Dezső Schuler

To identify the gene underlying Fanconi anemia (FA) complementation group I we studied informative FA-I families by a genome-wide linkage analysis, which resulted in 4 candidate regions together encompassing 351 genes. Candidates were selected via bioinformatics and data mining on the basis of their resemblance to other FA genes/proteins acting in the FA pathway, such as: degree of evolutionary conservation, presence of nuclear localization signals and pattern of tissue-dependent expression. We found a candidate, KIAA1794 on chromosome 15q25-26, to be mutated in 8 affected individuals previously assigned to complementation group I. Western blots of endogenous FANCI indicated that functionally active KIAA1794 protein is lacking in FA-I individuals. Knock-down of KIAA1794 expression by siRNA in HeLa cells caused excessive chromosomal breakage induced by mitomycin C, a hallmark of FA cells. Furthermore, phenotypic reversion of a patient-derived cell line was associated with a secondary genetic alteration at the KIAA1794 locus. These data add up to two conclusions. First, KIAA1794 is a FA gene. Second, this gene is identical to FANCI, since the patient cell lines found mutated in this study included the reference cell line for group I, EUFA592.

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.

This, the fifth official document of the SIOP Working Committee on Psychosocial Issues in Pediatric Oncology, develops another important topic: the Therapeutic Alliance between families and staff. This is addressed to the Pediatric Oncology Community as Guidelines that could be followed. Every parent, medical staff member, and psychosocial professional involved in the care of the child should be responsible for cooperating in the child's best interest. Everyone must work together toward the common goal of curing the cancer and minimizing its medical and psychosocial side-effects.

PURPOSE: An open-label, matched-pair (by diagnosis, stage of disease, age, and gender) pilot clinical trial was conducted to test whether the combined administration of the medical nutriment MSC (Avemar) with cytotoxic drugs and the continued administration of MSC on its own help to reduce the incidence of treatment-related febrile neutropenia in children with solid cancers compared with the same treatments without MSC. METHODS: Between December 1998 and May 2002, 22 patients (11 pairs) were enrolled in this study. At baseline, the staging of the tumors was the same in each pair (mostly pTNM = T2N0M0), with the exception of two cases in which patients in the MSC group had worse prognoses (metastasis at baseline). There were no significant differences in the average age of the patients, the length of treatment time (MSC) or follow-up, the number of patients with central venous catheters, the number of chemotherapy cycles, the frequency of preventive counterneutropenic interventions, or the type and dosage of antibiotic and antipyretic therapy used in the two groups. RESULTS: During the treatment (follow-up) period, there was no progression of the malignant disease, whereas at end-point the number and frequency of febrile neutropenic events significantly differed between the two groups: 30 febrile neutropenic episodes (24.8%) in the MSC group versus 46 (43.4%) in the control group (Wilcoxon signed rank test, P < 0.05). CONCLUSIONS: The continuous supplementation of anticancer therapies with the medical nutriment MSC helps to reduce the incidence of treatment-related febrile neutropenia in children with solid cancers.

Recognizing the importance of psychosocial issues in the care and cure of the child with cancer, the board of the International Society of Pediatric Oncology (SIOP) in 1991 constituted a Working Committee on Psychosocial Issues in Pediatric Oncology, with Giuseppe Masera as chair and John Spinetta as co-chair. This committee met for the first time in Rhodes, Greece, in October 1991. The committee discussed various psychosocial issues and developed a document on Aims and Recommendations, summarizing the experiences of major centers. This document was approved by the SIOP board, which recommended diffusion of the document to the pediatric oncology community.