Eva Landmann

Poor Outcome for Children and Adolescents With Progressive Disease or Relapse of Lymphoblastic Lymphoma: A Report From the Berlin-Frankfurt-Muenster Group

PURPOSE Little is known about the outcome of pediatric patients with lymphoblastic lymphoma (LBL) who suffer from progressive disease or relapse. PATIENTS AND METHODS We analyzed the pattern of LBL relapses after current non-Hodgkins lymphoma Berlin-Frankfurt-Muenster (BFM) frontline therapy between April 1990 and March 2003. Relapse therapy was according to acute lymphoblastic leukemia (ALL) -Relapse-BFM protocols or ALL-BFM protocols for high-risk patients. RESULTS Twenty-eight (11%) of 251 registered patients with precursor T-cell LBL (T-LBL) and six (8%) of 73 patients with precursor B-cell LBL (pB-LBL) suffered from relapse. Of the 28 patients with T-LBL, one died from infection during relapse chemotherapy, 18 failed to achieve stable remission and died from disease progression, and nine reached allogeneic stem-cell transplantation (SCT). Two of these nine patients who underwent SCT died from transplantation-associated toxicity, three died from disease progression, and four are still alive. These four patients are in second remission of their lymphoma for 48, 68, 125, and 131 months, respectively, after allogeneic SCT. One of the four patients developed colon adenocarcinoma 47 months after SCT. Of the six patients with pB-LBL who experienced relapse, one patient died as a result of toxicity of relapse chemotherapy, two died from disease progression after chemotherapy, and three received allogeneic SCT. Of these, two died from subsequent disease progression, and one is still alive 57 months after allogeneic SCT. CONCLUSION Using modern conventional therapy in the frontline treatment of LBL, 10% of patients suffer from progressive disease or relapse. Because of the extremely poor reinduction success, the salvage rate for these patients is poor, with only a 14% (SE = 6%) overall survival. Long-term survival was only achieved in those few patients who were able to undergo an allogeneic SCT.

Ponderal index for discrimination between symmetric and asymmetric growth restriction: Percentiles for neonates from 30 weeks to 43 weeks of gestation

Aims. The ponderal index describes body proportionality at birth thus distinguishing symmetric from asymmetric growth restriction. We aimed to develop ponderal index percentiles for preterm and term neonates born in a European population. Methods. Auxologic data were obtained from neonates born from January 1990 to December 1998 from the datasets reported to the perinatal quality assurance system of the Federal State of Hesse, Germany. We excluded data from neonates with lethal malformations, with chromosomal aberrations, from multiple births, from neonates with uncertain gestational age, and from neonates of a gestational age of less than 30 completed weeks. We calculated the weekly 5th, 10th, 25th, 50th, 75th, 90th, and 95th ponderal index percentile values. Results. A total of 480 841 neonates (233 662 females and 247 179 males) were included. Charts and tables of ponderal index values show percentiles for males, females, and for the total group. There were no significant differences between boys and girls. Conclusion. Our data offer the ability to refer a neonates body proportionality to updated percentiles. The percentiles allow the discrimination between symmetric and asymmetric growth restriction in preterm and term infants.

Outcome in preterm small for gestational age infants compared to appropriate for gestational age preterms at the age of 2 years: a prospective study

OBJECTIVES To investigate the effects of small for gestational age (SGA) in preterm infants on growth and development until the age of 22 months. STUDY DESIGN Seventy-four preterm infants being born SGA (birth weight <10th percentile) were compared with 74 appropriate for gestational age (AGA) infants matched prospectively according to gestational age with respect to growth parameters and neurodevelopment (using Griffiths developmental scores) at the age of 22 months corrected age. RESULTS Birth weight was significantly lower in SGA-infants compared to AGA-infants (1503 g (430-2205 g) versus 1995 g (680-3300 g); P<0.0001 (median and range)). There were no significant differences regarding the median gestational age (34 weeks), gender distribution, mode of delivery, umbilical artery pH, and APGAR-scores. Mean Griffiths-scores did not differ significantly between both groups (96.7% versus 97.6%). Developmental retardation was diagnosed in 9 SGA-infants versus 10 AGA-infants. Within the total group a positive correlation was observed between gestational age and developmental scoring. Body weight, head circumference, and height were significantly lower in SGA-infants at 22 months corrected age. CONCLUSION No significant differences regarding neurodevelopmental outcome at 22 months were observed between SGA- and AGA-infants. SGA-infants did not show catch-up growth.

