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Propranolol is used to treat problematic infantile hemangiomas (IHs), but its safety in infants5 weeks corrected age has not been established. The objective of this study was to assess the safety and efficacy of propranolol for treatment of IH in infants5 weeks corrected age, or 45 weeks corrected gestational age (CGA).We performed a single institution, retrospective review of patients treated with propranolol prior to the age of 6 months between 2017 and 2021. Patient characteristics, location of hemangioma(s), weight at initiation of treatment, dosing information, side effects, response, and duration of treatment were documented.Of 200 patients with IH treated with propranolol, 24 started treatment prior to 45 weeks CGA. Mean CGA at initiation of treatment was 42 weeks. Sixty-seven percent were female and 75% were white, non-Hispanic. Mean duration of treatment was 255 days. Twenty-two patients (92%) had clear benefit from treatment at a dose of 1-3 mg/kg/day. The most common side effects were sleep disturbance (21%), irritability (17%), and cool hands/feet (13%). There were no serious adverse events.In this cohort of 24 patients with corrected age5 weeks (CGA45 weeks), propranolol was safe and effective for the treatment of infantile hemangiomas. Larger, prospective studies are indicated to investigate propranolol in this age group.

PURPOSE For adolescents and young adults (AYAs) with cancer, fertility preservation (FP) decision making is complex and distressing. Racial/ethnic minority (REM) AYAs experience disparities in FP awareness, uptake, and outcomes. A turning point (TP) is a point of reflection, change, or decisive moment(s) resulting in changes in perspectives or trajectories. To enhance understanding of AYAs' diverse experiences, this study examined alignment and/or divergence of FP decisional TPs among non-Hispanic White (NHW) AYAs and REM AYAs. METHODS Qualitative semistructured interviews were conducted in person, by video, or phone with 36 AYAs (20 NHW and 16 REM [nine Hispanic and seven Black/multiracial Black). The constant comparative method was used to identify and analyze themes illustrating participants' conceptualization and/or experience of FP decisional TPs. RESULTS Seven thematic TPs emerged: (1) emotional reaction to discovering FP procedures exist; (2) encountering unclear or dismissive communication during initial fertility conversations with health care providers; (3) encountering direct and supportive communication during initial fertility conversations with health care providers; (4) participating in critical family conversations about pursuing FP; (5) weighing personal desire for a child against other priorities/circumstances; (6) realizing FP is not feasible, and (7) experiencing unanticipated changes in cancer diagnosis or treatment plans/procedures. TP variations include REM participants reported dismissive communication and suggested cost was prohibitive. NHW participants emphasized more forcefully that biological children may become a future priority. CONCLUSION Understanding how clinical communication and priorities/resources may vary for NHW and REM AYAs can inform future interventions aimed at reducing health disparities and enhancing patient-centered care.

The severe acute respiratory syndrome coronavirus (SARS-CoV-2) pandemic has disrupted normal health care utilization patterns worldwide, including decreasing emergency department (ED) visits for various medical emergencies. We examined whether this pattern was present in febrile pediatric oncology patients. In this single-center cohort study, we conducted a retrospective chart review of ED visits of febrile pediatric oncology patients during the first 4 months of the global SARS-CoV-2 pandemic and compared those data to the same time periods in the previous 2 years. During the first 5 months of the pandemic, 25 pediatric oncology patients with fever visited our ED; 65 children visited during the same time period in 2018; and 60 visited in 2019. Compared with 2018 and 2019, encounters for 2020 were decreased by 62% and 58%, respectively. A significantly higher percentage of febrile pediatric oncology patients (84%) were admitted to our hospital during the pandemic compared the previous years (58%). Of concern is the possibility that fear of exposure to coronavirus disease-19 (COVID-19) at our health care facility prompted caregivers of pediatric oncology patients to avoid seeking care for their child with fever. Consistent communication with families about the life-threatening nature of fever should be prioritized among pediatric oncology providers.

Deep sedation/general anesthesia is commonly used in pediatric oncoclogy patients undergoing lumbar puncture (LP). Propofol is often used for sedation, with or without a narcotic. We hypothesized that eutectic mixture of lidocaine and prilocaine (EMLA) would allow for lower cumulative doses of propofol and less movement. We performed a prospective, randomized, double blind, placebo-controlled trial in children undergoing sedation for LP. Standard initial weight-based doses of propofol and fentanyl were administered, with either EMLA cream or a placebo cream applied topically. The primary outcome was the total dose of propofol administered to each patient. We also tracked patient movement and complications. Twenty-seven patients underwent 152 LPs. Patients randomized to EMLA cream (n = 75) were significantly more likely to receive a lower dose of propofol (2.94 mg/kg, SE = 0.25, versus 3.22 mg/kg, SE = 0.19; p = 0.036) and to not require additional propofol doses (probability 0.49, SE = 0.08 versus 0.69, SE = 0.06; p = 0.001) compared to patients randomized to placebo cream (n = 77). In addition, patients with EMLA cream were significantly less likely to demonstrate minor or major movement. EMLA cream results in less movement and less propofol administration in pediatric oncology patients undergoing sedation for LP.

Caregivers of children with chronic illnesses experience elevated stress and reduced self-care. Although self-care can be beneficial, it is a form of disengagement coping, disengaging from the stressor to try and feel better, which has been characterized as a maladaptive coping strategy. In this study, we test the formulation that avoidance, avoiding the stressor and any thoughts related to it, is a maladaptive disengagement coping strategy, whereas distraction, taking a break from the stressor to do something pleasant, is an adaptive disengagement coping strategy. We assessed these strategies as well as psychosocial outcomes and trait predictors in caregivers of children with chronic illnesses. Results showed that those high in avoidance coping reported lower well-being, higher depression and higher stress. Alternatively, when controlling for avoidance, those high in distraction reported higher well-being, lower depression and lower stress. In addition, distraction exhibited strong relationships to increased positive emotions during caregiving situations and was associated with positive personality traits. These results suggest that not all disengagement coping strategies are equal; although avoidance may be a maladaptive strategy, distraction can be an effective positive emotional strategy for coping with the chronic stress of caregiving for a child with a chronic illness.

An 11-year-old girl with kaposiform lymphangiomatosis presented with recurrent chylous pericardial effusions that were refractory to pericardial drainage and medical therapy. Magnetic resonance imaging demonstrated a prominent lymphatic duct with anterior mediastinal extension into the left clavicular region and a region of high signal that was favored to represent a low-flow lymphatic malformation. The patient underwent direct access thoracic duct lymphangiography with thoracic duct embolization and sclerotherapy of the large left-sided neck and pericardial lymphatic malformation. After the procedure, her pericardial effusions resolved, and she has remained asymptomatic for 15 months.

