Search

Dendritic cells (DC) are important antigen-presenting cells (APC) of immune system that induce and modulate primary and secondary immune responses; they also induce of central and peripheral tolerance T lymphocytes to self-antigens. They interact with T, B and NK cells and promote activation, differentiation and effectory functions of these cells. The total number of 91 patients: 53 males and 38 females, aged from 1 month to 18 years (median 9 years) treated in the Department of Children Bone Marrow Transplantation, Oncology and Hematology, Medical University of Wroclaw, Poland (ALL--39, AML--15, NHL--8, HD--10, LCAL--4, solid tumors--15 children) were examined. Peripheral blood was collected at time of diagnosis, during chemotherapy, at time of relapse or progression disease and analyzed with used flow cyto-metric analysis. The subpopulations of CD were examined with use of specific markers for distinct blood dendritic cell populations: BDCA1 BDCA2, BDCA3 (Miltenyi Biotec). Both of activated DC CD83+ HLA-DR+ and lymphocytes T CD3+CD26+ were stained of monoclonal antibodies CD83 (Pharmingen), CD11c, HLA-DR, CD3, CD26, CD19 (BD Bisciencies). The results of our study showed increased level of blood DC in ALL and AML patients at time of diagnosis, relapse or during progressive disease in comparison with control group of healthy children, as well as in other patients. Those yields explained positive correlation with value of activated lymphocytes T (p < 0.05).

Between April 1994 and December 1999, 34 children aged from 5 to 20 years (23 females and 11 males) suffering from osteosarcoma, were treated according to the SFOP-94 protocol. The primary preoperative chemotherapy consists of adriamycin and high-dose methotrexate administration. There were 28 patients with non-metastatic tumours of the extremities and 6 children presented disseminated disease with pulmonary metastases. The primary localization included femur - 20 patients, tibia - 9 patients and humerus - 5 patients. In 26 patients limb-salvage surgery was applied. The programme of chemotherapy was changed in 4 children because of toxicity of methotrexate (1 patient) and progression of disease (3 patients). 26 out of 34 (76,5 %) children are alive including 24 out of 28 patients with localized disease. EFS calculated according to Kaplan-Meier analysis was 60 % at 67 months.

A total number of 608 cycles of G-CSF and/or GM-CSF was applied in 280 patients aged from 6 months to 20 years during neutropaenia associated with chemotherapy of children's neoplasms (NHL-124, NBL-42, RMS-36, Nephroblastoma-18, Osteosarcoma-17, Ewing's Sarcoma-14, Hepatoblastoma-6, Neurofibrosarcoma-6, PNET-5, Medulloblastoma-3, Fibrohistiocytoma-3, Angiosarcoma-2, other - 4). G-CSF - Neupogen (Filgastrim, Hoffman La Roche - 492 cycles) and GM-CSF - Leucomax (Molgramostim, Shering Plough - 116 cycles) were administered 5 mg/kg/day s.c. Forty one children with malignancies (NHL -21 cases, solid tumours -17) treated before cytokines were in use served as a control group. Our study demonstrated that G-CSF and GM-CSF therapy, gives a shorter period of neutropaenia, reduction of the number of febrile days, decreased frequency of infection and shortened its duration.

Total number of 252 cycles of GM-CSF-Leucomax Sandoz (5 mg/kg/day s.c.) and/or G-CSF Filgrastim Hoffmann-La Roche (5-10 mg/kg/day s.c.) was applied in 124 children aged from 0.5-20 years during neutropenia associated with chemotherapy of non-Hodgkin's lymphoma (NHL). Twenty four children with NHL treated according to the same chemotherapy protocol but without G-CSF and GM-CSF served as a control group. Our study have demonstrated the good efficacy of both G-CSF and GM-CSF therapy. They shortened the period of neutropenia, reduced the number of febrile days, infection's duration and decreased the frequency of infectious complications.

Between December 1989 and April 1998 twenty eight children aged from 5 to 20 years (18 female and 10 male) suffering from osteosarcoma were treated according to the OS-SFOP-94 protocol. Twenty four patients presented with localized tumor of extremities and four with pulmonary metastases. The majority of primary tumors exceeded 150 ml of volume. The primary preoperative chemotherapy consisted of adriamycin (70 mg/m2 every four weeks) and high-dose methotrexate (12 g/m2 every week). In 20 patients limb-salvage surgery was applied, in three children--amputation and in one child tibia resection with genu arthrodesis was applied. Five of 28 patients died, one because of treatment related infection, 2 non-responders with metastatic osteosarcoma due to progressive disease, and one because of local relapse with pulmonary metastasis non-responding to therapy, one because of treatment refusal. Twenty one from 25 children are alive from 5 to 51 months. Event frae survival of children with localized disease calculated according to Kaplan-Meier analysis was 64.17% in the 51st month. The main cause of failure in the treatment of osteosarcoma in children is primary and secondary progression of disease. The toleration and results of treatment for osteosarcoma in children according to the OS-SFOP-94 is satisfactory.

The Langerhans cell histiocytosis (LCH) is an enigmatic disease, usually occurring in the young. Its etiology is unknown, its pathogenesis is not correctly understood and the clinical course is unpredictable. In the years from 1975 to 1998 in Department of Paediatric Haematology and Oncology (Wrocław University School of Medicine) 32 children with diagnosis of the Langerhans Cell Histiocytosis (LCH) were treated. The study group included 19 boys and 13 girls, aged from 3 weeks to 14 years, median age 7.5 years. Investigations of immunological system were performed in the examined group. In all children lymphocytes' subsets were examined. We examined apoptosis with ELISA test in 3 patients, in 3--marked antigen CD44, in 12 marked sVCAM-1 by ELISA method. IL-1 in growing cell supernatants was determined in 17 children. In 15 children lower IL-1 production was observed before the beginning of therapy in comparison with control group. In all patients decreased concentrations of lymphocytes T were noted, but in 8 children lower CD4/CD8 rate was observed. In the study group higher expression of CD44 was noted. In 3 patients cell apoptosis was normal. In 12 patients lower expression of sVCAM-1 was observed. Abnormal expression of adhesion molecules may influence the pathogenesis of LCH. Disorders of immunological system were observed in the patients with LCH.

Total number of 306 cycles of GM-CSF-Leucomax Sandoz (5 mg/kg/day s.c.) and/or G-CSF Filgrastim Hoffmann-La Roche (5-10 mg/kg/day s.c.) was applied in 146 children aged from 0.5-18 years during neutropenia associated with chemotherapy of solid tumours. Seventeen children with malignancies served as a historical control group. Our study have demonstrated after both G- and GM-CSF therapy shorter period of neutropenia, reduction of the number of febrile days and a decreased frequency of infectious complications and infection's duration.

Langerhans cell histiocytosis (LCH) and Niemann-Pick disease are very rare diseases. Both LCH and Niemann-Pick disease are distinguished by complex etiology, pathogenesis and broad spectrum of clinical manifestations. In our study we presented case report of 2.5 year old girl in who the coexistence of both diseases was noted. General symptoms that led to diagnosis were: hepatosplenomegaly, cholestatic jaundice, cutaneous lesions and mental development retardation.