Comparison of intensive chemotherapy, allogeneic, or autologous stem-cell transplantation as postremission treatment for children with very high risk acute lymphoblastic leukemia: PETHEMA ALL-93 Trial.

PURPOSE

The optimal postremission therapy for children with very high-risk (VHR) acute lymphoblastic leukemia (ALL) is not well established. This randomized trial compared three options of postremission therapy: chemotherapy and allogeneic or autologous stem-cell transplantation (SCT).

PATIENTS AND METHODS

All 106 VHR-ALL patients received induction with five drugs followed by intensification with three cycles of chemotherapy. Patients in complete remission (CR) with an HLA-identical family donor were assigned to allogeneic SCT (n = 24) and the remaining were randomly assigned to autologous SCT (n = 38) or to delayed intensification followed by maintenance chemotherapy up to 2 years in CR (n = 38).

RESULTS

Overall, 100 patients achieved CR (94%). With a median follow-up of 6.5 years, 5-year disease-free survival (DFS) and overall survival (OS) probabilities were 45% (95% CI, 37% to 54%) and 48% (95% CI, 40% to 57%), respectively. The three groups were comparable in the main pretreatment ALL characteristics. Intention-to-treat analysis showed no differences for donor versus no donor in DFS (45%; 95% CI, 27% to 65% v 45%; 95% CI, 37% to 55%) and OS (48%; 95% CI, 30% to 67% v 51%; 95% CI, 43% to 61%), as well as for autologous SCT versus chemotherapy comparisons (DFS: 44%; 95% CI, 29% to 60% v 46%; 95% CI, 32% to 62%; OS: 45%; 95% CI, 31% to 62% v 57%; 95% CI, 43% to 73%). No differences were found within the different subgroups of ALL and neither were differences observed when the analysis was made by treatment actually performed.

CONCLUSION

This study failed to prove that, when a family donor is available, allogeneic SCT produces a better outcome than autologous SCT or chemotherapy in children with VHR-ALL.