ImportanceVascular malformations (VMs) are rare disorders of vasculogenesis associated with substantial morbidity. Improved understanding of their genetic basis is increasingly guiding management, but logistical barriers to obtaining genetic testing in patients with VM may constrain treatment options.ObjectivesTo examine the institutional mechanisms for and obstacles to obtaining genetic testing for VM.Design, Setting, and ParticipantsThis survey study invited members of the Pediatric Hematology-Oncology Vascular Anomalies Interest Group, representing 81 vascular anomaly centers (VACs) serving individuals up to 18 years of age, to complete an electronic survey. Respondents were mostly pediatric hematologists-oncologists (PHOs) but included geneticists, genetic counselors, clinic administrators, and nurse practitioners. Responses that were received between March 1 and September 30, 2022, were analyzed with descriptive methods. Requirements for genetic testing by several genetics laboratories were also reviewed. Results were stratified by size of the VAC.Main Outcomes and MeasuresVascular anomaly center and associated clinician characteristics and practice patterns for ordering and obtaining insurance approval for genetic testing for VMs were collected.ResultsResponses were received from 55 of 81 clinicians, for a response rate of 67.9%. Most respondents were PHOs (50 [90.9%]). Most respondents (32 of 55 respondents [58.2%]) replied that they order genetic testing on 5 to 50 patients per year and reported a genetic testing volume increase of 2- to 10-fold over the past 3 years (38 of 53 respondents [71.7%]). Most testing was ordered by PHOs (35 of 53 respondents [66.0%]), followed by geneticists (28 [52.8%]) and genetic counselors (24 [45.3%]). In-house clinical testing was more common at large and medium-sized VACs. Small VACs were more likely to use oncology-based platforms, which potentially miss low-frequency allelic variants in VM. Logistics and barriers varied by size of the VAC. Obtaining prior authorization was the duty shared among PHOs, nurses, and administrative staff, but the burden of insurance denials and appeals were on PHOs (35 of 53 respondents [66.0%]). Lack of administrative support; unclear institutional, insurance, and laboratory requirements; and lack of clinician education were barriers to genetic testing at VACs of all sizes. The effort to obtain genetic testing for patients with VM, compared with patients with cancer, was perceived as excessive, despite genetic testing being considered standard of care for this population.Conclusions and RelevanceResults of this survey study showed the barriers to genetic testing for VM across VACs, described differences between VACs based on size, and proposed multiple interventions to support clinicians ordering genetic testing for VM. The results and recommendations should have broader application to clinicians caring for patients for whom molecular diagnosis is important to medical management.

Children with hemophilia have the usual childhood risk of falls and head trauma. Head computed tomographies (HCTs) are fast, detailed, and readily available, but increased radiation exposure in the pediatric population is now recognized as causing increased brain malignancy. By examining the incidence of intracranial cerebral hemorrhage in this population, we will be able to weigh risks and benefits of HCT use more accurately.Using a retrospective chart review, we examined past medical records of pediatric patients, aged 0 to 15 years, with hemophilia presenting to 1 academic medical center. Primary outcomes included number of head CTs ordered, total and per patient over the years studied, and the incidence of positive findings, as defined by presence of blood products as documented by radiologist final read/interpretation.The mean number of head CTs per child was 2.5 (range, 1-10). None of the HCT scans were read as intracranial cerebral hemorrhage, and none of the patients had findings that lead to neurosurgical intervention. In a sensitivity analysis, applying Pediatric Emergency Care Applied Research Network head injury criteria, 11 HCT scans would be ordered for a reduction of 80 HCTs, or a decrease of 2 HCT scans per child. No incidence of intracranial cerebral hemorrhage would have been missed.Our findings suggest that in the child with hemophilia and a history of minor head trauma, exposure to the radiation of a HCT based on the diagnosis of hemophilia alone may not be necessary but that imaging decisions need to be made in conjunction with clinical examination findings and neurologic status.

Objective For adolescents and young adults (AYAs), cancer-related fertility concerns (FC) are salient, disruptive, and complex. Clinical communication about FC and fertility preservation options are suboptimal, increasing patient distress. The purpose of this study is to construct a conceptual model of FC among AYAs with cancer to inform future measurement development. Methods Concept elicitation interviews were conducted with a purposive sample of stakeholders: 36 AYAs (10 adolescents, 12 emerging adults, and 14 young adults), 36 AYA oncology health care providers, and 12 content experts in cancer-related infertility. The constant comparative method was used to identify themes and properties that illustrate AYAs' conceptualization and/or experience of FC. Results Thirteen themes characterized FC among AYAs with cancer, varying by stakeholder group and domain affiliations. Themes were grouped by four domains (e.g., affective, information, coping, and logistical), which organized the conceptual model. Affective experiences were further determined to be an important component within the other three domains. AYAs' fertility and fertility preservation experiences were shaped by communication factors and timing factors including placement along the lifespan/cancer continuum. Conclusions AYA FC are characterized by uncertainty and confusion that may contribute to future decisional regret or magnify feelings of loss. Results add to previous research by examining individual, relational, and health care factors that fluctuate to inform fertility preservation perceptions and decision-making across the AYA age spectrum. Findings will be used to develop and test new self-report measures of FC among AYAs with cancer and survivors using classic and modern measurement theory approaches.

Background Hemophagocytic lymphohistiocytosis (HLH) is an uncommon hyperinflammatory condition in children that may acutely mimic septic shock. Sudden out-of-hospital cardiac arrest in children is also uncommon and may be of unclear etiology upon initial presentation. Case Report A 10-year-old previously healthy child presented with sudden cardiac arrest after an insidious course of throat pain, fever, and progressive altered mental status. He was subsequently diagnosed with Epstein-Barr virus-associated HLH and suffered cerebral edema and death. Why Should an Emergency Physician be Aware of This? HLH has not previously been described as a cause of sudden out-of-hospital cardiac arrest in children. Rapid diagnosis of underlying cause of an unexpected cardiac arrest may help guide appropriate therapy to salvage organ function.

Sirolimus is an effective therapy for children with kaposiform hemangioendothelioma with or without the Kasabach-Merritt phenomenon. We report the case of a child with kaposiform hemangioendothelioma and the Kasabach-Merritt phenomenon who developed Pneumocystis carinii pneumonia (PCP) while on sirolimus and a prednisolone taper, after lack of adequate response to prednisolone, propranolol, and vincristine. He had a prompt positive clinical and laboratory response to sirolimus, but 4 weeks after starting it, at the age of 4 months, he developed PCP. This led to respiratory failure, which required extracorporeal membrane oxygenation. Sirolimus was temporarily discontinued, and he was successfully treated for PCP with sulfamethoxazole-trimethoprim and methylprednisolone. He was restarted on sirolimus 3 weeks after discharge and given sulfamethoxazole-trimethoprim prophylaxis. At the age of 22 months, while still on sirolimus, the lesion continued to improve with test results revealing stable hemoglobin and platelet counts. PCP is a rare but life-threatening side effect of sirolimus therapy, especially in the setting of concurrent steroid treatment. Pneumocystis prophylaxis should be considered for patients receiving sirolimus.

