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Neutrophils migrate into inflamed tissue, engage in phagocytosis, and clear pathogens or apoptotic cells. These processes require well-coordinated events involving the actin cytoskeleton. We describe a child with severe neutropenia and episodes of soft tissue infections and pneumonia. Bone marrow examination showed granulocytic hypoplasia with dysplasia. Whole-exome sequencing revealed a de novo heterozygous missense mutation in LCP1, which encodes the F-actin–binding protein Lymphocyte Cytosolic Protein 1. To determine its pathophysiological significance, we stably transduced cells with doxycycline-inducible wild-type LCP1 and LCP1 I232F lentiviral constructs. We observed dysplastic granulocytic 32D cells expressing LCP1 I232F cells. These cells showed decreased proliferation without a block in differentiation. In addition, expression of LCP1 I232F resulted in a cell cycle arrest at the G2/M phase, but it did not lead to increased levels of genes involved in apoptosis or the unfolded protein response. Both 32D and HeLa cells expressing mutant LCP1 displayed impaired cell motility and invasiveness. Flow cytometry showed increased F-actin. However, mutant LCP1-expressing 32D cells exhibited normal oxidative burst upon stimulation. Confocal imaging and subcellular fractionation revealed diffuse intracellular localization of LCP1, but only the mutant form was found in the nucleus. We conclude that LCP1 is a new gene involved in granulopoiesis, and the missense variant LCP1 I232F leads to neutropenia and granulocytic dysplasia with aberrant actin dynamics. Our work supports a model of neutropenia due to aberrant actin regulation.

Establishing the diagnosis of classical Hodgkin lymphoma (cHL) in a timely fashion can be a challenge, as there are no pathognomonic signs or symptoms. The percutaneous needle biopsy (CNB) of the tumor gained increased popularity due to its minimal invasiveness and expeditious recovery from procedure. The diagnostic accuracy of CNB depends upon patient size, mass accessibility, and feasibility to obtain diagnostic tissue assuming that the tumor is histologically homogenous. We report on a patient with cHL who underwent multiple CNB from different sites before the diagnosis was established. Yet, only the incisional biopsy of the most metabolically-active tumor site resulted in diagnostic success. It is imperative to thoroughly consider both the biopsy method and the biopsy site for establishing correct diagnosis.

Approximately 30–40% of relapses in pediatric acute lymphoblastic leukemia (ALL) are extra-medullary. KMT2A gene rearrangements are common in patients with infantile ALL. Chloromas are rare tumors composed of collections of acute leukemic cells that typically involve the bone or skin. Exceptionally uncommon, chloromas invade the peripheral nervous system, a phenomenon termed “neuroleukemiosis.” We describe A 6-year-old girl with a history of pre-B ALL with CNS involvement and KMT2A rearrangement diagnosed initially at 4 months of age. During continuation therapy she developed a scalp mass that was confirmed to be a leukemic relapse. She underwent re-induction chemotherapy followed by blinatumomab with subsequent remission and proceeded to allogeneic hematopoietic cell transplant (HCT). Three years following HCT, she presented with brachial plexus palsy and was found to have a lymphoblastic chloroma invading the brachial plexus. Review of existing literature shows relapse in pediatric ALL patients presenting as brachial plexus chloroma has only been documented once before. It has long been suggested that KMT2A gene rearrangements play a role in development of chloromas in patients with AML, however it is still unclear what role KMT2A has in ALL. Here we report a rare case of ALL relapse that presented as a left arm palsy secondary to a leukemic chloroma invading the brachial plexus and aim to explore the potential role of KMT2A in the formation of ALL chloromas.

Megaloblastic anemia causes macrocytic anemia from ineffective red blood cell production and intramedullary hemolysis. The most common causes are folate (vitamin B9) deficiency and cobalamin (vitamin B12) deficiency. Megaloblastic anemia can be diagnosed based on characteristic morphologic and laboratory findings. However, other benign and neoplastic diseases need to be considered, particularly in severe cases. Therapy involves treating the underlying cause-eg, with vitamin supplementation in cases of deficiency, or with discontinuation of a suspected medication.

