulin (ATG) for the prevention of chronic GVHD in patients receiving allogeneic peripheral-blood stem-cell transplantation from a human lymphocyte antigen (HLA)-identical sibling. 
|Antilymphocyte Globulin for Prevention of Chronic Graft-versus-Host Disease|
|Design||Prospective, multicenter, open-label, randomized phase 3 study; N= 168|
|Objective||Observe the effect of antihuman T-lymphocyte immune globulin (ATG) in a myeloablative conditioning regimen, for patients with acute leukemia, on the development of graft-versus-host disease (GVHD) two years after allogeneic peripheral-blood stem-cell transplantation from an HLA-identical sibling|
|Study Groups||Arm 1 (n= 83) received ATG 10 mg per kg on days 3, 2, and 1 before transplant.
Arm 2 (n= 72) did not receive ATC.
All patients were 18 to 65 years old, acute myeloid or lymphoblastic leukemia in remission, and indication for an allogeneic hematopoietic stem-cell transplantation, adequate function of major organ systems
|Methods||Patients were randomly assigned to arms in 1:1 ratio with stratification according to center and disease risk.
All patients received myeloablative conditioning, and regimens included cyclophosphamide (120 mg per kg of body weight) plus total body irradiation (12 Gy), cyclophosphamide (120 mg per kg of body weight) plus busulfan (16mg per kg orally or 12.8 mg per kg IV), or total body irradiation (12 Gy) plus etoposide (20- 60 mg per kg)
Of those enrolled, seven were excluded before randomization, two were not analyzed because they withdrew, four were not analyzed because of progressive disease.
Follow up lasted 24 months.
Cumulative incidence analyses were performed to assess chronic GVHD-free survival.
|Duration||December 2006 to February 2012|
|Primary Outcome Measure||Cumulative incidence of GVHD at two years|
|Average Age, y||39.0||43.5||0.04|
|Number acute myeloid leukemia||55||55||0.17|
|Number acute lymphoid leukemia||28||17||None|
|Number high cytogenetic risk||31||22||0.19|
|Number CMV IgG-positive recipients||50||42||0.90|
|Number total-body irradiation plus cyclophosphamide||23||18|
|Number busulfan plus cyclophosphamide||56||51|
|Number total-body irradiation plus etoposide||4||3|
|Acute GVHD within 100 days||21||25||0.20|
|Grade of acute GVHD 2-4||9||13||0.13|
|Grade of acute GVHD 3 or 4||22||46||0.10|
|Adverse Events||Common Adverse Events: No significant difference between arms|
|Serious Adverse Events: No significant difference between arms|
|Percentage that Discontinued due to Adverse Events: None reported|
|Study Author Conclusions||The inclusion of ATG resulted in a significantly lower rate of chronic GVHD after allogeneic transplantation than the rate without ATG. The survival rate was similar in the two groups, but the rate of a composite end point for chronic GVHD-free survival and relapse-free survival was higher with ATG.|
This new study contributes to the body of evidence that ATG can reduce the risk of chronic GVHD, and that ATG resulted in significantly lower rate of chronic GVHD in this specific patient population. [2,3]
- Socie G and Ritz J. Current issues in chronic graft-versus-host disease. Blood 2014; 124 (3): 374-384.
- Flowers MED and Martin PJ. How we treat chronic graft-versus-host disease. Blood 2015; 125 (4).
- Kroger N, et al. Antilymphocyte globulin for prevention of chronic graft-versus-host disease. N Engl J Med 2016; 374:43-53.