ELN 2017 classification significantly impacts the risk of early death in acute myeloid leukemia patients receiving intensive induction chemotherapy.

Early mortality remains a challenging therapeutic facet of the initial induction phase of intensive chemotherapy in patients with acute myeloid leukemia (AML). The impact of standard molecular evaluation and risk category of the European LeukemiaNet (ELN) 2017 classification model on early mortality has not been rigorously evaluated thus far. We reviewed the medical records of 320 consecutive adult patients with newly diagnosed AML treated with intensive induction chemotherapy in our center from 2007 to 2021. The median age was 56 years; 33 patients (10%) died during induction. Patient age, white blood cell count, hemoglobin level, platelet level, creatinine, uric acid, lactate dehydrogenase serum levels, and FLT3-ITD and CEBPA mutational status did not significantly impact early mortality. NPM1mut patients had a lower likelihood of early death compared to NPM1wt (5% versus 13%; p = 0.023) whereas patients with high-risk cytogenetic studies experienced higher rates of induction mortality compared with intermediate and favorable risk patients (20% versus 8 and 7%, respectively; p = 0.049). Adverse risk ELN 2017 was significantly more likely to die during induction compared with intermediate and favorable risk patients (20% versus 10 and 4%, respectively; p = 0.001). Patients treated in 2007-2011 experienced a significantly higher rate of induction death compared with patients in 2012-2021 (17% versus 8%; p = 0.039). Multivariate analysis confirmed adverse ELN 2017 [odds ratio (OR), 6.7; 95% confidence interval (CI), 1.74-25.3; p = 0.006) and treatment timeframe (OR, 0.35; 95% CI, 0.14-0.85; p = 0.019) as pivotal predictors of early mortality. ELN 2017 is a robust prognosticator of early mortality in intensively treated AML patients.

Acute Myeloid Leukemia Patients Requiring Two Cycles of Intensive Induction for Attainment of Remission Experience Inferior Survival Compared with Patients Requiring a Single Course of Induction Chemotherapy.

BACKGROUND: Achievement of initial remission remains the most important clinical factor predicting long term survival in acute myeloid leukemia (AML) patients treated with intensive chemotherapy. Yet, whether the patient subset in need of a second cycle of intensive induction chemotherapy to reach remission experiences inferior outcomes compared to patients reaching remission after a single cycle of therapy, remains uncertain. PATIENTS AND METHODS: Retrospective analysis of 302 consecutive AML patients treated with intensive induction chemotherapy in our institution in 2007-2020. RESULTS: Median patient age was 55 years with a median follow-up duration of 23 months. In terms of European LeukemiaNet (ELN) 2017 classification, 122 patients (40%) were designated as favorable risk disease, 108 patients (36%) were intermediate risk, and 71 patients (24%) were adverse risk. A hundred and seventy-seven patients (60%) attained remission following initial chemotherapy while 58 patients (20%) required an additional cycle of intensive chemotherapy for remission. Patients requiring 2 cycles to reach remission were less likely to be NPM1 mutated (33% versus 51%; P=.025) or be in the ELN 2017 favorable risk category (25% versus 57%; P<.001). In multivariate analysis achievement of remission following 2 cycles of intensive compared with a single cycle resulted in significantly inferior survival [hazard ratio (HR)=1.67, 95% CI, 1.07-2.59; P=.025] whereas leukemia-free survival was not significantly impacted (HR=1.26, 95% CI, 0.85-1.85) (P=.23). Relapse rates also did not differ to a significant degree between groups (45% versus 47%, P=.8). CONCLUSION: Attainment of an early remission significantly impacts long term survival in AML patients.

External validation and comparison of multiple prognostic scores in allogeneic hematopoietic stem cell transplantation.

Clinical decisions in allogeneic hematopoietic stem cell transplantation (allo-HSCT) are supported by the use of prognostic scores for outcome prediction. Scores vary in their features and in the composition of development cohorts. We sought to externally validate and compare the performance of 8 commonly applied scoring systems on a cohort of allo-HSCT recipients. Among 528 patients studied, acute myeloid leukemia was the leading transplant indication (44%) and 46% of patients had a matched sibling donor. Most models successfully grouped patients into higher and lower risk strata, supporting their use for risk classification. However, discrimination varied (2-year overall survival area under the receiver operating characteristic curve [AUC]: revised Pretransplantation Assessment of Mortality [rPAM], 0.64; PAM, 0.63; revised Disease Risk Index [rDRI], 0.62; Endothelial Activation and Stress Index [EASIx], 0.60; combined European Society for Blood and Marrow Transplantation [EBMT]/Hematopoietic Cell Transplantation-specific Comorbidity Index [HCT-CI], 0.58; EBMT, 0.58; Comorbidity-Age, 0.58; HCT-CI, 0.55); AUC ranges from 0.5 (random) to 1.0 (perfect prediction). rPAM and PAM, which had the greatest predictive capacity across all outcomes, are comprehensive models including patient, disease, and transplantation information. Interestingly, EASIx, a biomarker-driven model, had comparable performance for nonrelapse mortality (NRM; 2-year AUC, 0.65) but no predictive value for relapse (2-year AUC, 0.53). Overall, allo-HSCT prognostic systems may be useful for risk stratification, but individual prediction remains a challenge, as reflected by the scores' limited discriminative capacity.

Real-Life Glycemic Control in Children with Type 2 Diabetes: A Population-Based Study.

OBJECTIVES: To characterize children and adolescents with type 2 diabetes mellitus (T2DM) insured by a large health maintenance organization, and to identify variables associated with treatment quality and disease outcome. STUDY DESIGN: Children and adolescents diagnosed with T2DM over a 9-year period were identified from the database of Clalit Health Services, a large health maintenance organization in Israel (1 213 362 members aged 0-18 years). Demographic, anthropometric, clinical, and laboratory data were analyzed. RESULTS: A total of 96 patients (47 males) met our inclusion criteria. The mean age at diagnosis of T2DM was 14.25 ± 2.51 years. At the time of diagnosis, the median hemoglobin A1c (HbA1c) level was 7.8%, and additional components of the metabolic syndrome were present in 14.9%-67.4% of the patients. At the end of the follow-up period (3.11 ± 1.75 years), >50% of the patients were being treated with insulin; the median HbA1c value was 7.97%, and 44.6% of the patients achieved the target HbA1c of <7.0%. On multivariate linear regression analysis, the variables found to predict worse glycemic control (ie, higher HbA1c) were a higher HbA1c at diagnosis, a higher body mass index SD score at diagnosis, fewer annual HbA1c tests, and Arabic ethnicity [F(4,81) = 7.139; P < .001; R2 = 0.271]. CONCLUSION: This population-based study of pediatric patients with T2DM demonstrates that reasonable glycemic control can be achieved in both community and outpatient hospital settings. Nevertheless, there is room for improvement in intervention programs to optimize outcomes and decrease the risk of complications.