Caroline Hastings

10014 Background: Relapsed childhood B-ALL has a poor prognosis. Few risk factors beyond immunophenotype, timing, and site of relapse are known to affect outcome. MRD is a powerful predictor of outcome in newly diagnosed ALL, but its significance after relapse is less clear. We report an analysis of MRD and outcome from the AALL0433 protocol for childhood B-ALL with intermediate-risk relapse. Methods: AALL0433 is a Phase 3 study of intermediate-risk relapsed childhood B-ALL, defined as CNS/testicular relapse 36 mo. from diagnosis. Therapy is based upon the AALL01P2 / 9412 platforms. BM MRD was measured by flow cytometry at end-induction; results were blinded to investigators. Only matched family donor SCT was allowed on protocol. 271 eligible patients were enrolled. Outcome by treatment received remains blinded at this time. Results: The 3-yr. EFS/OS for the entire cohort of 271 patients were 60.7 ± 4.6% and 71.3 ± 4.3%, respectively. All 29 patients with isol...

Cancer patients undergoing chemotherapy often develop anemia, which can increase the risk for transfusions and fatigue. The recombinant erythropoiesis-stimulating agent darbepoetin alfa can effectively treat chemotherapy-induced anemia (CIA) in adults, but limited data are available regarding its use in pediatric cancer patients. The goals of this phase 1, open-label, uncontrolled study were to assess the pharmacokinetic profile and safety of darbepoetin alfa in pediatric patients with CIA. Pediatric patients with nonmyeloid malignancies and CIA received up to six doses of darbepoetin alfa 2.25 mcg/kg subcutaneously. After the first dose, the pharmacokinetic properties of darbepoetin alfa were assessed during a 14-day sampling period. All subsequent doses were given weekly with predose blood samples collected before study drug administration. After a single dose of darbepoetin alfa, the mean (SD) peak serum concentration was 10.5 (3) ng/ml, and the median time to peak concentration was 71.4 hr. Darbepoetin alfa exhibited a mean (SD) terminal half-life of 49.4 (32) hr. Upon repeated weekly administration, no evidence of darbepoetin alfa accumulation was observed though there was high intra- and inter-individual variability. In addition, darbepoetin alfa was well tolerated; some study patients experienced increases in hemoglobin. The pharmacokinetic profile of darbepoetin alfa indicated that it was slowly absorbed and exhibited a long terminal half-life in these pediatric study patients with CIA.

Cancer-and treatment-related anemia affects many children diagnosed with a variety of malignancies. The incidence of anemia in children with solid tumors or Hodgkin’s disease at the time of diagnosis has been reported to be 51–74% (Hockenberry et al. 2002). Several pediatric studies report a high incidence of anemia (over 50%) requiring intervention with transfusion in children receiving therapy for Wilms’

