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Background:Bloodstream infections (BSIs) are a frequent cause of morbidity in patients with acute myeloid leukemia (AML), due in part to the presence of central venous access devices (CVADs) required to deliver therapy.Objective:To determine the differential risk of bacterial BSI during neutropenia by CVAD type in pediatric patients with AML.Methods:We performed a secondary analysis in a cohort of 560 pediatric patients (1,828 chemotherapy courses) receiving frontline AML chemotherapy at 17 US centers. The exposure was CVAD type at course start: tunneled externalized catheter (TEC), peripherally inserted central catheter (PICC), or totally implanted catheter (TIC). The primary outcome was course-specific incident bacterial BSI; secondary outcomes included mucosal barrier injury (MBI)-BSI and non-MBI BSI. Poisson regression was used to compute adjusted rate ratios comparing BSI occurrence during neutropenia by line type, controlling for demographic, clinical, and hospital-level characteristics.Results:The rate of BSI did not differ by CVAD type: 11 BSIs per 1,000 neutropenic days for TECs, 13.7 for PICCs, and 10.7 for TICs. After adjustment, there was no statistically significant association between CVAD type and BSI: PICC incident rate ratio [IRR] = 1.00 (95% confidence interval [CI], 0.75–1.32) and TIC IRR = 0.83 (95% CI, 0.49–1.41) compared to TEC. When MBI and non-MBI were examined separately, results were similar.Conclusions:In this large, multicenter cohort of pediatric AML patients, we found no difference in the rate of BSI during neutropenia by CVAD type. This may be due to a risk-profile for BSI that is unique to AML patients.

Background Lack of health insurance coverage is associated with poor access and receipt of cancer care and survival in the United States. Disruptions in coverage are common among low-income populations, but little is known about associations of disruptions with cancer care, including prevention, screening, and treatment, as well as outcomes of stage at diagnosis and survival. Methods We conducted a systematic review of studies of health insurance coverage disruptions and cancer care and outcomes published between 1980 and 2019. We used the PubMed, EMBASE, Scopus, and CINAHL databases and identified 29 observational studies. Study characteristics and key findings were abstracted and synthesized qualitatively. Results Studies evaluated associations between coverage disruptions and prevention or screening (31.0%), treatment (13.8%), end-of-life care (10.3%), stage at diagnosis (44.8%), and survival (20.7%). Coverage disruptions ranged from 4.3% to 32.8% of patients age-eligible for breast, cervical, or colorectal cancer screening. Between 22.1% and 59.5% of patients with Medicaid gained coverage only at or after cancer diagnosis. Coverage disruptions were consistently statistically significantly associated with lower receipt of prevention, screening, and treatment. Among patients with cancer, those with Medicaid disruptions were statistically significantly more likely to have advanced stage (odds ratios = 1.2-3.8) and worse survival (hazard ratios = 1.28-2.43) than patients without disruptions. Conclusions Health insurance coverage disruptions are common and adversely associated with receipt of cancer care and survival. Improved data infrastructure and quasi-experimental study designs will be important for evaluating the associations of federal and state policies on coverage disruptions and care and outcomes.

Background The clinical presentation of acute lymphoblastic lymphoma is highly varied. While prognosis is good, recurrence of disease can occur. Gastrointestinal relapse, including intussusception, is well-described but the absence of abdominal pain in this setting is rare. Case summary We report a 13-year-old male with B-cell precursor acute lymphoblastic leukemia in remission presenting with anemia and weight loss. Examination was significant for absence of abdominal pain, but a stool sample was positive for occult blood. Pan-endoscopy was performed with colonoscopy revealing a mass filling the colonic lumen. Biopsy of the mass confirmed recurrence of recurrent B-cell lymphoma. Computed tomography scan revealed ileocolic intussusception resulting from the tumor. This case is unusual in that the patient had no abdominal pain despite the presence of intussusception. Conclusion While intestinal involvement with lymphoma has been well described in the literature, presentation as painless intussusception has not been reported. This case report highlights the wide spectrum of clinical manifestations of recurrent B-cell lymphoma involving the gastrointestinal tract, in particular the near absence of symptoms despite the finding of intussusception.

