[Clinical tolerance of high-dose methotrexate used in consolidation therapy in children with acute lymphoblastic leukemia]. / Tolerancja kliniczna metotreksatu, stosowanego w wysokich dawkach w leczeniu konsolidacyjnym ostrej bialaczki limfoblastycznej u dzieci.

The objective of the thesis was the evaluation of the clinical tolerance of methotrexate (Mtx), administered in two high doses (2 g/m2 and 3 g/m2) in 218 children with acute lymphoblastic leukemia in 829 chemotherapy cycles. The assessment of the frequency and intensity of the most common adverse early effects of the therapy was keeping with the extended toxicity scale according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC). Tolerance of HD-Mtx was good, observed toxicities were not severe (most commonly of grade 1 and 2) nor prolonged. The most common early complications of the HD-Mtx therapy were: hepatic dysfunction, nausea and vomiting and infections, affecting 60%, 45-50% and 40-55% of patients, respectively. Based on the present investigations, the high risk group for severe early complications and toxicities of Mtx therapy included: patients with delayed Mtx elimination, children above 10 years of life and patients during the first HD-Mtx cycle.

[Assessment of elimination and tolerance of high dose of methotrexate (3 g/m2) in children with standard-risk acute lymphoblastic leukemia]. / Ocena eliminacji i tolerancji wysokiej dawki metotreksatu (3 g/m2) u dzieci z ostra bialaczka limfoblastyczna standardowego ryzyka.

We assessed correlation between the elimination of methotrexate administered in dose 3 g/m2 during consolidation phase and the early complications in 129 children treated for acute lymphoblastic leukemia. Among 500 chemotherapy cycles included in the analysis the elimination of methotrexate was delayed in 66 (13.2%) cycles in 43 (33.3%) of patients. Influence of methotrexate on selected liver and renal function tests was analyzed. We made an attempt of early identification of patients with high risk for delayed methotrexate elimination and subsequent toxicities.

[Does the residual mediastinal mass have prognostic significance in children with Hodgkin's disease (HD)?]. / Czy obecnosc przetrwalej zmiany w sródpiersiu ma znaczenie prognostyczne w chorobie Hodgkina (HD) u dzieci?

Prognostic significance of residual mediastinal tumor mass in children treated for HD as well as the choice of the optimal management of these cases still remains unknown. In years 1994-2001 in 10 PPLLSG participating centers 480 children (age 2-19.7 years) were treated for HD (stages I-IV). In 338 cases initial mediastinal/lung hilus involvement was present. All patients with initial mediastinal/lung hilus involvement were treated with multidrug chemotherapy combined with involved field radiotherapy. In five cases remission was not achieved. Complete remission (CR) was achieved in 226 patients and uncertain complete remission (UCR) in 107 patients, in whom after completion of planned treatment residual changes in mediastinum/lung hilus were identified in radiological examinations. Twenty four children with persistent mediastinal tumor underwent thoracoscopy or thoracotomy. In only one case histopathological examination revealed the presence of neoplastic cells in mediastinal mass tissue, in 2 another cases cystic changes in mediastinum were present, in one case thymic tissue was identified, necrotic tissue was present in 20 cases. Among 107 children with residual mediastinal tumor and 226 patients with CR achieved, relapses occurred in 6 and 18 patients respectively. Over 5-year relapse-free survival was 92.4% and 91.3% respectively. Patients with the presence of mediastinal/lung hilus tumor after the completion of the treatment do not have an increased risk of relapse, but before the completion of therapy they require careful, clear-sighted and repeated examinations including computed tomography (CT), magnetic resonance imaging (MRI) and especially positron emission tomography (PET) to evaluate the nature of persistent lesions. Only in clinically and radiologically doubtful cases tumor biopsy with subsequent histopatological examination should be performed.

[Influence of age on treatment results in children and adolescents with Hodgkin's disease]. / Wplyw wieku na wyniki leczenia dzieci i mlodziezy z choroba Hodgkina.

