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Summary: The prognosis of t(1;19)(q23;p13)/transcription factor 3‐pre‐B‐cell leukaemia homeobox 1 (TCF3‐PBX1) in adolescent and adult patients with acute lymphoblastic leukaemia (ALL) treated with measurable residual disease (MRD)‐oriented trials remains controversial. In the present study, we analysed the outcome of adolescent and adult patients with t(1;19)(q23;p13) enrolled in paediatric‐inspired trials. The patients with TCF3‐PBX1 showed similar MRD clearance and did not have different survival compared with other B‐cell precursor ALL patients. However, patients with TCF3‐PBX1 had a significantly higher cumulative incidence of relapse, especially among patients aged ≥35 years carrying additional cytogenetic alterations. These patients might benefit from additional/intensified therapy (e.g. immunotherapy in first complete remission with or without subsequent haematopoietic stem cell transplantation). [ABSTRACT FROM AUTHOR]

Despite high complete remission (CR) rates with frontline therapy, relapses are frequent in adults with T‐cell acute lymphoblastic leukemia (T‐ALL) with limited salvage options. We analyzed the outcomes and prognostic factors for CR to salvage therapy and overall survival (OS) of patients with R/R T‐ALL included in two prospective measurable residual disease‐oriented trials. Seventy‐five patients (70 relapsed, 5 refractory) were identified. Relapses occurred in bone marrow, isolated or combined in 50 patients, and in the central nervous system (CNS; isolated or combined) in 20. Second CR was attained in 30/75 patients (40%). Treatment with FLAG‐Ida and isolated CNS relapse were independently associated with a higher CR rate after first salvage therapy. The median OS was 6.2 (95% confidence interval [CI], 3.9–8.6) months, with a 4‐year OS probability of 18% (95% CI, 9%–27%). No differences in survival were observed according to the treatment with hematopoietic stem cell transplantation in patients in CR after first salvage therapy. Multivariable analysis showed a ≥12‐month interval between first CR and relapse, CR after first salvage therapy and isolated CNS relapse as favorable prognostic factors for OS with hazard ratios (HR) (95% CI) of 1.931 (1.109–3.362), 2.958 (1.640–5.334), and 2.976 (1.157–7.655), respectively. This study confirms the poor outcomes of adults with R/R T‐ALL among whom FLAG‐Ida was the best of the rescue therapies evaluated. Late relapse, CR after first rescue therapy and isolated CNS relapse showed prognostic impact on survival. More effective rescue therapies are needed in adults with R/R T‐ALL. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

• We defined Complex Karyotype (CK) in T-ALL as the presence of ≥3 cytogenetic alterations. • T-ALL cases with CK ≥ 3 accounted for 16 % (22/139) of all evaluable karyotypes. • T-ALL patients with CK ≥ 3 showed a significantly inferior response to initial therapy. • CK ≥ 3 showed an adverse prognostic value in a multivariable test, independently of MRD. • The mutational profile CK ≥ 3 patients suggested a molecular mechanism of resistance. The potential prognostic value of conventional karyotyping in adult T-cell acute lymphoblastic leukemia (T-ALL) remains an open question. We hypothesized that a modified cytogenetic classification, based on the number and type of cytogenetic abnormalities, would allow the identification of high-risk adult T-ALL patients. Complex karyotype defined by the presence of ≥3 cytogenetic alterations identified T-ALL patients with poor prognosis in this study. Karyotypes with ≥3 abnormalities accounted for 16 % (22/139) of all evaluable karyotypes, corresponding to the largest poor prognosis cytogenetic subgroup of T-ALL identified so far. Patients carrying karyotypes with ≥3 cytogenetic alterations showed a significantly inferior response to therapy, and a poor outcome in terms of event-free survival (EFS), overall survival (OS) and cumulative incidence of relapse (CIR), independently of other baseline characteristics and the end-induction minimal residual disease (MRD) level. Additional molecular analyses of patients carrying ≥3 cytogenetic alterations showed a unique molecular profile that could contribute to understand the underlying molecular mechanisms of resistance and to evaluate novel targeted therapies (e.g. IL7R directed) with potential impact on outcome of adult T-ALL patients. [ABSTRACT FROM AUTHOR]