Objectives The purpose of this study was to investigate the patient population and outcomes of synovial sarcoma at a single institution. Methods A retrospective review of the medical records of 28 patients with synovial sarcoma diagnosed from 1992 to 2017 was performed. Demographics, staging, disease location, treatment, and response to treatment were reviewed. Results Individuals with larger tumors at the time of presentation had an increased risk of death. An additional factor associated with poor prognosis in synovial sarcoma was increasing patient age. The patient population had a higher rate of nonextremity disease and lower overall survival when compared with national averages. Conclusions Nonextremity disease and large size of tumor at presentation may have contributed to the disparity in institutional outcomes from the national averages. The advanced presentation of synovial sarcoma remains a significant challenge in improving patient survival.

Seven Children’s Oncology Group phase 2 trials for patients with relapsed/progressive solid tumors were analyzed to estimate the event-free survival (EFS) for relapsed/progressive Ewing sarcoma. One hundred twenty-eight Ewing sarcoma patients were enrolled and 124 events occurred. The 6-month EFS was 12.7%, demonstrating the poor outcome of these patients. Only docetaxel achieved its protocol-specified radiographic response rate for activity; however, the EFS for docetaxel was similar to other agents, indicating that a higher radiographic response rate may not translate into superior disease control. This EFS benchmark could be utilized as an additional endpoint in trials for recurrent Ewing sarcoma.

TPS11583 Background: Palbociclib (PD-0332991) is a highly selective, reversible, small molecule inhibitor of cyclin-dependent kinases (CDK) 4 and 6, administered orally. Functional dependence of Ewing Sarcoma (EWS) cell lines and tumor xenografts on Cyclin D1/CDK4 via genetic knockdown has shown both Cyclin D1 and CDK4 as critical dependencies for EWS cell line proliferation. The phase 1 portion of the study established the recommended Phase 2 dose (RP2D) with two chemotherapy backbones in children with solid tumors. The Phase 2 portion of the study now enrolls patients with EWS. The primary objective of this portion of the study is to determine whether the addition of palbociclib to irinotecan (IRN) and temozolomide (TMZ) will prolong event-free survival (EFS) of pediatric and young adult patients with recurrent or refractory EWS. Methods: Patients with recurrent or refractory EWS are randomized 2:1 to receive either palbociclib in combination with IRN and TMZ or IRN and TMZ alone. Randomization is stratified by type and time of disease recurrence (primary refractory or 1st recurrence st recurrence ≥2 years or 2nd or greater recurrence). The primary efficacy endpoint is EFS per investigator assessment. Secondary efficacy endpoints include objective response, progression-free survival and overall survival. An interim futility analysis will be conducted to allow for early stopping of the study due to futility/no signal of activity based on the primary endpoint of EFS. Safety and planned interim efficacy data will be assessed by an Independent Data Monitoring Committee (DMC). Key eligibility criteria include: recurrent or refractory EWS with evaluable disease, no known bone marrow metastases, histopathological confirmation of EWSR1-ETS or FUS-ETS rearrangement or availability of formalin fixed paraffin embedded (FFPE) tumor tissue sample for central testing, age ≥2 and 2 orally (either as a capsule or oral solution) once daily on Days 1-14 of each 21-day treatment cycle. TMZ will be administered orally once daily at 100 mg/m2 on Days 1-5 (intravenously (IV) if patient cannot swallow the TMZ capsule). IRN will be administered IV at 50 mg/m2 on Days 1-5. Patients randomized to the chemotherapy only treatment arm will receive IRN and TMZ at the same doses on Days 1-5 of the 21-day treatment cycle. Treatment will continue until disease progression, patient and/or legal guardian refusal, unacceptable toxicity , or up to 24 months of treatment, whichever occurs first. The Phase 2 enrolment has been initiated and 1/75 patients has been enrolled as of Jan 2022. Clinical trial information: NCT03709680.

The COVID-19 pandemic impacted the health care system in unprecedented ways. We reviewed the registry of new cancer patients who presented to the Children's of Mississippi Center for Cancer and Blood Disorders and showed the average number of new pediatric cancer diagnoses dropped during the initial COVID-19 months and rose significantly in June 2020. We must encourage families to seek health care when needed and keep scheduled appointments for routine vaccinations and health maintenance as we know the long-term sequela of delaying health maintenance far outweighs risks at present.

