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BACKGROUND Therapy outcomes for childhood acute lymphoblastic leukemia (ALL) had substantially improved in the last decades, but variability across racial and ethnic groups was identified in some clinical studies. In this study, we aimed to investigate whether such a difference in outcome is found in the diverse ethnicities in Israel as well. METHODS A retrospective study was conducted among 1154 patients (855 Jews, 195 Muslims, 52 Bedouins, 26 Druze, and 26 others) aged 1 to 21 years, who were diagnosed with ALL between 1989 and 2011 and were treated according to the same Berlin-Frankfurt-Muenster-based Israel National Study protocols. RESULTS Bedouins had a higher incidence of t(1;19) (16% vs 3% for non-Bedouins) and a lower incidence of high-hyperdiploidy (10% vs 25% for non-Bedouins) (P = 0.01). Five-year event-free survival (EFS) and overall survival (OS) were poorer for the Bedouins (60.3% ± 7.2% and 63.1% ± 7.2%, respectively) compared with the Jews, Muslims, and Druze (80.4% ± 1.4%, 77.3% ± 3.2%, and 84% ± 7.3%, respectively, for EFS [P = 0.02], and 86.3% ± 1.2%, 82.3% ± 2.9%, and 88.3% ± 6.4%, respectively, for OS [P = 0.002]). Adherence to intensive chemotherapy was similar between the Muslims and the Bedouins. CONCLUSIONS Our findings suggest that the Bedouins, a highly inbred ethnic Arab people, may be considered a higher risk group that may need more intensive chemotherapy and/or supportive care in order to improve their outcome.

Cytokines play a role in meningeal inflammation and leukocyte recruitment. Research has demonstrated that levels of different cytokines are elevated in aseptic and viral meningitis. Unfortunately, previous data were confounded by the inclusion of multiple viral agents as a study group. The aims of the study were to determine the cerebrospinal fluid concentrations of various cytokines in an outbreak of a single viral agent and to correlate between cytokine levels and leukocytes. Cerebrospinal fluid samples, collected during an outbreak of echovirus type 4 meningitis in infants and children in Israel, were tested for routine characteristics. In addition, cytokine levels were measured in 71 meningitis patients and compared with those of 11 nonmeningitis patients. Concentrations of interleukin-6 (2417 +/- 2713 vs 28 +/- 20 pg/mL; P0.01) and interferon gamma (36 +/- 38 vs 4.8 +/- 0.9 pg/mL; P0.01) were significantly higher in patients with meningitis than in the control group, whereas soluble intercellular adhesion molecule-1 (1.12 +/- 2.6 vs 0.06 +/- 0.1 ng/mL) levels did not differ significantly. In addition, only interleukin-6 levels correlated with leukocyte counts in viral meningitis patients. Interleukin-6 was the most sensitive and specific characteristic in predicting meningitis in this homogeneous group of patients. Furthermore, only interleukin-6 correlated with leukocyte counts in the cerebrospinal fluid.

Until recently, echovirus 13 has been a very rare cause of aseptic meningitis. We investigated an outbreak of echovirus 13 in central Israel during the summer of 2000 using a prospective case control study and a retrospective study. Echovirus 13 was isolated from 79 cerebrospinal fluid (CSF) specimens from different medical centres in central Israel. Patients' ages ranged from 10 days to 41 years (95% 3 with polymorphonuclears (PMN) predominant in >90% of our patients. In a case–control study there was no significant difference between patients and matched controls with regard to parameters such as: day care attendance, recreation in summer camp, swimming pools and at the beach, and consumption of tap water. All the patients in our series recovered fully with no neurological abnormalities. The illness caused by echovirus 13 was benign and involved mainly patients younger than 15 year of age. Several features that characterized this outbreak include relatively high WBC in the blood and a prominent CSF PMN response.

