Outcome of a pediatric-inspired therapy in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia (ALL): Final results of the GRAALL-2003 study

Abstract

7005 Retrospective comparisons have demonstrated that adolescents with ALL significantly benefit from pediatric rather than adult chemotherapy regimens. One explanation may be the larger amounts of steroids, vincristine (VCR), and L-asparaginase (L-aspa) administered in pediatric patients. However, the issue of whether a pediatric approach might also improve the outcome of older adults remained open. Two hundred twenty-five adults aged 15–60 years with Philadelphia chromosome-negative ALL were thus enrolled in the pediatric-inspired GRAALL- 2003 protocol. Treatment included a 5-drug induction, high dose-intensity consolidation blocks, delayed intensification, and 2-year maintenance. The comparison with the former LALA-94 adult protocol showed a 8.6-fold, 3.7-fold, and 16-fold increase in cumulative doses of prednisone, VCR, and L-aspa, respectively. Some adult options, such as allogeneic stem cell transplantation in first remission for patients with high-risk ALL, were nevertheless retained. Complete remission (CR) rate was 93.5%. At 48 months, EFS and overall survival were estimated at 55% (95% CI, 48 to 62%) and 58% (95% CI, 51 to 65%), respectively. At that time, cumulative incidence of relapse and death in first CR were estimated at 32% (95% CI, 26 to 38%) and 9% (95% CI, 6 to 14%), respectively. In patients eligible for stem cell transplantation (SCT) in first CR, no difference in outcome was observed in the donor versus no-donor group. In those who received chemotherapy, cumulative incidence of toxic deaths was significantly higher in patients aged more than 45 years, leading to lower EFS in older patients (46% [95% CI, 30 to 60] versus 58% [95% CI, 49 to 67]) despite a similar incidence of relapse. These results compared very favorably with those observed in the historical LALA-94 adult protocol, with more than 20% gain in relapse incidence, EFS, and OS. This study shows that a pediatric-inspired therapy markedly improved the outcome of adults with ALL at least up to the age of 45 years. The place of SCT should thus be re-evaluated in this new context. No significant financial relationships to disclose.