Background Patients with recurrent or refractory osteosarcoma have a poor prognosis with less than 30% surviving two years. Eribulin is a synthetic analog of halichondrin B, has a novel mechanism of action when compared with other microtubule inhibitors, and may have antitumor activity in osteosarcoma. Methods A prospective study was designed to assess the disease control success at four months and objective response rates in patients with recurrent or refractory osteosarcoma treated with eribulin. Eligible patients were between 12 and 50 years of age, had measurable tumor, and met standard organ function requirements. Patients were given eribulin 1.4 mg/m2 /dose on days 1 and 8 of each 3-week cycle for up to 24 months if there was no progressive disease. Response to therapy was assessed using RECIST 1.1 criteria after cycles 2 and 5 and every fourth cycle thereafter. Results Nineteen patients enrolled on the AOST1322 study. The median age of enrollment was 16 years (range, 12-25 years). Twelve patients were male and seven female. Eribulin was well tolerated, with neutropenia identified as the most common toxicity. The median progression-free survival was 38 days and no patients reached the four-month time point without progression. No objective responses were seen in any patient. Conclusion This study rapidly assessed the clinical activity of a novel agent in this patient population. Eribulin was well tolerated, but there were no patients who demonstrated objective response, and all patients had progression prior to four months.

Complex relationships between race and socioeconomic status have a poorly understood influence on psychologic outcomes in pediatric oncology. The Family Symptom Inventory was used to assess symptoms of depression and anxiety in pediatric patients with cancer and their caregivers. Separate hierarchical linear regression models examined the relationship between demographic variables, cancer characteristics, socioeconomic status, and access to care and patient or caregiver depression/anxiety. Participants included 196 pediatric patients with cancer (mean age, 11.21 y; 49% African American) and their caregivers. On average, caregivers reported low levels of depression/anxiety. Symptoms of depression and anxiety in patients were correlated with poorer mental health in caregivers (r=0.62; P0.01). Self-reported financial difficulty (β=0.49; P0.001) and brain cancer diagnosis for their child (β=0.42; P=0.008) were significantly associated with depression and anxiety in caregivers. Analysis did not reveal significant associations between race, household income, or access to care and patient or caregiver depression/anxiety. Perception of financial hardship can adversely impact mental health in caregivers of children with cancer. Psychosocial assessment and interventions may be especially important for caregivers of patients with brain tumors and caregivers who report feeling financial difficulty.

The increasing use of serial multimodality imaging in the management of pediatric osteosarcoma raises concern of over exposure to ionizing radiation in children, especially from repeated computed tomographic (CT) scans. This study reviews the utilization of multimodality imaging in patients with osteosarcoma at our institution and analyzes any potential radiation-related complications. Twenty-eight patients were identified. Three patients developed late complications-acute myeloid leukemia, myelodysplastic syndrome, and early menopause. Using the patient's age and body part imaged, CT dose length product and effective dose was estimated with the use of a conversion factor for 19 patients. The effective doses were higher in the 3 patients with late complications than the other patients in the cohort (P=0.018). These results suggest an increased risk for adverse effects with higher CT exposures and effective doses. On the basis of our data and published data, methods to decrease the doses of radiation from medical imaging need to be explored. The number of CT scans may be limited. Implementing the Image Gently concept to decrease radiation exposure can be beneficial in modification of CT acquisition parameters.

Wound dehiscence after chemo-port placement is a rare but potentially significant complication. We hypothesize that by using a simple running skin closure technique during chemo-port placement the rate of wound dehiscence and overall wound complications can be significantly decreased.IRB approval was obtained and patients18years that received a tunneled central line with port from June 2012 to April 2016 were analyzed. Data collected on patients included patient demographics, skin closure type, and wound complications within 30days. Chi-square was performed to examine the univariate association with skin closure technique and wound dehiscence. Logistic regression was performed to examine the multivariable association between skin closure type and wound dehiscence and to compute odds ratios.There were 259 ports placed in this cohort: 125 used simple running skin closure technique, and 134 used the subcuticular skin closure. Patients were found to not have any difference in rate of dehiscence or overall wound complications based on gender, age, location of port, or use of steroids or chemotherapy within 1week of port placement. When compared, only 1 case (0.80%) in the simple running group vs 10 cases (7.46%) in the subcuticular group experienced a wound dehiscence [unadjusted OR=14.07 (1.69, 116.99) p=0.0144]. When comparing overall wound complications the simple running group had 3 (2.4%) versus 12 (8.96%) in the subcuticular group [unadjusted OR=4.78 (1.27, 17.94) p=0.0203]. When adjusting for port-number both dehiscence and overall wound complications remained statistically significant.We conclude that the simple running skin closure for chemo-port placement in children has superior outcomes in regards to prevention of dehiscence and overall wound related complications when compared to the subcuticular technique.

