[Treatment regimen for children and adolescents with Hodgkin's disease designed to decrease late complications of radiotherapy]. / Program leczenia choroby hodgkina u dzieci i mlodziezy zmierzajacy do ograniczenia powiklan po radioterapii.

Between 1997 to 1999 in 9 centres of the Polish Paediatlic Leukemia/Lymphoma Study Group, 167 children and adolescents (aged 2-19 years) with stage 1 to IV Hodgkin's disease (HD) were treated according to a regimen with a limited use of radiotherapy (RT). All patients received B-DOPA and MVPP chemotherapy. The number of cycles of chemotherapy was adjusted in respective risk groups. In 13 children with stage IA and IIA disease with favourable prognostic factors chemotherapy alone was used. In other patients the dose of RT applied to lymphatic regions was 15-46,4 Gy. In case of a small tumour at presentation and good response to initial chemotherapy the RT dose was 15-16 Gy. In other cases doses of 25-30 Gy were planned. The use of higher doses, particularly exceeding 35 Gy, in eleven patients, was not justified. Among all the 167 patients, three oftliem (1.2%) with advanced disease (Stage III-1V) did not achieve first remission. The 4-year overall survival (OS), relapse free survival (RFS) and event free survival (EPS) were 99%. 93% and 90%, respectively. Relapses occurred in 8 children (first remission lasted for 4-29 (median = 9 months). All 13 children in whom chemotherapy alone was used remain in first remission. In the group of children who received RT in the dose of 15-16 Gy relapse occurred in one child. Our preliminary analysis indicates that limited use of RT in selected cases of HD in children and adolescents did not show worse results of treatment. However, the assessment of possible influence of this regimen on the decreased rate of late complications requires longer follow-up.

[Results of treatment of children with chronic myelogenous leukaemia (CML) obtained by the Polish Paediatric Leukaemia/Lymphoma Study Group]. / Wyniki leczenia dzieci chorych na przewlekla bialaczke, szpikowa (CML) w materiale Polskiej Pediatrycznej Grupy ds Leczenia Bialaczek i Chloniaków u Dzieci.

Retrospective analysis of 102 children with CML from 9 paediatric centres in Poland has been performed. A total number of 102 children: 58 boys and 44 girls aged 1-17 years (median 9.4 years old) with CML, treated in the period 1975-1999 were included in the study. Forty eight of 102 (47.1 %) children were treated with cytostatic drugs without IFN alpha: busulfan, hydroxyurea, 6-mercaptopurine or etoposide (VP-16). Fifty four of 102 (52.9%) patients were treated with interferon alpha (IFN alpha) after cytoreductive pretreatment. Thirty out of 102 (29.4%) patients underwent stem cell transplantation (SCT): 24 - matched related donor allo-BMT, 2 - matched unrelated donor allo-BMT, 1 - partially matched related donor T-cell depleted allo-PBPCT, 1 - syngeneic allo-BMT and 2 - autologous PBPCT. Overall survival analysis revealed that 46 of the 102 (45.1%) children remained alive: 5/35 (14.3%) children treated with cytostatics alone, 22/37 (59.5%) children treated with IFN alpha and 19/30 (63.3%) children treated with SCT. Among SCT survivors there are 10/17 (58.8%) children treated with IFN alpha prior to SCT and 9/13 (69.2%) children treated with cytostatics alone prior to SCT. The probability of 5-year survival is 0.51 in the group treated with SCT (median follow-up 58 months); 0.43 in the group treated with IFN alpha (median follow-up 53 months) and 0.23 in the group treated with cytostatics (median follow-up 31 months). Our data show, that BMT is the treatment of choice in CML in children. IFN alpha could be successfully applied as an alternative treatment for those, who do not have a suitable donor for allogeneic SCT. Better outcome in post BMT children, who were not treated with IFN alpha prior to SCT requires confirmation by studies on larger groups of patients. However, it seems to be justified to stop IFN alpha therapy at least 3 months before SCT. The main reason for unsuccessful treatment outcome in patients with CML in Poland remains the still insufficient access to MUD-BMT.

[The incidence and treatment of the first relapse in children with Hodgkin's disease]. / Wystepowanie i leczenie pierwszej wznowy choroby Hodgkina u dzieci.