Down syndrome patients with ALL (ALL-DS) have unique clinical and biologic features which can make treatment a challenge particularly in regards to toxicity. In order to evaluate the optimal treatment for ALL-DS with higher risk ALL we compared the outcomes of ALL-DS patients (n=51) enrolled on the Children’s Cancer Group (CCG) 1961 protocol for HR-ALL to those of their non-DS counterparts (n=2001). CCG-1961 was open from November 1996 to May 2002 for patients with ALL age 1–9 years and WBC ≥ 50,000 or age ≥ 10 years with any WBC. Rapid early responders (RER ≤ 25% blasts on day 7 bone marrow after 4 drug induction) were randomized in a 2 × 2 design to receive intensive post-induction intensification therapy (IPII) or standard post-induction intensification therapy (SPII) and 1 or 2 delayed intensification phases. Slow early responders (SER > 25% blasts on day 7 bone marrow) were treated with IPII, and randomized to receive idarubicin or doxorubicin. No up-front therapy modifications were prescribed for DS patients (only for toxicity as per protocol). All DS patients were over 2 years of age. DS patients were more likely to have WBC ≥ 50,000 than non-DS (76% vs 53%) and less likely to have T cell immunophenotype (4% vs 23%), lymphoma syndrome (10% vs 23%) or marked splenomegaly (4% vs 12%) at diagnosis. No differences in gender, race, or extramedullary disease were noted in the DS vs non-DS patients. There were 36 RER DS patients (16 randomized to IPII and 20 SPII) and 16 SER patients. There were 6 deaths in the DS patients: 4 early in induction, 1 in consolidation, and 1 in maintenance. All deaths were associated with toxicity and/or infection and 2 patients had progressive disease. DS patients were more likely to have grade 3–4 stomatitis during intensive treatment phases (15.2% vs 1.8% during induction, 23.1% vs 2.9% during delayed intensification #1). The 5-yr event free survival (EFS) was 69.1% (se 8.4%) for DS patients and 70.4% (se 1.5%) for non-DS patients. The 5-yr overall survival (OS) was equivalent for the two groups: 77.9% (se 7.5%) for DS patients compared to 80.9% (se 1.1%) for non-DS patients. The 5 year death as a first event assessment was 88.2% (se 6.6%) (RHR 2.6) vs 95.5% (se 0.7%) for non-DS patients, consistent with an increased incidence of early toxic deaths in the ALL-DS cohort. IPII therapy for RER DS patients resulted in excellent disease control (0 BM relapses vs 5 with SPII). The 4-yr EFS for the IPII DS patients (RER + SER) was 83.7% (se 6.7%) vs 78.8% (se 11.5%) for the RER DS randomized group only. This difference may be explained by the single event in the 16 SER patients; however the small number precludes a definitive conclusion. In conclusion, HR patients with ALL-DS treated with IPII therapy on CCG-1961 have similar OS and EFS to non-DS patients. These results compare favorably with those of other studies. The early mortality due to toxicity in the DS population does not result in decreased EFS or OS as compared to the non-DS population. IPII therapy is well tolerated and effective in HR ALL-DS, as evidenced by excellent outcomes in the RER and SER groups, and should be considered a reasonable standard of care for this patient population.

BackgroundNutritional deficiencies in children with cancer at time of diagnosis and during treatment may negatively affect disease outcome and increase treatment‐related toxicity. Yet zinc, an essential nutrient important for supporting immune function and known for reducing diarrheal episodes, is rarely assessed in these children.ProceduresFifty children (1 month to 18 years) with recently diagnosed cancer were enrolled in this study. An age and gender matched control group (n = 50) was also recruited. Plasma and urinary zinc, plasma copper, and C‐reactive protein (CRP) levels were measured at baseline, 3, and 6 months following diagnosis. A retrospective review of the toxicity profile was performed in the cohort of children with cancer for the first 4 years after initial diagnosis.ResultsCRP and plasma copper (both acute‐phase reactants) were elevated in patients with cancer compared to controls at baseline, bothp < .03. Plasma zinc levels were not significantly different from controls at baseline, but decreased by 11% in the cancer group over 6 months of treatment, 83.2 ± 15.6 to 74.3 ± 14.8 μg/dl,p = .01. Plasma zinc dropped to deficient levels in 35% of cases over the initial 6 months. Zinc deficiency at 6 months was related to an increased incidence of severe diarrhea during 4 years of follow‐up,p < .001.ConclusionsZinc deficiency is an underrecognized problem among patients undergoing treatment for cancer and is associated with severe diarrhea. Further studies are needed to evaluate causes for zinc deficiency, related effects, and a possible role for zinc supplementation.

doi:10.1182/blood-2007-02-070342Prepublished online November 26, 2007;2008 111: 2548-2555€€€€Cheryl Edens and Paul S. GaynonBertolone, Janet L. Franklin, Nyla A. Heerema, Torrey L. Mitchell, Allan F. Pyesmany, Mei K. La,J. Ettinger, David R. Freyer, Leonard A. Mattano, Jr, Caroline A. Hastings, Charles M. Rubin, Kathy Nita L. Seibel, Peter G. Steinherz, Harland N. Sather, James B. Nachman, Cynthia DeLaat, Lawrence€