INTRODUCTION Pediatric acute myeloid leukemia (AML) requires intensive chemotherapy that results in prolonged periods of neutropenia, placing patients at significant risk for life threatening infection. Current supportive care guidelines strongly recommend hospitalization after chemotherapy completion until neutrophil recovery. While approximately 70% of United States (US) centers adhere to this recommendation, there are little data to support inpatient over outpatient management. Therefore, we compared clinical outcomes (Aim 1), patient experiences (Aim 2), and patient quality of life (QoL) (Aim 3), between the two strategies in a nationally representative sample of newly diagnosed AML patients METHODS Aim 1 employed retrospective, standardized chart abstraction for AML patients treated between 2011 and 2019 at 17 centers in the US. Patients were observed from their first course of chemotherapy through treatment completion, stem cell transplant, site transfer, relapse, or death. The unit of analysis was chemotherapy courses, the primary exposure was inpatient versus outpatient management, and primary outcomes were bacteremia and time to next treatment course. Only courses in which the patient met "discharge eligible" criteria were included (Figure 1). Analyses excluded Induction I given the low rate of outpatient management. Log-binomial regression was used to compare the bacteremia incidence and generalized linear regression was used to compare time to next course. Generalized estimating equations were used in overall analyses to account for correlation between courses from the same patient. For Aim 2, patients/ families at 9 centers underwent semi-structured interviews that were transcribed and analyzed using a conventional content analysis approach (InVivo). For Aim 3, parent proxies at 14 centers completed a PedsQL before the start of chemotherapy and then after neutrophil recovery but prior to the start of the subsequent course. Only one chemotherapy course per patient was considered. Only "discharge eligible" patients were included. Parent-proxy generic core QoL scores at the end of the chemotherapy cycle were compared by exposure group using analysis of covariance accounting for baseline scores. RESULTS 573 patients contributed 1188 treatment courses for Aim 1 (Figure 1). Mean age was 9 ±6 years, 47% were female, and AML was classified as low, intermediate, and high risk, respectively in 65%, 4%, and 31%, respectively. Overall rates of bacteremia were not significantly different in patients receiving outpatient versus inpatient management (23.8% vs 29.0%, RR 0.76, 95% CI: 0.56, 1.03; p=0.07). Days to next course also did not differ between the groups (30.2 vs. 31.6, adjusted difference -1.6, 95% CI: -3.2, 0.5; p=0.17). In Aim 2, 86 interviews in 57 families (39 inpatient, 18 outpatient) were performed. 86% of families receiving inpatient management expressed satisfaction and 85% receiving outpatient management expressed satisfaction. Dissatisfaction with inpatient management was driven by concerns for hospital acquired infections and separation from family. Dissatisfaction with outpatient management stemmed from stress of caring for a neutropenic child at home. Patients/families reporting satisfaction with outpatient management emphasized that the approach would not be appropriate for all families. For Aim 3, mean (±SD) parent proxy PedsQL score did not differ between outpatient (74.3 ±18.3) and inpatient management (70.3 ±19.2), adjusted mean difference 3.95, 95% CI: -5.57, 13.5. CONCLUSION In this nationally representative sample of AML patients, outpatient management had bacteremia rates similar to inpatient management, with no difference in time to the start of next treatment course or patient QoL. Semi-structured interviews revealed strong alignment between patient/family satisfaction and center discharge practice. However, families experiencing outpatient management note high stress in caring for profoundly neutropenic patients at home and that this strategy would not be suitable for all families. These clinical and patient-centered results suggest that outpatient management during neutropenia is a viable approach without excess risk for children with AML. However, implementation studies are needed to identify patient/family characteristics that portend a positive experience with an outpatient strategy. Disclosures Raetz: Pfizer: Research Funding. Rubnitz:AbbVie: Research Funding. Fisher:Pfizer: Research Funding; Astellas: Other: Data Safety Monitoring Board Chair for an antifungal study; Merck: Research Funding.