From January 1988, to December 1997, among 447 children with Hodgkin's disease (HD) who underwent initial treatment in seven centres of the Polish Paediatric Leukaemia/Lymphoma Study Group, 442 patients obtained a complete remission (CR). The initial treatment consisted of multidrug chemotherapy (B-DOPA and MVPP) combined with local radiotherapy. Relapses occurred in 35 cases (7,9%). Two patients from other centres were also included in this analysis. Four patients were lost to follow-up; 33 patients with relapses were analysed. Early relapses (first complete remission (CR) shorter than 12 months) occurred in 17 cases. Treatment of the first relapse consisted of different types of multidrug chemotherapy. Six patients underwent high-dose chemotherapy and peripheral blood stem cells transplantation. Radiotherapy was used in 19 children. Second CR was achieved in 28 patients (85%). In 10 children (36%) second relapse occurred after 4 to 21 months (median = 10). In 17 cases the second CR lasted 12-14 (median=54) months. The probability of the 7-year freedom from second relapse was 64%. Eleven patients died; one of them in second CR due to toxic liver damage. Results of treatment in children with early relapses were significantly worse. In 17 patients with early relapse, and 16 children with late relapse, the second CR was achieved in 70% and 100% of cases, respectively. The probability of the 7-year overall survival, freedom from second relapse and event-free survival in children with early and late relapse was: 42, 58, 40%, and 94, 69, and 66%, respectively. The therapeutic results in the subgroups of children with relapses treated with different methods were not comparable because of the small number of children in each group. The use of multidrug chemotherapy with or without radiotherapy allows to achieve a long lasting second CR in more than 50% of children with HD who relapsed after initial combined modality treatment. The optimal treatment of relapsed HD in patients initially treated with multidrug chemotherapy with or without of radiotherapy, is currently unknown.

Childhood stage IV Hodgkin disease: therapeutic results of the Polish pediatric leukemia/lymphoma study group.

BACKGROUND: The therapeutic management in patients with stage IV Hodgkin disease is still controversial. PROCEDURE: Among 783 children with Hodgkin disease treated from 1971 to 1996, 56 patients (7.3%) were diagnosed with stage IV. The treatment consisted of MVPP or MVPP/B-DOPA chemotherapy combined with involved-field radiotherapy in 50 children. RESULTS: The results of treatment of stage IV patients were compared in the three sequential time periods, during which the therapy was modified. In these periods, the first complete remission was obtained in 67%, 86%, and 90% of children, respectively, and the 10-year event-free survival was 42%, 64%, and 85%, respectively. CONCLUSIONS: Alternate multidrug chemotherapy combined with low-dose involved-field radiotherapy is at present a satisfactory therapeutic method in children with stage IV Hodgkin disease.

[Does residual mediastinal mass in children with completed treatment of Hodgkin's disease affect the incidence of relapses?]. / Czy resztkowy guz sródpiersia przetrwaly po zakonczeniu leczenia choroby Hodgkina u dzieci ma wplyw na czestosc wystepowania wznów?

Four hundred and four children with Hodgkin's disease (stage I-IV) were treated in seven cooperating centers of Polish Paediatric Leukaemia/Lymphoma Study Group between 1988 and 1996. Mediastinal masses and/or hilar involvement were found in 261 (65%) patients. Remission was obtained in 256 (98%) of this group. In 31 (12%) children residual mediastinal/hilar masses were found after completing the treatment. For this reason in 13 cases the number of chemotherapy courses and/or the dose of radiation therapy were increased. In two cases thoracotomy or thoracoscopy were performed, and in one case gallium scan was performed. In none of these patients active disease was found. Relapses occurred in 4 (12.9%) from the group of 31 children with residual mediastinal/hilar involvement 8-15 months after cessation of the therapy. Twenty seven children have been in first remission for 5-113 months (median, 34). In 225 patients with a complete resolution of their mediastinal/hilar masses, relapses occurred in 13 (5.7%) cases. Patients with residual mediastinal mass should be carefully evaluated before making a decision to complete their treatment, including CT scan, MRI, and gallium scan. In doubtful cases histopathological verification should be done.

[The analysis of failures in the treatment of children with chronic myelocytic leukemia in the studies of Polish pediatric leukemia/ lymphoma group]. / Analiza niepowodzen w leczeniu dzieci chorych na przewlekla bialaczke szpikowa w materiale Polskiej Pediatrycznej Grupy ds. Leczenia Bialaczek i Chloniaków.

94 children with chronic myelocytic leukaemia--CML treated in period 1975-1998 were included in the study. Twenty seven of 60 children were treated with hydroxyurea or busulfan with 6 MP. In 33 children aged 1, 5-17 years IFN (Interferon alfa) was applied at the dose of 3 millions units every second day subcutaneously. Our data showed that IFN alfa could be applied as an alternative treatment in children with CML, who have not a donor for allogenic BMT (bone marrow transplantation).

[One center's experience with fibrinolytic treatment in children]. / Leczenie fibrynolityczne u dzieci: doswiadczenia wlasne.