Severe anemia in Jehovah's Witness patients has long been a complex and sometimes divisive issue, especially in children and adolescents. In adolescent patients old enough to express their wishes, the decision to transfuse becomes more complicated. We present the case of a 12-year-old Jehovah's Witness female with severe anemia (hemoglobin of 2.6 g/dL) secondary to menorrhagia. She was successfully managed without transfusion, for which the patient and her family were deeply grateful. This case demonstrates that it is possible to manage severe iron deficiency anemia without transfusion.

INTRODUCTION: The recent introduction of new therapies for people with hemophilia A and B (HA and HB) mandates careful monitoring of the safety of these treatments. The primary aim of ATHN 7: A Natural History Study of the Safety, Effectiveness, and Practice of Treatment for People with Hemophilia (NCT03619863) is to monitor the safety of current hemophilia therapies. METHODS: ATHN 7 is a longitudinal, prospective cohort study being conducted at 26 American Thrombosis and Hemostasis Network (ATHN)-affiliated sites. The study is approved by central and local institutional review boards. Any person with a diagnosis of congenital hemophilia A or B (factor VIII or IX activity < 50%) who receives care at a participating site is eligible for inclusion. Participants and/or a parent/guardian sign informed consent and assent prior to participation. Adverse events, including those events designated by the European Haemophilia Safety Surveillance group as well as other adverse events of special interest, are recorded and monitored. Demographic and clinical information are collected at baseline and at least quarterly through participant interview and medical record review. Descriptive statistics of medical history and demographic data as well as longitudinal data are used to characterize the study population. RESULTS: As of June 2021, a total of 391 participants had enrolled in ATHN 7. The median age of participants was 22.5 ± 17.8 years. Males represented 97.7% (382/391) of participants. Eighty-five percent (333/391) were not Hispanic. White participants comprised 82.6% (323/391) of the study population, while 7.9% (31/391) were Black/African American, 3.8% (15/391) were Asian, 1.8% (7/391) were of mixed race, and 3.8% (15/391) were of other or unknown race. The primary diagnosis of participants included 70.1% (274/391) with severe HA, 15.3% (60/391) with moderate HA, 7.2% (28/391) with mild HA, 4.1% (16/391) with severe HB, 2.0% (8/391) with moderate HB, and 1.0% (4/391) with mild HB. Nineteen percent (71/391) of participants had a documented history of an inhibitor at the time of enrollment with a mean peak inhibitor titer of 96.7 ± 214.3 Bethesda Units. Substitution therapy with a non-factor molecule was the primary medication for 43.4% (162/391) participants, while 4.3% (16/391) utilized a plasma-derived clotting factor concentrate, 28.4% (196/391) utilized a standard half-life, recombinant factor concentrate, 18.3% (126/391) utilized an extended half-life recombinant factor concentrate, 4.1% (28/391) utilized a bypassing agent, and 19.3% (133/391) utilized some other hemostatic agent. Continuous prophylaxis was the primary regimen for 79.1% (295/391) participants. The remaining 19.6% (73/391) of participants were on episodic therapy. Within the cohort of 391 participants, a total of 14 adverse events have been reported in 8 participants. No adverse events of special interest were reported. Redness or rash at injection site accounted for 64.2% (9/14) of the reported adverse events, all in participants receiving emicizumab. Two participants experienced bruising or bleeding while on emicizumab. Two participants on emicizumab were diagnosed with malignancy, neither found to be attributed to their therapy. One participant developed an allergic reaction to their standard half-life recombinant factor concentrate. DISCUSSION: Open to enrollment in January 2019, ATHN 7 has now collected 18 months of longitudinal safety data for therapies used to treat HA and HB in 391 participants, an addition of 12 months and 24 participants since our last report. As the study was designed to enhance representation of those utilizing substitution therapy, almost half of the participants were on emicizumab for prophylaxis of bleeding. Adverse events attributable to hemophilia therapy was limited to minor skin reactions. As previously reported, a single participant experienced delayed bleeding after closed head trauma (despite factor replacement and normal intracranial imaging at the time of the event), providing potentially important information on the risk of delayed bleeding from significant trauma in those receiving emicizumab. Over the coming year, participants in ATHN 7 will be transitioned to ATHN's new longitudinal natural history study, ATHN TRANSCENDS (NCT04398628). Disclosures Buckner: Pfizer: Honoraria; Takeda: Honoraria; Bayer: Honoraria; Sanofi: Honoraria; Spark: Honoraria; Genetech: Honoraria; CSL Behring: Honoraria; Novo Nordisk: Honoraria; Tremeau Pharmaceuticals: Consultancy, Honoraria; BioMarin: Consultancy, Honoraria; uniQure: Consultancy, Honoraria; American Thrombosis: Membership on an entity's Board of Directors or advisory committees; Hemostasis Network: Membership on an entity's Board of Directors or advisory committees. Carpenter: Hemophilia and Thrombosis Research Society: Membership on an entity's Board of Directors or advisory committees; Kedrion Pharmaceuticals: Honoraria; Genentech: Honoraria; Novo Nordisk: Honoraria. Raffini: Genentech: Consultancy; CSL Behring: Consultancy; HEMA Biologics: Consultancy; XaTek: Consultancy; Bayer: Consultancy. Zia: Takeda: Consultancy; Hemophilia and Thrombosis Research Society: Membership on an entity's Board of Directors or advisory committees. Recht: Hema Biologics: Consultancy; Kedrion: Consultancy; Novo Nordisk: Consultancy; Octapharma: Consultancy; Pfizer: Consultancy; Sanofi: Consultancy; Takeda: Consultancy; uniQure: Consultancy; Foundation for Women and Girls with Blood Disorders, Partners in Bleeding Disorders: Speakers Bureau; American Thrombosis and Hemostasis Network: Current Employment; Oregon Health & Science University: Current Employment; Genentech: Consultancy; CSL Behring: Consultancy; Catalyst Biosciences: Consultancy.

