A nonrandom chromosome 1p36 deletion has often been found in sporadic neuroblastoma. It has been suggested that the chromosome 1p36 region contains a putative neuroblastoma suppressor gene. We observed two siblings with neuroblastoma; deletion of 1p36 region was demonstrated in both tumors by loss of heterozygosity for the microsatellite loci and by loss of telomeric fluorescent signal by fluorescence in situ hybridization on interphase nuclei, whereas no chromosome Ip deletion was found in the constitutional DNA of the patients. The presence of 1p36 damage in the tumors of siblings suggests a common mutational event, occurring at the 1p36 region, that is involved in the neuroblastoma development.

Familial neuroblastoma occurs rarely. We studied a family with three children; one of them has a disseminated (stage 4) and another has a localized (stage 2) neuroblastoma. We observed subtelomeric locus D1Z2 (1p36) deletion in both tumors by using double-color fluorescence in situ hybridization. The MYNC gene was found in single copy in both tumors. Loss of heterozygosity (LOH) and restriction fragment length polymorphism analyses were performed by using DNA from frozen tumor cells and from microdissected tumor areas excised from paraffin-embedded sections. We detected somatic LOH at locus D1S468 (1p36) in a tumor-cell population with a trisomy 1 of the stage-2 patient. Neuroblastoma cells of the stage-4 patient were diploid and showed allelic loss at the following loci: D1S172, D1S80, D1S94, D1S243, D1S468, D1S214, D1S241, and D1S164. Haplotype study showed that the siblings inherited the same paternal 1p36→pter chromosome region by homologous recombination and that, in the two tumors, arm 1p of different chromosomes of maternal origin was damaged. Our results suggest that the siblings inherited the predisposition to neuroblastoma associated with paternal 1p36 region and that tumors developed as a consequence of somatic loss of the maternal 1p36 allele.

Medical and Pediatric OncologyVolume 30, Issue 1 p. 73-74 Letter to the Editor Letter to the editor: “Indwelling central venous catheter-related sepsis” Elio Castagnola MD, Corresponding Author Elio Castagnola MD Department of Infectious Diseases, Giannina Gaslini Children's Hospital, Genova, ItalyDepartment of Infectious Diseases, Giannina Gaslini Children's Hospital, Largo Gerolamo Gaslini, 5 16147 Genova, ItalySearch for more papers by this authorMassimo Conte MD, Massimo Conte MD Department of Hematology/Oncology and Bone Marrow Transplantation Unit, Giannina Gaslini Children's Hospital, Genova, ItalySearch for more papers by this authorAlberto Garaventa MD, Alberto Garaventa MD Department of Hematology/Oncology and Bone Marrow Transplantation Unit, Giannina Gaslini Children's Hospital, Genova, ItalySearch for more papers by this authorLoredana Tasso MD, Loredana Tasso MD Department of Infectious Diseases, Giannina Gaslini Children's Hospital, Genova, ItalySearch for more papers by this authorBruno De Bernardi MD, Bruno De Bernardi MD Department of Hematology/Oncology and Bone Marrow Transplantation Unit, Giannina Gaslini Children's Hospital, Genova, ItalySearch for more papers by this authorGiorgio Dini MD, Giorgio Dini MD Department of Hematology/Oncology and Bone Marrow Transplantation Unit, Giannina Gaslini Children's Hospital, Genova, ItalySearch for more papers by this authorPier Giorgio Mori MD, Pier Giorgio Mori MD Department of Hematology/Oncology and Bone Marrow Transplantation Unit, Giannina Gaslini Children's Hospital, Genova, ItalySearch for more papers by this authorLuisa Massimo MD, Luisa Massimo MD Department of Hematology/Oncology and Bone Marrow Transplantation Unit, Giannina Gaslini Children's Hospital, Genova, ItalySearch for more papers by this author Elio Castagnola MD, Corresponding Author Elio Castagnola MD Department of Infectious Diseases, Giannina Gaslini Children's Hospital, Genova, ItalyDepartment of Infectious Diseases, Giannina Gaslini Children's Hospital, Largo Gerolamo Gaslini, 5 16147 Genova, ItalySearch for more papers by this authorMassimo Conte MD, Massimo Conte MD Department of Hematology/Oncology and Bone Marrow Transplantation Unit, Giannina Gaslini Children's Hospital, Genova, ItalySearch for more papers by this authorAlberto Garaventa MD, Alberto Garaventa MD Department of Hematology/Oncology and Bone Marrow Transplantation Unit, Giannina Gaslini Children's Hospital, Genova, ItalySearch for more papers by this authorLoredana Tasso MD, Loredana Tasso MD Department of Infectious Diseases, Giannina Gaslini Children's Hospital, Genova, ItalySearch for more papers by this authorBruno De Bernardi MD, Bruno De Bernardi MD Department of Hematology/Oncology and Bone Marrow Transplantation Unit, Giannina Gaslini Children's Hospital, Genova, ItalySearch for more papers by this authorGiorgio Dini MD, Giorgio Dini MD Department of Hematology/Oncology and Bone Marrow Transplantation Unit, Giannina Gaslini Children's Hospital, Genova, ItalySearch for more papers by this authorPier Giorgio Mori MD, Pier Giorgio Mori MD Department of Hematology/Oncology and Bone Marrow Transplantation Unit, Giannina Gaslini Children's Hospital, Genova, ItalySearch for more papers by this authorLuisa Massimo MD, Luisa Massimo MD Department of Hematology/Oncology and Bone Marrow Transplantation Unit, Giannina Gaslini Children's Hospital, Genova, ItalySearch for more papers by this author First published: 07 December 1998 https://doi.org/10.1002/(SICI)1096-911X(199801)30:1<73::AID-MPO18>3.0.CO;2-9Citations: 6AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume30, Issue1January 1998Pages 73-74 RelatedInformation

