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9037 Background:Patients with very-high risk EFTs have a poor prognosis. Melphalan (L-PAM) has been widely used in myeloablative regimens in EFTs, without a prior demonstration of its effectiveness in this disease. Methods: From March 2001, a study was opened for very-high risk EFTs with the main aim to investigate the activity and toxicity of up-front L-PAM at non myeloablative doses. Treatment consisted of initial window-therapy with L-PAM (50 mg/m2 every 21 days × 2 courses) followed by 8 intensive chemotherapy courses, and consolidation with megatherapy+autologous PBSC rescue. PBSC collection was scheduled in responders after the 4th/6th chemotherapy course. Surgery and radiotherapy were employed on individual basis Results: As of September 2003, 17 consecutive patients (median age 16yrs, range 9–34) were enrolled. All patients were evaluable for toxicity and up-front L-PAM activity. No severe toxicities were reported, but for grade 3–4 hemopoietic toxicity. After L-PAM courses, grade 4 neutropenia, t...

Differentiation was studied in 73 paediatric peripheral primitive neurorectodermal tumours (pPNETs) of bone observed during 1974 through 1992. The presence of rosettes, pseudorosettes, and/or a rosette-like arrangement of tumour cells (the morphological neural marker, MNM) occurred in 29% of these cases. NSE and N-CAM were expressed by nearly all tumours; synaptophysin was present in 30% of cases, not significantly associated with the MNM status. Neuroendocrine (NE) markers were present in 25% (chromogranin B, secretogranin II) to 40% (chromogranin A, 7B2 protein) of cases. Focal expression of cytokeratins, S100 protein and/or desmin was also noted in a minority of cases. In univariate statistical analysis, only the presence of MNM conferred a significantly higher (about twofold) risk of death than its absence. This study demonstrates the occurrence of at least one immunocytochemical N and/or NE differentiation marker in all pPNETs of bone and a focal expression of cytokeratins, S100 protein and/or desmin in a minority of cases. Synaptophysin and MNM were present each in less than 1/3 of the cases, and no association was noted between them. Statistical analyses highlighted the prognostic role of MNM per se and discourage the sole use of immunocytochemistry in the assessment of neuroectodermal differentiation for prognostic purposes in paediatric pPNETs of bone.

Bone marrow cells of a patient with Letterer-Siwe disease were cultured for three weeks in long-term bone marrow culture (LTBMC) conditions and examined at one-week intervals with a large panel of monoclonal antibodies by immunohistochemistry and by the immunogold transmission electron microscopy (immunoTEM) technique. Although at diagnosis the bone marrow showed a slight increase of monocytes with a normal phenotype, a rapid expansion of cells expressing CD1a and CD1c was observed already after 1 week of culture. A progressive increase in CD4, CD11b and CD11c expression was also observed. ImmunoTEM of cultured cells demonstrated that CD1a+ cells had macrophage-like morphology, and did not contain Birbeck granules. These findings indicate that bone marrow monocytes acquire some phenotypical features of Langerhans cells in LTBMC and support the hypothesis that these cells may derive directly from a bone marrow monocytic precursor.

At Pediatric Oncology Centers, psychological intervention and psychotherapy are generally offered to children and adolescents for supporting their adjustment to disease and treatment. The clinical practice, however, point out that cognitive and emotional symptoms, such as psychic distortions, fatigue, anxiety, irritability and depression, are sustained by biological mechanisms connected with disease and treatment and not respondent to psychological consultation and to other psychosocial resources. These manifestations could interfere with treatment or with the long-term adjustment and call for psychopharmacological treatments. Biological factors able to cause these alterations are not yet studied in depth in clinical tradition and scientific literature on the integration of psychological and psychopharmacological intervention in pediatric oncology is still poor. In this paper organic components of psychic and behavioral alterations in the course of disease are illustrated, considering the symptoms, causes and possible remedies in the light of the most recent interdisciplinary views. The main mechanism connected with oncologic treatments - chemotherapy, surgery, radiotherapy - and responsible for psycho-organic alterations in children and adolescent with cancer are also described.

Expression of integrins, a superfamily of glycoprotein alpha/beta heterodimers which integrate the cytoskeleton with the extracellular matrix and/or mediate cell-cell adhesive interactions, was examined on normal and leukaemic bone marrow cells by immunohistochemistry and immunotransmission electron microscopy (immuno-TEM). Among the beta 1/VLA molecules studied, VLA-2 and 6 were expressed on megakaryocytes and platelets, while VLA-4 was present on 40% of haemopoietic cells, including monocytes, erythroblasts and immature cells; this molecule was typically localized at sites of intercellular contact, as seen by immuno-TEM, suggesting it may be involved in interactions among haemopoietic cells during differentiation. In human long-term bone marrow cultures (LTBMC), VLA-1 and 3 were present respectively on 35% and 40% of the adherent cells which included fibroblasts and endothelial cells, as shown by double-labelling experiments; VLA-2 was expressed only on a subpopulation of fibroblasts. beta 2/LeuCAM molecules were absent from platelets, megakaryocytes and HLA-DR+/myeloperoxidase- early myeloid precursors, and appeared progressively during maturation in both lymphoid and myeloid cells. Expression of beta 3/cytoadhesin molecules was restricted to megakaryocytes and platelets and, in the adherent layer of LTBMC, to endothelial cells. The regulated expression and specific localization of integrins in the bone marrow suggest that these molecules may have a role in normal haemopoiesis.

