Adolescents and young adults with acute lymphoblastic leukemia have a better outcome when treated with pediatric-inspired regimens: systematic review and meta-analysis.

Survival of adults with acute lymphoblastic leukemia (ALL) is inferior to that of pediatric patients. Strategies to improve the outcome of adult population are warranted. This study aims to evaluate the efficacy and safety of pediatric-inspired regimens given to adolescents and young adults (AYA), usually defined as 16-39 years, with ALL. Systematic review and meta-analysis of comparative trials of AYA patients with ALL given induction chemotherapy with either pediatric-inspired regimens or conventional-adult chemotherapy was conducted. Relative risks (RR) with 95% confidence intervals (CIs) were estimated and pooled. Our search yielded 11 trials, including 2,489 patients. AYA patients given pediatric-inspired regimens had a statistically significant lower all cause mortality rate at 3 years (RR 0.58; 95% CI 0.51-0.67). Complete remission rate after induction chemotherapy and event free survival were superior in the pediatric-inspired regimens arm (RR 1.05; 95% CI 1.01-1.10 and RR 1.66; 95% CI 1.39-1.99, respectively). Relapse rate was also lower in patients given pediatric-inspired regimens (RR 0.51; 95% CI 0.39-0.66) with comparable nonrelapse mortality between the two groups (RR 0.53, 95% CI 0.19-1.48). Pediatric-inspired regimens are superior to conventional-adult chemotherapy in AYA ALL patients. Further randomized controlled studies to investigate this approach in adult ALL patients are warranted.

Ram R ，Wolach O ，Vidal L ，Gafter-Gvili A ，Shpilberg O ，Raanani P ... -  《-》

Risk-Benefit Analysis of Pediatric-Inspired Versus Hyperfractionated Cyclophosphamide, Vincristine, Doxorubicin, and Dexamethasone Protocols for Acute Lymphoblastic Leukemia in Adolescents and Young Adults.

Guzauskas GF ，Villa KF ，Vanhove GF ，Fisher VL ，Veenstra DL ... -  《-》

Management of adult patients with acute lymphoblastic leukemia in first complete remission: systematic review and meta-analysis.

The optimal postremission therapy in adults with acute lymphoblastic leukemia (ALL) is still a matter of debate. The objective of this study was to compare the various potential therapeutic options for patients who achieved first complete remission. The authors conducted a systematic review and meta-analysis of randomized trials, including patients with standard-risk (SR) All and high-risk (HR) ALL who received first postremission therapy. Outcomes assessed were all-cause mortality (ACM), disease recurrence (relapse), and nonrelapse mortality (NRM). Relative risks (RRs) with 95% confidence intervals (CIs) were estimated and pooled. Overall, there was a significant reduction in ACM in the allogenic stem cell transplantation (alloSCT) arm (RR, 0.88; 95% CI, 0.8-0.97) compared with autologous stem cell transplantation (ASCT) or chemotherapy. Subgroup analyses revealed a similar pattern among SR patients (RR, 0.8; 95% CI, 0.68-0.94) but a nonsignificant advantage for alloSCT among HR patients (RR, 0.88; 95% CI, 0.76-1.01). There was an increase in NRM (RR, 2.99; 95% CI, 1.37-6.53) and a decrease in the relapse rate in the alloSCT arm (RR, 0.52; 95% CI, 0.33-0.83). There was no difference in ACM or the relapse rate between the ASCT and chemotherapy arms. Overall, alloSCT was superior to ASCT or chemotherapy for patients with ALL in first complete remission. The survival advantage was of greater statistical significance for patients with SR ALL than for patients with HR ALL.

Ram R ，Gafter-Gvili A ，Vidal L ，Paul M ，Ben-Bassat I ，Shpilberg O ，Raanani P ... -  《CANCER》

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

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). 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. 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%]). 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.

Ribera JM ，Morgades M ，Montesinos P ，Tormo M ，Martínez-Carballeira D ，González-Campos J ，Gil C ，Barba P ，García-Boyero R ，Coll R ，Pedreño M ，Ribera J ，Mercadal S ，Vives S ，Novo A ，Genescà E ，Hernández-Rivas JM ，Bergua J ，Amigo ML ，Vall-Llovera F ，Martínez-Sánchez P ，Calbacho M ，García-Cadenas I ，Garcia-Guiñon A ，Sánchez-Sánchez MJ ，Cervera M ，Feliu E ，Orfao A ，PETHEMA Group, Spanish Society of Hematology ... -  《Cancer Medicine》

[Acute lymphoblastic leukemia in adolescents and young adults].

Hayakawa F 《-》