Abstract 1264 Patients with familial myelodysplastic syndrome (MDS) associated with mutations in GATA2 are at increased risk of MDS and acute myeloid leukemia (AML). Specific clinical syndromes recently found to be due to mutations in GATA2 include MonoMAC (monocytopenia and mycobacterial infection), Emberger (MDS with severe lymphedema), and DCML (defects in dendritic cells, monocytes, and B and NK lymphoid cells). Features shared by many patients with these GATA2-associated syndromes include monocytopenia, markedly decreased B and NK cells, and clinical immunodeficiency manifested as warts and mycobacteria and fungal infections. MDS and/or AML occur with multilineage dyspoieses, particularly prominent in the megakaryocyte lineage (micromegakaryocytes, small mononuclear megakaryocytes, and large megakaryocytes with multiple separated nuclei). Several reports mention family members who are “asymptomatic,” without further details. We identified mutations in GATA2 in two of three families with familial MDS. In both families, one apparently healthy parent was found to have a GATA2 mutation; only in-depth laboratory examinations uncovered subtle findings consistent with familial GATA2 mutation in these clinically silent carriers. Family 1: The proband presented at age 15 with pancytopenia, and was found to have MDS and monosomy 7; he died from post-BMT complications including aspergillosis. His brother was found to have leukopenia, neutropenia and macrocytosis at age 13 during an infection with H1N1 influenza; the leukopenia and macrocytosis persisted. Six months later, repeat bone marrow showed early refractory anemia; the next year his marrow had myeloid dyspoiesis and dysplastic megakaryocytes; FISH showed −7 in 2.3% of cells, leading to classification as MDS-RCC. In retrospect, both boys had absolute monocytopenia (<100/uL). GATA2 sequencing of samples from the surviving brother and his 51 y.o. mother identified a deleterious mutation (c.1116_1130del15, p.C373del5). The mother had breast cancer at age 50, but otherwise was asymptomatic. Closer clinical examination revealed lower limb lymphedema, while laboratory studies revealed lymphopenia (360/uL), monocytopenia (110/uL), low lymphocyte subsets, especially CD19 (3/uL) and MCV = 100fL. Her marrow did not show overt dyspoiesis in myeloid or erythroid lineages; among mostly normal megakaryocytes there were occasional atypical forms, including some with hypolobulated or separated lobes; G-banded karyotyping and interphase FISH for −7/7q- were normal. She would not have been suspected to have GATA2-related MDS based on her clinical status, and is thus a silent carrier. Family 2: Three children in this family were diagnosed with MDS. The oldest had a history of warts and pancytopenia at age 18; his marrow showed MDS with trisomy 8. His brother was a compatible transplant donor, but he had mild pancytopenia and monocytopenia; his marrow had MDS and trisomy 8. Their sister was diagnosed at age 14 with MDS and trisomy 8; she, too, had monocytopenia. All 3 were transplanted. Subsequently, a mutation - c.1187G>A, p.R396Q - was found in GATA2, in all 3 brothers and their healthy father. He had normal blood counts (monocytes 500/uL) and immunoglobulins, but low B-cells in peripheral blood (CD20 23/uL) and bone marrow. His normocellular marrow had occasional atypical megakaryocytes with separated lobes, hypolobulation, and mononuclear and micromegakaryocytes. He, too, would not have been suspected to have GATA2-related MDS, and is also a clinically silent carrier. These two families indicate that familial GATA2-related MDS is a dominantly-inherited syndrome. In our two families, dominant inheritance was not initially considered, in part because the genetically affected parent was clinically asymptomatic. It is unclear whether GATA2 MDS shows “anticipation,” in which the younger generation is more severely affected than the parental generation. It is important that GATA2 be evaluated in families with apparently inherited childhood MDS,…