Histiocytic neoplasms are rare hematologic disorders accounting for less than 1% of cancers of the soft tissue and lymph nodes. Clinical presentation and prognosis of these disorders can be highly variable, leading to challenges for diagnosis and optimal management of these patients. Treatment often consists of systemic therapy, and recent studies support use of targeted therapies for patients with these disorders. Observation (“watch and wait”) may be sufficient for select patients with mild disease. These NCCN Guidelines for Histiocytic Neoplasms include recommendations for diagnosis and treatment of adults with the most common histiocytic disorders: Langerhans cell histiocytosis, Erdheim-Chester disease, and Rosai-Dorfman disease.

Introduction: As critical effectors of innate immune response, neutrophils migrate from the vasculature into inflamed tissue, where they engage in phagocytosis and clearance of pathogens and apoptotic cells. Migration, phagocytosis, and granule release require multiple well-coordinated events involving remodeling of the actin cytoskeleton. While mutations of some regulators of actin polymerization, such as Wiskott-Aldrich Syndrome gene (WAS) result in Severe Congenital Neutropenia (SCN), the role of actin cytoskeleton in regulating neutrophil ontogeny and functions remain poorly understood. Lymphocyte Cytosolic Protein 1 (LCP1) is an actin bundling protein encoded by LCP1 gene. A 7-year-old girl presented at age of 2 years with chronic severe neutropenia and frequent infections. Next generation sequencing did not reveal a variant in genes known to cause neutropenia. Whole exome sequencing identified a novel LCP1 p.I232F variant of unknown significance, which was not present in either parent. Bone marrow examination revealed a granulocytic hypoplasia with significant dysmorphic giant granulocytes with complex hypersegmentation and increased apoptosis. (Figure 1A) Based on these observations, we hypothesized that missense mutation in LCP1 (I232F) impairs granulocytic proliferation, and causes neutropenia. Aims: To investigate the role of LCP1 I232F, discovered in a child with severe symptomatic neutropenia, in granulopoiesis. Methods: in vitro experiments involving the expression of wild type and mutant LCP1 I232F in murine myeloblast cell (32D cells) and human cervical cancer HeLa cell. We deployed various biologic and functional studies to investigate the role of LCP1 I232F in granulocyte proliferation, differentiation, survival, and function. Results: To determine the pathophysiologic significance of LCP1 I232F, we stably transduced interleukin 3-dependent murine myeloblast 32D and human cervical cancer HeLa cell lines with a doxycycline-inducible lentiviral constructs containing the cDNA for either wild type LCP1 or LCP1 I232F. The mutant LCP1 I232F expressing 32D cells showed impaired proliferation with the appearance of dysplastic granulocytic cells. (Figure 1A, B) However, we did not observe block in differentiation. A cell cycle arrest at G2/M phase occurred only in the LCP1 I232F expressing cells (Figure 1B) and was associated with an upregulation of markers of cell cycle arrest (Cdkn1a and Tp53). LCP1 I232F overexpression did not lead to increased expression of genes involved in apoptosis or the unfolded protein response. The LCP1 I232F cells with dysplastic features were further analyzed by confocal microscopy, which demonstrated increased level of F-actin and enrichment of F-actin and LCP1 at the cell cortex. Flow cytometric evaluation of these cells further confirmed the presence of increased level of F actin. (Figure 1C) Expression of LCP1 I232F impaired cell motility and invasiveness in both 32D and HeLa cells. However, mutant LCP1 expressing 32D cells demonstrated normal oxidative burst upon treatment with N-formyl-Met-Leu-Phe (fMLP) and phorbol myristate acetate (PMA). Confocal imaging and subcellular fractionation revealed diffuse localization of LCP1, but only the mutant form was found in the nucleus. (Figure 1C) In LCP1, two tandem CH domains (CH1-CH2 and CH3-CH4) formed two actin-binding domains (ABD1 and ABD2) that bind to actin to participate in actin bundling. I232F is located at LCP1-CH1 that interacts with actin. To study how the mutation impacts LCP1-actin binding, we constructed a model of LCP1-ABD1 based on the cryo-EM structure of F-actin/LCP1-ABD2 and performed 40 ns of molecular dynamics (MD) simulations of LCP1-ABD1 and LCP1-ABD1 I232F alone to study their dynamical motions. We found that LCP1-ABD1 I232F adopted a more stable open conformation than LCP1-ABD1 to bind effectively with F-actin. The model implies a prolonged association of LCP1 I232F with actin than wild-type LCP1, and the consequence is the increased stabilization of actin bundles. Conclusions: Like the WAS gain-of-function mutations in SCN, LCP1 I232F resulted in severe neutropenia with dysplastic granulocytic precursors, cell cycle arrest, impaired motility, and increased F actin. We also found decreased proliferation of granulocytic progenitor and precursor cells. Our findings suggest that LCP1 is an important gene involved in granulopoiesis. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Background Beckwith-Wiedemann syndrome (BWS) is the most common pediatric overgrowth syndrome. BWS has a broad phenotypic presentation along with an increased propensity to develop various embryonal tumors. There are very few reported cases of gonadal hyperplasia in BWS patients in the existing literature. Case We describe a 13-year-old girl with BWS who presented with an episode of abdominal pain and was found to have torsion and necrosis of a markedly hyperplastic right ovary and fallopian tube. We present a brief literature review on ovarian hyperplasia in BWS patients for which we used an online search of the databases PubMed, Embase, Ovid Medline, and Cochrane. Results and Conclusion Through an extensive literature search, we only found 3 previous reports of ovarian hyperplasia in BWS patients, all in postmortem specimens. Our case highlights a potentially important aspect of visceral organ hyperplasia in patients with BWS that could remain indolent until adolescence and might present as an abrupt-onset abdominopelvic catastrophe.

