Early T-cell precursor (ETP) acute lymphoblastic leukemia (ALL), was first identified within cases of childhood T-ALL based on its unique immunophenotypic and genetic features of limited (early) T-cell differentiation associated with (some) myeloid and stem cell features. 1 Thus ETP-ALL blasts express CD7, dim CD5 (<75% positive cells), in the absence of CD1a and CD8, and positivity for ≥1 myeloid/stem cell related markers (i.e., CD34, CD13 or CD33). 1,2 In turn, ETP-ALL frequently shows myeloid-associated gene alterations such as FLT3, NRAS/KRAS, DNMT3A, IDH1 and IDH2 mutations, 3,4 with lower frequencies of other T-ALL-associated mutations (e.g., NOTCH1 and CDKN2A/B gene mutations). 5,6 The World Health Organization (WHO) 2016 classification of ALL included ETP-ALL for the first time, as a provisional entity, 7 but it failed to establish robust diagnostic criteria. Thus, after the first immunophenotypic characterization of ETP-ALL by Coustan-Smith et al. 1 the proposed criteria did not allow identification of all ETP-ALL cases as detected by gene expression profiling. 2 In addition, the "partial CD5 expression" criterion had a negative impact on the reproducibility of ETP-ALL diagnoses because of the lack of standardization of the method used for its assessment. Because of this, Zuubier et al. proposed refined immunophenotypic criteria by excluding CD5 expression while adding negativity for CD4. 2 From the clinical point of view early studies based on limited numbers of pediatric patients indicated that ETP-ALL was associated with a very poor outcome. 1,8,9 More recent data, based on larger series of children treated with more intensive therapy, showed no significant differences in outcome for ETP-ALL vs. other T-ALL cases. 10 In contrast, limited data have been reported for adult ETP-ALL, with conflicting results. 11,12 In one study, adult ETP-ALL was associated with a worse prognosis following different frontline chemotherapy schedules. 11 The

The need for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adults with Philadelphia chromosome-negative (Ph-neg) acute lymphoblastic leukemia (ALL) with high-risk (HR) features and adequate measurable residual disease (MRD) clearance remains unclear. The aim of the ALL-HR-11 trial was to evaluate the outcomes of HR Ph-neg adult ALL patients following chemotherapy or allo-HSCT administered based on end-induction and consolidation MRD levels. Patients aged 15-60 years (y) with HR-ALL in complete response (CR) and MRD levels (centrally assessed by 8-color flow cytometry) &lt;0.1% after induction and &lt;0.01% after early consolidation, were assigned to receive delayed consolidation and maintenance therapy up to 2y in CR. The remaining patients were allocated to allo-HSCT. CR was attained in 315/348 patients (91%), with MRD &lt;0.1% after induction in 220/289 patients (76%). By intention-to treat, 218 patients were assigned to chemotherapy and 106 to allo-HSCT. The 5-year (±95%CI) cumulative incidence of relapse (CIR), overall survival (OS) and event-free survival (EFS) probabilities for the whole series were 43%±7%, 49%±7% and 40±6%, respectively, with CIR and OS rates of 45±8% and 59±9% for patients assigned to chemotherapy and of 40±12% and 38±11% for those assigned to allo-HSCT, respectively. Our results show that avoiding allo-HSCT does not hamper the outcomes of HR Ph-neg adult ALL patients up to 60y with adequate MRD response after induction and consolidation. Better post-remission alternative therapies are especially needed for patients with poor MRD clearance. ClinicalTrials.gov (NCT01540812)

BACKGROUND: The use of rituximab together with intensive chemotherapy in Burkitt's lymphoma or leukemia (BL) has been scarcely explored. This study prospectively evaluated and compared the outcome and toxicity of human immunodeficiency virus (HIV)‐positive and HIV‐negative patients with BL who were treated in an intensive immunochemotherapy‐based and age‐adapted trial. METHODS: A total of 118 adult patients (80 HIV‐negative and 38 HIV‐positive) aged 15 to 83 years were treated with 4 (nonbulky stages I‐II) or 6 (stages II bulky, III‐IV) cycles of intensive chemotherapy combined with rituximab. Reduction in chemotherapy doses and modification of the cycle schedules was performed in patients older than 55 years. RESULTS: The clinical characteristics of HIV‐positive patients were comparable with those who were HIV‐negative. Complete remission rates were 82% and 87%, respectively, and 9 patients died in induction, 9 died in remission, and 7 relapsed. After a median follow‐up of 2.5 years, nonsignificant differences were observed in the 4‐year disease‐free survival and overall survival (OS) probabilities (77% and 63% for HIV‐positive and 80% and 78% for HIV‐negative patients, respectively). Young HIV‐infected patients presented higher incidences of grade 3 or 4 mucositis and severe infectious episodes. Poor general status and bone marrow involvement, but not advanced age, were associated with a shorter OS, allowing the definition of 3 prognostic groups, with the OS ranging from 50% to 92%. CONCLUSIONS: Age‐adapted intensive immunochemotherapy is highly effective in both HIV‐negative and HIV‐positive patients, with a higher toxicity in the latter group. Poor general status and bone marrow involvement had a negative impact on survival. Cancer 2013. © 2013 American Cancer Society.

In the European LeukemiaNet favourable risk category, allogeneic haematopoietic stem cell transplantation (alloSCT) is not indicated in first complete remission for patients with acute myeloid leukaemia (AML) with NPM1 mutations (ELNfav NPM1 AML), although a proportion of these patients will relapse. Given the prognostic importance of measurable residual disease (MRD), CETLAM-12 considered a pre-emptive intervention in patients with molecular failure (MF). We analyzed 110 ELNfav NPM1 AML patients achieving complete remission (CR) after induction chemotherapy. Two-year cumulative incidence of relapse (CIR), overall survival (OS) and leukaemia-free survival (LFS) were 17%, 81Á5% and 82%, respectively. Fortysix patients required additional therapy for MF (n = 33) or haematological relapse (HemR; n = 13), resulting in a molecular LFS (molLFS) and a cumulative incidence of MF at two years of 61% and 38% respectively. Two-year OS for these 46 patients was 66%, with a different outcome between patients with MF (86%) and HemR (42%) (P = 0Á002). Quantitative NPM1 detection at different timepoints was predictive of molLFS; an MRD ratio (NPM1mut/ ABL1 9 100) cutoff of 0Á05 after first consolidation identified two cohorts with a two-year molLFS of 77% and 40% for patients below and above 0Á05, respectively. In conclusion, MRD-based pre-emptive intervention resulted in a favourable outcome for ELNfav NPM1 AML patients.

Native or pegylated (PEG) asparaginase (ASP) are commonly used in treatment of acute lymphoblastic leukemia (ALL), but have been scarcely compared in the same trial in adult patients. Native vs. PEG-ASP administered according to availability in each center were prospectively evaluated in adults with high-risk ALL. Ninety-one patients received native ASP and 35 PEG-ASP in induction. No significant differences were observed in complete remission, minimal residual disease levels after induction and after consolidation, disease-free survival, and overall survival. No significant differences in grades 3-4 toxicity were observed in the induction period, although a trend for higher hepatic toxicity was observed in patients receiving PEG-ASP. In this trial the type of ASP did not influence patient response and outcome.