Irradiation of the head. Immediate effect on growth hormone secretion in children.

Plasma growth hormone (GH) was determined in samples obtained hourly from 1000 h to 0700 h before, and after a 3 week course of "prophylactic" cranial irradiation, in ten leukemic children who had no clinical or laboratory evidence of central nervous system involvement. The mean per hour value of GH prior to irradiation (4.1 +/- 2.4 ng/ml) was similar to that of 7 endocrinologically normal children (4.09 +/- 2.4 ng/ml), a finding strongly suggesting normal pituitary function prior to irradiation. Following irradiation GH levels at each hour were, in general, lower than before. The difference is statistically significant at 0100 h. The peak GH responses were lower following than preceeding irradiation (p less than 0.02). The findings suggest an immediate suppressive effect of irradiadiation on the apparently normal hypothalamic pituitary axis in children.

Cerebellar granulocytic sarcoma in an infant with CD56+ acute monoblastic leukemia.

Granulocytic sarcoma (GS) is a form of extramedullary leukaemia (EML). The presence of the neural cell adhesion molecule (NCAM) on the surface of the blasts, which is recognized by the CD56 monoclonal antibody, enhances their propensity for tissue penetration. GS within the central nervous system (CNS), in particular within the cerebellum, is extremely uncommon. We review the literature and describe an infant with isolated cerebellar GS relapse, which antedated a CD56+ acute monoblastic leukaemia bone marrow (BM) relapse.

Chromosome fragility and predisposition to childhood malignancies.

In order to clarify the possible connection between autosomal folate sensitive Fragile Sites (FS) and genetic susceptibility to haemopoetic disease in children we investigated the frequency and distribution of FS in the Peripheral Blood Lymphocytes (PBL) of 56 children with newly diagnosed and untreated haematologic malignancies and their parents. The incidence was compared with that of 146 normal controls (children and adults). In all patients the Bone Marrow (BM) karyotype was also determined. Heritable FS were detected in 49 patients (87.5%). 20 children had more than one FS and in all cases it was inherited from one of their parents, although there was a significant excess of transmitting mothers. 19 different FS were identified: 14 common, 4 rare and one, 22q11, which has not been previously reported, but it is considered as important as it coincides with the cancer breakpoint resulting in the formation of the Philadelphia (Ph) chromosome. The frequency of FS in the PBL of the patients was significantly higher than in the controls and this increase was independent of any abnormality detected in the malignant cells of the BM. However, patients with an abnormal BM karyotype displayed increased frequency of FS induction as compared to patients with a normal karyotype. In three cases the heritable FS was found to be at or near the breakpoints of the chromosomal rearrangements detected in the malignant cells. The findings are discussed with regard to cancer specific breakpoints, oncogene loci and sites where viral DNA can be inserted to the genome. The results of this study suggest that autosomal folate sensitive FS may increase the risk for haematologic malignancies through a complex mechanism which remains to be clarified.

Age of exposure to infections and risk of childhood leukaemia.

PIP: Between January and August 1992 in Greece, researchers conducted telephone interviews with parents of children with leukemia (136 cases, most in Attica [Athens and its environs] and the others on the island of Crete) and with parents of children not afflicted with leukemia (187 controls) to determine whether childhood leukemia may be a result of a subclinical infection at an earlier age. They controlled for place of residence when they conducted the multiple logistic regression analyses. They used attendance at a day care facility as a proxy for earlier infection because children come in close contact with each other at day cares, thereby exposing them to many infectious agents. Children who attended a day care had a lower relative risk of developing leukemia than those who did not attend day care (.67), but attendance did not have a significant protective effect. It did appear to have a significant protective effect for children who attended day care during infancy (for at least 3 months during the first 2 years of life), however, (relative risk = .28; p = .03). Significance remained even when the researchers considered different operational definitions of early attendance. Exposure to magnetic fields appeared to have a protective effect also against the development of childhood leukemia, but this effect did not reach significance (p = .07). The relative risk for 100 m from an electricity substation was 0.35. There was a slight, but insignificant increase in the relative risk for children living close to power lines, however (1.19 for 5 m; p = .63). Significant risk factors included young age at diagnosis and mothers with less than high school education.^ieng

Burnout, staff support, and coping in Pediatric Oncology.