Key Points Question What outcomes are associated with mucosal barrier injury–laboratory confirmed bloodstream infections in patients who undergo allogeneic hematopoietic stem cell transplant? Findings In a case-cohort study of 16 875 pediatric and adult patients who underwent allogeneic hematopoietic stem cell transplant between 2009 and 2016, the cumulative incidence of mucosal barrier injury–laboratory confirmed bloodstream infections was 13% by day 100, with infection occurring a median of 8 days after stem cell transplant. Overall survival was significantly decreased among patients who developed a mucosal barrier injury–laboratory confirmed bloodstream infection. Meaning Mucosal barrier injury–laboratory confirmed bloodstream infections are associated with significant morbidity and mortality and, by extension, increased use of health care resources., Importance Patients undergoing hematopoietic stem cell transplant (HSCT) are at risk for bloodstream infection (BSI) secondary to translocation of bacteria through the injured mucosa, termed mucosal barrier injury–laboratory confirmed bloodstream infection (MBI-LCBI), in addition to BSI secondary to indwelling catheters and infection at other sites (BSI-other). Objective To determine the incidence, timing, risk factors, and outcomes of patients who develop MBI-LCBI in the first 100 days after HSCT. Design, Setting, and Participants A case-cohort retrospective analysis was performed using data from the Center for International Blood and Marrow Transplant Research database on 16 875 consecutive pediatric and adult patients receiving a first allogeneic HSCT from January 1, 2009, to December 31, 2016. Patients were classified into 4 categories: MBI-LCBI (1481 [8.8%]), MBI-LCBI and BSI-other (698 [4.1%]), BSI-other only (2928 [17.4%]), and controls with no BSI (11 768 [69.7%]). Statistical analysis was performed from April 5 to July 17, 2018. Main Outcomes and Measures Demographic characteristics and outcomes, including overall survival, chronic graft-vs-host disease, and transplant-related mortality (only for patients with malignant disease), were compared among groups. Results Of the 16 875 patients in the study (9737 [57.7%] male; median [range] age, 47 [0.04-82] years) 13 686 (81.1%) underwent HSCT for a malignant neoplasm, and 3189 (18.9%) underwent HSCT for a nonmalignant condition. The cumulative incidence of MBI-LCBI was 13% (99% CI, 12%-13%) by day 100, and the cumulative incidence of BSI-other was 21% (99% CI, 21%-22%) by day 100. Median (range) time from transplant to first MBI-LCBI was 8 (, This cohort study examines the incidence, timing, risk factors, and outcomes of patients who develop mucosal barrier injury–laboratory confirmed bloodstream infection (MBI-LCBI) in the first 100 days after hematopoietic stem cell transplant (HSCT).

Background/Aims: Sporadic Burkitt lymphoma is rarely associated with orbital involvement. Methods: We present a case of sporadic Burkitt lymphoma with extramedullary subperiosteal leukemic infiltrates of the orbit and facial bones. Results: Follow-up examination after chemotherapy and disease remission reveals resolution of the subperiosteal infiltrates. Conclusion: Despite an aggressive presentation, cure is common with appropriate, intensive treatment. To our knowledge, this report is the first to photographically depict the resolution of extramedullary orbital subperiosteal leukemic infiltrates after appropriate chemotherapy.