BACKGROUND AND AIMS Children with Crohn disease are at increased risk for osteopenia and osteoporosis. Early development of osteopenia can increase the lifetime risk for fractures and may be amenable to early intervention. The gold standard for measuring bone mineral density (BMD) and fracture risk is dual x-ray absorptiometry (DXA), but this involves some radiation and specialized programs for measuring BMD in children. Bone density Z scores were evaluated with quantitative ultrasound (QUS) using a novel portable device and were compared with DXA in children with Crohn disease. METHODS Thirty-five children with documented Crohn disease (mean age 14.3 +/- 2.3 years) had speed of sound measured at the left radius and left tibia. Normative values for QUS Z scores were calculated from a cohort of 1,110 healthy children. A subgroup of 26 children with Crohn disease underwent both QUS and DXA. Z scores were calculated and compared for both groups. RESULTS The mean Z score using lumbar spine DXA was -1.04 +/- 1.51 SD, compared with -0.15 +/- 1.49 SD, using the lowest Z score for QUS ( < 0.05). Using height adjusted DXA, 50% of children with Crohn disease had osteopenia, whereas QUS detected only 19.2% of these children ( < 0.05). Significantly fewer cases of osteopenia were detected using QUS at Z scores up to -2 SD. CONCLUSIONS Quantitative ultrasound performed on the radius and tibia may not be sensitive enough to pick up osteopenia in children with Crohn disease.

Objective To determine the prevalence, importance, and the order of frequency of IgE-mediated food allergens among infants and young children in Israel. Study design and patients In a cross-sectional study, the prevalence of IgE-mediated food allergy was investigated in 9070 infants and young children (0-2 years) who were followed-up at 23 Family Health Centers (FHCs) in central Israel. Patients with suspected IgE-mediated food allergic reactions, were recruited for further evaluation (detailed questionnaire and skin-prick test (SPT)). Results We identified 150 out of 9070 (1.7%) patients with suspected IgE-mediated food allergy. Among them, 102/150 (67%) [59 males, 43 females; mean age 10.3 months] completed a detailed questionnaire and underwent SPT. Evaluation revealed 131 positive SPTs in 78/102 (76.5%) patients. Twenty-seven positive SPTs in 18 patients were considered clinically irrelevant based on previous consumption of the relevant foods without clinical symptoms. Thus, there were 104 relevant positive SPTs in 78 patients. The overall prevalence of clinically relevant IgE-mediated food allergic reactions among these patients is estimated to be 1.2% (104/9070). The most common food allergens were egg, cow's milk, and sesame. Anaphylaxis was the presenting symptom in 14/78 (18%) including six sesame-induced cases. A history of other atopic diseases was reported in 27 (35%) patients. In addition, 22 (28%) had a history of atopy in first-degree family members. Conclusions We found sesame to be a major cause of IgE-mediated food allergy in Israel. In fact, it is second only to cow's milk as a cause of anaphylaxis. We recommend that testing for food allergens be tailored to each community based on local experience and should include sesame in appropriate populations.

Articles dealing with the epidemiological aspects of asthma were carefully reviewed in order to support or reject our clinical impression of increased rate of asthma among immigrants. Particular emphasis was put on data on very high or very low rates of asthma. The proposed theories to explain these differences were critically examined. The prevalence of asthma in China and in Africa is 1-2% and 0.5-5%, respectively. The prevalence of the disease in other indigenous populations ranges between 0.5% and 12%. On the other hand, asthma is much more frequently seen in Australia and in New Zealand (approximately 20-25%), where peoples' ancestors immigrated from distant areas. Statistical meta-analysis found a significant difference between the rates of asthma in the two groups of populations (P < 0.001). Immunoglobulin E levels of immigrants in Sweden are higher than those of native Swedes. Similarly, cord blood immunoglobulin E concentrations are more elevated in neonates whose mothers emigrated to Germany from Eastern countries than in those of native German mothers. There is an increased rate of IgE-mediated asthma among immigrant populations.