GOALS OF WORK: The goals of the study were the following: (1) to study the rate of burnout of the staff in Pediatric Oncology and compare it with that of a group of staff in other pediatric specialties, (2) to find out if job satisfaction, role clarity, staff support, and ways of coping are related to the burnout of these two groups, and (3) as a secondary aim, to identify other parameters, i.e., profession, experience, having children, etc., which might affect burnout, staff support, and ways of coping. MATERIALS AND METHODS: The study group (n = 58) consisted of the staff of two Pediatric Oncology units and a Bone Marrow Transplantation unit, and the control group (n = 55) consisted of the staff of two Pediatric departments and one Pediatric Orthopedics department. The Maslach Burnout Inventory, the Staff Support Questionnaire, the Shortened Ways of Coping Questionnaire-Revised, and the Social Readjustment Scale were used. MAIN RESULTS: No differences were found in burnout between Pediatric Oncology staff and that of other specialties, the existing staff support, and the ways of coping. Decreased role clarity and wishful thinking, as a way of coping, were positively correlated to emotional exhaustion, whereas a negative correlation of the lack of role clarity existed with personal accomplishment. Not having children and less experience increased burnout in both groups studied. CONCLUSIONS: The hospital management and the heads of departments should be knowledgeable of ways to prevent burnout in their staff. Strategies targeting role clarity and wishful thinking are useful toward this goal.

Validity of a screening test for typing serum cholinesterase variants among Greek populations.

A screening method for determining the abnormal phenotypes of human serum cholinesterase variants in a population survey was investigated. The test appeared to be satisfactory in detecting abnormal genotypes, but not assigning them into correct classification. The results of the population survey indicate that there may be a higher frequency of ChU1ChD1 genotype than those reported earlier. Family studies of the suxamethonium-sensitive propositi in this population demonstrate that abnormal genes ChD1, ChF1 and ChS1 are segregating, according to the usual Mendelian type of inheritance pattern. The possibility of a relatively high frequency of these abnormal genotypes among the Greek population has been indicated.

Red cell 2,3-diphosphoglycerate levels in children with hereditary haemolytic anaemias.

The role of red cell 2,3-diphosphoglycerate (2,3-DPG) in increasing the availability of haemoglobin oxygen in neonatal jaundice and hereditary haemolytic anaemias was investigated. Measurements of 2,3-DPG were carried out on 58 normal children and six normal adults, 18 full-term newborns with neonatal jaundice and 57 cases (51 children and six adults) with hereditary haemolytic anaemias. In normal children and adults, with a mean haemoglobin of 12.69 g/dl, mean 2,3-DPG was 14.90 mumol/g Hb. In jaundiced newborns with a mean haemoglobin of 16.04 g/dl mean 2,3-DPG levels were 14.51 mumol/g Hb, i.e. normal. 2,3-DPG levels were increased in patients with beta-thalassaemia major, alpha-thalassaemia, sickle-cell disease, favism, hereditary spherocytosis and in heterozygotes for beta-thalassaemia with increased haemoglobin F. In heterozygotes for beta-thalassaemia with increased haemoglobin A2 only and in sickle cell trait 2,3-DPG levels were normal.

Abnormal glucose tolerance in children with acute leukemia. Effect of induction chemotherapy including L-asparaginase.

The glycemic and insulin response to an oral glucose load was studied in 17 children with acute lymphoblastic leukemia (ALL) and 13 normal controls. The patients were randomly assigned to either group A, receiving prednisone and vincristine, or group B, receiving these agents and, in addition, L-asparaginase from days 9-19 of the study. The glucose load was performed prior to (phase I), and on days 8 (phase II), and 19 (phase III) of chemotherapy. The mean glycemic response in both groups of patients was significantly higher than in controls at diagnosis and prior to any treatment, while mean insulin levels were not significantly different from controls. One week after initiation of treatment, the mean glycemic response improved, and was associated with hyperinsulinism. After the second week of treatment, the mean glucose and insulin response curves in group A were similar to controls. In group B, while insulin values returned to normal, blood glucose levels remained higher than in controls, but not significantly so. These findings suggest that: 1) The leukemic process itself, through mechanisms as yet undetermined, causes impairment of glucose tolerance, and 2) the diabetogenic effect of L-asparaginase is not manifested in all patients.

