Long-Term Results of ASCT in Adult High-Risk Acute Lymphoblastic Leukemia

Allogeneic hematopoietic stem cell transplantations (HCTs) from matched sibling donors (MSDs) and matched unrelated donors (MUDs) yielded similar long-term outcomes for patients with BCR-ABL-negative acute lymphoblastic leukemia (ALL), with improved non-relapse mortality for MUD HCT.

Minimal residual disease (MRD) had a strong impact on relapse risk, whereas age was the strongest predictor of non-relapse mortality, according to a large reference analysis published in Transplantation and Cellular Therapy.

“Allogeneic [HCT] is standard for adult high-risk ALL and contributed to the overall improved outcome,” wrote Dietrich W. Beelen, MD, Department of Bone Marrow Transplantation, West German Cancer Center, University of Duisburg-Essen, and colleagues.

The study authors reported on consecutive cohorts of prospectively defined high-risk patients treated in German Multicenter Study Group for Adult ALL trials with similar induction and consolidation therapy, and HCT in first remission.

A total of 542 patients aged 15 to 55 years with BCR-ABL-negative ALL were analyzed; 67% received HCTs from MUDs and 32% from MSDs. At 5 years, the incidence of non-relapse mortality was 20%, and incidence of relapse was 23% with MSDs versus 25% with MUDs.

Non-relapse mortality occurred after a median of 6.6 months, with the leading cause (46%) being infection. Non-relapse mortality with MUD-based HCT decreased from 39% to 16% (P <.00001), and age was the strongest predictor. MRD was the strongest predictor of relapse (45% for molecular failure vs 6% for molecular complete response; P <.0001).

The median follow-up was 67 months, and the 5-year survival rate was 58%. Age, subtype, MRD status, and acute GVHD were significant prognostic factors.

“We provide a large reference analysis with long follow-up confirming a similar outcome of MSD and MUD HCT and improved [non-relapse mortality] for MUD HCT over years. MRD has a strong impact on relapse risk whereas age was the strongest predictor of [non-relapse mortality],” Dr Beelen et al concluded.

“New adapted conditioning strategies should be considered for older patients combined with the goal to reduce the MRD level before [stem cell transplantation],” they added.

Source

Beelen DW, Arnold R, Stelljes M, et al. Long-Term Results of Allogeneic Stem Cell Transplantation in Adult Ph- Negative High-Risk Acute Lymphoblastic Leukemia. Transplant Cell Ther. Published online August 25, 2022:S2666-6367(22)015901. doi:10.1016/j.jtct.2022.08.024