BACKGROUND: We constructed an animal model to examine the possibility that erythrophagocytosis may contribute to decreased hemoglobin (Hgb) levels in acute infection in mice. METHODS: BALB/c mice weighing 20 to 25 g were injected (intraperitoneally) with lipopolysaccharide (LPS) (Escherichia coli serotype) of some concentrations. Control mice were injected intraperitoneally with saline (0.5 mL). Two and 4 hours after LPS administration, mice were bled (0.25 mL) for complete blood count measures and tumor necrosis factor-α and interleukin-6 levels. The mice were then killed, and their spleen, liver, and bone marrow were examined microscopically for erythrophagocytosis. RESULTS: After LPS administration, mouse Hgb and hematocrit levels dropped significantly. At 4 hours after LPS injection, all Hgb and hematocrit concentrations were found to be significantly lower compared with that of controls (P = 0.002 and 0.001, respectively). Significantly increased concentrations of tumor necrosis factor-α and interleukin-6 were evident after LPS injection. Prominent hepatic erythrophagocytosis was observed in the LPS-injected mice compared with controls. A significant across-group difference was observed at 4 hours, driven by significantly higher values in group 500 mcg versus controls (P = 0.005) and 100 mcg (P = 0.025). A significant increase in erythrophagocytes was observed at 2 to 4 hours in the 500 mcg LPS group (P = 0.044). CONCLUSIONS: Erythrophagocytosis may play a role in anemia associated with acute infection in mice.

BACKGROUND: Most acute wheezing episodes in preschool children are associated with rhinovirus. Rhinovirus decreases extracellular adenosine triphosphate levels, leading to airway surface liquid dehydration. This, along with submucosal edema, mucus plaques, and inflammation, causes failure of mucus clearance. These preschool children do not respond well to available treatments, even oral steroids. This calls for pro–mucus clearance and prohydration treatments such as hypertonic saline in wheezing preschool children. METHODS: Randomized, controlled, double-blind study. Forty-one children (mean age 31.9 ± 17.4 months, range 1–6 years) presented with wheezing to the emergency department were randomized after 1 albuterol inhalation to receive either 4 mL of hypertonic saline 5% (HS) (n = 16) or 4 mL of normal saline (NS) (n = 25), both with 0.5 mL albuterol, twice every 20 minutes in the emergency department and 4 times a day thereafter if hospitalized. The primary outcome measured was length of stay (LOS) and the secondary outcomes were admission rate (AR) and clinical severity score. RESULTS: The LOS was significantly shorter in the HS than in the NS group: median 2 days (range 0–6) versus 3 days (range 0–5) days (P = .027). The AR was significantly lower in the HS than the NS group: 62.2% versus 92%. Clinical severity score improved significantly in both groups but did not reach significance between them. CONCLUSIONS: Using HS inhalations significantly shortens LOS and lowers AR in preschool children presenting with an acute wheezing episode to the emergency department.

The course of hereditary spherocytosis (HS) may be subject to hemolytic episodes, sometimes requiring blood transfusion. The aim of this study was to evaluate the efficacy of a short course of steroid therapy in elevating hemoglobin levels during hemolytic crisis.The files of all patients followed for HS from 1968 to 2009 at our hospital were reviewed. Outcome of hemolytic crises was compared between steroid-treated and untreated patients; patients given packed red blood cell transfusion(s) or erythropoietin treatment were excluded. A good outcome was defined as an increase of at least 20% in hemoglobin level from the nadir within 1 week.Of the 118 patients with HS who attended our hospital during the study period, 20 were treated with steroids and 9 received no treatment. Mean nadir hemoglobin level in both groups was 6.9 g/dl. The study group had a total of 50 steroid-treated hemolytic crises of which 37 (74%) responded favorably to treatment. Treatment failure was significantly associated with a low dose (1 mg/kg/day) or short duration (1 week) of treatment. The nine untreated patients had 16 hemolytic crises, of which 25% had a good outcome. Steroid therapy was significantly more effective than no therapy in increasing hemoglobin level (P = 0.015) in these hemolytic crises.Steroid therapy may be effective in augmenting hemoglobin levels during hemolytic crises in patients with moderate HS and eventually will result in a reduced need for RBC transfusion.