INTRODUCTION The recent introduction of new therapies for hemophilia A and B (HA and HB) mandates careful monitoring of the safety of these treatments as their use becomes more widespread. The American Thrombosis and Hemostasis Network (ATHN) collects information about the use of all HA and HB therapies through the more than 140 ATHN-affiliated hemophilia treatment centers (HTCs) in the United States (US). The primary aim of ATHN 7: A Natural History Cohort Study of the Safety, Effectiveness, and Practice of Treatment for People with Hemophilia is to monitor the safety of current hemophilia therapies. Secondary aims include assessment over time of real-world effectiveness and patient experience of current therapies. METHODS ATHN 7 is being sponsored by ATHN. It is a longitudinal, prospective cohort study being conducted at over 20 ATHN-affiliated sites in the US. The study is approved by central and local institutional review boards. Any person with a diagnosis of congenital hemophilia A or B (factor VIII or IX activity < 50%) who receives care at a participating site is eligible for inclusion. All participants and parents/guardians sign informed consents and assents prior to participation. Patients are excluded if they have any other known bleeding disorder. Adverse events, including those events designated by the European Haemophilia Safety Surveillance (EUHASS) group as well as other adverse events of special interest, are recorded and monitored. Demographic and clinical information are collected at baseline and at least quarterly through patient interview and medical record review. Health status is measured using the 5-level EuroQoL-5D questionnaire (EQ-5D-5L). Descriptive statistics of the baseline medical history and demographic data are used to characterize the study population. RESULTS The first participant consented to ATHN 7 in February 2019. As of 06/30/2020, a total of 367 subjects were enrolled in the study from 24 sites. Baseline demographics, clinical characteristics, and treatments are shown in Table 1. Most participants (69.9%) had severe HA. Approximately half of the participants were being treated with clotting factor as their primary therapy and half with a bispecific antibody. Adverse events reported to date include allergic reactions/redness at the injection site, rash unrelated to treatment, and a severe subdural hematoma due to a fall, all in patients receiving emicizumab (Table 2). At baseline, problems with mobility, self-care, and completing usual activities were reported by 32.9%, 13.0%, and 33.7% of participants, respectively. Problems with pain and anxiety were reported by 52.4% and 34.1% of participants (Figure 1). The average health status rating was 83.4 out of 100 (Figure 2). DISCUSSION These results demonstrate the capability of ATHN 7 to enroll a large cohort of subjects from multiple sites, monitor safety events, and assess outcomes related to living with and being treated for HA and HB. Adverse events attributed to any hemophilia therapy have been limited to minor skin reactions and have not led to product discontinuation. One subject experienced a trauma-related subdural hemorrhage, which provides important information on the risk of bleeding from severe/significant trauma in those receiving emicizumab. We provide a sobering picture of the high prevalence of difficulties with activities of daily living, pain, and mental health concerns. Despite many advances in therapy, hemophilia continues to have a real, everyday impact on the lives of our patients. CONCLUSIONS During the first 16 months of enrollment in the ATHN 7 study, we observed skin reactions, as well as one severe, unanticipated bleeding event due to trauma. At baseline, pain, anxiety/depression, and impaired physical function were concerns for a significant proportion of the individuals in the study. Disclosures Buckner: Tremeau Pharmaceuticals: Consultancy; American Thrombosis and Hemostasis Network: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Consultancy; Takeda: Consultancy; Bayer: Consultancy; uniQure: Consultancy; Novo Nordisk: Consultancy; Kedrion: Consultancy; Spark: Consultancy; Genentech: Consultancy; Biomarin: Consultancy. Carpenter:Hemostasis & Thrombosis Research Society: Membership on an entity's Board of Directors or advisory committees; American Academy of Pediatrics: Other: PREP Heme/Onc editorial board; Shire: Research Funding; CSL Behring: Research Funding; American Thrombosis and Hemostasis Network: Membership on an entity's Board of Directors or advisory committees; Genentech, Inc.: Honoraria; Kedrion: Honoraria; Novo Nordisk: Honoraria. Croteau:ATHN: Research Funding; National Hemophilia Foundation: Honoraria; Spark Therapeutics: Research Funding; Novo Nordisk: Research Funding; Bayer: Consultancy; Hemophilia Federation of America: Honoraria; CSL-Behring: Consultancy; Pfizer: Consultancy; Genentech: Consultancy; Sigilon Therapeutics: Consultancy. Cuker:Synergy CRO: Consultancy; Alexion: Research Funding; Bayer: Research Funding; Novo Nordisk: Research Funding; Pfizer: Research Funding; Sanofi: Research Funding; Spark Therapeutics: Research Funding; Takeda: Research Funding; Novartis: Research Funding. Kempton:Spark Therapeutics: Honoraria; Octapharma: Honoraria; Pfizer: Honoraria; Genentech: Honoraria; Novo Nordisk: Research Funding. Malec:SOBI: Consultancy; Bayer: Consultancy; Takeda: Consultancy; CSL: Consultancy; Sanofi Genzyme: Consultancy, Research Funding, Speakers Bureau. Raffini:XaTek: Other: Advisory Board; CSL Behring: Other: Advisory Board; Bayer: Other: Advisory Board; HemaBiologics: Other: Advisory Board; Roche: Other: Advisory Board. Staber:Spark Therapeutics: Consultancy; Genentech: Consultancy; Sanofi: Consultancy; Takeda: Consultancy; Bayer: Consultancy. Wang:CSL Behring: Honoraria; Biomarin: Honoraria; Genentech: Honoraria; Bioverativ Inc: Honoraria; Bayer: Honoraria; Takeda: Honoraria. Recht:Novo Nordisk: Consultancy, Other: personal fees, Research Funding; Spark: Research Funding; uniQure: Consultancy, Other: personal fees, Research Funding; Takeda: Consultancy, Other: personal fees, Research Funding; BioMarin: Research Funding; Pfizer: Consultancy, Other: personal fees; Genentech: Consultancy, Other: personal fees, Research Funding; CSL Behring: Consultancy, Other: personal fees.

BACKGROUND: Hypoalbuminemia is a well-recognized finding associated with cancer, but its prevalence and prognostic significance have not been well studied in children with cancer. OBJECTIVE: To determine the prevalence of hypoalbuminemia prior to starting chemotherapy in children with cancer and its association with relapse-free survival (RFS) and overall survival (OS). DESIGN/METHOD: We performed a single institution, IRB-approved, retrospective review of pediatric oncology patients diagnosed between 1998 and 2012. Five-year survival was estimated using the Kaplan-Meier method; groups were compared using Cox regression. RESULTS: We identified 659 pediatric patients with a first diagnosis of cancer and a serum albumin level prior to starting chemotherapy. Mean age was 8.6 years (SD = 5.8); 62% were male and 92% were non-Hispanic. Hypoalbuminemia prior to starting chemotherapy was present at least once in 302 (45.8%). The five-year RFS and OS of those with hypoalbuminemia and without hypoalbuminemia were not significantly different. However, patients with severe hypoalbuminemia (defined as a value 10% or more below the lower limit of normal) had inferior RFS and OS for patients with hematologic/lymphatic malignancies, and inferior RFS for patients with metstatic Ewing sarcoma. CONCLUSION: Hypoalbuminemia prior to starting chemotherapy in pediatric oncology patients is common (nearly half in this cohort). Severe hypoalbuminemia was associated with inferior 5-year RFS in some subgroups.

Primary pediatric bone lymphoma is a rare form of non-Hodgkin lymphoma. Unlike nodal forms of lymphoma, imaging abnormalities in lymphoma of bone do not resolve rapidly in conjunction with treatment and radiologic findings can remain abnormal for years, making it difficult to evaluate treatment response. To evaluate the utility of imaging in assessment of patients with primary pediatric bone lymphoma. At our institution between 2004 and 2013, six cases of pathology-proven primary pediatric bone lymphoma were diagnosed. Retrospective chart review was performed to assess imaging utilization. Our data were qualitatively compared with existing literature to construct an algorithm for imaging patients with primary lymphoma of bone. Imaging evaluation of patients with primary pediatric bone lymphoma was highly variable at our institution. Conventional imaging was routinely used to evaluate response to treatment, despite lack of appreciable osseous change. Imaging in the absence of symptoms did not alter clinical management. Only positron emission tomography CT (PET/CT) proved capable of demonstrating imaging changes from the pretreatment to the post-treatment scans that were consistent with the clinical response to treatment. Surveillance imaging is likely unnecessary in patients with a known diagnosis of pediatric lymphoma of bone. Pretreatment and post-treatment PET/CT is likely sufficient to assess response. There is little data to support the use of interim and surveillance PET/CT.