Purpose: To improve the control of hyperuricemia in patients with leukemia or lymphoma, we tested a newly developed uricolytic agent, recombinant urate oxidase (SR29142; Rasburicase; Sanofi-Synthelabo, Inc, Paris, France), which catalyzes the oxidation of uric acid to allantoin, a highly water-soluble metabolite readily excreted by the kidneys. Patients and Methods: We administered Rasburicase intravenously, at 0.15 or 0.20 mg/kg, for 5 to 7 consecutive days to 131 children, adolescents, and young adults with newly diagnosed leukemia or lymphoma, who either presented with abnormally high plasma uric acid concentrations or had large tumor cell burdens. Blood levels of uric acid, creatinine, phosphorus, and potassium were measured daily. The pharmacokinetics of Rasburicase, the urinary excretion rate of allantoin, and antibodies to Rasburicase were also studied. Results: At either dosage, the recombinant enzyme produced a rapid and sharp decrease in plasma uric acid concentrations in all patients. The median level decreased by 4 hours after treatment, from 9.7 to 1 mg/dL (P 5 .0001), in the 65 patients who presented with hyperuricemia, and from 4.3 to 0.5 mg/dL (P 5 .0001) in the remaining 66 patients. Despite cytoreductive chemotherapy, plasma uric acid concentrations remained low throughout the treatment (daily median level, 0.5 mg/dL). The urinary excretion rate of allantoin increased during Rasburicase treatment, peaking on day 3. Serum phosphorus concentrations did not change significantly during the first 3 days of treatment, decreased significantly by day 4 in patients presenting with hyperuricemia (P 5 .0003), and fell within the normal range in all patients by 48 hours after treatment. Serum creatinine levels decreased significantly after 1 day of treatment in patients with or without hyperuricemia at diagnosis (P 5 .0003 and P 5 .02, respectively) and returned to normal range in all patients by day 6 of treatment. Toxicity was negligible, and none of the patients required dialysis. The mean plasma half-lives of the agent were 16.0 6 6.3 (SD) hours and 21.1 6 12.0 hours, respectively, in patients treated at dosages of 0.15 or 0.20 mg/kg. Seventeen of the 121 assessable patients developed antibodies to the enzyme. Conclusion: Rasburicase is safe and highly effective for the prophylaxis or treatment of hyperuricemia in patients with leukemia or lymphoma. J Clin Oncol 19:697-704. © 2001 by American Society of Clinical Oncology.

