IMPORTANCE Bloodstream infection (BSI) is a common, life-threatening complication of treatment for cancer. Predicting BSI before onset of clinical symptoms would enable preemptive therapy, but there is no reliable screening test. OBJECTIVE To estimate sensitivity and specificity of plasma microbial cell-free DNA sequencing (mcfDNA-seq) for predicting BSI in patients at high risk of life-threatening infection. DESIGN, SETTING, AND PARTICIPANTSA prospective pilot cohort study of mcfDNA-seq for predicting BSI in pediatric patients (<25 years of age) with relapsed or refractory cancers at St Jude Children's Research Hospital, a specialist quaternary pediatric hematology-oncology referral center. Remnant clinical blood samples were collected during chemotherapy and hematopoietic cell transplantation. Samples collected during the 7 days before and at onset of BSI episodes, along with negative control samples from study participants, underwent blinded testing using a mcfDNA-seq test in a Clinical Laboratory Improvement Amendments/College of American Pathologists-approved laboratory. MAIN OUTCOMES AND MEASURESThe primary outcomes were sensitivity of mcfDNA-seq for detecting a BSI pathogen during the 3 days before BSI onset and specificity of mcfDNA-seq in the absence of fever or infection in the preceding or subsequent 7 days. RESULTS Between August 9, 2017, and June 4, 2018, 47 participants (27 [57%] male; median age [IQR], 10 [5-14] years) were enrolled; 19 BSI episodes occurred in 12 participants, and predictive samples were available for 16 episodes, including 15 bacterial BSI episodes. In the 3 days before the onset of infection, predictive sensitivity of mcfDNA-seq was 75% for all BSIs (12 of 16; 95% CI, 51%-90%) and 80% (12 of 15; 95% CI, 55%-93%) for bacterial BSIs. The specificity of mcfDNA-seq, evaluated on 33 negative control samples from enrolled participants, was 82% (27 of 33; 95% CI, 66%-91%) for any bacterial or fungal organism and 91% (30 of 33; 95% CI, 76%-97%) for any common BSI pathogen, and the concentration of pathogen DNA was lower in control than predictive samples. CONCLUSIONS AND RELEVANCEA clinically relevant pathogen can be identified by mcfDNA-seq days before the onset of BSI in a majority of episodes, potentially enabling preemptive treatment. Clinical application appears feasible pending further study. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT03226158JAMA Oncol.

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 &lt;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 &lt;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 &lt;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 &lt;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.

Background: As survival rates for children with acute lymphoblastic leukemia (ALL) improve, awareness of treatment complications becomes important. Osteonecrosis (ON) is a serious disabling complication in treated ALL patients. The aim of the study was to define the frequency of ON identified by magnetic resonance imaging (MRI) and to study the risk factors for ON. Patients and methods:The frequency of ON was evaluated retrospectively in 858 patients with ALL who were diagnosed at Children's Cancer Hospital of Egypt from January 2009 to December 2012. Patients were treated with St Jude Total Therapy Study XV.Results: Of 858 patients evaluated, 665 were eligible for the study and 65 (9.7%) developed ON.The cumulative 5-year incidence of ON was 11.96% (SE, 0.131%). Of 154 patients aged 10 years and older, 40 (26%) developed ON. The mean age of patients with ON was 10.7 years. The prognostic factors with a significant relationship with ON were age 10 years and older (P = 0.0001) and intermediate-/high-risk group (P = 0.0001). However, gender did not have a significant relationship. At the onset of ON, the mean cumulative dexamethasone dose was 796 mg/m 2 , and the mean total corticosteroid dose, calculated as prednisolone equivalence, was 6,431 mg/m 2 .Out of 43 patients who developed ON while on corticosteroid therapy, 36 (84%) required dexamethasone dose modification and/or discontinuation. Conclusion:The frequency of ON among the studied patients was 9.7%. Risk factors with a significant association with ON were older age and more intensive corticosteroid therapy.

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Treatment of acute lymphoblastic leukemia (ALL) necessitates continuous risk assessment of leukemic disease burden and infections that arise in the setting of immunosuppression. This study was performed to assess the feasibility of a hybrid capture next-generation sequencing panel to longitudinally measure molecular leukemic disease clearance and microbial species abundance in 20 pediatric patients with ALL throughout induction chemotherapy. This proof of concept helps establish a technical and conceptual framework that we anticipate will be expanded and applied to additional patients with leukemia, as well as extended to additional cancer types. Molecular monitoring can help accelerate the attainment of insights into the temporal biology of host-microbe-leukemia interactions, including how those changes correlate with and alter anticancer therapy efficacy. We also anticipate that fewer invasive bone marrow examinations will be required, as these methods improve with standardization and are validated for clinical use.