Determinants of survival after first relapse of acute lymphoblastic leukemia: a Children's Oncology Group study.

Limited prognostic factors have been associated with overall survival (OS) post-relapse in childhood Acute Lymphoblastic Leukemia (ALL). Patients enrolled on 12 Children's Oncology Group frontline ALL trials (1996-2014) were analyzed to assess for additional prognostic factors associated with OS post-relapse. Among 16,115 patients, 2053 (12.

Minimal residual disease predicts outcomes in KMT2A-rearranged but not KMT2A-germline infant acute lymphoblastic leukemia: Report from Children's Oncology Group study AALL0631.

We measured minimal residual disease (MRD) by multiparameter flow cytometry at three time points (TP) in 117 infants with KMT2A (lysine [K]-specific methyltransferase 2A)-rearranged and 58 with KMT2A-germline acute lymphoblastic leukemia (ALL) on Children's Oncology Group AALL0631 study. For KMT2A-rearranged patients, 3-year event-free survival (EFS) by MRD-positive (≥0.01%) versus MRD-negative (<0.

FLT3 inhibitor lestaurtinib plus chemotherapy for newly diagnosed KMT2A-rearranged infant acute lymphoblastic leukemia: Children's Oncology Group trial AALL0631.

Infants with KMT2A-rearranged acute lymphoblastic leukemia (KMT2A-r ALL) have a poor prognosis. KMT2A-r ALL overexpresses FLT3, and the FLT3 inhibitor (FLT3i) lestaurtinib potentiates chemotherapy-induced cytotoxicity in preclinical models. Children's Oncology Group (COG) AALL0631 tested whether adding lestaurtinib to post-induction chemotherapy improved event-free survival (EFS).

Scoliosis in Children Treated With Photon Craniospinal Irradiation for Medulloblastoma.

Purpose: Scoliosis is a well-recognized complication after abdominal radiation therapy but not reported frequently after craniospinal irradiation (CSI). We examined the incidence and risk factors for scoliosis after CSI in long-term survivors with medulloblastoma.

Methods And Materials: The records of patients with medulloblastoma seen at one institution from 1996 to 2006 were analyzed for the use of CSI and development of scoliosis as documented on physical examination and spinal imaging.

Defining the Inflammatory Plasma Proteome in Pediatric Hodgkin Lymphoma.

Hodgkin lymphoma (HL) histopathology is characterized by rare malignant Reed-Sternberg cells among an inflammatory infiltrate. We hypothesized that characteristics of inflammation in pediatric HL lesions would be reflected by the levels of inflammatory cytokines or chemokines in pre-therapy plasma of children with HL. The study objectives were to better define the inflammatory pre-therapy plasma proteome and identify plasma biomarkers associated with extent of disease and clinical outcomes in pediatric HL.

Association of GSTM1 null variant with anthracycline-related cardiomyopathy after childhood cancer-A Children's Oncology Group ALTE03N1 report.

Background: Anthracycline-related cardiomyopathy is a leading cause of late morbidity in childhood cancer survivors. Glutathione S-transferases (GSTs) are a class of phase II detoxification enzymes that facilitate the elimination of anthracyclines. As free-radical scavengers, GSTs could play a role in oxidative damage-induced cardiomyopathy.

The Population Pharmacokinetics of High-Dose Methotrexate in Infants with Acute Lymphoblastic Leukemia Highlight the Need for Bedside Individualized Dose Adjustment: A Report from the Children's Oncology Group.

Background: Infants with acute lymphoblastic leukemia (ALL) treated with high-dose methotrexate may have reduced methotrexate clearance (CL) due to renal immaturity, which may predispose them to toxicity.

Objective: The aim of this study was to develop a population pharmacokinetic (PK) model of methotrexate in infants with ALL.

Methods: A total of 672 methotrexate plasma concentrations were obtained from 71 infants enrolled in the Children's Oncology Group (COG) Clinical Trial P9407.

Disparities in Neurotoxicity Risk and Outcomes among Pediatric Acute Lymphoblastic Leukemia Patients.

Methotrexate chemotherapy can be associated with neurologic complications during therapy and long-term neurologic deficits. This study evaluated demographic and clinical factors associated with incidence of methotrexate neurotoxicity and described the impact of neurotoxicity on acute lymphoblastic leukemia (ALL) therapy in pediatric patients. Patients were enrolled between 2012 and 2017 from three pediatric cancer treatment centers in the United States.

Comparison of height and weight after 12 vs. 18 Gy cranial radiation therapy in pediatric acute lymphoblastic leukemia (ALL) patients.

Purpose: To compare the effect of 12 versus 18 Gy cranial radiation therapy (RT) on height and weight indices among pediatric patients with acute lymphoblastic leukemia (ALL).