INTRODUCTION Chapter 1 - Objectives Resident Responsibilities ANEMIA Chapter 2 - Evaluation of Anemia Table 1 Normal RBC Values Table 2 Diagnostic Approach Table 3 History Table 4 Physical Exam Table 5 Evaluation of Iron Deficiency Oral Iron Challenge Parenteral Iron Erythropoietin Algorithm 1 Approach to Child with Anemia Algorithm 2 Diagnostic Approach to the Child with Microcytic Anemia Algorithm 3 Approach to the Newborn with Anemia Chapter 3 - Helolytic Anemia Algorithm 4 Approach to the Child with Hemolytic Anemia Chapter 4 - Sickle Cell Disease Fever and Infection Algorithm 5 Fever in a Child with Sickle Cell Disease Vaso-Occulusive Episodes Pain Management: Outpatient Inpatient Acute Chest Syndrome Algorithm 6 Sickle Cell Disease with Acute Pulmonary Infiltrate Priapism Stroke Splenic Sequestration Aplastic Crisis Avascular Necrosis Retinopathy/Hyphema Hyperbilirubinemia Peri-Operative Care Table 6 Immunization Recommendations Chapter 5 - Thalassemia Table 7 Classification of the Thalassemias Alpha Thalassemia Table 8 Alpha Thalassemia Syndromes Beta Thalassemia Table 9 Summary of Common Thalassmia Syndromes Neonatal Screening Management of Chronically Transfused Patients TRANSFUSION THERAPY Chapter 6 - Blood Products Red Blood Cells Sickle Cell Disease Oncology Platelets Granulocytes Plasma Preparation of Blood Products Chapter 7 - Transfusion Reactions Table 10 Drugs used in the Treatment of Nonhemolytic Transfusions Reactions Chapter 8 - Chelation Therapy Desferal Desensitization Protocol THE CHILD WITH A BLEEDING DISORDER Chapter 9 - Initial Evaluation Table 11 Obtaining a Bleeding History Table 12 Interpretation of Laboratory Studies Algorithm 7 Laboratory Evaluation of the Bleeding Child Chapter 10 - Inherited Bleeding Disorders von Wilebrand's Disease Factor VIII Deficiency Factor IX Deficiency and Other Rare Coagulation Deficiencies Chapter 11 - Management of Acute Hemorrhage Treatment of vWB Disease and Hemophelia Factor Administrative Instructions THE CHILD WITH THROMBOSIS Chapter 12 - Evaluation of the Child with Thrombosis Low Molecular Weight Heparin Therapy Table 13 Age-Dependent Dose of Enoxaparin NEUTROPENIA Chapter 13 - Neutropenia Algorithm 8 Approach to the Child with Neutropenia THROMBOCYTOPENIA Chapter 14 - Immune-Mediated Thrombocytopenia Neonatal Alloimmune Thrombocytopenia Table 14 Differential Diagnosis of Thrombocytopenia Algorithm 9.1 Approach to the Child with Thrombocytopenia Algorithm 9.2 Approach to the Child with Isolated Thrombocytopenia Algorithm 9.3 Approach to the Child with Thrombocytopenia/Anemia Chapter 15 - Non-Immune Mediated Thrombocytopenia Decreased Platelet Production THE CHILD WITH A MALIGNANCY Chapter 16 - Presentation and Initial Evaluation Table 15 Common Chief Complaints Table 16 Presenting Signs and Symptoms Table 17 Indications for Head CT with Headache Evaluation of the Child with Suspected Leukemia Evaluation of the Child with an Abdominal Mass Chapter 17 - Supportive Care General Measures/Prophlaxis Table 18 Ondansetron (Zofran) Dosing Guidelines Table 19 Immunization of the Children with Cancer Table 20 Passive Immunization of the Children with Cancer Table 21 A Quick Guide to Common Chemotherapy Drugs Guidelines for use of G-CSF Chills and Fever After a Broviac or Mediport Flush Guidelines for Clearing Obstructed Central Venous Catheters Chapter 18 - Fever and Neutropenia Algorithm 10 Evaluation of the Child with Fever and Neutropenia Chapter 19 - Oncologic Emergencies Superior Vena Cava Syndrome Abdominal Emergencies/Typhlitis Hyperleukocytosis Tumor Lysis Syndrome Chapter 20 - Guide to Oncologic Procedures IT Chemotherapy Intra-Ommaya Chemotherpay Bone Marrow Aspirate and Biopsy Chemotherpay (per PIV) APPENDIX Formulary INDEX

Background:Patients with late, ≥18 months post-diagnosis, isolated central nervous relapse (iCNS-R) of B-acute lymphoblastic leukemia (ALL) have excellent outcomes with chemotherapy plus cranial radiotherapy, with 5-yr overall survival (OS) approaching 80% in POG 9412. Subsequent relapse and radiation-related morbidity remain the causes of treatment failure and long-term sequelae. COG AALL02P2 aimed to maintain outcomes in patients with late iCNS-R using intensified chemotherapy and a decrease in cranial irradiation from 1800 to 1200 cGy.Procedures:COG AALL02P2 enrolled 118 eligible patients with B-ALL and late iCNS-R who received intensified systemic therapy, triple intrathecal chemotherapy and 1200 cGy cranial irradiation delivered at 12 months, with maintenance chemotherapy continuing until 104 weeks post-diagnosis.Results:The 3-yr event-free and overall survival (EFS) and OS were 64.3±4.5% and 79.6±3.8%, with 46.1% (18/39) of second relapses including the CNS. Of the 112 patients who completed therapy, 78 received protocol-specified radiation. Study enrollment was closed after interim monitoring analysis showed inferior EFS compared to POG 9412. Patients with initial NCI standard risk classification fared better than high risk patients.Conclusions:COG AALL02P2 showed inferior EFS but similar OS compared to POG 9412. Limitations included a small sample size, more intensive prior therapies, and a significant number of patients (34/118, 29%) who did not receive protocol-directed radiation due to early relapse prior to 1 year or did not otherwise follow the treatment plan. New approaches are needed to improve outcome for these patients and determine the optimal timing and dose of cranial radiation in the treatment of iCNS-R.