To test a new device designed to salvage red blood cells (RBCs) from blood samples drawn from preterm infants, with the intent of decreasing blood loss and lowering the requirements for RBC transfusions.A case-controlled pilot study was conducted in two Israeli neonatal intensive care units in large municipal hospitals. Twenty low-birthweight preterm infants were randomly and equally divided into the ErythroSave group or a control group. All blood tests in the study group (except for complete blood count and coagulation parameters) were obtained during the first week of life by the new device in the study group and by ordinary syringes in the control group. The main outcome measure was the total number of units of blood needed.The average volume of blood obtained for laboratory analyses from each infant was 27 mL in the ErythroSave group and 24 mL in controls (not significant). The average volume of transfused packed cells was 6.4 mL for the ErythroSave group and 21.3 mL for the controls (p = 0.008).The use of ErythroSave for sampling blood significantly reduced blood transfusion requirements in premature infants compared to sampling by conventional syringes.

Platelet counts were studied in preterm infants with the respiratory distress syndrome (RDS), excluding patients with significant perinatal and postnatal hypoxia. Counts fell to a nadir on day 4 (p < 0.000). Exploratory analysis indicated that severity of RDS (levels of FiO2 and mean airway pressure), airleak syndrome, grade of intraventricular hemorrhage (IVH) and low platelet count on day 1 were correlated with low platelet count on days 4 and 5. Further analysis by stepwise removal of each variable demonstrated statistically that FiO2 exerted a unique influence on the change in platelet count between day 1 and days 4/5 (p < 0.002). It is concluded that the severity of RDS is strongly associated with the fall in platelet count in the first few postnatal days. The effect of IVH on platelet count may be secondary to the effect of the RDS.

Community-acquired bronchopneumonia in children is frequently accompanied by extreme leukocytosis, whereas in adults with the same diagnosis a high leukocyte count is uncommon. Data regarding differences in the serum levels of inflammatory cytokines between children and adults are limited.To compare leukocyte counts and blood levels of various inflammatory cytokines in children and adults diagnosed with community-acquired bronchopneumonia.We prospectively evaluated all pediatric and adult patients admitted for bronchopneumonia based on clinical and chest X-ray findings. Blood was drawn for complete blood count and serum concentration of the following cytokines: granulocyte colony-stimulating factor, interleukins-6, 8 and 10, interferon-gamma, tumor necrosis factor, as well as matrix metalloproteinase-9 and intercellular adhesion molecule-1.There were 31 children and 32 adults. The patients in both groups had similar parameters of infection severity. None of them required admission to the Intensive Care Unit. Mean (+/- SD) leukocyte counts in the pediatric and adult groups were 21,018/mm3 (+/- 10,420) and 12,628/mm3 (+/- 6735) respectively (P = 0.02). Age was inversely correlated with leukocytes in the pediatric group (P = 0.0001). A significant inverse correlation was also found between age and platelet counts. Although cytokine levels in both groups were not significantly different, age was directly correlated with MMP-9 (P= 0.03), IL-8 (P= 0.03) and G-CSF (P= 0.014).The immune response in community-acquired bronchopneumonia is, at least partly, age-dependent.

We recently published preliminary evidence on the effectiveness of hypertonic saline in infants with viral bronchiolitis.To further establish the efficacy of nebulized hypertonic saline in these infants.In a continuing, second-year randomized, doubleblind controlled trial, an additional 41 infants (age 2.6 +/- 1 months) hospitalized with viral bronchiolitis were recruited during the winter of 2001-2002. The infants received inhalation of 1.5 mg epinephrine dissolved either in 4 ml normal (0.9%) saline (Group I, n=20) or 4 ml hypertonic (3%) saline (Group II, n=22). The therapy was repeated three times daily until discharge. Pooling our 2 years of experience (2000-2002), a total of 93 hospitalized infants with viral bronchiolitis were recruited; 45 were assigned to Group I and 48 to Group II.The clinical scores at baseline were 7.6 +/- 0.7 for Group I vs. 7.4 +/- 1.3 for Group II (P = NS). However, the clinical scores at days 1 and 2 after inhalation differed significantly between the two groups, invariably favoring Group II: 7 +/- 1 vs. 6.25 +/- 1.1 (P0.05), 6.45 +/- 1 vs. 5.35 +/- 1.35 (P0.05), respectively. Adding aerosolized 3% saline to 1.5 mg epinephrine reduced the hospitalization stay from 3.5 +/- 1.7 days in Group I to 2.6 +/- 1.4 in Group II (P0.05). The pooled data of both years revealed that adding 3% saline to the inhalation mixture decreased hospitalization stay from 3.6 +/- 1.6 to 2.8 +/- 1.3 days (P0.05).This second-year experience and our 2 year pooled data analysis strengthen the evidence that the combination of 3% saline/1.5 mg epinephrine benefits hospitalized infants with viral bronchiolitis.

