Thiotepa-based intensified reduced-intensity conditioning (RIC) may improve survival outcomes among patients undergoing cord-blood transplantation (CBT) compared with standard RIC, according to a study published in Biology of Blood and Marrow Transplantation.
The standard RIC regimen of fludarabine 200 mg/m2, cyclophosphamide 50 mg/kg, and 200 cGy or 300 cGy total body irradiation (TBI; the “Minnesota” RIC) is among the most published and well tolerated RIC CBT regimens but is also associated with high rates of relapse. The study authors hypothesized that intensification of conditioning may improve relapse rates without worsening transplant-related mortality (TRM).
For this retrospective cohort comparison, researchers assessed the outcomes of 99 patients who underwent CBT; 51 patients received standard RIC and 47 received intensified RIC with fludarabine 150 mg/m2, cyclophosphamide 50 mg/kg, thiotepa 10 mg/kg, and 400 cGy TBI. Acute myeloid leukemia (AML) was the primary indication for transplant among both treatment arms. The median age at transplant was 67 years for patients receiving intensified-RIC and 54 years among those receiving standard-RIC.
Results demonstrated that patients who received intensified-RIC had a significantly reduced cumulative incidence (CI) of relapse compared with patients who received standard RIC. The 1-year CI of relapse was only 8% in the intensified-RIC arm vs 36% in the standard-RIC arm; these findings were maintained even after multivariate analyses.
Both study arms had comparable TRM, but overall survival (OS) was significantly prolonged; the OS was not reached in the intensified-RIC compared with 17 months in the standard-RIC arm.
The CI of grade 2-4 acute graft-versus-host disease (GVHD) was significantly higher in the intensified-RIC cohort, but the CI of grade 3-4 acute GVHD, moderate-to-severe GVHD, and any chronic GVHD, was comparable between both study arms.
The authors concluded that although the study had its limitations (eg, retrospective in nature, heterogeneity of disease states) “while older and more comorbid patients might experience increased TRM with the thiotepa based intensified-RIC, our data suggest that this regimen should be considered in otherwise fit patients and extended into the 50 to 65 age group.”
Sharma P, Pollyea DA, Smith CA, et al. Thiotepa based intensified reduced-intensity conditioning adult double-unit cord blood hematopoietic stem cell transplantation results in decreased relapse rate and improved survival compared to transplantation following standard reduced-intensity conditioning: a retrospective cohort comparison[published online April 20, 2018]. Biol Blood Marrow Transplant. doi: 10.1016/j.bbmt.2018.04.019