Nomenclature and definition in asymmetric regional body overgrowth

We designate a novel term “isolated lateralized overgrowth” (ILO) for the findings previously described as “isolated hemihypertrophy” and “isolated hemihyperplasia.” ILO is defined as lateralized overgrowth in the absence of a recognized pattern of malformations, dysplasia, or morphologic variants. ILO is likely genetically heterogeneous. Further study is required to determine more of the underlying genetic etiologies and potential associations with currently unrecognized patterns of malformation.National Cancer Institute, Grant number: K08CA193915; Alex’s Lemonade Stand Foundationfor Childhood Cancer; St. Baldrick’s Foundatio

Multicluster nosocomial outbreak of parainfluenza virus type 3 infection in a pediatric oncohematology unit: a phylogenetic study.

Background Human parainfluenza virus type 3 (hPIV-3) has been reported to cause nosocomial outbreaks of respiratory infection, in particular among hematopoietic stem cell transplantation recipients. From September 2007 through January 2008 several episodes of hPIV-3 infection were observed among young patients followed at the Oncohematology Unit (OHU) or other units of the Pediatrics Department. In 32 young patients (median age 3.5 years, range 21 days-27 years), hPIV-3 infection was diagnosed by direct fluorescent antibody staining of cells from respiratory secretions, and virus quantified by real-time RT-PCR in nasopharyngeal aspirates or bronchoalveolar lavage samples. In addition, the epidemiologic relatedness of hPIV-3 strains was investigated by sequencing two variable regions of the hemagglutinin-neuraminidase gene (nt 1-569 and nt 762-1239). Of the 32 hPIV-3-positive patients, 19 were hematopoietic stem cell transplantation recipients, 8 had hematologic malignancies, and 5 were immunocompetent children. Sixteen patients had upper, and 16 lower respiratory tract infection. All patients but one had high viral load in nasopharyngeal aspirates (>1.0x10(6) RNA copies/mL). One patient died from respiratory failure with a high viral load in bronchoalveolar lavage. Phylogenetic analysis showed that 16/32 strains were identical. Besides this major cluster, three other clusters were identified, each one defining a smaller outbreak. Phylogenetic analysis allows identification of the role of a single or multiple hPIV-3 strains in the person-to-person transmission within an outbreak occurring in clinical units

The changing role of stem cell transplantation in childhood

Over the past decade, relevant improvements and refinements have significantly changed the indications, technique and results obtained with allogeneic hematopoietic SCT (HSCT) in childhood. A fundamental turning point in the history of allogeneic HSCT is represented by the use of placental blood, which was first employed in 1988 in a patient with Fanconi anemia, successfully transplanted with cord blood cells from an HLA-identical sibling. Since then, thousands of children were given an allograft of cord blood-derived hematopoietic progenitors, mainly from an unrelated donor. This large clinical experience has documented that, as compared with BMT, cord blood transplantation (CBT) is associated with reduced incidence and severity of GvHD. The outcome of recipients given unrelated CBT has been reported to be at least as good as that of patients transplanted with either BM or peripheral blood mobilized cells of an unrelated volunteer. Another emerging strategy of HSCT is that of using HLA-partially matched relatives as donors of hematopoietic progenitors. The infusion of a huge number of positively in vitro-selected CD34+ cells, with the concomitant removal of T cells, has been demonstrated to permit sustained engraftment of donor hematopoiesis, without the occurrence of GvHD in the majority of patients transplanted from an HLA-disparate relative. In adults given this type of transplantation, the most favorable results have been reported for AMLs and when the donor displays alloreactivity of natural killer cells. It remains to be definitively proved whether these findings documented in adults maintain their value in pediatric patients transplanted from an HLA-disparate family donor. Finally, the last few years have witnessed the emergence of approaches of adoptive cell therapy aimed at optimizing the results of allograft through strategies able to reinforce immune competence against pathogens, as well as against tumor cells, or at modulating donor T-cell alloreactivity

Efficacy and safety of intrathecal liposomal cytarabine for the treatment of meningeal relapse in acute lymphoblastic leukemia: experience of two pediatric institutions

The treatment of meningeal relapse in acute lymphoblastic leukemia (ALL) remains a challenging clinical problem. Liposomal cytarabine (DepoCyte) permits to decrease frequency of lumbar punctures, without loss of efficacy, because intrathecal levels of the drug remain cytotoxic for up to 14 days. We investigated the efficacy and safety of intrathecal DepoCyte in six children with meningeal relapse, treated in two pediatric institutions. DepoCyte was well tolerated in all patients, who achieved complete clearance of blasts from the cerebrospinal fluid after the first three intrathecal drug administrations. Five of the six patients were concurrently treated with high-dose administration of systemic cytarabine, without additional neurological side effects. Our results suggest that DepoCyte is a valid option for children with ALL experiencing meningeal relapse; it deserves further investigation in intensive treatment regimens, taking into due consideration potential neurotoxicity

Adult height in patients treated for isolated growth hormone deficiency: role of birth weight

To evaluate the effect of growth hormone (GH) administration on adult height (AH) in two groups of isolated GH-deficient (IGHD) children born either small (birth weight below -2 SD) or appropriate (birth weight above -2 SD) for gestational age (GA). Out of 35 prepubertal IGHD children, 14 small for GA (SGA, group A) and 21 appropriate for GA (AGA, group B) were examined. All patients received continuous GH treatment at a median dose of 0.028 mg/kg/day (range 0.023-0.032) in group A and 0.024 (range 0.023-0.028) in group B. GH treatment was administered for a period of 67.0 months (range 42.37-96.05) in group A and 54.31 months (range 47.14-69.31) in group B. All children were measured using a Harpenden stadiometer every 6 months until they reached AH (growth velocity >1 cm/year). The patients underwent a retesting a few months after stopping GH therapy. A significant difference was found between (range -2.87 to -2.29) and -0.73 (range -1.30 to 0.14) respectively (p < 0.000001) and interestingly also for body mass index SDS (BMI SDS) at retesting, 0.08 (range 0.30 to -1.51) and 0.61 (range 0.73 to -1.10) respectively (p < 0.04). We observed no significant differences between groups A and B in height (expressed as the SDS for chronological age, height SDS) at diagnosis (p = 0.75), height SDS at start of puberty (p = 0.51), height SDS at retesting (p = 0.50), target height SDS (TH SDS) (p = 0.47), AH SDS (p = 0.92), corrected height SDS (height SDS-TH SDS) (p = 0.60), BMI SDS at diagnosis (p = 0.25), GH dosage (p = 0.34) and therapy duration (p = 0.52). GH treatment with a standard dose in short IGHD children leads to a normalization of AH without any significant difference between SGA and AGA patients