GTPase of immunity-associated protein 5 (Gimap5) is linked with lymphocyte survival, autoimmunity, and colitis, but its mechanisms of action are unclear. Here, we show that Gimap5 is essential for the inactivation of glycogen synthase kinase-3β (GSK3β) following T cell activation. In the absence of Gimap5, constitutive GSK3β activity constrains c-Myc induction and NFATc1 nuclear import, thereby limiting productive CD4+ T cell proliferation. Additionally, Gimap5 facilitates Ser389 phosphorylation and nuclear translocation of GSK3β, thereby limiting DNA damage in CD4+ T cells. Importantly, pharmacological inhibition and genetic targeting of GSK3β can override Gimap5 deficiency in CD4+ T cells and ameliorates immunopathology in mice. Finally, we show that a human patient with a GIMAP5 loss-of-function mutation has lymphopenia and impaired T cell proliferation in vitro that can be rescued with GSK3 inhibitors. Given that the expression of Gimap5 is lymphocyte-restricted, we propose that its control of GSK3β is an important checkpoint in lymphocyte proliferation., Loss of function GIMAP5 mutation is associated with lymphopenia, but how it mediates T cell homeostasis is unclear. Here the authors study Gimap5−/− mice and a patient with GIMAP5 deficiency to show how this GTPAse negatively regulates GSK3β activity to prevent DNA damage and cell death.

Patients who undergo stem cell transplants are at a significant risk of infections. Cytomegalovirus (CMV) is an organism of particular concern in this population. Current treatments options for CMV include ganciclovir, valganciclovir, foscarnet, and cidofovir. These treatment options have adverse effects such as myelosuppression or nephrotoxicity, making them less than ideal as a treatment options. Increasing rates of drug resistance is another concern. The need for alternative treatment options is paramount. Many patients require secondary prophylaxis. Letermovir is a newly approved CMV DNA terminase complex inhibitor indicated for prophylaxis of CMV infection and disease in adults. Its role in secondary prophylaxis has not been clearly defined. We report the case of an 11-year old male who had undergone a 4/6 HLA-matched cord blood transplant for Fanconi Anemia. The patient developed CMV viremia that later progressed to CMV colitis and pneumonitis. He was initially treated with ganciclovir then was found to have UL97 mutation. He was then switched to foscarnet for induction therapy, to which the patient showed a good response. The patient was subsequently transitioned to cidofovir for maintenance therapy where CMV viremia recurred. Foscarnet was re-initiated with good response then transitioned to cidofovir maintenance therapy. Unfortunately, CMV viral load began to increase prompting a change to high-dose ganciclovir. Due to concerns for myelosuppression with using high-dose ganciclovir he was switched back to foscarnet. While on foscarnet the patient had nephrotoxicity and electrolyte disturbances and the decision was made to re-initiate high-dose ganciclovir. When the patient's CMV viral load was undetectable the patient was transitioned to letermovir 480 mg daily with successful suppression of CMV viral load. Letermovir has been well tolerated and the patient has experienced no adverse effects associated with it. The patient has not required further therapy for CMV viremia since starting letermovir. Letermovir prophylaxis was stopped after four months of therapy. The patient's CMV viral load began to rise after stopping for one month with the peak at 381 copies/mL. After restarting letermovir the CMV viral load became undetectable and has remained so. Letermovir could be useful in secondary prophylaxis in pediatric patients with ganciclovir-resistant CMV who are at risk of recurrences. Further investigation is warranted for the use of letermovir in the pediatric population.