Spermatogonial stem cell (SSC) loss due to cancer treatment, developmental disorder or genetic abnormality may cause permanent infertility. Cryopreservation of ejaculated sperm is an effective method of fertility preservation in adult males at risk of infertility. However this is not an option in pre-pubertal boys because spermatogenesis has not yet started, and it is difficult in adolescents who are not sexually mature. Therefore testicular tissue cryopreservation to preserve SSCs for future generation of spermatogenesis, either in vivo or in vitro, could be an option for these groups of patients. Although SSC transplantation has been successful in several species including non-human primates, it is still experimental in humans. There are several remaining concerns which need to be addressed before initiating trials of human SSC autotransplantation. Establishment of a testicular tissue banking system is a fundamental step towards using SSC technology as a fertility preservation method. It is important to understand the consultation, harvesting the testicular tissue, histological evaluation, cryopreservation, and long term storage aspects. We describe here a multidisciplinary approach to establish testicular tissue banking for males at risk of infertility.

Wilms tumor is the most common childhood renal cancer. To identify mutations that predispose to Wilms tumor, we are conducting exome sequencing studies. Here we describe 11 different inactivating mutations in the REST gene (encoding RE1-silencing transcription factor) in four familial Wilms tumor pedigrees and nine non-familial cases. Notably, no similar mutations were identified in the ICR1000 control series (13/558 versus 0/993; P < 0.0001) or in the ExAC series (13/558 versus 0/61,312; P < 0.0001). We identified a second mutational event in two tumors, suggesting that REST may act as a tumor-suppressor gene in Wilms tumor pathogenesis. REST is a zinc-finger transcription factor that functions in cellular differentiation and embryonic development. Notably, ten of 11 mutations clustered within the portion of REST encoding the DNA-binding domain, and functional analyses showed that these mutations compromise REST transcriptional repression. These data establish REST as a Wilms tumor predisposition gene accounting for ∼2% of Wilms tumor.

Chemotherapy-induced nausea and vomiting remain common, distressing side effects of chemotherapy. It has been reported that acupressure prevents chemotherapy-induced nausea in adults, but it has not been well studied in children.In this multicenter, prospective, randomized, single-blind, sham-controlled trial, the authors compared acute-phase nausea severity in patients ages 4 to 18 years who were receiving highly emetic chemotherapy using standard antiemetic agents combined with acupressure wrist bands, the most common type of acupressure, versus sham bands. Patients wore acupressure or sham bands continuously on each day of chemotherapy and for up to 7 days afterward. Chemotherapy-induced nausea severity in the delayed phase and chemotherapy-induced vomiting control in the acute and delayed phases also were compared.Of the 187 patients randomized, 165 contributed nausea severity assessments during the acute phase. Acupressure bands did not reduce the severity of chemotherapy-induced nausea in the acute phase (odds ratio [OR], 1.33; 95% confidence limits, 0.89-2.00, in which an OR1.00 favored acupressure) or in the delayed phase (OR, 1.23; 95% CL, 0.75-2.01). Furthermore, acupressure bands did not improve daily vomiting control during the acute phase (OR, 1.57; 95% CL, 0.95-2.59) or the delayed phase (OR, 0.84; 95% CL, 0.45-1.58). No serious adverse events were reported.Acupressure bands were safe but did not improve chemotherapy-induced nausea or vomiting in pediatric patients who were receiving highly emetic chemotherapy. Cancer 2018;124:1188-96. © 2017 American Cancer Society.

Individuals harboring germ-line DICER1 mutations are predisposed to a rare cancer syndrome, the DICER1 Syndrome or pleuropulmonary blastoma-familial tumor and dysplasia syndrome [online Mendelian inheritance in man (OMIM) #601200]. In addition, specific somatic mutations in the DICER1 RNase III catalytic domain have been identified in several DICER1-associated tumor types. Pituitary blastoma (PitB) was identified as a distinct entity in 2008, and is a very rare, potentially lethal early childhood tumor of the pituitary gland. Since the discovery by our team of an inherited mutation in DICER1 in a child with PitB in 2011, we have identified 12 additional PitB cases. We aimed to determine the contribution of germ-line and somatic DICER1 mutations to PitB. We hypothesized that PitB is a pathognomonic feature of a germ-line DICER1 mutation and that each PitB will harbor a second somatic mutation in DICER1. Lymphocyte or saliva DNA samples ascertained from ten infants with PitB were screened and nine were found to harbor a heterozygous germ-line DICER1 mutation. We identified additional DICER1 mutations in nine of ten tested PitB tumor samples, eight of which were confirmed to be somatic in origin. Seven of these mutations occurred within the RNase IIIb catalytic domain, a domain essential to the generation of 5p miRNAs from the 5' arm of miRNA-precursors. Germ-line DICER1 mutations are a major contributor to PitB. Second somatic DICER1 "hits" occurring within the RNase IIIb domain also appear to be critical in PitB pathogenesis.

Vascular anomalies include vascular tumors and vascular malformations. With growing pharmacologic options and parallels to cancer treatment and biology, the hematologist-oncologist has assumed a more prominent role in clinical care and research relating to these diagnoses. This also is a growing area for targeted therapies and drug repositioning. We performed a review of contemporary options for medical management of these lesions. PubMed was searched for "vascular anomaly", "hemangioma", "vascular malformation", "arteriovenous malformation", "capillary malformation", "cerebral cavernous malformation", "lymphatic malformation", and "venous malformation", each with "drug treatment" as a modifier. Manuscripts were reviewed to verify diagnoses, indications for treatment, dose-schedules, evidence of effectiveness, toxicities, and mechanisms of action. ClinicalTrials.gov also was reviewed for relevant trials. More than 20 agents were identified which have been used to treat vascular anomalies. Rigorous studies are lacking for many of these. The rarity of these tumors has limited development of medical approaches to treatment. Cooperative group trials will be needed to prove the effectiveness of drugs which have shown promise in cases and small series. The observant clinician remains a powerful tool for identifying potential new treatments for vascular tumors and malformations.