Methods And Materials: Records of children with ALL who were 2 to 14 years old at the time of RT and were treated at a single institution between 2000 and 2011 were reviewed. Patients' height, weight, and body mass index were converted into z-scores using the Centers for Disease Control growth charts to normalize the values to number of standard deviations from the mean.

A Pilot Study of Intensified PEG-Asparaginase in High-risk Acute Lymphoblastic Leukemia: Children's Oncology Group Study AALL08P1.

AALL08P1 was designed to determine whether biweekly intensified pegaspargase (I-PEG) was feasible and safe in pediatric patients with newly diagnosed high-risk B-precursor lymphoblastic leukemia when given with Children's Oncology Group hemiaugmented BFM therapy. High-risk average (HR-Avg) patients received standard pegaspargase dosing (6 doses), whereas high-risk high (HR-High) patients received I-PEG biweekly from the start of Consolidation until day 1 of Maintenance. Feasibility and safety were defined in advance as ≥65% of patients tolerating at least 8 doses of I-PEG and 90% requiring ≤49 weeks from day 1 of Consolidation to the initiation of Maintenance.

CELF4 Variant and Anthracycline-Related Cardiomyopathy: A Children's Oncology Group Genome-Wide Association Study.

Purpose: Interindividual variability in the dose-dependent association between anthracyclines and cardiomyopathy suggests that genetic susceptibility could play a role. The current study uses an agnostic approach to identify genetic variants that could modify cardiomyopathy risk.

Methods: A genome-wide association study was conducted in childhood cancer survivors with and without cardiomyopathy (cases and controls, respectively).

Activity and Toxicity of Intravenous Erwinia Asparaginase Following Allergy to E. coli-Derived Asparaginase in Children and Adolescents With Acute Lymphoblastic Leukemia.

Background: Erwinia asparaginase is antigenically distinct from E.coli-derived asparaginase and may be used after E.coli-derived asparaginase hypersensitivity.

Decreased induction morbidity and mortality following modification to induction therapy in infants with acute lymphoblastic leukemia enrolled on AALL0631: a report from the Children's Oncology Group.

Background: Infants with acute lymphoblastic leukemia (ALL) have a poor prognosis. Intensification of therapy has resulted in fewer relapses but increased early deaths, resulting in failure to improve survival.

Procedure: AALL0631 is a Phase 3 study for infants (<366 days of age) with newly diagnosed ALL.

Intensified chemotherapy without SCT in infant ALL: results from COG P9407 (Cohort 3).

Background: Infants with acute lymphoblastic leukemia (ALL) present with aggressive disease and a poor prognosis. Early relapse within 6-9 months of diagnosis is common. Approximately 75% of infants have MLL-rearranged (MLL-R) ALL with event free survival (EFS) ranging from 20% to 30%.

Hyaluronan synthase 3 variant and anthracycline-related cardiomyopathy: a report from the children's oncology group.

Purpose: The strong dose-dependent association between anthracyclines and cardiomyopathy is further exacerbated by the co-occurrence of cardiovascular risk factors (diabetes and hypertension). The high morbidity associated with cardiomyopathy necessitates an understanding of the underlying pathogenesis so that targeted interventions can be developed.

Patients And Methods: By using a two-stage design, we investigated host susceptibility to anthracycline-related cardiomyopathy by using the ITMAT/Broad CARe cardiovascular single nucleotide polymorphism (SNP) array to profile common SNPs in 2,100 genes considered relevant to de novo cardiovascular disease.

Safety profile of asparaginase Erwinia chrysanthemi in a large compassionate-use trial.

Background: L-Asparaginase is an integral component of standard chemotherapy regimens for the treatment of acute lymphoblastic leukemia (ALL). Clinical hypersensitivity, a common reason for treatment discontinuation, has been reported in 10-30% of patients receiving Escherichia coli-derived asparaginase. After hypersensitivity, E.

Potent obatoclax cytotoxicity and activation of triple death mode killing across infant acute lymphoblastic leukemia.

Survival in infants younger than 1 year who have acute lymphoblastic leukemia (ALL) is inferior whether MLL is rearranged (R) or germline (G). MLL translocations confer chemotherapy resistance, and infants experience excess complications. We characterized in vitro sensitivity to the pan-antiapoptotic BCL-2 family inhibitor obatoclax mesylate in diagnostic leukemia cells from 54 infants with ALL/bilineal acute leukemia because of the role of prosurvival BCL-2 proteins in resistance, their imbalanced expression in infant ALL, and evidence of obatoclax activity with a favorable toxicity profile in early adult leukemia trials.