Aims and Background This study investigates the psychological status in a population of female patients who received chest irradiation for a childhood cancer and were screened for second primary breast cancer. Methods Sixty-eight consecutive such young women were included. Compilation of the Crown-Crisp Index questionnaire was requested and 49/68 patients accepted to fill it in; 14 women in the sample had children (28%). Results Twenty-seven of 49 patients achieved a normal score, whereas in 22 the score was slightly above the normal range in at least one scale. Pathological scores were more frequent among the women without children. Conclusions Quality of life in this series of long-term survivors does not seem to be severely affected by previous treatment for cancer nor by the concern for the onset of a second primary malignancy.

A case of cystic partially differentiated nephroblastoma with immunohistochemical and serological demonstration of alpha-fetoprotein (AFP) production is described. To our knowledge, this is the first such case reported. The morphological heterogeneity of this rare tumor led us to describe the criteria of its nosological classification and of its differential diagnosis with intrarenal teratoma. AFP, besides being a marker of germline-derived tumor, was associated to this rare variant of Wilm's tumor. Although the tumor did not show regression either on clinical or pathologic assessments, serum AFP levels decreased after preoperative chemotherapy and returned to normal limits after nephrectomy.

Aims and Background The treatment applied in our Institution to children with localized osteosarcoma between 1991 and 1999 consisted of four interleukin 2 (IL-2) courses (9 x 106 IU/mL/daily x 4), alternated with pre- and post-operative polichemotherapy. The aims of the present study were to quantify the modifications of some immunological parameters induced by IL-2 and to verify whether polychemotherapy could reduce them. An additional aim was to assess whether any correlation between the immune modifications and the clinical outcome could be found. Patients and Methods We evaluated in 18 consecutive patients the following changes, induced in blood by each IL-2 course: number of lymphocyte subpopulations and natural killer (NK) cells, lymphokine activated killer (LAK) and NK activities. Results Chemotherapy did not influence the modifications of the number of NK and CD4+ cells and of the LAK and NK activities, induced by each of the four courses of IL-2. The magnitudo of the NK activity and the peak of the NK absolute counts significantly correlated with the clinical outcome. Conclusions The results show that the use of IL-2 permitted a repeated immune activation despite the intensive chemotherapy. Furthermore, although the limited number of cases precludes any definitive conclusion, the results suggest a possible role of the NK cells in the control of osteosarcoma.

We evaluated the frequency of serum antineuronal antibodies in a cohort of 39 neuroblastoma patients and related their presence to clinical features. Twelve patients displayed antineuronal antibodies at immunocytochemistry. Only one of these 12 patients suffered from a clinically overt paraneoplastic syndrome. No significant differences emerged between autoantibody-positive and autoantibody-negative patients in terms of progression-free and overall survival, although when only patients evolving to disease progression were considered, the time interval between diagnosis and progression was slightly longer in autoantibody-positive patients.

Aims To restrospectively study the DNA content in a series of childhood Ewing Family Tumors (EFT), and to investigate its prognostic value. Methods The study was performed on a series of 27 EFTs (osseous Ewing's sarcoma, 18 cases; extraos-sous Ewing's sarcoma, 2; peripheral neuroepithelioma, 4; Askin Rosai tumors, 3). Ploidy was investigated using both flow cytometry (FCM) and image cytometry (ICM) on tumor cell suspensions from formalin-fixed paraffin-embedded specimens or fresh frozen tissue obtained from the primary tumor at diagnosis. Results Ploidy was evaluable by FCM in all cases, and by ICM in 23/27. When fresh frozen tissue and paraffin-embedded samples from the same tumor were available for analysis, they yielded equal results. The rate of agreement between FCM and ICM was 82%. The majority of cases were diploid, and in the present series aneuploidy seemed to be associated with a poor outcome. Conclusions These results suggest that aneuploidy could be an indicator of a bad prognosis in EFT; however, the small number of cases precludes any conclusion of statistical value. Larger restrospective studies on ploidy using archival material could be performed and their reliability is supported by the concordance of results from fresh and formalin-fixed tissue.

The death of a child or adolescent due to cancer is a dramatic event that poses important bereavement problems, primarily for the immediate family, but also for the medical and nursing staff whose professional roles have led them to establish an intense and lengthy relationship with the patients and their families. The gravity of the death of a child prompts the need to provide emotional support for the families, but there are relatively few reports in the literature on the possible means for offering this support, not on an episodic basis but as an integrated part of the treatment process. The assumption is that, initially at least, the parents of deceased pediatric patients feel better able to express certain psychological needs in the hospital environment that has become familiar to them. Communication with the mourning families is an integral part of the relation built up between parents and medical staff during the treatment, in every single phase of the disease. The aim of this study was to assess the psychological needs of families of children dying of cancer on the basis of a review of the scientific literature and a clinical analysis of the case series developed at the Pediatric Oncology Unit of the Istituto Nazionale Tumori of Milan, in order to identify suitable methods and specific practical action for supporting the parents’ bereavement process.