PurposeIn the absence of a standardized tool to assess the quality of pediatric hematology/oncology training programs, the Education Program Assessment Tool (EPAT) was conceptualized as a user‐friendly and adaptable tool to evaluate and identify areas of opportunity, pinpoint needed modifications, and monitor progress for training programs around the world.MethodsThe development of EPAT consisted of three main phases: operationalization, consensus, and piloting. After each phase, the tool was iteratively modified based on feedback to improve its relevance, usability, and clarity.ResultsThe operationalization process led to the development of 10 domains with associated assessment questions. The two‐step consensus phase included an internal consensus phase to validate the domains and a subsequent external consensus phase to refine the domains and overall function of the tool. EPAT domains for programmatic evaluation are hospital infrastructure, patient care, education infrastructure, ...

BACKGROUND Head Start 4 is a randomized clinical trial to determine whether dose-intensive tandem consolidation, compared with a single cycle, with autologous hematopoietic progenitor cell rescue provides a survival benefit in pediatric patients with medulloblastoma or other embryonal tumors. The trial incorporates upfront molecular subgrouping and non-mandatory, prospective blood and cerebrospinal fluid (CSF) collection. This pilot study aimed to identify exosomal non-coding RNAs (exo-ncRNAs) that might serve as novel diagnostic and/or treatment response biomarkers. METHODS CSF(1-2mLs) from 11 controls (non-tumor) and 27 medulloblastoma participants including 23 obtained at baseline, 22 at the end of induction, 3 post-consolidation, and 4 relapse time points, were profiled. Exosome isolation and small RNA-sequencing were performed by System Biosciences. Differential gene expression (DGE) was performed in R (DESeq2). Variations in gene expression profiles between samples were visual...

Advances in RNA and DNA profiling have identified four core molecular subgroups of medulloblastoma of prognostic significance: Sonic Hedgehog (SHH) subtype, WNT subtype, Group 3, and Group 4. Infants and young children with SHH medulloblastoma have demonstrated a favorable outcome in clinical trials utilizing either high-dose chemotherapy (“Head Start”) or a combination of intravenous and intraventricular methotrexate (HIT-SKK). Two recently conducted clinical trials (COG ACNS1221 and St. Jude – SJYC07) failed to demonstrate similar survival advantage with conventional dose chemotherapy and without intraventricular methotrexate. “Head Start” 4 (HS 4) is a prospective randomized clinical trial that tailors treatment based on medulloblastoma molecular subgroups and response to induction chemotherapy to compare the efficacy of one versus versus three (tandem) cycles of myeloablative therapy. Eligibility includes newly diagnosed children less than six years of age with localized medullo...

Additional file 1. Supplemental Data: Case Summaries on Compassionate Use HPβCD to accompany the manuscript "Expanded access with intravenous hydroxypropyl-β-cyclodextrin to treat children and young adults with Niemann-Pick disease Type C1: A case report analysis". Narratives.

BackgroundSeveral scales have been developed in the past two decades to evaluate Niemann–Pick disease Type C (NPC) severity in clinical practice and trials. However, a lack of clarity concerning which scale to use in each setting is preventing the use of standardised assessments across the world, resulting in incomparable data sets and clinical trial outcome measures. This study aimed to establish agreed approaches for the use of NPC severity scales in clinical practice and research.MethodsA Delphi method of consensus development was used, comprising three survey rounds. In Round 1, participants were asked nine multiple-choice and open-ended questions to gather opinions on the six severity scales and domains. In Rounds 2 and 3, questions aimed to gain consensus on the opinions revealed in Round 1 using a typical Likert scale.ResultsNineteen experts, active in NPC paediatric and adult research and treatment, participated in this study. Of these, 16/19 completed Rounds 1 and 2 and 19/...