[Leucaemoid reaction due to cytomegalovirus infection in a new born infant (author's transl)]. / Maladie des inclusions cytomégaliques avec leucose aiguë transitoire chez un nouveau-né

A newborn infant with low birth weight, jaundice, petechiae of the skin and enlargement of spleen and liver is presented. His general condition was severe and progressive aggravation of it was noticed. Bilirubin levels was up to 44 mg/100 ml, most of it indirect and severe anaemia was present. Furthermore leucaemoid reaction of the white cells was developed. Inclusion bodies in the urine and increased title of complement fixation antibodies in the peripheral blood were detected. The diagnosis of cytomegalovirus disease was established. The patient, when he was forty days old, seemed to be fairly well, but mental retardation was noticed, which persisted at the fifth month of his age.

Immune response of immunocompromised children with malignancies to a recombinant hepatitis B vaccine.

The aim of this study was to interpret the antibody response to hepatitis B vaccination following an intensified four-dose schedule in 140 cancer patients who presented at our clinic between January 1, 1993 and December 31, 1994. According to therapy status, the patients were divided into two groups: group A consisted of 76 patients undergoing chemotherapy and group B of 64 patients in complete remission and off treatment. The eligibility requirements were negative hepatitis B virus (HBV), HCV, and human immunodeficiency virus serologic markers. A total of four dose (20 micrograms per dose) of recombinant HB vaccine was administered intramuscularly in the deltoid region at 0, 1, 2, and 6 months. Blood from the vaccinated subjects was obtained at months 1, 2, 3, and 7 in order to measure anti-HBs titer levels. Protective anti-HBs titers were considered to be those > or = 10 mIU/mL. The overall seroconversion rate 1 month after the fourth dose was 57% (80/140 patients), and the seroconversion rates for groups A and B were 31.5% (24/76 patients) and 87.5% (56/64 patients), respectively. Our results indicated that immunocompromised children undergoing chemotherapy (although less responsive than children in complete remission and off treatment) still preserved their potential to produce protective titers of anti-HBs. On this basis we recommend (1) HB vaccination after diagnosis of malignancy in pediatric patients whenever a high prevalence of HB infection exists and (2) vaccination of patients of therapy and in complete remission.

Clinical and morphological features of paediatric myelodysplastic syndromes: a review of 34 cases.

BACKGROUND: The clinical and morphological spectrum of myelodysplastic syndromes (MDS) during childhood has not yet been completely documented. We herein present the clinical features and morphological data from peripheral blood (PB), bone marrow aspirates (BMA) and bone marrow biopsies (BMB) of a series of paediatric MDS patients, with particular emphasis on their specific morphological characteristics and their diverse underlying genetic background. PATIENTS AND METHODS: Thirty-four patients with MDS (median age 8.45 y) were consecutively diagnosed and treated during a period of 15 y (1988-2002). Diagnosis was based on clinical manifestations, morphology of PB, BMA and BMB, and cytogenetic analysis of BM cells. Clonogenic methylcellulose cell cultures were performed in 23/34 patients. Patients were categorized into group A [26 primary/de novo MDS, i.e. refractory anaemia (RA) 18, RA with excess of blasts (RAEB) 2, RAEB in transformation (RAEB-t) 6] and group B (8 secondary MDS, i.e. RA 4, RAEB 1, RAEB-t 3). Treatment options varied according to protocols active during the period of the study and the availability of a suitable BM donor. Survival probabilities were estimated using the Kaplan-Meier method. RESULTS: Dysplastic features of the erythroid, myeloid and megakaryocytic lineage were detected at BMA in 85%, 50% and 90% of the patients, respectively, while decreased cellularity was found at BMB in 21/34 patients (60%). RA patients of group A presented at BMB significant hypocellularity (14/18) as a prominent finding due to decrease of the myeloid (13/18 patients) and/or the megakaryocytic (14/18 patients) lineage. Hypocellularity in RA was accompanied by dysplasia of the erythroid (17/18 patients) and megakaryocytic (16/18 patients) lineage, the presence of abnormal localization of immature precursors (ALIP, 8/18 patients), fibrosis (5/18) and stromal changes (11/18). Chromosomal aberrations were revealed in 17/34 patients, of which monosomy 7 was present in seven. Cell cultures demonstrated abnormal myeloid and/or erythroid in vitro clonal growth pattern in all the examined patients. An associated disorder or inherited disease, was identified in 14/26 patients (54%) with primary MDS. Cumulative survival of group A patients was 44.2% (RA 66.6%, RAEB/RAEBt 14.6%; p = 0.001), and of the whole group 42.4%, at 14 y. CONCLUSIONS: Hypocellularity of significant degree is a constant and prominent feature among paediatric MDS, especially those with RA. A large variety of associated disorders underlies the clinical appearance of paediatric MDS, reflecting their marked heterogeneity. RA represents the prominent subtype during childhood (69% in this study), and it appears to have the best prognosis, while prognosis of RAEB/RAEBt remains extremely poor.