Factors favoring blood stream infections associated with gastrointestinal mucosa versus skin organisms were explored. An observed difference was attributable to bacteremia from oral flora in patients with acute myelogenous leukemia or mucositis. Our data do not support the conclusion that isolation of enteric Gram-negatives is unrelated to the central catheter.Infect Control Hosp Epidemiol 2015;00(0): 1–4

Background AYA patients have a myriad of specific psychosocial and other challenges which may influence their ability to obtain appropriate treatment. Healthcare disparities regarding access to healthcare have been well described in this population. We hypothesized that hurdles faced by the AYA patient population also apply to patients with AML requiring allogeneic hematopoietic cell transplantation (HCT), resulting in AYAs having a longer TTT compared to older adults. Objectives In this study we aimed to compare TTT, defined as time from diagnosis to transplant for AML in CR1 between AYAs and older adults. Additionally, we aimed to determine if TTT has changed over time for this cohort and to identify factors associated with TTT. Methods BMT Program database was used to identify allogeneic HCT recipients with AML in CR1 from January 2007 to June 2018 for AYAs (age 18-39 years) and older adults (age 40-60 years). All the identified patients underwent allogeneic stem cell transplant in complete remission 1 (CR1). Patients receiving cord blood graft source were excluded. AYA and older adults were compared with Wilcoxon, Chi-square, or Fisher's exact test. Change in TTT over time was assessed with Spearman correlation (r). Factors associated with TTT were assessed with Wilcoxon or Jonckheere-Terpstra test. Results A total of 105 patients were identified: 24 AYAs and 81 older adults. Baseline characteristics were similar between AYAs and older adults aside from Karnofsky performance status; AYAs had better performance status than older adults (p=0.012) . Time to Transplant did not differ from between AYA and older adults (median 4.1 vs 4.0 months, p=0.61). There was no evidence of a change in TTT in more recent years in AYA (r=0.15, p=0.48) or older adults (r=-0.02, p=0.85). The only variable associated with TTT, as expected, was donor type (unrelated donors median 4.3 vs related donors 3.8 months, p=0.022) (Table 1). Conclusion Time to transplant for AYAs in AML is comparable to older adults and has not changed over time. Our analysis is limited to experience from a single center and a larger multicenter effort that takes into account other sociodemographic mediators of healthcare disparities is needed to better describe the association of age and time to allogeneic HCT in AML CR1. Our next step is to explore various psychosocial factors in this cohort and determine if they play a role in the TTT and also determine if TTT has an impact on outcomes.

Sjogren's syndrome (SS) is a systemic autoimmune disease characterized by the infiltration of lymphocytes into exocrine glands, resulting in the typical sicca symptoms. Unlike adults, primary SS is a very rare condition in childhood, and the risk of malignancy in juvenile SS (JSS) has not been defined. We report the detection of extranodal marginal zone B-cell lymphoma (EMZL) occurring in two children with SS. Fine needle aspiration of the salivary glands (SG) showed nonspecific findings that led to delayed diagnosis of SS. The diagnosis of B-cell lymphoma associated with JSS was based on morphologic and immunohistochemical staining done during the biopsy. To highlight awareness of EMZL as a timely and appropriate update of an unusual complication in children with SS.

Myeloid sarcoma manifesting in the testis is rare and may occur concomitantly with bone marrow disease or as a separate entity. We describe our experience with a 6-month-old boy who presented with painless scrotal swelling and was found to have bilateral testicular masses on ultrasonography. The patient underwent unilateral radical inguinal orchiectomy. Surgical pathology revealed myeloid sarcoma of the testicle. He developed peripheral blood involvement 1 week postoperatively. Bone marrow biopsy showed acute myeloid leukemia. He is in remission after 2 cycles of induction chemotherapy, local radiation therapy, and allogeneic bone marrow transplantation.

Transient abnormal myelopoiesis (TAM) is a disorder of Down syndrome newborns characterized by megakaryocytic blasts indistinguishable from acute myeloid leukemia (AML), which undergoes spontaneous remission. Acquired GATA1 mutations are present in blasts of both TAM and the subsequent AML which sometimes develops. We present a unique case of a newborn with leukemic megakaryoblasts indistinguishable from those of TAM who had neither extra material from chromosome 21 in the germline or blasts, nor evidence of GATA1 mutations. These findings suggest there are other genetic abnormalities that can lead to TAM besides GATA1 mutation in the setting of trisomy 21. Pediatr Blood Cancer 2015;62:353-355. © 2014 Wiley Periodicals, Inc.

Latent Epstein-Barr virus infection is associated with several lymphoid and epithelial malignancies. This is the first reported case of a patient presenting with synchronous nasopharyngeal carcinoma and Hodgkin lymphoma associated with Epstein-Barr virus. A 17-year-old previously healthy African-American male presented with anterior mediastinal mass and a nasopharyngeal mass. Histology from biopsy of both lesions revealed evidence of Epstein-Barr virus. The patient successfully completed sequential therapies with chemo radiation with no evidence of active disease. Simultaneous occurrence of the two malignancies is undoubtedly a rare event, and their coexistence raises the question of a common etiologic factor.