Over the last few years, treatment failures (progression, relapse) in Hodgkin's disease (HD) occurred mainly in elder children treated in the Polish Pediatric Leukemia/Lymphoma Study Group (PPLLSG) participating centers. That is why analysis of the influence of age on the treatment outcome in children and adolescents treated with the protocol introduced in 1997 was performed. In years 1997-2001, in 10 centers of PPLLSG, 280 patients (age 2.3-18.8 years) were treated for HD. In all patients MVPP and B-DOPA chemotherapy with or without radiotherapy was introduced. Among 280 treated children the first remission was achieved in 275 patients (98.2%). Relapses occurred in 11 patients (4%). The 5-year probability of overall survival, relapse-free survival (RFS) and event-free survival (EFS) was 99%, 93% and 90%, respectively. All children with relapse were over 10 years old at the time of diagnosis (range: 10.6-17.1, median 14.6 years); mediastinal tumor mass was present in all of them. The logistic regression analysis did not reveal the border value for increasing the probability of relapse or event, thus age of 10 years (age of the youngest child with relapse) was identified as the border value. The probability of 5-year EFS and RFS for children over and under the 10th year of age was 98%, 92% and 100%, 92%, respectively. The differences were not statistically significant. Among children over the 10th year of age some features of the disease occurred more frequently: female sex, shorter history of the disease, presence of mediastinal tumor, greater stage of the disease, NS histopathological type of the disease, presence of general signs and ESR over 50 mm, greater tumor burden and higher number of involved lymphatic regions. Among the patients over the 10th year of age, the presence of the general signs and mediastinal tumor influenced the occurrence of relapses substantially. The aim of the further treatment modifications ought to comprise the need of better treatment outcome, especially in patients over the 10th years of age in which unfavorable prognostic factors are identified. child with relapse) was identified as the border value. The probability of 5-year EFS and RFS for children over and under the 10th year of age was 98%, 92% and 100%, 92%, respectively. The differences were not statistically significant. Among children over the 10th year of age some features of the disease occurred more frequently: female sex, shorter history of the disease, presence of mediastinal tumor, greater stage of the disease, NS histopathological type of the disease, presence of general signs and ESR over 50 mm, greater tumor burden and higher number of involved lymphatic regions. Among the patients over the 10th year of age, the presence of the general signs and mediastinal tumor influenced the occurrence of relapses substantially. The aim of the further treatment modifications ought to comprise the need of better treatment outcome, especially in patients over the 10th years of age in which unfavorable prognostic factors are identified.

[Over 30-year experience of Polish Pediatric Leukemia/Lymphoma Study Group for treatment of Hodgkin's disease in children and adolescents: improvement curability and decrease of serious complications]. / Ponad 30-letnie doswiadczenie Polskiej Grupy ds. Leczenia Bialaczek i Chloniaków w leczeniu choroby Hodgkina u dzieci i mlodziezy: poprawa wyleczalnosci i zmniejszenie powaznych powiklan.

Currently over 90% of children with HD can be cured thanks to use of chemotherapy (CT) combined with involved field radiotherapy (IF-RT). From 1971 to 2001, 1062 children and adolescents with HD (stage I to IV) were treated in 10 oncological centers PPLLSG. Majority of patients were treated with CT combined with IF-RT. Year by year the intensity of therapy (CT and RT) was gradually adjusted to the risk-factor groups, and invasive methods of staging were also gradually limited. Supportive care was improved at the same time. Along with the modified therapy protocol, five consecutive periods of time (I: 1971-82; II: 1983-87; IIII: 1988-93; IV: 1994-96; V: 1997-2001) were analyzed. In the first period the basic CT was MVPP (mechlorethamine, vinblastine, procarbazine, prednisone), while later B-DOPA (bleomycin, dacarbazine, vincristine, prednisone, doxorubicin) was gradually introduced alone or alternately with MVPP. In order to decrease the incidence of late complications, the dose of IF-RT from 45 Gy to 15-30 Gy was reduced in the next periods. In V period in 21 children with stage IA and IIA with favorable prognostic factors, CT alone was used. The probability of over 5-year: overall survival, relapse free survival and event free survival were in the I period: 92%, 83% and 77%, in the II period: 97%, 92% and 89%, in the III period: 97%, 93% and 91%, in the IV period: 95%, 91% and 90%, in the V period: 95%, 95% and 93%. Decreased rate of serious complications was also observed. Intensity of therapy should be tailored to the stage of disease, and to other significant prognostic factors. The current strategy of diagnosing and treatment of HD is aimed at balancing between the highest possible cure rates and risk of late complications.