To compare the utility of the hood versus the face mask for delivery of inhaled medications to infants hospitalized with viral bronchiolitis.Randomized, double-blinded, controlled trial; 49 hospitalized infants with viral bronchiolitis, age 2.75 +/- 2.2 months (mean +/- SD), were grouped to either the hood (n = 25) or the mask (n = 24). Each subject received inhalation treatments with the use of both devices. Half of the Hood Group received the active drug treatment (1.5 mg epinephrine in 4 mL saline [3%]) via hood followed immediately by placebo treatment (normal saline) via mask, whereas the other half received the opposite order. Half of the Mask Group received the active drug treatment via mask followed immediately by placebo treatment via hood, whereas the other half received the opposite order. Therapy was repeated 3 times daily until discharge. Outcome measures included clinical scores and parental preference.Percent improvement in clinical severity scores after inhalation was significant in both groups on days 1, 2, and 3 after admission (Hood Group: 15%, 15.4%, and 16.4%, respectively; Mask Group: 17.5%, 12.1%, and 12.7%, respectively; P.001). No significant difference in clinical scores improvement between groups was observed. Eighty percent (39/49) of parents favored the hood over the mask; 18% (9/49) preferred the mask and 2% (1/49) were indifferent.In infants hospitalized with viral bronchiolitis and in whom aerosol treatment is considered, aerosol delivery by hood is as effective as by mask. However, according to parents, the tolerability of the hood is significantly better than that of a mask.

Background The clinical spectrum of respiratory syncytial virus (RSV) bronchiolitis in previously healthy infants is extremely variable. Thus, it is likely that factors such as genetic heterogeneity contribute to disease severity. Toll-like receptor 4 (TLR4) and CD14 are part of a receptor complex involved in the innate immune response to RSV. Methods The association of the TLR4 mutations (Asp299Gly and Thr399Ile) and the CD14/-159 polymorphism were analyzed in 99 infants hospitalized with severe RSV bronchiolitis (group I). Eighty-two ambulatory infants with mild RSV bronchiolitis (group II) and 90 healthy adults (group III) composed the 2 control groups. The TLR4 mutations and the CD14/-159 polymorphism were genotyped by use of reverse-transcriptase polymerase chain reaction and restriction fragment-length polymorphism analysis, respectively. Results Each of the TLR4 mutations, either alone or in cosegregation, were associated with severe RSV bronchiolitis: the Asp299Gly and Thr399Ile mutations were significantly overrepresented in group I, compared with groups II and III. No association between the CD14/-159 polymorphism and RSV bronchiolitis was found. Conclusions These findings suggest that TLR4 mutations, but not the CD14/-159 polymorphism, are associated with an increased risk of severe RSV bronchiolitis in previously healthy infants.

Recently, we found sesame to be a major cause of severe IgE-mediated food allergic reactions among infants and young children in Israel. The purpose of this study was to describe the different patterns of sesame sensitivity. We have identified three subgroups among our patients (n = 32). Group I (n = 23, M/F; 14/9) consisted of cases with IgE-mediated sesame allergy. The mean age of the first allergic reaction was 11.7 months. Although the main clinical manifestation was urticaria/angiedema (n = 14, 60%), anaphylaxis was the presenting symptom in seven (30%) patients; all of them were younger than 1 year. Sixteen (70%) were found to be allergic to other foods, and other atopic diseases were identified in 18 (78%) patients. Three patients 'outgrew' their allergy within 1-2 years. Group II (n = 2) included cases in whom sesame allergy was ruled out based on a negative skin prick test (SPT) together with a negative open oral challenge. Group III (n = 7) consisted of patients that were found to be SPT positive for sesame as part of a screening for other food allergies. Although sesame products have become fashionable in westernized countries, early exposure may cause sesame to share eventually the same 'noteriety and fate' as peanut - a major cause of severe food allergic reactions.