Background Errors and near misses are common in medicine. Checklists and similar interventions are feasible and can reduce the incidence of errors and improve patient outcomes. This study assessed the feasibility and efficacy of a checklist in a pediatric oncology clinic. Procedure Errors and near misses of all types were systematically tracked for 1 month in a pediatric oncology clinic. Following the initial 1 month time period (baseline), a 10-item checklist was implemented for each patient encounter during a 4-month period. During month 5 of the study while the checklist was being used, errors and near misses were again systematically tracked for 1 month. Results The use of a checklist was associated with a significant reduction of errors in our clinic. The total number of errors (including documentation errors) decreased from 133 in month 1 to 39 in month 5 (P

History of the present illness This patient was in good health until September 2009, when she fell while running. At that time she felt a “pop” and developed right ankle pain followed by limping. Two weeks after the injury she went to her primary care physician, who obtained radiographs of her ankle, which were normal per the family. The patient continued to have right ankle pain and subsequently developed right knee pain. In November 2009 she was evaluated by an orthopedist and reported a temperature of 100.2°F the previous week. On examination she was noted to have an antalgic gait favoring the right side, right ankle swelling, and tenderness to palpation of the right ankle, the right knee, and bilateral distal femurs. Radiographs of her bilateral legs with attention to her right knee and ankle were obtained and did not reveal any bone abnormality. The orthopedist’s impression was a Salter-Harris I fracture of the right distal tibia and a right patellar tendon strain; she was treated with a long cam walker. The patient returned to the orthopedic clinic 2 weeks later and was no longer having pain. The cam walker was discontinued and the patient was instructed to resume activity as tolerated. In December 2009, the patient’s knee pain returned and she was seen again in the orthopedic clinic. At that visit she was noted to have occasional limping and avoidance of physical activity. She was given a knee brace and crutches in addition to pain medication. Laboratory evaluations revealed an elevated white blood cell (WBC) count of 14.3 1,000/ l (normal range 4.5– 13.5), a hemoglobin level of 11.9 gm/dl (normal range 11.0–14.6), a platelet count of 432 1,000/ l (normal range 150–400), an erythrocyte sedimentation rate (ESR) of 60 mm/hour (normal range 0–22), and a rheumatoid factor (RF) of 30 IU/ml (normal range 0–20). The patient continued to have intermittent pain through mid-December. The pain did not wake her at night, nor did she experience morning stiffness. While she did have some improvement of her pain on naproxen, further diagnostic imaging was pursued. Magnetic resonance imaging (MRI) of her right knee without contrast showed mild distal femoral periostitis without any evidence of effusion, synovial enhancement, or marrow edema. Small lymph nodes were present in the popliteal fossa. The patient continued on her current therapeutic regimen of naproxen. The patient subsequently began to have right shoulder pain after a mechanical fall on the shoulder while using her crutches. Because the patient’s pain persisted into late December, she was prescribed a 5-day course of prednisone (15 mg daily) and referred to a pediatric rheumatologist. The patient was given an appointment to be seen in the clinic the following week and in the interim, a 3-phase bone scan was recommended. The bone scan revealed no abnormality within the knees; however, there was increased uptake on all 3 phases within the right distal tibia/ankle. After these results were reported, the patient was directly admitted to the hospital for further evaluation and management. Upon presentation to the hospital, the patient endorsed having temperatures ranging from 99– 101°F as well as a 3-pound weight loss. The patient had had some blood work done a week prior to admission to the hospital by her primary care physician that showed a normal WBC count of 7.1 1,000/ l, a hemoglobin level of 12.2 gm/dl, a platelet count of 461 1,000/ l, an elevated C-reactive protein (CRP) level of 104.8 mg/liter, and an ESR of 80 mm/hour.

BACKGROUND: Optimal imaging for children with pediatric melanoma (MM) is unknown. METHODS: We reviewed clinical and imaging findings of patients with AJCC stage IIC-IV MM treated on our institutional MEL06 trial. All patients had baseline brain MRI/CT, PET/CT, CT chest, abdomen, and pelvis (CTCAP). Patients on stratum A (PEG-interferon; AJCC IIC, IIIA, IIIB) (n=16) had imaging every 6 months; stratum B1 (PEG-interferon and temozolomide; unresectable measurable disease, metastatic, or recurrent, n=2) had PET-CT scans every 2 months and brain imaging studies every 4 months; stratum B2 patients (PEG-interferon and temozolomide; unresectable non-measurable, metastatic, or recurrent, n=3) had imaging every 4 months. Off therapy imaging was done every 6 months for 3 years RESULTS: There were 21 patients (11 female, 11 spitzoid, median age 14 years, head/neck (6), trunk (7), extremities (8)). Patients with spitzoid melanoma underwent 236 imaging studies in total (86 PET/CT, 81 CTCAP, 11 CT chest, 10 CT brain, 48 MRI brain) at a median cost per patient of $32,718. Thirteen studies (5.8%) had findings that led to 2 biopsies (one positive). For conventional MM, 162 studies (61 PET/CT, 57 CTCAP, 8 CT chest, 7 CT brain, and 29 MRI brain) were performed with a median cost per patient of $23,420. Twenty (14%) had findings leading to six biopsies (4 positive). At 6.3 years (range 0.4–9.2) 17 patients remain disease free. CONCLUSION: Children with spitzoid melanoma require minimal imaging at diagnosis and follow-up. Patients with conventional MM should be imaged according to adult guidelines.

Music is widely used to enhance well-being. We wished to assess music’s effect on pediatric oncology outpatients. Patients who had leukemia and were in maintenance or consolidation outpatient treatment served as their own control at two visits. At visit 1, children rested for 20 min; at visit 2, for 20 min they listened to music designed to increase vitality and improve heart rate variability (HRV). At both visits, parents completed before and after treatment visual analog scales (VAS) of their child’s relaxation, well-being, vitality, anxiety, stress, and depression; patients’ heart rates were monitored during treatments to calculate HRV. The 47 patients with complete VAS data and 34 patients with usable HRV data were similar. At baseline, VAS scores for negative states were low (average of 10). Relaxation improved more with music than rest (p < 0.01). The HRV parasympathetic parameter was significantly lower with music than rest. No other differences were significant. Further studies are needed to better delineate the relationship between subjective and objective measures of well-being among patients who are not in severe distress.

The prognosis for most patients with newly diagnosed Wilms’ tumor (WT) is excellent, but those who have recurrent or refractory disease have a significantly worse prognosis. High dose chemotherapy (HDT) requiring autologous stem-cell rescue has been tried for recurrent WT with variable results, but no randomized clinical trial has ever been performed. A recent review by T.C. Ha and colleagues of the published cases to date suggests HDT may be beneficial to the very high risk subset of patients with recurrent WT, but this conclusion is fraught with the caveats of any retrospective review. A prospective clinical trial would be challenging to complete but with careful planning and international collaboration it could be accomplished. Such a trial is likely the only way to know with certainty the safety and efficacy of HDT for recurrent WT.

We will review the 2005 and 2006 literature on pediatric genitourinary tumors.Survival continues to improve for primary renal, bladder/prostate and testicular tumors in childhood. The addition of more intensive chemotherapy for anaplastic histology disease, recognition of loss of heterozygosity for chromosomes 1p and 16q as an adverse prognostic factor in favorable histology Wilms' tumor, and the utilization of molecular markers to better characterize all renal tumors will better enable individualized therapy. Recognition and treatment of anaplastic histology and bilateral Wilms' tumor remains a challenge. In rhabdomyosarcoma, genitourinary site and embryonal histology confer a relatively favorable prognosis.Advances in molecular oncology, diagnostic imaging, surgical approaches and long-term follow-up of childhood cancer survivors drive risk-stratified therapy in pediatric genitourinary tumors.

