[Innovation approaches to treatment of children with malignant tumors of the musculoskeletal system].

The Department of Musculoskeletal System Tumors was formed in November 1989 within Research Institute of Pediatric Oncology and Hematology of N. N. Blokhin Russian Oncological Scientific Center of Russian Academy of Medical Sciences. Treatment is carried out with the newest achievements in oncopediatrics applied; priority is given to limb-sparing techniques. The total 5-year survival rate of patients with Ewing's sarcoma is 65.6%, the total 2-year survival rate of patients with soft tissue sarcomas is 62.2%, and the total 2-year survival rate of children with osteosarcoma is 76%. Study of complications and side-effects of chemotherapy, as well as the development of methods of their prevention and correction, present a separate direction in the department's activity. In 1999, the team of the institution's researchers was awarded Russian Federation State Prize for outstanding scientific achievements in the work Development and Clinical Application of Combined Methods of Treatment of Osteogenic Sarcoma. In 2003 and 2004, leading researcher N. M. Ivanova was awarded the institution's diplomas as a part of Biotech prize for the development of new methods of treatment of malignant tumors in children.

Immunophenotypic peculiarities of mobilized stem (CD34+) cells in blood from patients with severe spinal cord injury.

Immunophenotype of mobilized stem blood cells (CD34+) was studied in 29 patients with late post-traumatic spinal lesions. The CD34+ cells demonstrated different levels of expression of CD45, CD38, monomorphic determinants HLA-DR and gp130 epitopes. Most patients presented with a CD34+ cell fraction with no or low expression of common leukocytic antigen CD45. Only 2 patients had greater than 15 percent of HLA-DR-CD38- cells in the CD34+ fraction. A common transducer molecule of interleukin-6 family cytokines gp130 was expressed on stem (CD34+) cells in all the cases, 26 percent of the patients had an activated gp130 phenotype, i.e. a combination of C7+ and A1- epitopes.

[Study of tumor cells sensitivity in patients with acute leukemia to cytokines and their combined use with drugs in vitro by MTT analysis]. / Izuchenie chuvstvitel'nosti opukholevykh kletok bol'nykh ostrym leikozom k tsitokinam i ikh sochetannomu primeneniiu s khimiopreparatami in vitro metodom MTT-analiza.

MTT analysis has yielded data on the sensitivity of leukemia cells isolated from 64 patients with acute leukemia to the cytokines G-KSF?, GM-KSF, interferon-alpha 2b and their combined use with drugs, such as cytosar, vepeside, doxorubicin, vincrastine, L-asparaginase. The mean in vitro survival of leukemia cells in children with acute lymphoblast cell leukemia (ALCL) was 1.9 times less than that in acute myeloblast cell leukemia (AMCL) (p < 0.001), that in new cases of ALL was 2.3 times less than in relapses (p = 0.024). The stimulating effect of GM-KSF on the survival rates of leukemia cells was seen in 64.7% of patients with AML. That of GM-KSF was recorded in 21.4% of cases. The survival of lymphoblast cells isolated from children with ALL did not differ greatly in the absolute majority of cases (by more than 30%) in the presence of growth factor in the medium. The cytotoxicity of XII with medium growth factor decreased in most cases. However, some cases (more frequently in AML than ALCL) displayed a higher cytotoxicity of XII, particularly cytosar in the presence of G-KSF and GM-KSFG; LC50 of Ara-C decreased by 30% or more in the presence of growth factor in 36% of patients. Incubation with interferon alpha 2b caused a reduction in the survival of leukemia cells, which was more pronounced in children with ALL. Interferon-alpha 2b caused an increase in the cytotoxic effect of XII on leukemia cells in ALL to a greater extent; cytosar, vepeside, and doxorubicin enhanced the effect by 1.47, 1.39, and 2.35 times, respectively.

[Blood stem cell transplantation in pediatric oncology]. / Transplantatsiia stvolovykh kletok krovi v detskoi onkologii.

Large-dose chemotherapy (LDCT) with auto- and allogenic transplantation of blood stem cells (BSC) in pediatric oncology remains so far the last hope for many patients. The number of such procedures made in Europe increases by 10% every year. At the same time many issues of the place and role of transplantation in pediatric oncology remains unclear. Based on 240 sessions of cytopheresis, the author show that BSC can be sampled from severe pretreated patients despite the drug therapy regimen. The efficacy of G-KSF and GM-KSF used to stimulate BSC secretion is similar. After LDCT with BSC autotransplantation, the relapse-free survival rates in patients with Ewing's sarcoma and acute myeloblast-cell leukemia were 55.4 and 44.4%, respectively (in the first and second remissions). Consolidation as LDCT with BSC autotransplantation without cleansing the material from malignant cells is not a sufficient therapeutical measurement in disseminated neuroblastoma. Whether partial compatible related BSC transplantation can be possible made after non-myeloablative preparation regimens is shown.

[ES-IPO-97 treatment protocol for prognostically poor Ewing's sarcoma forms in children: results of implementation]. / Rezyl'taty provedeniia protokola ES-IPO-97 lecheniia detei s prognosticheski neblagopriiatnymi formami sarkomy Iuinga.