Fifteen children treated with fibrinolytic agents are presented. The most frequent indication was thromboembolic disease (TED). Eleven patients received streptokinase, 5-urokinase and 3-tissue plasminogen activator. Concomitant heparin was administered to 9 patients with TED. Total resolution was achieved in 9 children, partial improvement in 5; 1 child died during treatment without any improvement. Bleeding complications were observed in 6 patients, 1 of them died due to haemorrhagic stroke. According to the literature and our own experience, we recommend fibrinolytic agents as the treatment of choice for severe TED also in children.

[Symptomatic cytomegaly in a 6-month old infant]. / Objawowa cytomegalia u 6-miesiecznego niemowlecia.

The aim of our study is to present diagnostic and therapeutic problems in the case of 6-month old infant with cytomegaly infection. We observed typical symptoms of cytomegaly infection (central nervous system and liver damage, coagulopathy, anaemia) as well as electrolyte and serum lipid disturbances and urine densification abnormalities.

Can busulfan replace fractionated total body irradiation as conditioning regimen for allogeneic bone marrow transplantation in children with acute lymphoblastic leukemia.

The results of allogenic bone marrow transplantation (allo-BMT) in 26 children with ALL treated with the same initial- and relapse-BFM-protocols, but transplanted in different centers (Poznan, Wroclaw, Hannover) after conditioning with two different regimens have been compared. Ten children (6 in Poznan, 4 in Wroclaw) were conditioned for BMT with busulfan and cyclophosphamide when fractionated TBI (FTBI) was not available there. Sixteen children obtained FTBI and etoposide (11 in Hannover, where in children with ALL exclusively chemoradioconditioning regimen has been employed, and 5 in Poznan). It has been found, that the chemoconditioning procedure was probably less effective (5-year EFS 18%) than the regimen with FTBI (7-year EFS 60%). Therefore, TBI seems to be at this point still mandatory in pediatric ALL patients, unless combinations of chemotherapeutic drugs might be able to substitute the radiation in the future.

[Embryonal rhabdomyosarcoma of the uvula in a 5-year-old child]. / Rhabdomyosarcoma embrionale uvulae u 5-letniego dziecka.

A case of rhabdomyosarcoma embrionale uvulae in 5 years old girl was described. The child was treated at the beginning surgically, then chemotherapy was given according to schema IRS-III. After 2 years observation the child is in a good condition.

[Exchange transfusion in children with blastic hyperleukocytosis in acute lymphoblastic leukemia]. / Transfuzja krwi wymienna u dzieci z hiperleukocytoza blastyczna w przebiegu ostrej bialaczki limfoblastycznej.

In 10 children with acute lymphoblastic leukaemia (mean leucocyte count 452 x 10(9)/l) 17 exchange transfusions were done for rapid reduction of this count. The control group comprised 11 children with similar values of white blood cell counts (mean 324 x 10(9)/l) treated initially with small, increasing doses of corticosteroids. In contrast to acute myeloid leukaemia the results do not support the usefulness of exchange transfusions in children with hyperleukocytosis during ALL.

[Allogeneic bone marrow transplantation in proliferative blood diseases in children and adolescents (preliminary observations)]. / Transplantacja szpiku allogenicznego w chorobach rozrostowych krwi u dzieci i mlodziezy obserwacje wstepne.

Transplantation of allogeneic bone marrow was done in 4 patients during the second remission of acute lymphoblastic leukaemia (3 cases) and B-cell non-Hodgkin lymphoma with dissemination to bone marrow (1 case). The engraftment and complete haematological reconstruction was achieved.

Evaluation of the LSA2L2 protocol for treatment of childhood non-Hodgkin's lymphoma. A report from the Polish Children's Leukemia/Lymphoma Study Group.

From 1979 to 1982, 97 previously untreated children with non-Hodgkin's lymphoma were treated with the LSA2L2 protocol proposed by Wollner. Staging was done according to the criteria proposed by Wollner and re-staged according to Murphy's criteria. Each patient, regardless of clinical stage and histologic group, was given the same chemotherapy. A total of 28 nonrandomized patients received either cranial irradiation or intermediate-dose intravenous methotrexate as CNS prophylaxis. The complete remission rate was 72.6%. The 3-year actuarial estimate of survival was 73% and the disease-free survival rate was 62% for all responders, and was influenced by stage and main clinical features present at the time of initial presentation. The overall survival rate at 3 years is 52%. Of 26 children who failed to achieve complete remission, 21 had presented with disseminated disease. Also, 20/67 patients who entered remission have suffered relapses: four in the bone marrow, seven in the CNS, and nine with local relapses. Only one of 28 children who received CNS prophylaxis developed CNS disease as the site of first relapse, whereas six of those who received only intrathecal chemotherapy did so. This study confirms the improved outlook in comparison with a historical group for children with non-Hodgkin's lymphoma by the use of an intensive multiple-drug regimen and CNS prophylaxis.