During the influenza A (H3N2) season of 2003–2004, several influenza-related complications and deaths were reported in children. Hemophagocytic lymphohistiocytosis complicating influenza A infection is very rare. We report a 3-year-old girl who presented with severe pneumonia and hemophagocytic lymphohistiocytosis associated with influenza A infection. Clinicians should be aware of hemophagocytic syndrome as a serious complication of influenza A infection.

HIV infection predisposes to cancer during childhood. In addition to the AIDS-defining non-Hodgkin lymphoma (NHL) and Kaposi sarcoma, a range of other lymphoid malignancies and solid tumors have been described. We report the first case of an HIV-positive child with thymic carcinoma in the setting of regressing thymic cysts. The tumor expressed CKIT but failed to respond to imatinab mesylate after a transient response to multiagent chemotherapy. This case extends the spectrum of pediatric malignancy in the setting of HIV and suggests that patients with presumed benign thymic cysts require ongoing surveillance. Pediatr Blood Cancer 2007;49:1004–1007. © 2005 Wiley-Liss, Inc.

Purpose In pediatric patients with acute lymphoblastic leukemia (ALL), the optimal time for central venous line (CVL) insertion and the optimal type of CVL (internal v external) is unclear. This study was undertaken to compare complication rates between early versus late line insertion, and between internal versus external lines in children with lesser risk ALL. Patients and Methods We performed a retrospective analysis of patients enrolled onto Pediatric Oncology Group (POG) protocol 9201. Data regarding demographics, CVL types and insertion dates, blood counts, and complications were reviewed through week 25 of therapy. Results Of 697 patients enrolled onto POG protocol 9201, 362 patients had sufficient data for analysis. When compared to late line placement (> day 15 of induction), early CVL placement (≤ day 15 of induction) was associated with an increased risk of having a positive blood culture (odds ratio, 2.2; 95% CI, 1.0 to 5.0; P = .05). When compared with internal CVLs (“ports”), external CVLs were associated with a positive blood culture (odds ratio, 3.1; 95% CI, 1.3 to 7.5; P = .01), thrombosis (odds ratio, 3.9; 95% CI, 1.5 to 10.3; P = .006), and CVL removal (odds ratio, 5.6; 95% CI, 2.7 to 11.6; P < .001). Conclusion In pediatric patients with lesser risk ALL, internal lines (ports) should be the preferred CVL type due to a lower risk of infectious and thrombotic complications. In addition, CVLs placed early in induction are associated with a higher risk of positive blood culture than those placed later in induction.

Significant advances in the treatment of medulloblastoma and primitive neuroectodermal tumors have been made in the past three decades. Maximal surgical resection is a mainstay of therapy. However, unlike many other central nervous system neoplasms, medulloblastoma and primitive neuroectodermal tumors are radiation and chemotherapy responsive. Despite this response, the prognosis for patients with these tumors remains variable and is relatively poor in infants and patients with metastatic disease. These tumors most commonly arise in children, thus most clinical trials emphasize the reduction of long-term sequelae, in addition to improving survival. All newly diagnosed patients who are eligible should be offered participation in a clinical trial. If a patient is ineligible or declines consent/ assent for a clinical trial, the best current treatment approach is surgical resection, followed by radiation therapy (except for children younger than 3 years) with weekly vincristine. For high-risk patients, 36 Gy of craniospinal irradiation should be delivered plus a boost of 19.8 Gy to the posterior fossa/primary tumor bed and sites of bulk metastatic disease. For average-risk patients, the craniospinal irradiation dose may be lowered to 23.4 Gy plus 32.4 Gy to the posterior fossa/tumor bed. After radiation therapy, intensive multimodal chemotherapy should be used for all patients.

We report a 5-year-old female who presented with unexplained acute renal failure (ARF) and hyperuricemia and who was subsequently diagnosed of T-cell acute lymphoblastic leukemia (ALL). Peripheral smear was initially unremarkable. She required hemodialysis. Two weeks later, peripheral smear showed 40% blasts and bone marrow demonstrated T-cell ALL. Our case was the fifth and the youngest case of ALL with spontaneous tumor lysis syndrome. However, in contrast to previous reports in ALL or acute myeloid leukemia, our patient did not have blasts noted on periphereal blood smear and her white blood cell count and serum lactate dehydrogenase level were normal on admission, a time when dialysis-dependent ARF and severe hyperuricemia were present. Occult hematologic malignancy should be considered in cases of ARF and hyperuricemia of unknown etiology even when peripheral hematologic findings are not informative. Pediatr Blood Cancer 2010;54:773–775. © 2009 Wiley-Liss, Inc.

The outcome for 82 pediatric patients with Ewing sarcoma (ES) and primitive neuroectodermal tumor (PNET) of bone is reported; the patients were treated at the Dana-Farber Cancer Institute (DFCI) and Children's Hospital (CH) in Boston, MA (USA) from 1971-1988. The charts of all patients with ES/PNET of bone treated during this period were reviewed for disease status, therapy, sites of relapse, information on second malignancies, and survival status. Eighty-two patients with ES/PNET of bone treated at DFCI/CH were identified. The 10-year event-free survival (EFS) rates were 12% (95% confidence interval [CI] 0, 27%) and 38% (95% CI 26, 51%) for patients with and without metastases, respectively (P = 0.002); the overall survival (OS) rates were 17% (95% CI 1, 33%) and 48% (95% CI 35, 61%) for patients with and without metastases (P = 0.001). Median follow-up for surviving patients is 10.2 years. Primary site in the pelvis also was associated with a poor outcome for patients with no metastatic disease (P = 0.006 OS, P = 0.03 EFS). Thirty-one patients survived in first remission at least 5 years from diagnosis, and of these, five experienced relapse of original disease, and five experienced secondary malignancies. Pediatric patients treated for ES/PNET of bone remain at risk for life-threatening events into the second decade of follow-up. After 5 years, the risk of second malignant neoplasm is at least as high as the risk of late relapse. Prolonged follow-up of patients with ES and PNET of bone is indicated.

Ewing sarcoma is the second most common type of malignant bone tumor in children and young adults. We report 2 patients with a history of Ewing sarcoma who were diagnosed with recurrent tumor during or immediately after pregnancy. To determine whether the hormonal milieu of pregnancy might have contributed to recurrence, we performed immunohistochemistry for estrogen and progesterone receptors on available tumor tissue. These receptors were not detected by immunohistochemistry. Increased medical surveillance during pregnancy may have resulted in ascertainment of recurrence in these 2 patients.

To determine the incidence and importance of abnormal cerebrospinal fluid (CSF) protein in children with acute leukemia, we performed a retrospective chart review. On 160 pediatric patients a total of 2,172 LPs were performed (median per patient = 15; range 1–38). Overall, 314 (14%) of CSF protein measurements were abnormal: 141 (7%) were abnormally low ( 45 mg/dL). In no case did an abnormal CSF protein impact patient management. We conclude that routine measurement of CSF protein is not indicated in children with acute leukemia. Pediatr Blood Cancer 2008;51:428–430. © 2008 Wiley-Liss, Inc.

