Legacy data show that approximately 40% of children with acute lymphoblastic leukemia (ALL) were cured with limited antimetabolite-based chemotherapy regimens. However, identifying patients with very-low-risk (VLR) ALL remains imprecise. Patients selected based on a combination of presenting features and a minimal residual disease (MRD) level of <0.01% on day 19 of induction therapy had excellent outcomes with low-intensity treatment. We investigated the impact of MRD levels between 0.001% and <0.01% early in remission induction on the outcome of VLR ALL treated with a low-intensity regimen. Between October 2011 and September 2015, 200 consecutive patients with B-precursor ALL with favorable clinicopathologic features and MRD levels of <0.01%, as assessed by flow cytometry in the bone marrow on day 19 and at the end of induction therapy, received reduced-intensity therapy. The 5-year event-free survival was 89.5% (± 2.2% SE), and the overall survival was 95.5% (± 1.5% SE). The 5-year cumulative incidence of relapse (CIR) was 7% (95% CI, 4% to 11%). MRD levels between 0.001% and <0.01% on day 19 were detectable in 29 patients. These patients had a 5-year CIR significantly higher than that of patients with undetectable residual leukemia (17.2% ± 7.2% vs 5.3% ± 1.7%, respectively; P = .02). Our study shows that children with VLR ALL can be treated successfully with decreased-intensity therapy, and it suggests that the classification criteria for VLR can be further refined by using a more sensitive MRD assay.

Aggresomes are inclusion bodies for misfolded/aggregated proteins. Despite the role of misfolded/aggregated proteins in neurological disorders, their role in cancer pathogenesis is poorly defined. In the current study we aimed to investigate whether aggresomes-positivity could be used to improve the disease subclassification and prognosis prediction of pediatric medulloblastoma. Ninety three pediatric medulloblastoma tumor samples were retrospectively stratified into three molecular subgroups; WNT, SHH and non-WNT/non-SHH, using immunohistochemistry and Multiplex Ligation Probe Amplification. Formation of aggresomes were detected using immunohistochemistry. Overall survival (OS) and event-free survival (EFS) were determined according to risk stratification criteria. Multivariate Cox regression analyses were carried out to exclude confounders. Aggresomes formation was detected in 63.4% (n = 59/93) of samples. Aggresomes were non-randomly distributed among different molecular subgroups ( P = 0.00002). Multivariate Cox model identified aggresomes’ percentage at ≥20% to be significantly correlated with patient outcome in both OS (HR = 3.419; 95% CI, 1.30–8.93; P = 0.01) and EFS (HR = 3; 95% CI, 1.19–7.53; P = 0.02). The presence of aggresomes in ≥20% of the tumor identified poor responders in standard risk patients; OS ( P = 0.02) and EFS ( P = 0.06), and significantly correlated with poor outcome in non-WNT/non-SHH molecular subgroup; OS ( P = 0.0002) and EFS ( P = 0.0004).

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