Increased urinary catecholamines in an infant with the diencephalic syndrome.

In an infant of 15 months with the diencephalic syndrome, urinary excretion of norepinephrine was moderately raised and epinephrine greatly so. It is suggested that catecholamine secretion may be due to sympathetic stimulation at the level of the diencephalon, by a space-occupying lesion pressing on the thalamohypothalamic pathway. Some of the symptoms of the diencephalic syndrome such as euphoria, irritability, skin pallor, and hypertension may be the result of catecholamine secretion.

Seventeen years of experience with chronic idiopathic thrombocytopenic purpura in childhood. Is therapy always better?

Between 1975 and 1992 450 children with idiopathic thrombocytopenic purpura (ITP) were diagnosed, and of those 100 (22%) developed the chronic form of the disease. Approximately half the patients with chronic ITP presented with mild to moderate hemorrhagic manifestations at the onset of purpura (30 cases) and/or later during the course of the disease (25 cases). The incidence of intracranial hemorrhage was 1%, and the mortality rate due to overwhelming septicemia after splenectomy was also 1%. Overall one-third of the patients received no therapy; two-thirds of them went into spontaneous remission within 8 months to 8 years from the onset of ITP. Steroids given in conventional or high doses (51 cases) achieved a transient (if any) rise in platelet count, but in no case were steroids curative. Remission related to intravenous immune globulin (IVIG) therapy was noticed in 38.5% of the children (10 of 26) after variable courses. The response rate to splenectomy was 95.0%. Ultimately the long-term outcome in children with chronic ITP was as follows: remission, 58 cases (spontaneous, 30; after IVIG therapy, 10; after splenectomy, 18); hemostatic platelet values, 22 cases (spontaneous, 16; after IVIG, 5; after splenectomy, 1). Thirteen children were lost in follow-up, and 7 remain thrombocytopenic but asymptomatic. These data indicate that chronic ITP in childhood runs a benign course in most cases and may remit with or without therapy even several years from onset. Therefore, therapeutic intervention has to be individualized, and splenectomy, which is not always safe, should be reserved for problematic cases that fail to respond to conventional therapeutic modalities.

Diabetes mellitus and exocrine pancreatic insufficiency in a girl with auto-immune haemolysis.

A 7-year-old girl developed diabetes mellitus and exocrine pancreatic insufficiency after 3.5 years of almost continuous treatment with azathioprine and/or prednisone for idiopathic auto-immune haemolytic anaemia. Although both drugs have been reported to preserve endogenous insulin secretion and to interrupt the diabetogenic process they may be responsible for diabetes and exocrine pancreatic insufficiency in our patient.

Secondary malignancies in a child with Hodgkin's disease: T-cell lymphoma and myelodysplastic syndrome evolving into acute nonlymphoblastic leukaemia.

Hodgkin's disease (HD) has been linked to an increase risk of second malignant neoplasms (SMN), especially non-Hodgkin's lymphoma (NHL) and acute nonlymphoblastic leukaemia (ANLL). The mutagenic property of cytotoxic therapy as well as defective immunity have been implicated as playing a major role in the development of SMN in patients previously treated for HD. We report a case of a 14-year-old girl with HD who developed two different second malignancies within a latent period of 28 months following HD diagnosis. The patient presented initially with bilateral cervical and supraclavicular as well as mediastinal and paraaortic lymphadenopathy. She was staged as IIIA, nodular sclerosing type HD, and was given eight alternative cycles of MOPP-ABVD followed by "mantle" field radiotherapy to a total dose of 3.3 Gy plus 0.4 Gy to the upper mediastinum. Within 8 months following the completion of therapy, a period of myelodysplasia and progressive severe immune deficiency, considered as a result of initial treatment, occurred. Eighteen months after HD diagnosis while the patient was continuously neutropenic and heavily immunocompromised, a peripheral T-cell lymphoma of the angiocentric immunoproliferative lesion type (AIL) Grade III, appeared in both lungs within and beyond the radiation field, with no evidence of HD in biopsy specimens. After institution of a new chemotherapy regimen (L17M), a satisfactory response regarding NHL lesions was noted. However, 10 months later the myelodysplastic syndrome (MDS) accompanied by complex chromosomal abnormalities evoluted to frank ANLL with a rapid fatal course. This case supports the hypothesis that combined modality treatment accompanied by severe immunodeficiency may result in the development of multiple second malignancies even within a very short latent period, especially in a subgroup of HD patients who may be particularly increased risk of second cancers.