Adolescence is the time of life in which the most important transformations take place. There is also an evolutionary “ break down”, a period in which the somatic and the psychic evolution run along very different paths and at different speeds. Both contracting a potentially lethal disease and facing such hard treatment as bone marrow transplantation create strong interference of the growth process. In our Bone Marrow Transplantation-Unit over the past year we began observing 7 patients who were between 12 and 17 years of age, starting from when diagnosis was communicated and for the whole time they were under treatment. Simultaneously we studied 7 adolescents who had undergone transplantation and were off treatment for at least two years. We preferred to carry out psychodynamic interviews rather than psychometric tests because we realized that the latter were not well accepted by the adolescents. The data obtained from the observation and interviews reveal that the most disturbing facts regard the “ fragmentation of the ego”, fantasies about death and resurrection and above all about their sexual identities when the donor is of opposite gender. We saw two adolescents who developed psychotic access. In one case this took place during hospitalisation and in the other at release. Some very meaningful data regard the high frequency of “ panic attacks”. In our country this disturbance is at present more frequent than it ever was in the past, yet however is lower than in adolescents who have undergone transplantation.

The prognosis for children with leukemia has improved dramatically in the last 20 years based on prospective clinical investigations of best choice and scheduling of combinations of several agents, considering the risk factors of each patient. The authors review childhood leukemia with respect to epidemiology, classification, laboratory findings (including studies of morphology, cytochemistry, immunologic surface markers, biochemical cytoplasmic markers, cytogenetics with the most frequent chromosome anomalies, molecular biology, immunoglobulin gene and T cell receptor gene rearrangements), clinical manifestations, differential diagnosis, prognostic factors treatment. In respect of patients, it is actually followed the concept of a "total therapy", which includes the purpose the eradicate the invading leukemic cells preserving the expression of normal progenitors, and the psychological and social aspects. The authors consider the clinical trials, the role of bone marrow transplantation (BMT), the supportive care, the evaluation of the minimal residual disease, the study of sequelae and late effects in the survivors, the ethical aspects.

PSYCHOLOGICAL AND SOCIAL COMMITMENT IN GENETIC COUNSELLING AND IN PRENATAL DIAGNOSIS OF HEMOPHILIA 190

Central Venous Catheter (CVC) allows the administration of drugs, parenteral nutrition and blood sample taking for laboratory tests, avoiding continuous damage to the peripheral veins. Most of the psychological traumas caused by crude treatments also decrease and therefore CVC may initially be experienced as the end of continuous physical injuries. Nevertheless, it often happens that other sorts of psychological trauma, due to fantasies and fears elicited by the CVC, arise in children and their families. The CVC is often felt as a dangerous and invasive "foreign body". Moreover after it has been used for a long time it may create a psychological state of dependency and it frequently becomes the only means of salvation. This makes removal particularly difficult and it is felt as a "cutting" of the CVC at the end of the therapy. Young patients elaborate complex fantasies about the starting point, the route and the end point of the catheter. Their parents are often unknowing accomplices of these fears, partially because they project their own experience and also because they are conditioned by the way they have elaborated the information provided by the assistance staff. Since the handling of CVC is under the parent's responsibility when the child is not in Hospital, we should be able to help the patients and their families to cope with this experience in the most suitable way. This makes it possible to avoid both excessive worries and the tendency to underestimate the risk of infection. This is why we consider that submitting children and their family members to interviews, surveys and spontaneous drawing is wise in order to evaluate the existence, nature and extent of the fantasies. This helps to modify possible distortions both of perception and behavior.

