Pál Kajtár

The adverse effect of prolonged prednisolone pretreatment in children with acute lymphoblastic leukemia

Between 1971 and 1981, 699 children were diagnosed to have acute lymphoblastic leukemia (ALL) in Hungary. 34 of these children had received prednisolone therapy prior to the establishment of the diagnosis. The most frequent presumptive diagnoses that prompted steroid treatment were aplastic conditions and arthritic disorders. Leukemia was diagnosed when the presenting symptoms reappeared usually several weeks after the initiation of steroid therapy and often following withdrawal of the drug. Initial leukemic burden, as judged by leukocyte count and hepatosplenomegaly, was smaller in these patients than in other children with leukemia at the time of diagnosis. Although they entered remission at the same rate as the other patients, the length of continuous complete remission was significantly shorter in the prednisolone pretreated group. It appears that prolonged prednisolone therapy given before remission induction imparts a distinct unfavorable prognosis.

Large cell neuroblastoma: a distinct phenotype of neuroblastoma with aggressive clinical behavior.

Among cases of undifferentiated and poorly differentiated tumors in the neuroblastoma (Schwannian stroma–poor) category, the authors histologically identified a group of rare tumors, known as large cell neuroblastomas (LCNs), that are composed of large cells with sharply outlined nuclear membranes and 1–4 prominent nucleoli.

Prevention and treatment of hyperuricemia with rasburicase in children with leukemia and non-Hodgkin's lymphoma

To prevent acute renal failure in children at risk for developing tumor lysis syndrome due to acute lymphoblastic leukemia or non-Hodgkin’s lymphoma treated according to international BFM protocols, we investigated recombinant urate oxidase (rasburicase) in the first Central European openlabeled, prospective, multicenter phase IV trial. Rasburicase was administered intravenously, at 0.2 mg/kg for 5 consecutive days to 36 patients. Blood levels of uric acid, creatinine, phosphorus, calcium, lactate dehydrogenase and complete blood count were measured daily during rasburicase treatment and on days 6, 7 and 12. Initial uric acid level decreased significantly by 4 hours (from 343 μmol/L to 58 μmol/L, p<0.001), except for one steroid-resistant patient who required hemodialysis on day 14 after having introduced combined cytostatic treatment. Comparing the data of a subgroup of 12 patients receiving rasburicase with that of a historic cohort of 14 patients treated with allopurinol indicated the superiority of rasburicase over allopurinol in prophylaxis and treatment of hyperuricemia in children with leukemia and lymphoma.

Hungarian experience with Langerhans Cell Histiocytosis in childhood

The Langerhans cell histiocytosis (LCH) in children is relatively rare and the long-term analysis of therapy results has not been done yet in Hungary. The aim of this study was to investigate the incidence, clinical features, prognostic risk factors, and treatment results of childrens LCH in Hungary in a 20-year period. Children less than 18 years of age with newly diagnosed LCH in Hungary were entered in this study. Clinical data of all children with LCH were reported to the National Childhood Cancer Registry in Hungary from 1981 to 2000. The clinical files were collected and abstracted for information regarding age at diagnosis, gender, disease characteristics, treatment, and outcome of treatment. Median follow-up duration of surviving patients is 10.98 years. Between January 1981 and December 2000, 111 children under 18 years of age were newly diagnosed with LCH in Hungary. The annual incidence of LCH in children younger than 18 years of age was 2.24/million children. The male–female ratio was 1.36:1; the mean age was 4 years 11 months. Thirty-eight children had localized disease and in 73 cases systemic dissemination was found already at the time of diagnosis. Twenty-two patients were treated only by local surgery, 7 by surgery with local irradiation, and 5 children got only local irradiation. In 2 cases remission was achieved with local steroid administration. Seventy-five patients received chemotherapy. In the 20 years of the study 14 children died, 9 due to the progression of the disease. Sixteen patients had relapse with a mean of 2.16 ± 1.29 years after the first diagnosis. Three patients with relapse got chemotherapy generally used in lymphoma and remission was achieved. The overall survival of all patients (n = 111) was 88.3 ± 3.1% at 5 years and 87.3 ± 3.2% at 10 and 20 years. Childhood LCH is a well-treatable disease and the survival rate is high. Even disseminated diseases have a quite good prognosis in childhood.

Long-term follow-up of cancer in neonates and infants: a national survey of 142 patients