BackgroundNutritional deficiencies in children with cancer at time of diagnosis and during treatment may negatively affect disease outcome and increase treatment‐related toxicity. Yet zinc, an essential nutrient important for supporting immune function and known for reducing diarrheal episodes, is rarely assessed in these children.ProceduresFifty children (1 month to 18 years) with recently diagnosed cancer were enrolled in this study. An age and gender matched control group (n = 50) was also recruited. Plasma and urinary zinc, plasma copper, and C‐reactive protein (CRP) levels were measured at baseline, 3, and 6 months following diagnosis. A retrospective review of the toxicity profile was performed in the cohort of children with cancer for the first 4 years after initial diagnosis.ResultsCRP and plasma copper (both acute‐phase reactants) were elevated in patients with cancer compared to controls at baseline, bothp < .03. Plasma zinc levels were not significantly different from ...

BackgroundPatients with late, ≥18 months postdiagnosis, isolated central nervous relapse (iCNS‐R) of B‐acute lymphoblastic leukemia (ALL) have excellent outcomes with chemotherapy plus cranial radiotherapy, with 5‐year overall survival (OS) approaching 80% in POG 9412. Subsequent relapse and radiation‐related morbidity remain the causes of treatment failure and long‐term sequelae. COG AALL02P2 aimed to maintain outcomes in patients with late iCNS‐R using intensified chemotherapy and a decrease in cranial irradiation from 1800 to 1200 cGy.ProceduresCOG AALL02P2 enrolled 118 eligible patients with B‐cell ALL (B‐ALL) and late iCNS‐R who received intensified systemic therapy, triple intrathecal chemotherapy, and 1200 cGy cranial irradiation delivered at 12 months, with maintenance chemotherapy continuing until 104 weeks postdiagnosis.ResultsThe 3‐year event‐free survival (EFS) and OS were 64.3% ± 4.5% and 79.6% ± 3.8%, with 46.1% (18/39) of second relapses including the CNS. Of the 112 ...

Large scale genomic efforts have shown that a significant percentage of infant high-grade gliomas (HGG) carry targetable gene fusions. Given the rarity of congenital spinal HGGs, little is known about the molecular features of these tumors and their response to treatment. We describe a case of a patient with congenital spinal glioblastoma. A full-term female infant with symmetric IUGR was noted to have weakness with little movement of her upper extremities. MRI of the spine showed an infiltrative and hemorrhagic intraspinal cervicothoracic neoplasm with a large hemorrhagic intramedullary component. A biopsy was done and revealed a high-grade glial neoplasm with pan-TRK expression. Next generation sequencing (NGS) confirmed a MEF2D-NTRK1 gene fusion. Prior to the result of her molecular testing, the patient clinically deteriorated with decreased movement and increased apneic episodes despite steroid treatment. She was then started on treatment with carboplatin and etoposide per Macy ...

Outcomes after relapse of childhood B-acute lymphoblastic leukemia (B-ALL) are poor, and optimal therapy is unclear. Children’s Oncology Group study AALL0433 evaluated a new platform for relapsed ALL. Between March 2007 and October 2013 AALL0433 enrolled 275 participants with late bone marrow or very early isolated central nervous system (iCNS) relapse of childhood B-ALL. Patients were randomized to receive standard versus intensive vincristine dosing; this randomization closed due to excess peripheral neuropathy in 2010. Patients with matched sibling donors received allogeneic hematopoietic cell transplantation (HCT) after the first three blocks of therapy. The prognostic value of minimal residual disease (MRD) was also evaluated in this study. The 3-year event free and overall survival (EFS/OS) for the 271 eligible patients were 63.6% +/- 3.0% and 72.3% +/- 2.8% respectively. MRD at the end of Induction-1 was highly predictive of outcome, with 3-year EFS/OS of 84.9 +/- 4.0% and 93...