Carnitine deficiency secondary to renal Fanconi's tubulopathy has been described in only a few inborn errors of metabolism : cystinosis, galactosemia, and Fanconi-Bieckel syndrome. We report a 27-month-old infant who presented with a sudden change in gait owing to proximal muscle weakness. The laboratory evaluation showed carnitine deficiency associated with Fanconi's tubulopathy. Eventually, tyrosinemia type I was diagnosed. Carnitine deficiency can contribute to the clinical picture of hepatorenal tyrosinemia and should therefore be evaluated and treated. ( J Child Neurol 2001;16:642-644).

Oral budesonide in adult studies is a potent corticosteroid with decreased systemic bioavailability and an improved adverse effect profile in comparison with prednisone. It has recently been introduced for the treatment of inflammatory bowel disease in Europe, Canada, and Israel. Benign intracranial hypertension has rarely been associated with corticosteroid therapy but has not been reported in association with budesonide therapy. Three adolescents with Crohn's disease and poor nutritional status developed benign intracranial hypertension while receiving oral budesonide. All three patients had previously received multiple courses of prednisone during the course of their disease, without developing intracranial hypertension. Benign intracranial hypertension resolved after medication withdrawal and did not recur with subsequent use of prednisone. Evaluation for benign intracranial hypertension should be considered in patients with inflammatory bowel disease who develop headache while receiving oral budesonide. This side effect may be associated with poor nutritional status. (J Child Neurol 2001;16:458-461).

Background. Immunotherapy given post-autologous stem cell transplantation may eliminate residual tumor cells escaping the conditioning protocol. Methods. Five children suffering from stage IV neuroblastoma were treated by recombinant interleukin-2 (IL-2) post-autologous peripheral blood stem cell transplantation. The patients’ peripheral mononuclear cells were monitored for CD3+ and CD56+ levels, their proliferative response and killing of various cell lines targets. Results. An increase in the level of total lymphocytes, mainly due to expansion of T cells, and enhanced proliferative response to phytohemaglutinin were observed. Elevated cytotoxicity against K562 and neuroblastoma target cells was detected in four patients and against K562 targets in one patient. Toxicity included mild thrombocytopenia, and fever in four patients and mild to moderate encephalopathy which necessitated withdrawing one patient from the protocol. Three of five patients studied are alive today, one of them whose IL-2 was stopped, is in relapse. Two patients have died. Conclusions. Immunotherapy with s.c. intermediate-high dose IL-2 is feasible and results in expansion of T cells and in stimulation of killing activity against several targets including in some cases, neuroblastoma tumor cells.

Neutrophil counts were studied in 62 preterm infants receiving mechanical ventilation for neonatal respiratory distress syndrome (NRDS). Exploratory analysis indicated that the severity of NRDS, as demonstrated by fractional inspired oxygen (FiO 2 ), mean airway pressure (MAP), arterial-alveolar PO 2 ratio (a/APO,) and oxygenation index (OI), was correlated with percentage change of neutrophil counts during the first 5 days of life, Further analysis demonstrated that infants with NRDS who subsequently developed chronic lung disease (CLD) (n = 21) had statistically significant differences in variation of neutrophil counts when compared with the remainder (n = 41) without CLD (-35.0% ± 4.3 vs. -16.9% ± 5.8, p < 0.02). It is concluded that significant variations in neutrophil counts during the first 5 days of life may be found in infants with NRDS who subsequently develop CLD and that these changes may have predictive value regarding the development of CLD.