Background: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. The U.S. Surveillance Epidemiology and End Results (SEER) registry reports that Hispanic children have the highest incidence of ALL, however, it is unclear if this is due to genetic factors, unique environmental exposures, or both. Previous reports have shown an association between CYP1A1 variants and ALL. Methods: To explore the contribution of CYP1A1 polymorphisms to ALL susceptibility in different ethnic groups, we conducted a case–control analysis in Caucasian, Hispanic, and African-American children. Results: Increased risk of developing ALL was found in the whole sample group for homozygosity of variant alleles at CYP1A1*2C (OR 2.51, 95% CI 1.18–5.33, P = 0.016) and CYP1A1*2B (OR 3.24, 95% CI 1.43–7.34, P = 0.005). Stratified analyses showed increased risks in the Hispanic group (CYP1A1*2A, OR 2.70, 95% CI 1.27–5.74, P = 0.010; CYP1A1*2C, OR 2.47, 95% CI 1.13–5.38, P = 0.023; and CYP1A1*2B, OR 3.28, 95% CI 1.40–7.69, P = 0.006) but not for the other ethnic groups. Hispanic control subjects were significantly more likely to be carriers of variant alleles as compared to Caucasians (P < 0.0001) and African Americans (P = 0.005). Conclusions: Our study suggests that polymorphisms in CYP1A1 may contribute to the increased risk of ALL in Hispanic children due to both their impact on leukemia susceptibility and the increased prevalence of the at-risk alleles in the Hispanic population. Impact: Our study provides a novel and specific link between CYP1A1 polymorphisms and ethnic influence on ALL risk that may help explain varying susceptibilities across groups to environmental toxins. Cancer Epidemiol Biomarkers Prev; 20(7); 1537–42. ©2011 AACR.

Background: Hispanic children have both a higher incidence and a poorer outcome in acute lymphoblastic leukemia (ALL). Moreover, a higher incidence for therapy-related acute myeloid leukemia with 11q23 translocations after treatment with topoisomerase II (topo II) inhibitors has been observed in Hispanic children with ALL. We sought to determine the potential role of genetic variants within the topoisomerase IIα gene (TOP2A), within the mixed lineage leukemia gene (MLL) and two of its translocation partners, cyclin AMP response element-binding protein gene (CREBBP) and E1A binding protein gene (EP300) in the increased sensitivity of Hispanic children with ALL to topo II inhibitors. Methods: Fifty-two tagged single nucleotide polymorphisms (SNP) covering the four genes were genotyped in 241 samples (66 children with ALL and 175 age matched controls) of self-identified Hispanic origin. Results: Two SNPs within MLL (rs525549 and rs6589664) and three SNPs within EP300 (rs5758222, rs7286979, and rs20551) were significantly associated with ALL (P = 0.001–0.04). A significant gene-dosage effect for increasing numbers of potential high-risk genotypes (OR = 16.66; P = 2 × 10−5) and a major haplotype significantly associated with ALL (OR = 5.68; P = 2 × 10−6) were found. Replication in a sample of 137 affected White children and 239 controls showed that only rs6589664 (MLL) was significantly associated in this ethnic group. Conclusions: Our findings indicate that the association between ALL and common genetic variants within MLL and EP300 is population specific. Impact: Replication of our findings in independent Hispanic populations is warranted to elucidate the role of these variants in ALL susceptibility and define their importance in the ethnic specific differences in ALL risk. Cancer Epidemiol Biomarkers Prev; 20(6); 1204–12. ©2011 AACR.

BACKGROUND Gram-positive bacteremia is a common infection in pediatric oncology and stem cell transplant (SCT) patients requiring therapy with vancomycin. Optimal dosing of vancomycin in this patient population has not been well established. METHODS All pediatric oncology and SCT patients receiving vancomycin between October 2006 and March 2007 were included in this study. Therapeutic levels were defined as levels between 10 and 15 mg/dL and low therapeutic levels were between 5 and 9 mg/dL. Information regarding any recent or concurrent nephrotoxic medications was collected. RESULTS Fifty-six patients received 82 courses of vancomycin during the study period. More patients (53.7%) received vancomycin for empiric therapy and 78% had recent or concurrent use of nephrotoxic medications. Using standardized vancomycin dosing guided by a computerized provider order entry system, there were significantly more patients who were in the subtherapeutic range than the supratherapeutic range (P=0.0023). There were also significantly more patients in the low therapeutic than the therapeutic range (P

