The addition of thymoglobulin 4.5 mg/kg to graft-vs-host disease (GVHD) prophylaxis does not negatively affect survival outcomes for patients utilizing reduced intensity conditioning (RIC) regimens compared with myeloablative conditioning (MAC) regimens, according to research published in Annals of Hematology.

The study authors retrospectively compared the outcomes of 122 patients with acute myeloid leukemia (AML) who underwent unrelated donor peripheral blood stem cell transfusion (URD PBSCT). Of the 122 patients, 58 received the RIC regimen and 64 received the MAC regimen. All patients received granulocyte colony-stimulating factor mobilized peripheral blood stem cells, tacrolimus, mycophenolate mofetil, and thymoglobulin for GVHD prophylaxis.

MAC regimen consisted of:


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  • IV busulfan 130 mg/m2 daily for 4 days
  • IV fludarabine 30 mg/m2 daily for 5 days

RIC regimen consisted of:

  • IV busulfan 130 mg/m2 daily for 2 days
  • IV fludarabine 30 mg/m2 daily for 5 days
  • Total body irradiation: 200 cGy at day 0

The study endpoints were to compare cumulative incidence and severity of acute and chronic GVHD, overall survival, and relapse rate between the RIC and MAC regimens.

The cumulative incidence of grades 2 to 4 acute GVHD at 6 months was 26.6% in the RIC group (95% CI, 16.4-37.9) and 55.6% in the MAC group (95% CI, 41.6-67.5; P =.009), whereas the cumulative incidence of grades 3 to 4 acute GVHD at 6 months was 6.2% in the RIC group (95% CI, 2-14) and 26.1% in the MAC group (95% CI, 15.5-38; P =.009).

At 1 year, the cumulative incidence of chronic GVHD was similar between the RIC and MAC groups (41.2% vs 44.8%, respectively; P =.75). After adjusting for age and other factors, there was no significant difference in acute or chronic GVHD between the 2 groups.

The 1-year relapse rate for all patients was 25%. RIC had a higher relapse rate than MAC, but the difference was not statistically significant (29.9% vs 20.7%, respectively; P =.24). Data shows that patients with acute GVHD had a higher risk of chronic GVHD (hazards ratio, 2.73; P =.002). Both regimens saw similar risk of infections.

The study was limited by its retrospective nature. The conditioning regimen chosen was based on physician discretion, so selection bias may have been present.

“[I]n vivo T cell depletion with thymoglobulin does not affect survival in recipients of RIC compared to MAC regimens in AML patients undergoing URD PBSCT,” the study authors concluded, although “thymoglobulin was associated with a marginally reduced rate of severe acute GVHD when used with a RIC regimen.”

Reference

Modi D, Singh V, Kim S, et al. Comparison of myeloablative and reduced intensity conditioning unrelated donor allogeneic peripheral blood stem cell transplant outcomes for AML using thymoglobulin for GVHD prophylaxisAnn Hematol. Published online February 16, 2021. doi:10.1007/s00277-021-04445-8