Effect of inhaled corticosteroid treatment on exhaled breath condensate leukotriene E4 in children with mild asthma

Chronic airway inflammation in children with asthma might be present even in the absence of pathological lung function tests and is known to increase the risk of permanent pulmonary damage. Thus, we aimed at investigating to what extent inflammatory markers such as leukotrienes (LTs) in exhaled breath condensate (EBC) or fractional exhaled nitric oxide (FE(NO)) reflect therapeutic effects in these patients. Fifty steroid-naive patients (aged 8.8 +/- 2.7 years) were included in the study. EBC was collected before and 6 months after therapy with inhaled corticosteroids. LTs were determined by using commercially available ELISA. In addition, FE(NO) was measured by means of a chemiluminescence analyzer. Conventional lung function testing was performed revealing vital capacity, forced expiratory volume, maximum expiratory flow, and specific resistance. In EBC, LTE(4) but not LTB(4) levels significantly decreased after steroid therapy from 45.3 +/- 36.0 pg/mL to 17.2 +/- 11.4 pg/mL (p < 0.0001) concomitant with a slight, but significant improvement of lung function parameters. Mean FE(NO) also indicated therapeutic success; however, in 20 of 50 patients, exhaled NO concentrations were higher after therapy. These findings suggest that LTE(4) in breath condensate may be helpful in latent inflammatory activity in the bronchial mucosa in children with asthma.

Ovarian tumor in a 12-year old female with severe hypothyroidism: A case of Van Wyk and Grumbach syndrome

We report a 12‐year‐old female presenting with an abdominal tumor. Diagnostic workup revealed giant bilateral ovarian cysts, severe hypothyroidism as well as an elevation of CA 125. We refrained from ovariectomy, which would be necessary for a malignant tumor, in view of an evident Van Wyk and Grumbach syndrome. The patient promptly responded to L‐thyroxine with complete regression of all symptoms. Hypothyroidism should be considered in the evaluation of ovarian cysts. Although the Van Wyk and Grumbach syndrome is rare, it is crucial to rule it out in order to avoid unnecessary ovarian surgery when thyroid replacement is completely sufficient. Pediatr Blood Cancer 2009;52:677–679.

Capnovolumetry: a new tool for lung function testing in children with asthma.

In capnovolumetry, the expiratory CO2 concentration of exhaled air is plotted against the volume and thereby allows to determine functional dead space volumes. This method might offer additional information in lung function testing in children and adolescents with bronchial asthma. We aimed at determining whether a bronchospasmolysis (BSL) effect in the lower airways could also be detected by capnovolumetry as reflected by changes in the functional threshold dead space volumes (VDT). In 47 patients (aged 4–16 years) with a mild persistent bronchial asthma, VDT were determined before and after bronchodilation prior to starting therapy with inhaled steroids and after 6 months of treatment. Additionally, spirometry and body plethysmography were performed in all patients. There were significantly higher VDT values after BSL before and after 6 months of therapy (P<0·0001). VDT values before BSL were tendatively higher after 6 months of therapy compared with baseline values (P = 0·07). VDT values correlated with parameters derived from conventional pulmonary function testing, i.e. vital capacity, forced expiratory volume in 1 s (FEV1), and maximum expiratory flow (MEF50). As VDT values particularly reflect the volumes of the lower bronchi this method may provide supplementary information to conventional lung function tests which are based on breathing mechanics. This seems to be especially helpful in situations where body plethysmography is not available or cooperation in forced expiration manoeuvres is insufficient.

Prematurity Is Not Associated with Intra-Abdominal Adiposity in 5- to 7-Year-Old Children

OBJECTIVE To compare body composition and abdominal fat partitioning between 5- to 7-year old children born preterm and born at term. We hypothesized children born preterm to have a higher body fat percentage and higher percentage of intra-abdominal adipose tissue (%IAAT) compared with their peers born at term. STUDY DESIGN A total of 236 children aged 5-7 years, ie, 116 children born preterm (gestational age 29.8 ± 2.6 [30; 24-33] weeks [mean ± SD {median; range}]) and 120 children born at term were included. Body composition was measured by bioelectrical impedance analysis and %IAAT by magnetic resonance imaging. Body mass index, skin fold thickness, and waist-to-hip ratio were investigated as further measures of body composition. Dietary records were compared between both groups. RESULTS Children born preterm were shorter (120 cm vs 123 cm, P < .001), lighter (21.8 kg vs 24.3 kg, P < .001), and had a lower body mass index (15.1 kg/m(2) vs 15.9 kg/m(2), P = .003) compared with controls. There were no differences in %IAAT (n = 154), and body fat mass although energy uptake was higher in preterms (335 kJ/kg/d vs 302 kJ/kg/d, P = .03). CONCLUSIONS At the age of 5-7 years, children born preterm showed neither increased fat mass nor intra-abdominal adiposity.