Background: HCT is physically and psychologically challenging and patients are prone to QoL impairments. AYAs are a unique population that faces hurdles due to dynamic changes in several aspects of their life, and may be particularly prone to QoL issues during HCT. The aim of this study was to determine if QoL differences exist between AYA and older adult HCT recipients pre- and post-HCT. Additionally, we aimed to determine if there has been a change in QoL for AYA transplant recipients in recent years, as more focus has been placed on supporting this unique population. Methods: QoL data were collected prospectively pre-HCT (baseline [BL]) and in follow-up post-transplant on patients undergoing HCT from Jun 2003 through Dec 2017 at Cleveland Clinic. Autologous HCT recipients are followed routinely through day +42 post-transplant, while allogeneic recipients are followed through at least one year or more. QoL was self-reported by patients using the Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) questionnaire. FACT-BMT consists of five domain scores (Physical Wellbeing [PWB], Social Wellbeing [SWB], Emotional Wellbeing [EWB], Functional Wellbeing [FWB], and Additional Concerns [AC]) and two summary scores (trial outcome index [TOI, PWB+FWB+AC], and Total FACT Score. Scores were compared for younger AYA (age 15-29 years), older AYA (age 30-39 years) and older adults (age 40-60 years). We excluded patients >60 years from analysis as this group may have their own unique challenges. Repeated measures analysis of variance was used to assess differences among age groups and among time points. Pearson correlation (r) was used to determine if BL QOL had improved from 2003-2017 in AYA cohort. Separate analyses were performed for autologous and allogeneic cohorts. Results: Autologous HCT cohort included 128 AYA patients (56 younger AYA) and 355 older adults, and allogeneic HCT cohort included 136 AYA patients (76 younger AYA) and 295 older adults Autologous patients in all three groups were similar for baseline characteristics except for diagnosis (table 1). Among allogeneic patients similar rates of graft-versus host disease were seen for all three groups, and baseline characteristics were similar except for ECOG performance status (table 1). Among autologous recipients, no single QoL domain or composite score differed among the three age groups at baseline or at day +42 post-HCT (Figure 1a). In all age groups, QoL improved from baseline to D+42 in autologous HCT recipients (mean Total Score 149 vs. 152, p=0.001). Similarly, among the allogeneic HCT recipients, no single QoL domain or composite score differed among the three age groups at baseline, day +100, +180, or +365 post-HCT (Figure 1b). Among all patients compared to BL (mean 146), total FACT score improved at day +180 (150, p=0.022) and +365 (152, p=0.005), but not at day 100 (145, p=0.57). Among autologous recipients, none of the BL FACT domains improved over time since 2003. In contrast, AYA allogeneic recipients also had no significant change in BL scores since 2003 for PWB, SWB, EWB, FWB, however there was improvement in AC (r=0.26, p=0.003, TOI (r=0.23, p=0.008), and total FACT score (r=0.19, p=0.03). Conclusions: AYA HCT recipients do not have inferior QoL compared to older adults in the first 42 days after autologous HCT and the first year after allogeneic HCT. Interestingly, QoL improvements in AYA patients have occurred in recent years for allogeneic but not autologous patients. Improvements in QoL of allogeneic patients is driven by the AC domain, which addresses multiple psychosocial aspects which have been emphasized in recent years. Continued efforts to tailor treatment and support for AYA HSCT recipients is critical to improving outcomes. Disclosures Advani: Glycomimetics: Consultancy; Novartis: Consultancy; Amgen: Research Funding; Pfizer: Honoraria, Research Funding. Majhail:Atara: Honoraria; Anthem, Inc.: Consultancy; Incyte: Honoraria.

Pediatric transplantation medicine is universally complicated by infection, with research interests divided roughly into the domains of prevention, surveillance, treatment, and the description of novel pathogens. Publication of these results is not easily centralized; here we review several key studies published in 2006–2007.