Indwelling central venous catheter-related bacteremias are an important complication in patients with cancer. In general they are due to Staphylococcus aureus and Candida, while bacteremias caused by Gram-negatives are less common and often related to infusate contaminans. We describe a survey of etiological surveillance of Broviac catheter-related infections at G. Gaslini Children's Hospital of Genoa, Italy. In the period 1989-1992 an increase of Broviac catheter-related bacteremias due to Gram-negatives was demonstrated as compared with previous years (1985-1988). At home parental management was suspected as an important risk factor, since this complication was frequently due to infusate contaminants and no epidemic cluster or positive surveillance culture was observed in the Hospital. Therefore at home management was changed, especially regarding heparin storage. The subsequent, prospective follow-up from July 1993 to December 1995 showed a significant decrease in catheter-related bacteremias due to Gram-negatives (P = 0.003, chi-square test). In conclusion, a strict control on at home catheter management procedures must be maintained in order to reduce the risk of indwelling central venous catheter-related infections in children with cancer.

Combinations of beta-lactams plus aminoglycosides have been standard therapy for suspected infections in granulocytopenic cancer patients, especially those with profound long-lasting granulocytopenia. With the advent of new broad-spectrum bactericidal antibiotics such as extended-spectrum cephalosporins or carbapenems, the need to combine beta-lactams with aminoglycosides became more controversial. The objective of this prospective randomized multicenter study was to compare the efficacy, safety, and tolerance of meropenem monotherapy with those of the combination of ceftazidime plus amikacin for the empirical treatment of fever in granulocytopenic cancer patients. Of 1,034 randomized patients, 958 were assessable in the intent-to-treat analysis for response to antibacterial therapy, including 483 in the meropenem group and 475 in the ceftazidime-plus-amikacin group. The median durations of neutropenia were 16 and 17 days, respectively. A successful outcome was reported in 270 of 483 (56%) patients treated with monotherapy compared with 245 of 475 (52%) patients treated with the combination group (P = 0.20). The success rates in the monotherapy group and the combination group were similar by type of infection (single gram-negative bacteremia, single gram-positive bacteremia, clinically documented infection, and possible infection). The occurrence of further infections assessed in patients for whom the allocated regimen was not modified did not differ between the two groups (12% in both groups). Mortality due to the presenting infection or further infection was relatively low (8 patients treated with the monotherapy compared with 13 patients treated with the combination). A total of 1,027 patients were evaluable for adverse events; the proportion of those who developed adverse effects was similar between the two groups (29% in both groups), and only 19 (4%) patients in the monotherapy group and 31 (6%) in the combination group experienced an adverse event related or probably related to the study drug. Allergic reactions were the only reason for stopping the protocol antibiotic(s) (3 and 5 patients, respectively). This study confirms that monotherapy with meropenem is as effective as the combination of ceftazidime plus amikacin for the empiric treatment of fever in persistently granulocytopenic cancer patients, and both regimens were well tolerated.

COMETTA, ALAIN MD; VISCOLI, CLAUDIO MD; CASTAGNOLA, ELIO MD; MASSIMO, LUISA MD; GIACCHINO, RAFFAELE MD; GIBSON, BRENDA MD; GIACCHINO, MAREVA MD; BALBO, LUCIANO MD; ENGELHARD, DAN MD; SHAPIRO, MERRWYN MD; AMSALLEM, DANIEL MD; ESTAVOYER, JEAN-MARIE MD; FERSTER, ALINA MD; GLAUSER, MICHEL P. MD Author Information

