for madubois63--progress on graft vs host disease prevention

[Lani]

Graft vs Host Risk Cut With Anti-T-Cell Globulins



The frequency of graft versus host disease (GVHD) declined significantly with the addition of anti-T-cell globulins (ATG) to cyclosporine and methotrexate in patients undergoing allogeneic hematopoietic cell transplantation.

The incidence of grade III-IV acute GVHD declined by 50% and chronic GVHD was reduced by almost 80% in patients who received ATG, comopared to those who received standard prophylaxis, investigators reported in the Aug. 19 issue of Lancet Oncology.

Neither relapse nor nonrelapse mortality increased with the investigational GVHD prophylaxis.

"With regard to less severe forms of acute GVHD (grade II-IV and grade I-IV) even larger differences in favour of ATG were seen," Jurgen Finke, MD, of Universitatsklinikum Freiburg in Germany, and colleagues reported.
Action Points
Explain to patients that an investigational regimen to prevent GVHD after hematopoietic cell transplantation reduced acute and chronic GVHD compared with the standard regimen.
Despite advances in transplantation science, GVHD remains a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation.
Researchers have tried various, experimental ATG conditioning regimens in hopes of preventing GVHD, the authors noted. However, the potency and dose of the regimens have differed substantially, leading to inconsistent clinical results that have included increased mortality.

Promising results came from phase II clinical trials of rabbit anti-Jurkat cell-line T-lymphoblasts (ATG-Fresenius) added to cyclosporine and methotrexate for patients receiving matched and mismatched cells from unrelated donors, the authors continued.

Investigation of the regimen continued in a phase III trial, comparing cyclosporine and short-course methotrexate with or without ATG-Fresenius.

The trial involved 201 patients with hematologic malignancies treated by transplantation of peripheral blood cells (82%) or bone marrow (18%) from unrelated donors.

All patients underwent myeloablative conditioning therapy with whole-body irradiation, systemic agents, or a combination. Supportive care was provided in accordance with the treating center's standards. Use of growth factors was not permitted.

All patients received cyclosporine and methotrexate at standard doses and were randomized to ATG-Frenisius or no additional prophylaxis. The primary endpoint was the composite of grade III-IV GVHD or death within 100 days of transplantation.

In the ATG-Fresenius group, 12 patients developed grade III-IV and 10 died during the first 100 days, resulting in a total event rate of 21.4%.

Among patients who did not receive ATG-Fresenius, 24 developed severe GVHD and nine died, resulting in a total event rate of 33.7%. The difference between groups translated into an adjusted hazard ratio of 0.59 in favor of ATG-Fresenius (95% CI 0.30 to 1.17).

The cumulative incidence of grade III-IV acute GVHD was 11.7% in the ATG-F group and 24.5% in the control group (HR 0.50, 95% CI 0.25 to 1.01, P=0.054). However, only one patient in the ATG group died as a result of GVHD, compared with nine in the control group.

The addition of ATG-Fresenius reduced the incidence of grade II-IV acute GVHD from 51% in the control group to 33% (HR 0.56, 95% 0.36-0.87, P=0.011).

The two-year cumulative incidence of chronic GVHD was 12.2% in the ATG group and 42.6% in the control arm, resulting in an adjusted hazard ratio of 0.22 (P<0.0001).

"There were no differences between treatment groups with regard to relapse, nonrelapse mortality, overall survival, and mortality from infectious causes," the authors reported.

The significant reduction in chronic GVHD emerged as a key message from the study, Francesco Frassoni, MD, of Ospedale San Martino in Genova, Italy, wrote in an invited commentary.

"Outpatient wards treat many patients for chronic GVHD, and this number has increased with the use of mobilized peripheral-blood sources, as was used for many patients in the study by Finke and colleagues," said Frassoni

"Although not analyzed in the study, patients in the ATG-Fresenius group surviving hematopoietic cell transplantation are also likely to have a better quality of life than those in the control group," he added.