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Background Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a progressive autosomal recessive disorder characterized by cachexia, gastrointestinal (GI) dysmotility, ptosis, peripheral neuropathy, and brain magnetic resonance imaging (MRI) white matter changes. Bi-allelic TYMP mutations lead to deficient thymidine phosphorylase (TP) activity, toxic accumulation of plasma nucleosides (thymidine and deoxyuridine), nucleotide pool imbalances, and mitochondrial DNA (mtDNA) instability. Death is mainly due to GI complications: intestinal perforation, peritonitis, and/or liver failure. Based on our previous observations in three patients with MNGIE that platelet infusions resulted in a transient 40% reduction of plasma nucleoside levels, in 2005 we performed the first hematopoietic stem cell transplantation (HSCT) worldwide as a life-long source of TP in a patient with MNGIE. Procedure HSCT was performed in a total of six patients with MNGIE. The multiple factors involved in the prognosis of this cohort were analyzed and compared to the literature experience. Results Cell source was bone marrow in five patients and peripheral stem cells in one, all from fully human leukocyte antigen (HLA)-matched related donors, including four who were TYMP mutation carriers. Four of six (66%) survived compared to the 37% survival rate in the literature. Reduced intensity conditioning regimen contributed to secondary graft failure in two patients. Fifteen years post HSCT, the first transplanted patient is seemingly cured. Severe GI symptoms before transplantation were mostly irreversible and were poor prognostic factors. Conclusions Allogenic HSCT could constitute a curative therapeutic option for carefully selected, young, presymptomatic, or mildly affected patients. Timing, donor selection, and optimal conditioning protocol are major determinants of outcome. HSCT is inadvisable in patients with advanced MNGIE disease.

Background As cord blood (CB) is being used frequently as a source for heamtopoetic stem cell transplantation defining risk factors for transplantation outcome is an important issue. Procedure The data of all single unit CB transplantation preformed in Israel from 1992 to 2011 were collected. The risk factors for myeloid engraftment, event free survival (EFS) and overall survival (OS) were studied in 87 children. Results There were 49 children with hematological malignancies and 38 with non-malignant diseases. Cumulative rate of neutrophil recovery was 78.3%, while median time to myeloid recovery was 26 days. The incidence of platelet engraftment at 150 days was 53%, and the median time to platelet recovery was 36 days. ABO blood group matching between CB unit and recipient was associated with superior myeloid engraftment. Acute graft versus host disease of grades II–IV occurred in 33% of the patients. Chronic graft versus host disease occurred in 16% of patients. Probabilities of EFS and OS at 1 year were 45% and 57%, respectively. Factors associated with inferior OS were Rh major mismatch versus matched Rh and transplantation from unrelated donor versus related donor. Conclusions These results indicate that matching of ABO blood groups is an important factor that affects engraftment, and also that Rh matching seem to have an impact on OS, which was not previously described in the setting of CB transplantation. Pediatr Blood Cancer 2013;60:2007–2011. © 2013 Wiley Periodicals, Inc.

Background Many survivors of pediatric brain tumors (SPBTs) suffer from long-term late effects (LEs). Our aim was to create a practical screening tool for detecting LEs in this population. Such a screening tool will improve our ability to identify those patients who may benefit from treatment in LE clinics while focusing on individual relevant issues. Procedure We developed the Treatment-Oriented Screening Questionnaire (TOSQ); a self-reported, risk-based questionnaire that addresses all LEs SPBTs can potentially suffer. As a basis for the TOSQ design we used the Long-Term Follow-Up Guidelines published by the Children's Oncology Group. Output includes individual recommendations for further treatment. We prospectively assessed whether the TOSQ can accurately detect treatment targets in SPBTs by comparing patient and caregiver questionnaire scores with physician evaluations. Data are presented from 41 SPBTs. Results The TOSQ is a precise screening tool for identifying LEs in SPBTs based on the significant correlation (P

Heparanase is an endo-beta D-glucuronidase capable of cleaving heparan sulfate side chains, yielding heparan sulfate fragments. Heparanase activity has been correlated with the metastatic potential of tumor-derived cells, angiogenesis, autoimmunity and inflammation. We performed a study of heparanase expression in specimens obtained from patients with Langerhans cell histiocytosis (LCH). Paraffin embedded slides from 25 patients were studied by immunohistochemistry for heparanase. Most patients had positive staining for heparanase (21/25). There was no positive association with severity of disease and other clinical characteristics. Further studies are required to clarify the role of heparanase in the pathogenesis of LCH. Pediatr Blood Cancer 2014; 61:1883–1885. © 2014 Wiley Periodicals, Inc.

Background Busulfan (BU), often used in high dose for myeloablation before hematopoietic stem cell transplantation (HSCT), has been implicated in certain HSCT toxicities, including the occurrence of hepatic veno-occlusive disease (HVOD). In addition to weight and age, gene polymorphisms in specific members of the glutathione-transferase (GST) gene family (A1, P1, M1, and T1), involved in BU metabolism, may play a role in the wide inter-patient variability in systemic BU concentrations. Procedure The present study integrated clinical data regarding the occurrence of HVOD, graft versus host disease (GVHD), BU pharmacokinetics and GSTA1, GSTP1, GSTM1, and GSTT1 genotypes of 18 children who received BU in their pre-HSCT conditioning regimen. The children were all treated for congenital hemoglobinopathies and were all of Arab Moslem descent. Results The data demonstrate an association between GSTA1 and GSTP1 genotypes and BU-maximal concentration (Cmax) (P = 0.01, P = 0.02, respectively), area under the concentration-time curve (AUC) (P = 0.02, P = 0.01, respectively) and oral BU clearance/kg body weight (P