Abstract. To determine the mortality and survival rates, side effects of surgery and adjuvant chemo- and radiotherapy, somatic development, and fertility, the data of 142 patients under the age of 1 year operated upon for solid malignant tumors from 1975 through 1983 were analyzed. The follow-up period ranged from 16 to 25 years (mean 20); 79 patients survived. The male/female ratio of the survivors was 51/28. Investigations were based on the Hungarian Tumor Registry, personal interviews with the patients and their parents, and detailed questionnaires. Fifty-one patients died, 44 of them before the age of 3 years; 13 were lost to follow-up. Of the 79 survivors, 48 had abdominal and 31 extra-abdominal tumors (35 neuroblastomas, 21 renal tumors, 15 soft-tissue sarcomas, 5 gonadal tumors, 2 sacrococcygeal carcinomas, 1 hepatic tumor). Side effects of surgical intervention included partial urinary incontinence (2), partial fecal incontinence (1), intestinal obstruction (2), nerve injury (1), thorax deformity (4), and scar formation resulting in psychological problems (12). Chemotherapy alone (41 patients) resulted in side effects in 19 patients, radio- and chemotherapy in combination (23) caused side effects in 20. Fifteen patients did not receive adjuvant therapy. The most serious late side effects were 24 spinal deformities, one-half of them severe, breast underdevelopment, muscular deformity, and renal damage. In 19 patients more then one side effect was detected. Height and weight gain decreased (P < 0.01 and <0.05, respectively) in the first 8–10 years of follow-up and accelerated significantly (P < 0.05 and <0.05, respectively) in the second half of follow-up. The short follow-up time (16–25 years) permitted only limited analysis of infertility. Whenever possible, surgical excision should be the treatment of choice. No routine aggressive chemotherapy is indicated. Radiation therapy, which frequently results in long-term musculoskeletal morbidity, should be avoided. Catch-up somatic development occurred in the second part of the follow-up period.

Childhood acute lymphoblastic leukaemia in relation to population mixing around the time of birth in South Hungary

In a retrospective epidemiological study of 481,984 live births in South Hungary, we investigated whether higher levels of population mixing around the time of birth is a risk factor for acute lymphoblastic leukemia (ALL) under age 5 years. Poisson regression was used to investigate the relationship between risk of ALL and the population‐mixing index based on the number of incomers in each county district for each year, standardized to have a range of 0–1. Among all children, the risk of ALL increased significantly with increasing population mixing around the time of birth (trend across the range of 0–1 RR = 2.1 95% CI: 1.02–4.44). This effect was more marked for boys (RR = 3.1 95% CI: 1.13–8.51), which supports a sex‐specific effect of exposures on risk of ALL. Pediatric Blood Cancer

A novel IL2RG mutation associated with maternal T lymphocyte engraftment in a patient with severe combined immunodeficiency

AbstractSevere combined immunodeficiency (SCID) represents a genetically heterogeneous group of primary immunodeficiency disorders. Irrespective of the genetic defect, patients with SCID may be engrafted with transplacentally derived maternal T-lymphocytes that in a subset of cases may be responsive to phytohemagglutinin. Here, we present, from a genetic perspective, an SCID patient who not only harbored a novel mutation in the gene encoding the common γ chain (γc) of the IL-2 receptor (IL2RG), but also carried reactive maternal T lymphocytes that produced a karyotype that was initially perplexing.

Rare sellar region tumors

We present three cases of rare intracranial midline tumor in the sellar region, often mimiking pituitary adenomas clinically. We describe their symptoms, radiological and pathomorphological features. The first case is a pituitary adenoma producing growth hormone with ganglion cell differentiation. In addition, a rare intracranial granular cell tumor of sellar region and germinoma of pituitary fossa are also presented. All tumors were resected and histologically analyzed. Their biological behaviour was favorable with a 10-year follow-up demonstrating no recurrent tumor mass.

Seasonality of birth and acute lymphoblastic leukemia

Sir, There is a growing body of evidence that exposure to infection is a risk factor for childhood leukemia. Recent epidemiological studies have suggested that environmental hazards (including infections), before or around birth, may also be associated with the risk of leukemia. In addition, a cyclic trend in occurrence could be interpreted as supportive evidence of exposure to infection. Various methods of estimating and evaluating cyclic trends have been reported. The methodology for studying seasonal variation ranges from simple graphical means to more advanced and efficient techniques. The aim of the current study was to investigate whether the seasonal trends of time of birth of children aged 0–4 years who were subsequently diagnosed with acute lymphoblastic leukemia (ALL). Children born during 1981–1997 in South Hungary were evaluated. Data were available from the Central Demographic Agency on the number of births for each month over the study period. Registrations of first malignancies of children, born and diagnosed with ALL, under the age of five years in Hungary, before the end of 2002 were obtained from the Hungarian Pediatric Oncology Group. Two methods for the detection of seasonal variations in epidemiological data were applied: Walter-Elwood’s method and the logistic regression model including periodic functions (a sine and a cosine function, simultaneously). The magnitude of the seasonal variation as expressed by the amplitude of a simple harmonic oscil-

Cytogenetic Profile of Primary Pituitary Germinoma

We present a case of a germinoma in the sellar region of a 10-year-old female patient who presented with a history of polydipsia, polyuria and visual disturbances. The tumor was resected and histologically analyzed. Interphase cytogenetics was performed using chromosome specific (peri)-centromeric DNA probes for all the somatic and X chromosomes on fresh frozen tissues. Fluorescent in situ cell hybridization demonstrated accumulated cytogenetic abnormalities involving significant alterations of chromosome 1, 4, 5/19 and 15. The child was treated postoperatively by radiation and now appears well with only minor neurological deficits. At 3-year follow-up no recurrent tumor mass could be demonstrated.