Molecular characterization of a novel chromosomal translocation t(12;14)(q23;q11.2) in T-lymphoblastic lymphoma between the T-cell receptor delta-deleting elements (TRDREC and TRAJ61) and the hypothetical gene C12orf42

Chromosomal aberrations have diagnostic, prognostic, and therapeutic relevance in hematologic malignancies. By combining fine‐tiling comparative genomic hybridization (FT‐CGH) and ligation‐mediated PCR (LM‐PCR), we established a fast, robust approach to precisely characterize chromosomal breakpoints. Using this approach, we clarified at the molecular level novel chromosomal translocation t(12;14)(q23;q11.2) in T‐lymphoblastic lymphoma. The translocation occurred during the deletional rearrangement of the T‐cell receptor delta gene (TRD), which is a pivotal step in T cell differentiation toward the alpha/beta vs. the gamma/delta lineage. We found that this rearrangement disrupted the hypothetical gene C12orf42 and brought the Achaete‐scute complex homolog 1 gene into proximity of the TRA enhancer, which encodes a member of the basic helix‐loop‐helix family of transcription factors and is overexpressed in thyroid and lung cancers.

Secondary non‐Hodgkin lymphoma (NHL) in children and adolescents after childhood cancer other than NHL

The emergence of non‐Hodgkin lymphoma (NHL) during childhood and adolescence as a secondary neoplasm (SN) after previous cancer other than NHL is rare. To describe the characteristics and outcome of NHL following previous cancer other than NHL in children and adolescents, this study analysed the data of patients reported to the NHL‐Berlin‐Frankfurt‐Münster study centre from 1986 to 2005. Out of the total of 2968 NHL‐patients registered, 11 patients were assessed as having suffered from NHL as a proven SN. Four additional children had most likely suffered from NHL as an SN, but a late relapse of the first neoplasm could not be ruled out unequivocally. In the patients with proven SN, median age at diagnosis of the primary malignancy was 3·9 years (range 2–11·7). The median age at diagnosis of NHL was 7·6 years (range 4·7–18). Only lymphoblastic (n = 7) and diffuse large B‐cell (n = 4) lymphomas were diagnosed as SN. The estimated 5‐year event‐free survival from time of diagnosis of NHL was 91% [95% confidence interval (CI) 74–100%] in patients with proven SNs and 84% (95% CI 63–100%) when the patients with probable SNs were included in the analysis. We concluded that secondary NHL in children and adolescents confers a favourable prognosis.

Influence of polymorphisms in genes encoding for insulin-like growth factor (IGF)-I, insulin, and IGF-binding protein (IGFBP)-3 on IGF-I, IGF-II, and IGFBP-3 levels in umbilical cord plasma.

Background/Aims: In postnatal life, polymorphisms in the promoter region of IGFBP3 were associated with insulin-like growth factor binding protein (IGFBP)-3 plasma levels. Whether these associations exist in utero has not been studied yet. Polymorphisms in the IGF1 promoter (polymorphic CA-repeat) and the insulin gene variable number tandem repeats locus (INS VNTR) are further polymorphisms of interest, because associations with birth weight have been reported. We aimed to investigate associations between polymorphisms in the promoter regions of IGF1 (wild type 192 bp), IGFBP3 (rs2854744; rs13241830), and INS VNTR (rs689) with cord plasma levels of IGF-I, IGF-II, and IGFBP-3. Methods: We measured IGF-I, IGF-II, and IGFBP-3 concentrations in cord blood from 677 neonates and genotyped the selected polymorphisms. Results: Carriers of the minor allele of both polymorphisms in the IGFBP3 gene had, on average, 4–5% lower IGFBP-3 levels per copy of the respective minor allele (p = 0.002 and p = 0.028) when compared to wild type carriers. The IGF1 promoter and the INS VNTR polymorphisms were not associated with IGF-I, IGF-II, or IGFBP-3 levels. Conclusions: Our data show associations of cord plasma IGFBP-3 levels and the IGFBP3 gene variants but not of IGF1 promoter and INS VNTR polymorphisms with IGF-I, IGF-II, or IGFBP-3 levels in utero.