A pediatric regimen for adolescents and young adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: Results of the ALLRE08 PETHEMA trial

Cancer Med. 2020 Apr;9(7):2317-2329. doi: 10.1002/cam4.2814. Epub 2020 Feb 5.

Abstract

Background: Pediatric-based or -inspired trials have improved the prognosis of adolescents and young adults (AYA) with Philadelphia chromosome-negative (Ph-neg) acute lymphoblastic leukemia (ALL).

Methods: This study reports the results of treatment of the ALLRE08 trial, a full pediatric trial for AYA aged 15-30 years with standard-risk (SR) ALL.

Results: From 2008 to 2018, 89 patients (38 adolescents [15-18 years] and 51 young adults [YA, 19-30 years], median age: 20 [15-29] years) were enrolled in the ALLRE08 trial. The complete response (CR) was 95%. Twenty-two patients were transferred to a high-risk (HR) protocol because of poor marrow response on day 14 (n = 20) or high-level of end-induction minimal residual response (MRD ≥ 0.25%, n = 2). Cumulative incidence of relapse (CIR) at 5 years was 35% (95%CI: 23%-47%), with significant differences between adolescents and YA: 13% (4%-28%) vs 52% (34%-67%), P = .012. No treatment-related mortality was observed in 66/66 patients following the ALLRE08 trial vs 3/23 patients moved to a HR trial. The estimated 5-year overall survival (OS) was 74% (95%CI: 63%-85%), with significantly higher rates for adolescents vs YA: 87% (95%CI: 74%-100%) vs 63% (46%-80%), P = .021. Although CIR or OS were lower in patients who were transferred to a HR trial, the differences were not statistically significant (CIR: 34% [21%-47%] vs 37% [14%-61%]; OS: 78% [66%-90%] vs 61% [31%;91%]).

Conclusion: A full pediatric trial is feasible and effective for AYA with Ph-neg, SR-ALL, with better results for adolescents than for YA. Outcome of patients with poor early response rescued with a HR trial was not significantly inferior.

Keywords: acute lymphoblastic leukemia; adolescents and young adults; pediatric treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Clinical Trials as Topic
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm, Residual / drug therapy*
  • Neoplasm, Residual / genetics
  • Neoplasm, Residual / pathology
  • Philadelphia Chromosome
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Prognosis
  • Remission Induction
  • Survival Rate
  • Young Adult