Ventricular fibrillation (VF) is a leading cause of sudden death. Electrical defibrillation is the primary modality of treatment, but evidence is accumulating that its use in the late stage of VF prior to providing ventilation, chest compressions and the administration of appropriate medication is detrimental. In VF of5 min duration a 'shock first' strategy is effective. In VF of 5min duration a 'perfuse first' approach is more effective. Because of the difficulty in determining the duration of VF in the clinical setting we have sought to develop method which analyze 5 s intervals of VF waveform and quickly provide an estimate of duration. Such methods would be useful in directing clinical interventions. Using methods of nonlinear dynamics and fractal geometry we have previously derived a quantitative measure of VF duration, namely the scaling exponent (ScE). In this study we report on a novel method also based on nonlinear dynamics, the angular velocity (AV). By constructing a flat, circular disk-shaped structure in a three-dimensional phase space and measuring the velocity of rotation of the position vector over time, a statistic is developed which rises from 58 rad/s at 1 min to 79 rad/s at 4 min and then decreases in a linear manner to 32 rad/s at 12.5 min. Using ScE and AV probability density estimated, VF of5 min duration can be identified with 90% sensitivity on the basis of a single 5 s recording of the waveform. The combination of ScE and AV can be used in developing strategies for the treatment of VF during the different clinical phases of VF.

We describe the first reported pediatric patient to our knowledge with a spindle cell pseudotumor caused by Mycobacterium genavense in a hematopoietic stem cell transplant recipient, and review the literature of such an entity in the transplant population.

Transient abnormal myelopoiesis (TAM) is a disorder of Down syndrome newborns characterized by megakaryocytic blasts indistinguishable from acute myeloid leukemia (AML), which undergoes spontaneous remission. Acquired GATA1 mutations are present in blasts of both TAM and the subsequent AML which sometimes develops. We present a unique case of a newborn with leukemic megakaryoblasts indistinguishable from those of TAM who had neither extra material from chromosome 21 in the germline or blasts, nor evidence of GATA1 mutations. These findings suggest there are other genetic abnormalities that can lead to TAM besides GATA1 mutation in the setting of trisomy 21. Pediatr Blood Cancer 2015;62:353-355. © 2014 Wiley Periodicals, Inc.

The novel 2009 H1N1 influenza virus has been reported to have increased severity in patients with underlying cardiovascular and lung disease. Pediatric patients also appear to have an increased incidence of infection. The impact on cardiothoracic transplant recipients, especially in pediatric recipients, has not been established. We report the case of a 12-year-old boy with history of congenital heart disease who was transplanted in June 2001. In October 2009, it was found that he had developed severe acute respiratory distress syndrome (ARDS) secondary to novel 2009 H1N1 influenza virus. Extracorporeal membrane oxygenation (ECMO) was given as support. Importantly, the initial specimen evaluated by real-time reverse transcriptase-polymerase chain reaction was negative for novel 2009 H1N1 influenza virus. The patient was successfully weaned from ECMO after 24 days, extubated at 6 weeks, and continues to make steady rehabilitative progress. Early suspicion for infection and initiation of treatment, even with negative testing, is essential for cardiothoracic transplant recipients during the current pandemic of novel 2009 H1N1 influenza virus.

AYAs with cancer have been designated as a vulnerable population by the National Cancer Institute. This group, defined by the ages of 16-39 years, has not enjoyed the same survival improvements over the past several decades as older and younger cohorts. The reasons for outcome disparities among AYA leukemia patients are not well understood. Recent studies have compared outcomes of AYA HCT recipients with younger and older cohorts and reported no lag in survival improvements over time. However, long-term survival after allogeneic HCT in this age group has not been well described. We analyzed outcomes for 226 AYA patients with acute and chronic leukemia, myelodysplastic syndromes, aplastic anemia and lymphoma who were transplanted at our institution from 1/2000-3/2013. The median age at HCT was 29 years (range 15-39) and their median follow up was 5 years (range, Table: 10 year outcomes after allogeneic HCT in AYAs Probability (95% CI) Overall survival 43% (35-50) Relapse free survival 36% (29-43) Relapse* 29% (22-35) Non-relapse mortality* 37% (30-44) Second cancers* 7% (2-12) * Cumulative incidence estimates Figure: Survival of AYA HCT recipients who were alive at 2 years vs. survival of age-, sex-, and race-matched general population Figure:. Survival of AYA HCT recipients who were alive at 2 years vs. survival of age-, sex-, and race-matched general population Disclosures No relevant conflicts of interest to declare.