[Treatment results in patients treated from 1980 to 2004 for Wilms' tumour in a single centre]. / Lécebné výsledky pacientu lécených v letech 1980-2004 na jediném pracovisti pro nefroblastom.

BACKGROUNDS: The principle behind the treatment of nephroblastoma has been similar for at least 4 decades, based on vincristine and dactinomycine, radiotherapy in selected stages. The last three decades have been characterised by the aim to reduce the intensity and length of treatment. DESIGN: To retrospectively compare survival rates and treatment success in a cohort of patients aged under 19 years, treated from 1980 to 2004 at a single centre by five consecutive treatment protocols. MATERIALS AND METHODS: The outcome was evaluated in patients treated consecutively by two protocols established at the centre before 1980 and modified in 1986, and from 1988 consecutively by three accepted protocols, SIOP9, SIOP93 and SIOP2001. RESULTS: Overall survival as well as event-free survival rates were evaluated by Kaplan-Meier functions in 315 patients (52.7% women). The average age at diagnosis was 3.9 +/- 2.9 years, median 3.3, range 0.01-17.2 years. Age over 12 years in 2.2% patients. The average follow-up time was 13.1 +/- 7.8, median 13.6, range 0.2-27.8 years. The original 104 weeks of protocol KDO86 treatment had a 10-year overall survival rate of 91.9 +/- 3.2%. Overall survival significantly fell with radiotherapy reduction in lower clinical stages and treatment diversification in protocols with substantial treatment length reduction. Overall survival returned to the original value of KDO86 only in 1994, when SIOP93 was accepted with a 10-year overall survival rate of 92.47 +/- 3.0% and event-free survival 85%, with similar trends in the latest protocol, SIOP2001. In the entire cohort two coincident malignancies (tumour duplicities) were found: one B-lymphoma, one neuroblastoma. A second malignancy occurred in one patient--superficial spreading melanoma. CONCLUSION: from the retrospective view the accepted SIOP9 protocol has a significantly worse outcome in both the overall survival and in event-free survival rate compared with the original therapy. Only the SIOP93 and SIOP2001 protocols accepted after 2003 have an acceptable 10-year overall survival rate (around 92%) as well as event-free survival (85%) with substantially reduced length and intensity of treatment, lowering the risk of late effects.

[Late effect of treatment of nephroblastoma in patients treated in 1980-2001 in a single centre]. / Pozdní následky Wilmsova tumoru a jeho lécby u pacientu lécených v letech 1980-2001 na jediném pracovisti.

BACKGROUNDS: The aim of the study was to describe the late effects in a cohort of patients in long-term remission (> 5 years from end of treatment) diagnosed and treated for nephroblastoma at the single paediatric centre during 1980- 2001. PATIENTS AND METHODS: 151 patients were examined for renal function, lipid profile, sonography, echocardiography, exercise capacity and postural status. Age at diagnosis was 3.7 +/- 2.7 years, median 3.1, range 0.01-17.2 years. The cohort included 55% of women. Age in the study 19.4 +/- 5.8, median 19.6 years, range 7.8-36 years. Anthracyclines (ATC) were administered to 25.9% of the cohort. Abdominal radiotherapy (RTA) was required in 34.2%. RESULTS: Creatinine clearance was on average 1.56 +/- 0.56 ml/s/1.73m2, (median 1.49 ml/s/1.73m2). Proteinuria was 0.18 +/- 0.30 g/24 h/m2, median 0.13 mg/24 h/m2. Three patients had proteinuria above 1 g/24 h with a normal glomerular filtration rate and s-albumin. Hypertension was treated in 8.6% of patients (6% by pharmacotherapy). Increased diastolic blood pressure (DBP) and systolic blood pressure (SBP) was found in adolescents: DBP > 90 Torr was found in 10.2% of patients and SBP > 135 Torr in 8.3%, all of them above the age of 15 years. ECHO did not reveal any pathology even in patients treated by ATC. Plasma cholesterol, LDL, HDL, triglycerides were outside the recommended range in two or more parameters in 28.9% of the cohort. Lipoprotein Lp(a) > 500 mg.l(-1) (more than 200% higher than the upper limit) was found in 15.2%. Low peak oxygen consumption (VO2peak) was found in 40% of the cohort. Scoliosis (Sc) was anamnestically found in 46%. Prevalence of Sc according to the age of treatment has a similar trend as the reduced use of the RTA. Pulmonary function test showed a moderate increase in the functional residual capacity (the average Z-score of 1.35). VO2 peak correlates positively with the inspiratory capacity (p < 0.05). CONCLUSION: Based on the found pathologies and known risks, a schedule of late effect prevention and monitoring of patients in long-term NFB remission was established. It should include clinical examination, kidney function and blood pressure monitoring, sonographic and echocardiography examination, long-term physiotherapeutic care and prevention of cardiovascular diseases.