[Epidemiology of acute leukemia of childhood in Greece (author's transl)]. / Epidémiologie de la leucémie aiguë chez l'enfant en Grèce

A retrospective study of 151 aged less than 15 years children suffering from acute leukaemia is reported, the parameters studied were male: female ratio, type of leukemia, age and seasonal distribution of the illness. The disease started in spring in 53 children (35,1%), in summer in 34 (22,6%), in autumn in 36 (23,8%) and in winter in 28 (18,5%). The difference between spring and winter was statistically highly significant (X2 = 10,54, P less than 0,005). Sixty two children (41%) were 3-5 years old. The male female ratio was 1.75. The disease was of the acute lymphoblastic type in 88,1% of the cases.

Electrolyte abnormalities in lymphosarcoma after chemotherapy.

A 12-year-old female with lymphosarcoma responding to treatment including vincristine and cyclophosphamide developed clinical and laboratory findings compatible with the syndrome of inappropriate secretion of antidiuretic hormone. Some additional findings were observed, i.e. uremia, hypopotassemia and alkalosis, that have not so far been recorded in that syndrome. All abnormalities were corrected upon water restriction. A similar episode occurred after a 2nd drug course. It too was corrected upon water restriction. The patient was clinically free from her malignancy in both episodes. It is suggested that our child had probably an expanded form of the syndrome of inappropriate secretion of antidiuretic hormone.

Auxologic data and hormonal profile in long-term survivors of childhood acute lymphoid leukemia.

PURPOSE: Eighty patients, 50 girls and 30 boys 13.5 +/- 4.09 years of age, on continuous first remission, were evaluated 7.9 +/- 3.2 years after the diagnosis of acute lymphoid leukemia (ALL). PATIENTS, METHODS AND RESULTS: All patients were treated according to current protocols. Cranial irradiation dose was 1,800 rad in 10 fractions for 50 patients, and 2,400 rad in 18 fractions for the remaining 30. The mean percentile and SDS for height were 42.5 +/- 26 and -0.3 +/- 1.1 for boys, and 37.8 +/- 15.3 and -0.54 +/- 0.9 for girls, respectively. The final height and the corresponding SDS was 171 +/- 5.75 cm and -0.35 +/- 0.8 for boys, and 158 +/- 7.1 cm and -0.89 +/- 1.1 for girls, respectively. Using skin fold thickness, obesity was observed in a high percentage of patients. The head circumference (HC) percentile was 36.8 +/- 24 for boys and 40.9 +/- 29 for girls, and was even lower (30.96 +/- 25.5) for those who received a radiation dose of 2,400 rad. Menarche was earlier in girls with ALL than in normal girls (11.6 +/- 1.5 vs. 12.4 +/- 1.02 years). Testicular size was within normal limits, except in three boys whose size was at or below the third percentile. In two of them, testes had been irradiated. The mean thyroxin, thyroid-stimulating hormone, and prolactin values were within normal limits (8.6 +/- 2 micrograms/dl, 2.6 +/- 1.1 microU/dl, and 5.9 +/- 4.8 ng/ml, respectively). The somatomedin-C values for patients in the prepubertal stage were 1.49 +/- 0.85 versus 0.96 +/- 0.6 in the controls (p < 0.05), whereas for patients in the pubertal stage they were 1.92 +/- 1 versus 1.88 +/- 1 in the controls. The sex steroid and dehydroepiandrosterone sulfate values were within normal limits. In a high percentage of children, follicle-stimulating hormone and luteinizing hormone values were above the normal range for their age, sex, and pubertal stage. The mean glycosylated hemoglobin values were normal. CONCLUSIONS: 1. Linear growth, although impaired in the group as a whole, is within the normal range for the majority of children with ALL. A small percentage of children have significantly impaired growth, and must be identified early and receive appropriate therapy. 2. Obesity is more frequently present in patients with ALL. 3. HC is lower than expected, indicating impaired brain growth, which is worse in children irradiated with 2,400 rad. 4. Menarche is earlier and the gonadotrophin level is higher than normal, suggestive of either hypothalamic dysfunction, subtle ovarian failure, or both.