Hemoglobin (Hb) variants may be associated with low oxygen saturation and exacerbated episodes of anemia from common stressors such as viral infections. These attributes frequently cause increased clinical concern and unnecessary and expensive testing if not considered early in the evaluation of the patient. Some clinically significant Hb variants result in a normal Hb electrophoresis result, which can be method-dependent. Herein we describe a patient with low oxygen saturation and a history of hemolytic anemia who was subsequently found to carry a novel, unstable β-globin variant that we have named Hb Allentown [β137(H15)Val→Trp (GTG>TGG) HBB: c.412_413delinsTG, p.Val138Trp] for the place of identification of the variant. Hb Allentown is formed by a rare double nucleotide substitution within the same codon. Additionally, positive identification of rare Hb variants characterized by a single method is discouraged, as the Hb variant was misclassified as Hb S-South End or β6(A3)Glu→Val;β132(H10)Lys→Asn (HBB: c.[20A > T;399A > C]) by the initial laboratory.

Histone deacetylase inhibitors (HDACi) have been evaluated in patients with Ewing sarcoma (EWS) but demonstrated limited activity. To better understand the potential for HDACi in EWS, we evaluated the combination of the HDACi vorinostat, with DNA damaging agents SN-38 (the active metabolite of irinotecan and topoisomerase 1 inhibitor) plus the alkylating agent temozolomide (ST). Drugs were evaluated in sequential and simultaneous combinations in two EWS cell lines. Results demonstrate that cell viability, DNA damage and reactive oxygen species (ROS) production are dependent on the sequence of drug administration. Enhanced cytotoxicity is exhibited in vitro in EWS cell lines treated with ST administered before vorinostat, which was modestly higher than concomitant treatment and superior to vorinostat administered before ST. Drug combinations downregulate cyclin D1 to induce G0/G1 arrest and promote apoptosis by cleavage of caspase-3 and PARP. When ST is administered before or concomitantly with vorinostat there is activation of STAT3, MAPK and the p53 pathway. In contrast, when vorinostat is administered before ST, there is DNA repair, increased AKT phosphorylation and reduced H2B acetylation. Inhibition of AKT using the small molecule inhibitor MK-2206 did not restore H2B acetylation. Combining ST with the dual ALK and IGF-1R inhibitor, AZD3463 simultaneously inhibited STAT3 and AKT to enhance the cytotoxic effects of ST and further reduce cell growth suggesting that STAT3 and AKT activation were in part mediated by ALK and IGF-1R signaling. In summary, potent antiproliferative and proapoptotic activity were demonstrated for ST induced DNA damage before or simultaneous with HDAC inhibition and cell death was mediated through the p53 pathway. These observations may aid in designing new protocols for treating pediatric patients with high-risk EWS.

Efficacy of therapeutic strategies relative to patient- and family-centered outcomes in pediatric oncology must be assessed. We sought to identify outcomes important to children with acute myeloid leukemia and their families related to inpatient versus at-home management of neutropenia. We conducted qualitative interviews with 32 children ≥8 years old and 54 parents. Analysis revealed the impact of neutropenia management strategy on siblings, parent anxiety, and child sleep quality as being outcomes of concern across respondents. These themes were used to inform the design of a questionnaire that is currently being used in a prospective, multiinstitutional comparative effectiveness trial.

Chondrosarcoma is a malignant bone tumour common in adults, third to myeloma and osteosarcoma, but is exceptionally rare in children. Here we discuss a 9-year-old girl presenting with occlusive right pulmonary artery neoplastic embolus, resulting from a primary right proximal humerus chondrosarcoma. To the best of our knowledge, this the first pediatric and only second overall case reported in the United States of a neoplastic pulmonary embolus resulting from a primary chondrosarcoma.

Cutaneous Ewing sarcoma is a rare variant that has been poorly characterized and has no standard therapy. We report 2 patients with cutaneous Ewing sarcoma and review 76 other cases reported in the literature for demographics, presentation, treatment, and outcome. Only 2 patients presented with metastatic disease, and only 8 patients developed metastatic disease. Ninety-one percent of all patients are alive despite wide variations in treatment regimens. On the basis of this summary, treatment consisting of local control with surgery and/or radiation and abbreviated chemotherapy is proposed as a treatment option for this less aggressive Ewing sarcoma.