Changes of blood count, lymphocyte subpopulations and immunoglobulin levels in nephroblastoma long term survivors.

The aim of this study was to investigate the frequency of blood count, lymphocyte subpopulations, and immunoglobulin levels alterations in a group of healthy nephroblastoma long-term survivors. The group included 122 nephroblastoma longterm survivors who were at least five years post anticancer therapy and free of any sign of recurrence The proportion of lymphocyte subpopulations was analyzed by flow cytometry using antibodies anti CD45 FITC/CD14 PE, anti CD3 FITC/ CD16+CD56 PE, anti CD4 FITC/ CD8 PE and anti CD20 FITC. Immunoglobulin G, A, and M levels were evaluated by immunoturbidimetry. Total blood count was also examined. The occurrence of decreased immunoglobulin levels, leukocytes, lymphocytes, and granulocytes count, proportion of T lymphocytes and their CD4+ subpopulation are not frequent. The most frequently decreased lymphocyte subpopulation was CD8 (15.5%). The most frequent abnormal findings were increased proportion of NK cells (38.5 %), B lymphocytes (38,52 %), decreased number of erythrocytes (25.2 %), hemoglobin levels (41.7 %) and hematocrit (13.9 %). The only significant differences between results of immunological examination and course of the disease were more frequently decreased proportion of CD4+ lymphocytes in recurrent disease survivors and lower IgA levels in survivors after radiotherapy. We found decreased at least one immunological parameter in one fifth of the survivors. The most frequently altered parameter was hemoglobin, which was decreased in 41.7 % of survivors. Decraesed hemoglobin may worsen quality of survivors life. Key words: nephroblastoma long-term survivors, blood count, lymphocyte subpopulations, immunoglobulin G, A, M serum levels.

[Treatment results of Langerhans cell histiocytosis with LSH II protocol]. / Výsledky lécby histiocytózy z Langerhansových bunek protokolem LCH II.

BACKGROUND: The aim of study was to evaluate outcome of international treatment protocol LCH II for children with Langerhans cell histiocytosis treated in FN Motol. METHODS AND RESULTS: Between November 1995 and December 2003, 46 children were treated, sex ratio M:F 29:17 and median age at diagnosis 6 years 8 months. 28 children (60.9%) suffered from monosystem disease with majority of bone lesions (23 times) with skull predominance (16 times). Surgery was primary treatment modality for monosystem disease. Five children with recurrence were successfully treated by protocol LCH II - LR (3x) and LCH III - LR /G2/, respectively. Eighteen children (39.1%) suffered from multisystem disease. 6 out of 18 patients were treated according to low-risk protocol LCH II - LR and 12 children by high-risk scheme LCH II - HR at the non-randomized branch included etoposide. Recurrence was revealed in 11 patients and 10 of them reached 2nd or 3rd complete remission (CR) by 2 - chlorodeoxyadenosine (CDA) monotherapy, and 1 child reached 2nd CR by LCH II - HR scheme. Two children underwent irradiation after bone lesion excision as well as 1 child as supplemental treatment. Totally, 29 children (63.0%) achieved 1st CR, 14 (30.4%) 2nd CR, 2 (4.4%) 3rd CR, and 1 child died because of LCH progression. There were no severe side effects of chemotherapy. Follow-up median time was 5 years 8 months (range 9 months - 9 years 6 months). CONCLUSIONS: LCH II protocol is safe and effective. Results revealed that treatment of patients with multisystem disease might demand some treatment modification.

Lymphocyte subpopulations and immunoglobulin levels in Hodgkin's disease survivors.

We investigated the frequency of lymphocyte populations (CD3+ /T lymphocytes/, CD4+ /helpers/, CD8+ /suppressor and cytotoxic/, CD3- CD16+ /NK cells/, CD3+ HLA-DR+ /activated T lymphocytes/, and CD20+ /B lymphocytes/) and immunoglobulin G, A, M, and E levels in a group of two hundred twenty nine Hodgkins disease long term survivors. The most frequent pathological findings were increased IgE levels, decreased CD3+ and CD4+ proportions, an increased CD20+ proportion and especially a low CD4/CD8 proportion. Decreased CD3+ and CD4+ and increased CD20+ proportions were more frequently found in the group with recurrent infections. IgM and IgA levels were positively correlated with plasmatic cholesterol and triacylglycerols levels. We suppose that immunological defects (increase of IgE levels, decreased T and helper lymphocytes) in Hodgkins disease survivors are inherent and are not related to atopy. Examination of lymphocyte subpopulations may be helpful in the prediction of an increased risk of recurrent infections.