Is thiotepa-based reduced-intensity conditioning effective before cord blood stem cell transplantation?

This study examined the effectiveness of thiotepa-based RIC in leukemia and lymphoma patients undergoing stem cell transplantation. The authors concluded that this treatment improved outcomes compared to standard RIC.

Before undergoing stem cell transplantation, patients with lymphoma or leukemia must undergo conditioning treatment. This is generally high-dose chemotherapy, with or without radiation therapy. Older patients or those with other medical conditions may not be able to tolerate high-dose chemotherapy. These patients may undergo reduced-intensity conditioning (RIC) instead (lower doses or different combinations of chemotherapies).

Umbilical cord stem cells are an option for patients who do not have a matched related stem cell donor. The most common RIC for this type of transplant is the Minnesota regimen (fludarabine and cyclophosphamide combined with total body irradiation). This is associated with high rates of disease relapse and transplant failure. It is thought that by increasing the intensity (lowering the dose of fludarabine, increasing the radiation dose, and adding thiotepa) may improve outcomes in these patients.

The records of 99 patients were examined in this study. 52 patients received standard RIC. 47 patients received intensified RIC. 55.6% of patients were treated for acute myeloid leukemia. 12% were treated for non-Hodgkin’s lymphoma. 9% were treated for acute lymphoblastic leukemia. Patients were followed for an average of 15 to 22 months.

Two patients in each treatment group experienced engraftment failure (the transplanted stem cells failed to start making new blood cells).

The 1-year incidence of acute graft-versus-host disease (when the transplanted cells attack healthy tissue) was 55% in the intensified RIC group and 29% in the standard RIC group. Over the first 100 days after transplantation, 60 infections were reported in the standard RIC group. 85 infections were reported in the intensified RIC group.

The 1-year incidence of relapse was significantly higher with standard RIC (36%) compared to intensified RIC (8%). Mortality related to treatment was not significantly different between the treatment groups. Average overall survival (time from treatment until death from any cause) was 17 months for the standard RIC group. It had not been reached for the intensified RIC group.

This study concluded that thiotepa-based intensified RIC improved outcomes compared to standard RIC. The authors suggest that it may be considered in fit older adults.