Clinical Outcomes of Younger Adults With Philadelphia-Negative Acute Lymphoblastic Leukemia, Treated With A Pediatric-Like Regimen Based on the GIMEMA LAL1308 Protocol. A Campus ALL Study

Introduction: While pediatric-based protocols have significantly improved survival rates in adolescents and young adult (AYA) patients with Philadelphia-negative acute lymphoblastic leukemia (Ph- ALL), limited information is available on the applicability of pediatric-like chemotherapy in real life outside of clinical trials. Methods: We retrospectively collected clinical data from 36 AYA patients (median age 21 years, range 18-38) with Ph- ALL (28) or lymphoblastic lymphoma (LL) (8) who received a frontline treatment inspired by the GIMEMA LAL1308 pediatric protocol in a multicenter real-life setting, across centers participating in the Campus ALL network. Results: A morphologic or radiologic/metabolic complete remission was documented in 31/36 (86.1%) ALL/LL patients after induction Phase Ib. Measurable residual disease (MRD) negativity was reached in 17/23 (73.9%) evaluable ALL patients at the prognostic timepoint at the end of Ib induction cycle. Consolidation/maintenance approaches followed risk-adapted indications, with 20 (55.6%) patients receiving an allogeneic hematopoietic stem cell transplantation (allo-HSCT) because of either adverse prognostic factors, resistance to induction treatment, morphologic relapse, or MRD positivity. The 5-year overall, disease-free, and event-free survival rates were 76.4%, 69.1%, and 59%, respectively. No significant differences in outcomes were observed according to the ALL/LL diagnosis, B/T lineage, risk stratification, allo-HSCT procedure, and, surprisingly, MRD status, probably due to the limited sample size or to optimal risk-adapted and MRD-driven intensification strategies. Conclusions: The implementation of this unmodified pediatric regimen to Ph- AYA ALL patients appears feasible in a real-life context, with results that compare favorably to those of other pediatric-based regimens not yet incorporating frontline immunotherapy.