BACKGROUND Preventive cranial radiotherapy (CRT) in childhood acute lymphoblastic leukemia (ALL), although effective, may be associated with neurologic sequelae and second malignancies. Attempts to replace CRT with intensified intrathecal therapy (IT) have shown promise in lower risk subgroups. In the Israel National Study (INS) 89 trial, the efficacy of extended triple IT (TIT) alone for cranial prophylaxis in an enlarged non-high risk group (Non-HRG) was assessed in the context of a modified ALL-Berlin–Frankfurt–Munster (BFM) systemic chemotherapy program. METHODS Non-HRG patients included the standard-risk group (SRG) and the risk group (RG), as defined in ALL-BFM 86. In the INS 89 protocol, all Non-HRG patients were treated with extended TIT × 18 times and systemic therapy based on the BFM 86 protocol, with the addition of etoposide × 4 times. The HRG patients, classified according to BFM 86 criteria, were treated with the BFM 90 HRG protocol including CRT. RESULTS A total of 250 patients were enrolled. At a median follow-up of 58 months (range, 2–8.5 years), the overall 5-year event free survival (EFS) was 73.5% ± 3% (standard error [SE]), and the cumulative central nervous system (CNS) recurrence rate was 4.3% ± 1.4% (SE) (isolated, 2.3%; combined, 2%). Of the 220 eligible children, 189 (86%) were in the Non-HRG group, and their 5-year EFS was 77.8% ± 3% (SE). The cumulative CNS recurrence rate for patients without CNS disease at presentation was 3.1% ± 1% (SE) (isolated, 1.7%; combined, 1.4%). Within the risk subsets defined by the BFM 86 of the Non-HRG, the 5-year EFS rates of the RG (148 patients) and the SRG (41 patients) were 74.8% ± 4% (SE) and 89.5% ± 5% (SE), respectively, and the rates of CNS recurrence (isolated and combined) were 4% and 0%, respectively. For the HRG (31 patients), the 5-year EFS and CNS recurrence rates were 47.9% ± 9% (SE) and 8.5% ± 6% (SE), respectively. CONCLUSIONS Early extended TIT therapy in the context of modified BFM 86 systemic chemotherapy was found to provide adequate CNS protection and systemic leukemia control in patients with nonhigh risk ALL. However, no benefit for etoposide could be proven in this study. Cancer 2000;88:205–16. © 2000 American Cancer Society.

We present a 72-year-old patient with chronic lymphocytic leukemia (CLL). About a year following therapy with chlorambucil and prednisone, he suffered from anemia, thrombocytopenia and organomegaly. The patient received fludarabine with a favorable response. Concomitantly with the clinical improvement of the CLL there was a remarkable flare-up of scalp squamous cell carcinoma (SCC) lesions, initially noted 4 years previously. The lesions were multiple and grew rapidly. Fludarabine depresses the T lymphocyte population, cells that play a pivotal role in the regression of the SCC. We suggest, that the flare-up and exacerbation of the SCC lesions of the patient were triggered by the fludarabine therapy.

We report a case of an adolescent boy with acute lymphoblastic leukemia whose blasts had three chromosomal abnormalities: trisomy 8, a t(5;15), and an extra “marker” chromosome. The patient presented with huge hepatosplenomegaly and pancytopenia. The response to treatment (ALL BFM 90 protocol) was very rapid, and the patient is in complete remission 1 year after diagnosis.

1. Tai PC, Holt ME, Denny P, Gibbs AR, Williams BD, Spry CJF. Deposition of eosinophilic cationic protein in granulomas in allergic granulomatosis and vasculitis: the ChurgStrauss syndrome. Br Med J 1984;289:400-2. 2. Deviller P, Gruart V, Prin L, et al. Detection of an eosinophil derivated neurotoxin in the urine of a patient with idiopathic chronic eosinophilic pneumonia. Clin Chim Acta 1991;201:105-12. 3. Tardy F, Bulle C, Prin L, Cordier JF, Deviller P. High concentrations of eosinophil-derived neurotoxin in patients' urine mimic lysozyme far-cathodic bands in agarose gel electrophoresis. Clin Chem 1993;39:919-20. 4. Morita H, Kihara T, Tatsumi Y, Kitano Y, Sagami S. Allergic granulomatosis and angiitis of Churg-Strauss. A case of high serum level of eosinophil cationic protein. Acta Derm Venereol 1992;72:201-2. 5. Hertzman PA, Blevins WL, Mayer J, Greenfield B, Ting M, Gleich GJ. Association of the eosinophilia-myalgia syndrome with the ingestion of tryptophan. N Engl J Med 1990;322:869-73. 6. Peterson CBG, Venge P. Interaction and complex formation between the eosinophil cationic protein (ECP) and alpha-2macroglobulin. Biochem J 1987;245:781-7. 7. Janin A, Torpier G, Courtin P, et al. Segregation of eosinophil proteins in alveolar macrophage compartments in chronic eosinophilic pneumonia. Thorax 1993;48:57-62. 8. Wallen N, Kita H, Weiler D, Gleich GJ. Glucocorticoids inhibit cytokine-mediated eosinophil survival. J Immunol 1991;147:3490-5.

