High dose methotrexate (HDMTX)-induced acute kidney injury (AKI) is a well-known adverse event in hemato-oncology patients. Our purpose was to define factors and setup cutoffs that may help better identify patients at-risk for developing AKI following HDMTX. All consecutive patients who received MTX dose ≥1 g were retrospectively reviewed. We compared patients with or without renal toxicity. We used a logistic regression model to define baseline variables associated with AKI. Overall survival (OS) was estimated by the Kaplan-Meier method employing log-rank test. Between 2012 and 2017, 160 patients were included with a total of 265 courses. Indications included: primary central nervous system (CNS) lymphoma, CNS prophylaxis in other lymphoma types, acute lymphatic leukemia and others. Median age at diagnosis was 58 years (range, 18-84), 54% were males, median MTX dose was 1941 mg/m 2 (range, 743-5442) and AKI developed in 9% of drug administrations (n = 24). In univariate analysis: age > 40, LDH > 380 units/L, eGFR < 112 mL/min, albumin <3.6 mg/dL at baseline and Charlson comorbidity index (CCI) were associated with AKI. In multivariable analysis, only LDH > 380 units/L (OR = 4.1, 95% confidence interval [CI] 1.04-20.9, P = .04) and albumin levels <3.6 g/dL (OR = 4.17, 95% CI 1.04-6.5, P = .04) remained significant. In patients with AKI, median drug elimination was longer (8 days vs 5 days). In 80% of cases, the creatinine levels returned to normal within 1 month. Yet, the median survival of patients who developed AKI was 37 months, compared to 145 months in patients without AKI (Log rank = 0.015). In conclusion, LDH > 380 units/L and albumin <3.6 g/dL were the strongest factors associated with AKI in patients receiving HDMTX. Although the rise in creatinine levels was almost uniformly reversible, AKI was associated with increased mortality rates.

Rituximab, the first anti‐CD20 monoclonal antibody, has dramatically improved outcomes for patients with B‐cell lymphoproliferative disorders. Obinutuzumab was developed to potentiate activity and overcome resistance to rituximab. Clinical data suggest that obinutuzumab is superior to rituximab in follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL). Yet, it has increased toxicity. This systematic review and meta‐analysis compiled all randomized controlled trials (RCTs) comparing obinutuzumab‐based regimens with rituximab‐based regimens to better assess their toxicity profile. Primary outcome was grade 3–4 infections; secondary outcomes included any adverse events (AE), grade 3–4 AE, drug discontinuation rate, and 3‐years mortality. Relative risks (RRs) were estimated and pooled using a fixed‐effect model, unless there was significant heterogeneity, in which case a random‐effects model was used. Our comprehensive search yielded five RCTs conducted between 2009 and 2014, including 4247 patients. The trials included FL patients, CLL and diffuse large B cell lymphoma. Monoclonal antibodies were given with different chemotherapy regimens (in four trials) or as monotherapy (in one trial). The point estimate favored increase in both grade 3–4 infections rate (RR 1.17 [95% CI, 1.0–1.36]) and any AE rate (RR 1.05 [95% 1–1.1]) with obinutuzumab, although this was not statistically significant. There was a significantly increased rate of grade 3–4 AE (RR 1.15 [95% CI, 1.09–1.2]), as well as grade 3–4 toxicities including thrombocytopenia (RR 2.8 [95% CI, 1.92–4.06]), infusion related reactions (RR 2.8 [95% CI, 2.16‐3.64]) and cardiac events (RR 1.65 [95% CI, 1.11‐2.46]). There was no significant difference in grade 3–4 anemia and neutropenia nor in the 3‐year mortality rate. The point estimate favored increase in discontinuation rate due to AE with obinutuzumab, although without statistical significance (RR 1.24 [95% CI, 1.0–1.54]). In conclusion, physicians need to weigh the clinical benefits of this agent against higher toxicity.

Significant advances have been made in recent years in the field of Philadelphia-negative acute lymphoblastic leukaemia (ALL). New insights into the biology and genetics of ALL as well as novel clinical observations and new drugs are changing the way we diagnose, risk-stratify and treat adult patients with ALL. New genetic subtypes and alterations refine risk stratification and uncover new actionable therapeutic targets. The incorporation of more intensive, paediatric and paediatric-inspired approaches for young adults seem to have a positive impact on survival in this population. Minimal residual disease at different time points can assist in tailoring risk-adapted interventions for patients based on individual response. Finally, novel targeted approaches with monoclonal antibodies, immunotherapies and small molecules are moving through clinical development and entering the clinic. The aim of this review is to consolidate the abundance of emerging data and to review and revisit the concepts of risk-stratification, choice of induction and post-remission strategies as well as to discuss and update the approach to specific populations with ALL, such as young adult, elderly/unfit and relapsed/refractory patients with ALL.