[Fates of children with many-year remission in lymphatic system neoplasms. Follow-up from 6 to 15 years].
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Biomedical subjects
Publications and source records attributed to W Balwierz.
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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.
Lymphocyte depletion Hodgkin's disease (LDHD) was diagnosed in 8 of 40 children with Hodgkin's disease treated from July 1969 to September 1976. All of the children received conventional radiotherapy and combination chemotherapy with mustine, vinblastine, procarbazine, and prednisone (MVPP). In LDHD children the disease was associated with severe anemia, splenomegaly presence of mediastinal enlargement, and dissemination at the time of diagnosis. Three children with LDHD did not achieve remission and died with uncontrolled disease. In two others, relapses occurred and led to death in one. Only three children remain in their first remission. Only 3 of 32 patients with non-LDHD relapsed and entered second remission. All 32 patients were free of disease at the time of evaluation, with mean survival of 88.2 months. We conclude that LDHD in childhood is frequently associated with clinically advanced disease and still has a bad prognosis. Alternative approaches to its therapy are needed.
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Until recently chemotherapy in retinoblastoma was used as adjuvant therapy after enucleation in cases with extraretinal spread of the disease (weal extension, orbital extension, neoplastic infiltrates of the optic nerve at resection line, intracranial metastasis and generalized disease). Recent experience has proved that use of chemotherapy for intraocular retinoblastoma before local treatment (so called "chemoreduction") has allowed not only to decrease the number of enucleations and indications for external beam irradiation or limit the extension of local therapy; but also to increase the chances for vision preservation and to decrease the risk of severe complications. Twenty children aged 0,5-96 months (with lesions in 29 eyes) in whom intraocular retinoblastoma was diagnosed between January 1996 and June 2000, were the subject of this study. Among 29 children, in 15 (52%) stage V according to Reese-Ellsworth was established. Enucleation before chemotherapy was necessary in 9 cases, and in two more children the eye had to be removed after 1-2 courses of chemotherapy. In 11 remaining children (with 18 involved eyes) VEC chemotherapy combined with delayed local therapy (cryotherapy, photocoagulation, brachytherapy) was employed. Out of 18 treated cases enucleation could be avoided in 13 (72%), including 12 qualified as Reese-Ellsworth stage II or I. No eye with stage V could be saved. First-line chemotherapy combined with local treatment should be standard treatment for intraocular retinoblastoma groups I and II. More effective therapy is required for advanced cases particularly for Reese-Ellsworth eye group V.
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.
Within the past 16 years, 2004 children with the acute lymphoblastic leukemia were treated at the Centres of the Polish Pediatric Study Group. The treatment was completed in 887 patients (44.3%) with the first remission. Recurrence was noted in 180 children (20.3%). This group was analysed in view of the type of therapy and its effect on the survival rate, significance of recurrence following therapy, character and localization of recurrent disease, and further fate of patients. It was found, that patients with isolated late nuclear recurrence have greatest chances to achieve subsequent remission. Most frequent and severe is recurrent bone marrow involvement which requires intensive chemotherapy combined with bone marrow transplantation due to unfavourable prognosis. Patients with the first recurrence of the acute lymphoblastic leukemia have a chance to achieve subsequent remission and long-term survival.
Recurrence was noted in 18.5% of 194 children, in which chemotherapy with MVPP regimen produced complete I remission. In 6 out of 36 children with recurrent disease MVPP regimen was repeated, while the remaining children were treated with B-DOPA alone or combined with MOPP regimen. Local radiotherapy was used in 17 children. The second complete remission was achieved in 30 (83.7%) children. Thirteen out of 36 patients died because of the progress of the disease (11 children), and for complications (2 children). Percentage of persisting 5- and 10-year II remissions are 58.2% and 54.6%, respectively. A 5- and 10-year survival rates in children with recurrent disease are 80.5% and 60.5%, respectively. Our relatively favourable results we associate--first of all--with the chemotherapy intensity.
In two out of 59 children with Hodgkin's disease treated with MVPP regimen combined with local irradiation and followed up over 10 years the secondary neoplasms were detected, i.e. in 3.4% with persisting remission of the underlying disease. Chondrosarcoma was diagnosed in one patient in the field of irradiation (after 13 years). This patient died. In the second patient two different tumors (squamous epithelioma and fibrosarcoma) developed after 7 and 9 years following irradiation of two different areas. Actually, there are not any symptoms in this female patients (working). To decrease the incidence of these serious complications of Hodgkin's disease treatment regimens introduced by the Polish Pediatric Leukemia Study Group since 1988, the use of alkylating agents in limited, and the dose of local irradiation is decreased.
Totally 209 children were treated within 1971-1982. Complete remission was achieved in 95.6%. Recurrence was noted in 36 patients (18.6%); 20 patients (9.9%) died due to progression of the disease and 9 patients (4.4%) because of complications. The first remission remains constantly in 150 patients for 63-206 months, including that after completion of therapy during 45-206 months. Asymptomatic 5- and 10-year survivals are the following: 82.9% and 80.1% respectively; 5- and 10-year survivals 91.9% and 89.8%, respectively. Expanded experience served as base to design a new regimen (introduced in 1988) which is being supposed to reduce untoward reaction by decreasing the number of MVPP cycles and irradiation doses.
The second remissions were achieved i 63% out of 46 children with relapsing non-Hodgkin's lymphoma. Therapy was terminated in 10 children (21%). Six of them are in the second remission, three children are in the third--the fifth remission after termination of therapy, one child died during the second relapse which occurred two years after the termination of therapy in the second remission. It seems that preliminary low stage of the disease and localization of the relapse in the lymph nodes or CNS favourably influence the prognosis.
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