[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.

[High risk acute lymphoblastic leukaemia in children. Preliminary report after introducing a new version of New York (1997) protocol adjusted to the age of the patients. Report of the Polish Paediatric Leukaemia/Lymphoma Study Group]. / Ostra bialaczka limfoblastyczna u dzieci w grupie duzego ryzyka. Wstepne obserwacje po wprowadzeniu kolejnej modyfikacji (1997) protokolu Nowy York dostosowanej do wieku. Raport Polskiej Pediatrycznej Grupy ds. Leczenia Bialaczki i Chloniaków.

The paper presents the experience of the Polish Paediatric Leukaemia/Lymphoma Study Group in the treatment of high-risk acute lymphoblastic leukaemia in children using a new version of the New York (1997-1999). Protocol with treatment intensity adjusted according to the age of the patients. From April 1997 to December 1999 a group of 49 children with leukocytosis ranging from 50 900/mm3 to 580 000/mm3 (median 122 000/mm3) and 6 children with leukocytosis below 50 000/mm3 and poor response to steroids were treated with this protocol. Children below 10 years (43 patients) were treated according to the previous protocol, children above 10 years (12 patients) were treated with intensified protocol (high doses of ARA-C in consolidation and intermediate doses of Mtx in maintenance). Induction was identical for all patients. Complete remission was achieved in 92.6% patients. There were 2 relapses. Six children died - 3 without remission, 2 due to a relapse, 1 due to treatment complications. The current opinions concerning classification of HRG-ALL and treatment possibilities in this group of children are discussed.

[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.

Immunologic status of children with Hodgkin's disease (HD).

Concentration of serum immunoglobulins IgG, IgM, IgA, E-, EAC-rosette forming lymphocyte counts and phagocytic activity of granulocytes to Staphylococcus aureus were studied in venous blood of 12 children with HD and 15 normal controls during the combined long term radio- and polichemotherapy. The decrease in E- and EAC-rosette forming lymphocyte counts at diagnosis and during the combined radio- and chemotherapy single cycle and long-lasting treatment were found. The quantity of serum immunoglobulins IgA and IgM was above normal limits at diagnosis and decreased during 2 years of treatment. The impairment of phagocytic activity before treatment and during long term therapy was found. Analysis of the survival rate curves suggests the prognostic value of the initial T- and B-lymphocyte numbers in peripheral blood.

Immunological follow-up of non-Hodgkin's lymphoma (NHL) in children.

Concentrations of immunoglobulins IgG, IgM, IgA, E-, EAC-rosette forming lymphocyte counts and phagocytic function of granulocytes to Staphylococcus aureus were studied during the long-term polychemotherapy in 19 children with NHL and in the control group consisting of 15 healthy children. The decrease in levels of IgA and IgM, E and EAC rosetting lymphocyte counts following intensive long therapy was observed. No significant variations in immunoglobulin subclasses levels before and after single cytostatic cycle were found. The granulocyte phagocytic activity in NHL patients was above normal range. For evaluation of the prognostic value of NHL immunological classification survival rate curves were analyzed. It has been demonstrated that T-lymphoblasts proliferation is an unfavorable prognosis marker.

Leukocyte functions study during the treatment of acute lymphoblastic leukemia (ALL).

In 40 children with acute lymphoblastic leukemia (ALL) and 15 healthy children the leukocyte capillary migration, the phagocytic activity of peripheral granulocytes and monocytes to Staphylococcus aureus, Escherichia coli and Candida albicans were studied. The examinations were performed at diagnosis prior to any therapy, after remission induction, after cranial irradiation and 6 times during the maintenance therapy. The decreased phagocytic activity of monocytes to three studied microorganisms was found during two-year-observation, while the impairment of granulocytes phagocytosis only to Escherichia coli and Candida albicans was observed. It was suggested that degree of phagocytosis defect may depend on the stage of ALL and that it differs in respect of microorganisms used.

The study of T-lymphocytes, granulocyte's phagocytic activity, and adherent cells in patients with acute lymphoblastic leukemia during levamisol therapy.

12 children with acute lymphoblastic leukemia remaining in remission for 1-3 years, were studied during levamisol therapy. T-lymphocytes count, phagocytic activity of granulocytes the adherent cell number were investigated. The clinical state of patients before, during and after levamisol treatment was evaluated. The increased resistance to infections after levamisol therapy was noted. The rise of T-lymphocyte and phagocyting granulocytes number was observed in 70% of patients after 6 weeks of therapy. At the same time the decrease of phagocytic index was found. No essential variations in adherent cells count were noted. The patients who did not respond to the levamisol treatment relapsed in 2-3 months.

The study of phagocytic activity of granulocytes during the treatment of acute lymphoblastic leukemia.

The phagocytic function of granulocytes from peripheral blood of 14 children with ALL before and during therapy was studied. The children were treated according Pinkel's Protocol VIII. Peripheral blood granulocytes were evaluated for their phagocytic activity by tube phagocytosis test with Staphylococcus aureus. The transient decrease of phagocytic activity after cranial irradiation was noted. This impairment was coupled with increased incidence of infections.