Calcyclin gene, a Ca(2+)-binding protein with homology to S-100, has been found to be expressed at different levels in leukaemic cells and in other tumour cells. We recently reported the expression of the gene in human neuroblastoma (NB) cell lines, and suggested a possible role of calcyclin in cell differentiation. To extend our findings, we investigated the expression of the gene in NB cells induced to differentiate by retinoic acid (RA), using the reverse transcriptase-polymerase chain reaction (RT-PCR) technique. Time-course experiments employing LA-N-5 cells showed that calcyclin mRNA appeared 2 h after RA treatment, long before the cells were blocked in the G1 cell-cycle phase and before the neurite-like structures outgrew from the cell bodies. This suggests the involvement of the gene in the early phase of cell differentiation. Furthermore, we investigated mRNA expression in a series of fresh neuroblastomas. NB tumours showed a heterogeneous pattern of calcyclin expression, although calcyclin seemed to be expressed more frequently in cases with a favourable Shimada histology. We also studied the expression of the protein in formalin fixed and paraffin embedded tissues, by using a specific anticalcyclin antibody. The protein was detected in stromal cells which characterise a more mature histological type, and in nerve sheaths, whereas neuroblasts were negative. The tissue that expressed calcyclin protein showed a Schwann-like differentiation and, unlike S-100 protein, calcyclin was expressed in the perineurium.

Malignant osteopetrosis is an autosomal recessive disorder characterized by extreme sclerosis of all bones. The obliteration of bone marrow cavity leads both to extramedullary hematopoiesis and release of immature cells in the peripheral blood (PB). Long term culture (LTC), self-supported by intrinsic production of growth factors, was investigated in four patients with osteopetrosis (three infants with the malignant form and a 12 year old boy with the benign form). LTC from PB mononuclear cells, with evidence of stromal layer formation, was established from one infant. Our data suggest that stromal cells in PB assume different aspects depending on the stage of the disease. Since bone marrow transplantation (BMT) is the only curative treatment for malignant osteopetrosis, we were prompted to seek further information to better identify those patients who may benefit from this procedure. LTC establishment from PB could account either for a more severely damaged bone marrow microenvironment or for the release of a more primitive cell. The first event might represent an unfavorable prognostic factor for BMT.

Objective. To compare the efficacy and toxicity of single daily dosing of amikacin and ceftriaxone with that of multiple daily dosing of amikacin and ceftazidime for febrile episodes in patients with cancer and granulocytopenia.Design: A prospective, randomized, unblinded, multicenter trial.Setting: Twenty-one tertiary care or university medical centers.Patients: Six hundred seventy-seven patients with cancer and granulocytopenia (858 febrile episodes).Interventions: Random assignment to empiric therapy with a single daily dose of amikacin (20 mg/kg) and ceftriaxone (adults, 30 mg/kg; children, 80 mg/kg) (24-hour group) or with multiple daily doses of amikacin (6.5 mg/kg every 8 hours) and ceftazidime (33 mg/kg every 8 hours) (8-hour group).Measurements: Percentage response to each regimen and occurrence of nephrotoxicity and ototoxicity.Results. Single daity dosing of amikacin and ceftriaxone was as effective as multiple daily dosing of amikacin and ceftazidime (71% compared with 74%; difference, -3%; 95% CI, -10% to 3%; P > 0.2). Equivalent responses also were noted for each category of infection. Median peak (30 minutes after a 60-minute infusion) serum concentrations of amikacin were higher in the 24-hour group than in the 8-hour group (45.6 compared with 21 mug/mL, P < 0.001), whereas trough (preinfusion) levels were lower (0.9 compared with 2 mug/mL, P < 0.001). Nephrotoxicity was 3% in the 24-hour group and 2% in the 8-hour group (difference, 1%; CI, -1% to 4%). Increases in serum creatinine, however, were delayed (P = 0.048) and smaller (P = 0.06) in the 24-hour group than in the 8-hour group and occurred almost exclusively after other nephrotoxic drugs were added. Audiometry was only done in 144 patients (21%). Ototoxicity was 9% in the 24-hour group and 7% in the 8-hour group (difference, 2%; CI, -7% to 11 %; P > 0.2). Further infections developed in 15% and 12% of patients, respectively (difference, 3%; CI, -2% to 9%). The overall mortality rate was 11% in both treatment groups (difference, 0%; CI, -5% to 5%).Conclusions: Single daily dosing of amikacin and ceftriaxone was as effective and no more toxic than multiple daily dosing of amikacin and ceftazidime for the empiric therapy of infection in patients with cancer and granulocytopenia.

From an extended series neuroblastoma cases evaluated for MYCN amplification (MNA) at the "G. Gaslini" Hospital 15 (4 with and 11 without NMA) underwent myeloablative therapy and bone marrow transplantation (MAT-ABMT). Such cases ranged in age at diagnosis from 13 months to 7 years and were followed up at least 8 months after MAT-ABMT. MNA was present in 2/10 cases dead for disease, in 0/1 cases alive with disease, and in 2/4 cases presently in complete clinical remission. This preliminary evidence would discourage to consider MNA as a marker capable of predicting the final outcome of patients with metastatic Nb.