The paper shows the high efficiency and moderate toxicity of inductive treatment in children with Young sarcoma and primitive neuroectodermal tumors by ES-Ipo-97 protocol that includes alternate chemotherapy by the scheme: vincristine, 1.5 mg/m2/day, on days 1, 8, 15; adriamycin, 37.5 mg/m2/day, on days 1 and 2 as 24-hour infusion; cyclophosphanum, 2.1 g/m2/day, on days 1 and 2 (Block A); iphosphamide, 2.4 g/m2/day on days 1 to 5, etoposide, 100 mg/m2/day, on days 1-5 (Block B). It provides evidence for that this therapy is promising and awaits further developments.

[Use of subgrafting doses of peripheral stem cells is a new approach to overcoming hematological toxicity of multiple intensive courses of chemotherapy in children]. / Ispol'zovanie subtransplantatsionnykh doz perifericheskikh stvolovykh kletok - novyi podkhod k preodoleniiu gematologicheskoi toksichnosti mnogokratnykh intensivnykh kursov khimioterapii u detei.

The authors examined 8 patients with pretreated relapsing or resistant solid tumors (Wilms'--4, rhabdomyosarcoma--3, synovial sarcoma--1) who received 16 courses of chemotherapy: iphosphamide, 1800 mg/m2/day (days 1-5), vepeside, 100 mg/m2/day (days 1-5), and carboplatin 500 mg/m2/day (day 1) (IVC) and 18 courses of therapy wherein iphosphamide was replaced by cyclophosphanum, 400 mg/m2/day (days 1-5) (CVC). The patients received 2-4 induction courses (n = 18) and 1-5 consolidation courses (n = 16) with reinfusion of peripheral stem cells (PSC). All PSC separations were performed after the first or second courses of IVC/CVE. There were no significant increases in the duration of leukopenia and thrombocytopenia, in the incidence of infection with a higher ordinal of a course performed by PSC maintenance. The findings suggest that the small doses of PSC stimulated by colony-stimulating factor can maintain hemopoiesis and decrease the rate of the estimated bone marrow depletion long after repeated courses of chemotherapy in patients with prognostically poor solid tumors.

[Experience in treating Nephroblastomas]. / Nash opyt lecheniia nefroblastom.

The treatment of nephroblastomas which accounts for 72% of all malignant neoplasms in children is one of the topical problems of pediatric oncology. To detect the tumor at early stages of a tumorous process is one of the main conditions of successful treatment for nephroblastomas. The histological types of nephroblastoma, its international classifications and present-day treatment policy are given. A role of radiation treatment is shown at pre- and postoperative therapeutical stages. Drugs, their combinations, and the efficiency of polychemotherapy regimens in use are outlined. The importance of comprehensive examination of the patient to determine the extent of malignancy and to choose adequate antitumor treatment regimens is emphasized.

[The interferon system in children with the initial stages of diabetes mellitus]. / Sistema interferona u detei s nachal'nymi stadiiami sakharnogo diabeta.

The content of interferon in plasma and interferon reaction of leukocytes (IRL) were studied in 28 children with initial stages of diabetes mellitus. IRL in these children was found to be the same as in controls. Some kinds of insulin: zink-insulin, protamine-zink-insulin, insulin-protamine as well as vincristin were capable of reducing in vitro the interferon-producing activity of leukocytes 3--6 fold. The content of interferon in plasma was determined in 22 children: in 20 of them the concentration of interferon was below 10 units/ml, in 2 was 10 units/ml.

[Interferon deficiency syndrome in children with lymphosarcoma]. / Sindrom nedostatochnosti interferona u detei, bol'nykh limfosarkomoi.

The capacity of the peripheral blood mononuclears to produce leukocyte (alpha) and immune (gamma) interferons as well as interferon concentrations in the serum were studied in 101 children suffering from lymphosarcoma. In the blood serum of the patients interferon titres did not exceed 4 units/ml. The lowered capacity of the peripheral blood mononuclears to produce one of the interferon species in titres below 32 units/ml is a bad prognostic factor. The syndrome of interferon deficiency in children suffering from lymphosarcoma is observed in one per 5 cases.

[High-dose thiotepa chemotherapy in children]. / Tiofosfamid v rezhimakh vysokodoznoi khimioterapii u detei.

High-dose thiotepa (800-900 mg/m2) polychemotherapy following combined treatment resulted in high toxicity and lethality. 600 mg/m2 proved optimal for double-conditioning regimens since it exerted antitumor effect without causing fatal complications.

[ICO-10 (Thy-1) and K-20 (gp 120/200) monoclonal antibodies in immunophenotyping of solid tumors in man]. / Monoklonal'nye antitela IKO-10 [Thy-1] i K-20 [gp 120/200] v immunofenotipirovanii solidnykh opukholei cheloveka.

ICO - 10 (Thy-1 antigen) and K 20 (gp 120/200) monoclonal antibodies proved suitable for immunophenotyping solid tumors. The following typical antigen combinations were identified with regard to reaction with those antibodies: ICO - 10+ K 20- (neuroblastoma, malignant schwannoma, neurosarcoma and soft tissue sarcomas); K 20+ ICO - 10- (cancer of the tongue and esophagus, adenoma of the adrenal cortex, adenocarcinoma of the stomach, hepatoblastoma and nephroblastoma); ICO - 10+ K 20+ (immature teratoma and cervical and esophageal leiomyoma) and ICO - 10+ K 20- (malignant fibrous histiocytoma).