Idiopathic thrombocytopenic purpura (ITP) in childhood is a benign disease, as only 10% to 20% of (he patients have a chronic course. A retrospective study of 57 ITP patients ranging in age from four months to two years revealed that 30% of them proceeded to chronicity. Unlike ITP in the general pediatric population, chronic infantile ITP was characterized by male predominance, a high frequency of preceding viral infections, and lack of responsiveness to any of the known modalities of treatment.

The purpose of this study was to examine some aspects of umbilical cord blood collection for autologous transfusion in premature infants. All 120 microbacterial cultures (aerobic and anaerobic) of cord blood samples as well as 30 cultures of mycoplasma were treated. Cord prothrombin fragment (F 1 + 2) concentrations were quantified at one and 10 minutes after clamping of the cord. F 1 + 2 concentrations assessed on 25 newborn infants were similar and no linear association with time of clamping could be drawn. This means that cord blood thrombosis is not activated for at least 10 minutes following clamping of the cord. As far as is known, the first newborn infant to benefit from this method of transfusion is reported here. The premature infant received two portions of autologous blood (on days 5 and 7). No untoward effects were noted. Blood, collected from the umbilical cord, is a safe source for autotransfusion, provided that bacteriological testing has been carried out.

High-dose intravenous immunoglobulin G (IVIgG) therapy results in a rapid reversal of thrombocytopenia in over 80% of children with acute immune thrombocytopenic purpura (ITP). Comparable results were observed in eleven infants with an analogous condition, neonatal autoimmune thrombocytopenia (NATP), who received IVIgG (2 g/kg body weight) administered alone (n = 6) or in combination with steroids (n = 5). The median platelet count pre-IVIgG therapy was 25 X 10(9)/l (range 5 to 74 X 10(9)/l). The overall response rate to IVIgG therapy, administered alone or in combination with steroids was 75% (12 of 16 treatment episodes). A good response to therapy was defined as an increase in the platelet count to greater than or equal to 50 X 10(9)/l and at least twice the pre-treatment value at 48 h after completion of the IVIgG infusion. The rapid and generally excellent response to IVIgG therapy in infants with NATP suggests that this treatment approach should be considered as first-line therapy for severely thrombocytopenic infants with this self-limiting but potentially serious disorder.

The association between platelet counts and mechanical ventilation was assessed in 61 newborn infants with respiratory distress syndrome, 10 infants with congenital diaphragmatic hernia, and 10 infants with tracheoesophageal fistula. A significant decrease in platelet counts was observed during mechanical ventilation: (mean +/- SD) reduction of 39% +/- 5%, 42% +/- 5.6%, and 11.9% +/- 5.4% in the three groups, respectively, independent of other causes. In the group with congenital diaphragmatic hernia, there was a significant correlation between mean airway pressure and the reduction in platelet counts. In a subsequent series of experiments, platelet counts were recorded before and during ventilation in rabbits. A significant mean decrease of 37.3% in platelet counts was associated with ventilation with either air or pure oxygen. Results of these studies indicate that mechanical ventilation itself may cause a major decrease in platelet count in newborn infants.

Sixteen children with high risk acute lymphoblastic leukemia (ALL) who had one or more of the following risk factors: white cell count over 50 X 10(9)/liter, mediastinal mass, age under 2 or over 10 years, extramedullary involvement, or T-cell markers, were treated by a new protocol. All attained complete remission and 11 are still in their continuous first remission for 6-53 months. High activity of adenosine deaminase (ADA) in the leukemic cells seems to be an independent risk factor, as in the high ADA level group, 4 out of 7 patients relapsed and died, while none of the 8 patients with low ADA levels relapsed or died.