Background Childhood ITP can have a negative impact on the child and his/her family even though it is typically a benign disorder with low risk of serious bleeding. In adults and now children, romiplostim increases the platelet count without significant adverse effects. In this study, the impact of romiplostim treatment on the HRQoL of children with chronic ITP was assessed using the Kid's ITP Tools (KIT). Procedure Subjects 1–18 years old, with chronic ITP (>6 months), were enrolled in a multi-center, randomized, double-blind, placebo-controlled phase 1/2 treatment study with romiplostim (reported elsewhere). Subjects and/or proxies completed the KIT at baseline, week 5, and week 13. Scores were computed for child self-report (children >7 years), proxy-report, and parent impact. Changes in mean scores from baseline to week 13 were computed. Results Twenty-two children (17 receiving romiplostim, 5 placebo) and/or their parents provided data. Change in mean scores demonstrated significant improvement in HRQoL for romiplostim versus placebo for parent impact (24 ± 17 vs. −6 ± 8; P = 0.008). Change scores for child self-report trended toward improvement with romiplostim and decreased with placebo (5 ± 10 vs. −7 ± 17; P = 0.29). Romiplostim proxy-report mean change scores were 6 points higher than placebo (8 ± 16 vs. 2 ± 12; P = 0.50). Conclusions Romiplostim significantly reduced parental burden in this study. Whether the same and/or additional improvements in HRQoL would be demonstrated by a larger, longer study of romiplostim-treated children with ITP remains to be determined. Pediatr Blood Cancer 2012; 58: 395–398. © 2011 Wiley Periodicals, Inc.

To determine the contribution of susceptibility loci in explaining the genetic basis of acute lymphoblastic leukemia (ALL), we genotyped 29 high-potential candidate genes with 672 tagged single-nucleotide polymorphisms (SNPs) in a sample (163 cases and 251 healthy controls) of Caucasian children. Fifty SNPs in 15 genes were significantly associated with ALL risk at the P < 0.05 level. After correction for multiple testing, rs442264 within the LIM domain only 1 (LMO1) gene at 11p15 remained significant [odds ratio (OR) = 1.90, P = 3 × 10(-5)]. In addition, a major haplotype within LMO1 comprising 14 SNPs with individual risk associations was found to significantly increase ALL risk (OR = 1.79, P = 0.0006). A stratified analysis on subtype indicated that risk associations of LMO1 variants are significant in children with precursor B-cell leukemia. These data show that genetic variants within LMO1 are associated with ALL and identify this gene as a strong candidate for precursor B-cell leukemogenesis.

Ewing sarcoma (EWS) is a bone tumor occurring primarily in adolescence and young adulthood. Multi-institutional clinical trials have improved the outcome for patients with nonmetastatic EWS, but not with metastatic EWS. Furthermore, although 30% of EWS recur, multi-institutional studies have not been completed for this high-risk group. Planning such studies has been hampered by both the lack of novel therapies and the inability to incorporate the biology of EWS. While the importance and detail of the EWS-FLI-1 translocation between chromosomes 11 and 22 are described, these have not yet led to new drug development for this orphan tumor. However, recent evidence supporting novel cytotoxic therapy, antiangiogenic therapy, and receptor-targeted therapy provides reason for optimism for patients with high-risk disease.

To the Editor: A recent letter in this journal described methemoglobinemia and hemolysis due to rasburicase in a patient with glucose-6-phosphate dehydrogenase (G6PD) deficiency [1]. We would like to report on the management of a patient with rasburicase induced methemoglobinemia and G6PD deficiency. DS is a 12-year-old Laotian male who presented with a white blood cell count of 533,900/mm (89% blasts), hemoglobin 10.1 mg/dL, and platelets of 27,000/mm and was diagnosed with T-cell Acute Lymphoblastic Leukemia. Metabolic labs were normal except BUN 23 mg/dL, LDH 4,698 mg/dL, and uric acid 22.1 mg/dL. Rasburicase (Elitek) 10.5 mg (0.2 mg/kg) was administered. One hour later his uric acid was 18.1 mg/dL, and 10 hr later it was