We report the case of a 14-year-old male treated with arsenic trioxide for recurrent acute promyelocytic leukemia. He developed hyperleukocytosis (WBC 111.6 x 10(9)/L) which then resolved while continuing daily arsenic. Hyperleukocytosis without other complications may not be an indication for adding cytotoxic therapy or steroids, nor for discontinuing arsenic trioxide therapy in children.

The diagnosis of Burkitt lymphoma by thoracentesis has been rarely reported in the literature, particularly in children. From 1995 to 2004, we diagnosed six pediatric patients with mature B-cell neoplasms using thoracentesis as the initial diagnostic procedure. The cytology, immunophenotyping, and cytogenetic results of the pleural fluid cells were consistent with mature B-cell malignancies. We conclude that thoracentesis for the diagnosis of Burkitt lymphoma in children is safe, fast, and accurate. It should be strongly considered as an initial diagnostic procedure for pediatric patients with pleural effusions who are suspected of having B-cell malignancies. Pediatr Blood Cancer 2007;49:90–92. © 2005 Wiley-Liss, Inc.

Roseomonas is a newly described genus of pink-pigmented, gram-negative bacteria. Human infections caused by Roseomonas species are very rare. We report two cases of central venous catheter-related bacteremia associated with Roseomonas species (one case with R. gilardii and one with R. fauriae), and review the clinical spectrum of previously reported cases in the literature. Clinicals should be aware that Roseomonas species may cause serious infections in children.

BACKGROUND Infants with acute lymphoblastic leukemia (ALL) have a very poor prognosis. Since 1985, we have intensified therapy for infants with ALL by including a month of high dose multiagent chemotherapy after remission induction. METHODS Between 1985 and 1995, we treated 23 infants (age < 12 months). We compared the presenting characteristics and outcomes of these infants with the 11 infants treated on our protocols between 1973 and 1985, an era prior to the intensification of therapy. Available bone marrow samples from infants treated since 1985 were analyzed for the presence of MLL gene rearrangements by Southern blot analyses and for TEL-AML1 gene fusion by reverse transcriptase-polymerase chain reaction. RESULTS With a median follow-up of 5.6 years, the 50-month event free survival (EFS) (± standard error) for the 23 infants was 54 ± 11%, a significant improvement (P = 0.001) compared with the outcome for the 11 infants treated on our protocols prior to 1985 (EFS = 9 ± 9%). Of the seven infants found to have a rearranged MLL gene, three (43%) remained in first complete remission. None of the nine infant bone marrow specimens tested had evidence of TEL-AML1 gene fusion. The intensified therapy was complicated by a high incidence of infections, including septicemia in 52% of patients and Pneumocystis carinii pneumonitis in 22% of patients. Late effects identified in the 13 long term survivors (median age, 6 years) included developmental delay and learning disabilities of varying severity (82% of evaluable patients), asymptomatic cataracts (67%), asymptomatic echocardiographic abnormalities (30%), obesity (27%), and short stature (18%). CONCLUSIONS Intensification of therapy significantly improved the EFS of infants with ALL compared with previous, less intensive regimens and with the experience of other investigators. Future treatment for infants should attempt to improve efficacy while minimizing toxicity. Cancer 1997; 80:2285-95. © 1997 American Cancer Society.

Physicians are taught to think critically and practice evidence-based medicine. They read articles and review the works or others with a critical eye. But do physicians verbally criticize other physicians to patients? This study by McDaniel et al. suggests that they do, at a surprisingly high rate.1 This study covertly recorded conversations between standardized patients (actors) and consenting physicians (oncologists and family physicians), and then qualitatively analyzed the content. The standardized patient portrayed a middle-aged man who had been treated elsewhere for advanced lung cancer and was getting established in a new community. The investigators report that in 14 of 34 encounters (41 %), a total of 42 comments were made about the care they received by a previous physician. Two-thirds of those comments were critical, despite the fact that the patient received appropriate care as currently defined by the National Comprehensive Cancer Network. Importantly, these critical comments were initiated by the physicians and not the patients. Of the remaining comments, 29 % were supportive, and 4 % were neutral. Why is this important? When physicians criticize other physicians, patient satisfaction and quality of care may be adversely affected. The American Medical Association and American College of Physicians consider such criticism as disruptive and unprofessional.2,3 Education and effective training may help prevent this behavior. Creating a “culture of respect” is important for improving communication, safety, job satisfaction, and, ultimately, patient outcomes.4 If a physician has concerns about a patient’s previous care, speaking directly to the previous physician is usually the best approach.1 This study is limited by the use of standardized patients, a relatively small number of encounters in one community, and a single clinical scenario. Nevertheless, the findings are important and warrant follow-up. Future studies, potentially with real patients, should study this phenomenon in larger numbers and assess methods for reducing this behavior. Of course there is room for disagreement between physicians. Medicine is, after all, an art and not a science. But there is no place in medicine for unprofessional or disruptive behavior. This study is an important early contribution in a respectful “conversation.”

We report a case of PELVIS (perineal hemangioma, external genital malformations, lipomyelomeningocele, vesicorenal abnormalities, imperforate anus and skin tag) syndrome in which hemangioma in the perineal area was misdiagnosed at birth as diaper rash. Investigations revealed associated vesicorenal and spinal abnormalities. We emphasize careful diagnosis of suspicious lesions at birth and confirm the successful use of propranolol in treating ulcerated segmental hemangiomas.

Nat. Genet. 47, 1471–1474 (2015); published online 9 November 2015; corrected after print 8 February 2016 In the version of this article initially published, the authors failed to acknowledge funding from the NIHR Biomedical Research Centre at Great Ormond Street Hospital for Children NHS FoundationTrust and University College London to Neil Sebire.

A 15-year-old, right-handed Hispanic boy with B-cell acute lymphoblastic leukemia (ALL) was transferred for acute onset of stroke-like symptoms. Appoximately 6.5 hours prior to arrival, the patient was in his normal state of health. At that time, he developed abrupt onset of headache and left arm tingling described as “ants crawling on my arm.” He described associated dysarthria, dysphagia, and progression of symptoms over the first hour to include left lower extremity paresthesias. By the time of neurologic consultation, he reported some subjective improvement in left leg sensory deficits but was weak throughout his left hemibody. Past medical history was notable for B-cell ALL diagnosed 3 months earlier, for which the patient had undergone induction chemotherapy with vincristine, daunorubicin, pegylated asparaginase, and intrathecal methotrexate (IT-MTX) and cytarabine. He achieved remission and was being treated with consolidation chemotherapy consisting of systemic cyclophosphamide, cytarabine, mercaptopurine, vincristine, pegylated asparaginase, and IT-MTX. His most recent lumbar puncture with IT-MTX was 10 days prior to presentation, at which time CSF analysis had shown white blood cells 2/mm3, red blood cells 2/mm3, and unremarkable cytology (a few normal-appearing lymphocytes). Family history was negative for stroke. The patient …