[Selective depletion of alloreactive T cells and study of anti-tumor activity of specific T cell clones in patients with leukemia]. / Selektivní deplece aloreaktivních T lymfocytu a studium protinádorové aktivity specifických klonu T lymfocytu u pacientu s leuikémií.

BACKGROUND: Graft-versus-host disease (GVHD) is a severe complication of allogeneic transplantation of hematopoietic stem cells. Donor T cells play a major role in GVHD leading to the host tissue damage, mainly the skin, liver, and gastrointestinal tract. A selective depletion using an anti-CD25 immunotoxin can eliminate harmful alloreactive T cells while preserving other donor T cells with antileukemic and antiinfectious reactivity. PATIENTS AND METHODS: We performed 15 mixed lymphocyte reactions with clinical specimens from 12 patients with various types of leukemia (7x AML, 3x ALL, 1x CML, 1x CLL) and PBMC from 15 healthy volunteers from Transfusive station FN Brno Bohunice. RESULTS: In our experiments we have demonstrated, that antileukemic (GVL) effect of donor, especially CD4+ T cells was well preserved (7.46%), while unfavourable alloreactive (GVH) reaction of donor T cells was completely removed. The graft-versus-host (GVH) reactivation of donor cells was negligible ever after repeated stimulation with irradiated patient's PBMC. CONCLUSION: We have shown that anti-CD25 immunotoxin (IT), RFT5-SMPT-dgA, launched against alpha chain for human interleukin 2 (IL-2), led to long-term selective depletion of alloreactive donor T cell clones while their antileukemic activity was well preserved. Base on our results the clinical phase I/II study was designed. This study was initiated in year 2007 in three clinical centers in Czech Republic.

[Thrombosis in childhood--etiologic role of congenital thrombophilic conditions]. / Trombóza v detském veku--etiologická role kongenitálních trombofilních stavu.

BACKGROUND: Increasing frequency of thrombosis in podiatry brings about high morbidity and mortality. From published sets of clinical cases with thromboembolic complications can be concluded, that contrary to adults, origin of thrombosis in children is more frequently based on congenital thrombophilic states. The main of the work is: 1. To identify prevalence of the congenital thrombophilic states in the set of patients with venous and arterial thrombosis. 2. Formulate recommendations for the laboratory investigation. 3. Evaluate results of the thrombosis treatment in our set of patients. METHODS AND RESULTS: Set of 24 patients of the average age 6.7 years at the time of thrombosis (16 time venous, 8 times arterial) was retrospectively investigated for the presence of the factor V-Leiden mutation, prothrombine 20210A mutation, deficiency of C and S protein, and antithrombin III. Presence of acquired risk factors was also evaluated. Congenital thrombophilic state was identified in 5 patients (31.2%) with venous thrombosis and in 1 patient (12.5%) with arterial thrombosis. Mutation of the factor V-Leiden was found most frequently. It was identified at 3 patients (18.7%) with venous thrombosis and 1 patient (12.5%) with arterial thrombosis. The central venous catheter was the most frequent acquired risk of thrombosis (50%). In 1 patient with venous thrombosis and in 4 patients with arterial thrombosis no acquired or congenital risks of thrombosis were identified. Results of treatment confirmed beneficial effects of heparinisation and subsequent wafarinszation for the period of increased risk of thrombosis. Systemic thrombolysis was done 3 times without complications. CONCLUSION: Congenital thrombophilic states play significant role in the manifestations of thromboses in children. In majority of children with manifesting thrombosis at least one risk factor was identified. Cerebral infarcts in infants remain largely unrevealed.

[Consolidation of therapy of acute myeloid leukemia with the AML-BFM 93 protocol in children in the Czech Republic]. / Sjednocení lécby detí s akutní myeloidní leukémií v Ceské republice podle protokolu AML-BFM 93.

BACKGROUND: Acute myeloid leukemia (AML) in children is rare. Although more resistant to chemotherapy than acute lymphoblastic leukemia, its responsiveness and survival rates have considerably improved during the last 15 years by virtue of intensification of chemotherapy and due to the better supportive care. Relapses still remain the main cause of treatment failure. Management of children with AML was unified in the Czech Republic in 1993 according to AML-BFM 93 Study protocol. METHODS AND RESULTS: Treatment results were evaluated in 61 patients, of whom 45 (73.8%) achieved complete remission. Five-year event-free-survival (EFS) was found in 42.3%, and overall survival was 45.3%. Prognosis of the standard-risk patients was significantly better than in the high-risk group (EFS 62.5% vs. 29.7%, p = 0.03). The most important prognostic factor was the early treatment response. Compared to chemotherapy, allogeneic stem-cell transplantation did not significantly improve the outcome of high-risk patients. CONCLUSIONS: Treatment results of children with AML in the Czech Republic are comparable to those achieved by leading leukemia study groups in the world. The aim of the next study is to increase the complete-remission rate by reducing early deaths.

Treatment of Hodgkin's disease in children with VAMP (vinblastine, adriamycin, methotrexate, prednisone) and VEPA (vinblastine, etoposide, prednisone, adriamycin).

Treatment of Hodgkin's disease in children should be directed at maximizing cures and minimizing the long-term effects of alkylating agents, anthracyclines, and bleomycin. In this study methotrexate and etoposide were used in the VAMP/VEPA regimens to treat 60 clinically staged pediatric patients with Hodgkin's disease. Twenty-nine patients with stages I-IIA received four courses of VAMP plus low-dose radiotherapy. Thirty-one IIA bulky disease and IIB-IVB patients received four or six courses of VEPA plus low-dose radiotherapy. There were 6 partial remissions after the completion of chemotherapy and all of these patients relapsed, but 4 were successfully salvaged with ABMT. Two patients have died. The 3.1-year overall survival rate is 97% (100% VAMP, 94% VEPA) and the event-free survival rate is 88% (97% VAMP, 77% VEPA). These results suggest that VAMP is a reasonable treatment for low stages of Hodgkin's disease, but more advanced disease is not adequately treated by VEPA and low-dose radiotherapy.