International note: second malignant neoplasms in children: a multicenter study of the Polish Pediatric Leukemia/Lymphoma Group.
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Child↗
Biomedical subjects
W Balwierz
Publications and source records attributed to W Balwierz.
Dexrazoxane has no impact on sensitivity of childhood leukemic blasts to daunorubicin.
Dexrazoxane (DEX) prevents the formation of free radical, lipid peroxidation and cardiotoxicity caused by anthracyclines. Due to a concern about its possible interference with anthracyclin cytotoxicity, the in vitro effect of DEX on daunorubicin (DNR) cytotoxicity, cell cycle and induction of apoptosis by annexin-V was investigated. The sensitivity to DEX, DNR and their combination was tested by the MTT assay in human promyelocytic leukemia HL-60, the erythroid blast crisis CML K562 cell lines and in 45 children with ALL and AML. Cell cycle analysis and annexin-V expression were performed by flow cytometry. It has been observed that DEX itself weakly, but significantly caused cytotoxicity in both cell lines and in patient samples, especially in initial ALL samples. DEX sensitized K562 and HL60, but not patient samples, to cytotoxicity of DNR. The percentage of necrotic/apoptotic cells, as detected in cell cycle analysis and annexin V staining, was higher after exposure to DEX +/- DNR, when compared to respective samples not treated with DEX, in both cell lines but not in patient samples. Expression of annexin V induced by DEX in both cell lines was enlarged, regardless of the presence of DNR. This difference was not observed in patient samples, however, the number of cells expressing annexin V was higher after exposure to DEX +/- DNR in comparison to respective samples not treated with DEX. In conclusion, it seems that DEX possibly has no impact on the sensitivity of childhood leukemic blasts to DNR, however, has weak cytotoxic properties itself.
Adolescent↗
In vitro comparative antileukemic activity of various glucocorticoids in childhood acute leukemia.
Resistance to glucocorticoids is nowadays one of the strongest adverse risk factors in the treatment of childhood acute lymphoblastic leukemia (ALL). Differential in vitro antileukemic activity of various glucocorticoids and their cross-resistance pattern in childhood acute lymphoblastic and myeloblastic leukemia was determined by means of the MTT assay in 49 successfully tested samples of childhood acute leukemia. The equivalent antileukemic concentrations of respective drugs against lymphoblasts in de novo ALL samples were: 35 microM of hydrocortisone; 8 microM of prednisolone; 1.6 microM of methylprednisolone; 0.47 microM of dexamethasone and 0.23 microM of betamethasone. In comparison to initial ALL samples, the group of relapsed ALL was more resistant to: prednisolone (38-fold, p=0.004), dexamethasone (>32-fold, p=0.004), methylprednisolone (37-fold, p=0.039), betamethasone (38-fold, p=0.018) and hydrocortisone (33-fold, p=0.030). The group of acute myeloid leukemia (AML) samples were resistant to: prednisolone (>83-fold, p<0.001), dexamethasone (>32-fold, p<0.004), methylprednisolone (>65-fold, p=0.003), betamethasone (>66-fold, p=0.004) and hydrocortisone (61-fold, p=0.007), when compared to ALL at presentation. A significant cross-resistance between all used glucocorticoids as well as between glucocorticoids and other tested anti-leukemic drugs was found. In some individual cases in vitro glucocorticoid cross-resistance was less pronounced and relatively good antileukemic activity of betamethasone was observed.
Antineoplastic Agents↗
Induction of apoptosis and bcl-2 expression in acute lymphoblastic leukaemia and non-Hodgkin's lymphoma in children.
bcl-2 expression is associated with the expression of the multidrug resistance molecule (p-gp) and the resistance of leukaemia cells to the induction of apoptosis. The activity of p-gp is the main mechanism of resistance of leukaemia cells to chemotherapy. This study assessed the induction of apoptosis of acute lymphoblastic leukaemia (ALL) and non-Hodgkin's lymphoma (NHL) blastic cells following in vitro treatment with dexamethasone (DXM), vincristine (VCR), and tumour necrosis factor (TNF) in relation to the expression of bcl-2 and p-gp. Common ALL (cALL; n = 24 patients), common ALL with co-expression of myeloid antigens (cALL + My; n = 9), ALL-T (n = 9), and NHL [n = 6 (T type, n = 2; B type, n = 4)] were included. The expression of bcl-2 and p-gp and apoptosis were assayed by flow cytometry. Spontaneous apoptosis was low (< 5%) in cALL and ALL-T and higher (> 8%) in NHL and cALL + My. A high frequency of bcl-2 expression was noted in cALL and cALL + My. A high frequency of p-gp expression was observed in cALL + My, ALL-T, and NHL. There was a reverse association between bcl-2 expression and spontaneous apoptosis. DXM-induced apoptosis was observed in 52.63%, TNF-induced in 42.85%, VCR-induced in 36.36%, and GM-CSF-induced in 33.3% of leukaemia and lymphoma cases. DXM and GM-CSF-driven apoptosis was reversibly associated with bcl-2-expression (bcl-2-dependent mechanism). VCR and TNF-driven apoptosis was not associated with bcl-2 expression, suggesting a different, bcl-2-independent, mechanism(s) of its induction. The in vitro induction of apoptosis was not associated with expression of p-gp.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Expression of CD20 on acute lymphoblastic leukemia cells in children.
CD20 determinant expressed on B precursors is associated with regulation of proliferation, apoptosis and maturation of these cells. The acute lymphoblastic leukemia "common" type (cALL) based on expression of CD20 is subdivided in type I and II. However, the clinical significance of CD20 expression on cALL and significance of cALL type I and II discernment are not fully elucidated. The association of CD20 expression with the expression of multidrug resistance molecule (MDR), CD34, atypical immunophenotypes of leukemia cells and response to induction therapy were determined in the group of 147 patients with acute lymphoblastic leukemia (ALL) B progenitor type (ALL-proB -14 patients) and common type (cALL-133 patients). The expression of CD20 on leukemia cells was studied routinely at diagnosis before the therapy. This expression was noted on leukemia cells of 6 ALL-proB patients (42.8%) and 66 cALL patients (49.6%). The expression of CD20 showed no association with the expression of CD34, CD22 and MDR. The reverse association was observed between CD20 expression and the presence of co-expression of myeloid (CD13, CD33, CD65, CD15) and T lymphoid determinants (CD2, CD5, CD7) on leukemia cells. The effect of induction therapy analyzed as time of blast cells cytoreduction in peripheral blood and time of reaching the complete remission showed the slower clearance of peripheral blood from blast cells associated with expression of CD20. There was no association of CD20 expression with the time of reaching the hematological remission. The above results suggested a "protective" role of CD20 against co-expression of other determinants (myeloid and lymphoid) and no association with the results of induction therapy.
Adolescent↗
[Evaluation of growth and body weight in children and adolescent during and after treatment of acute lymphoblastic leukemia].
The aim of the study was to estimate growth curve and body mass during and after a treatment of ALL. Retrospective study group included 48 children (27 boys and 21 girls). The age at the start of the treatment varied from 1.4 up 17 years, during our evaluation 4.6-25.4 years. Patients were treated according to modified American (New York Protocol) and German (BFM) protocols. 43 children received central nervous system radiation in a dose of 14-24 Gy. All children completed the treatment protocol and are in the remission. Growth velocity and body mass were estimated during and after the ALL treatment. During the treatment growth retardation was observed at 34 children (2/3 patients). No significant difference in growth velocity was found between group of standard and high risk of ALL. Combined radiotherapy and chemotherapy has probably more influence for growth retardation than chemotherapy alone. Obesity was stated at 13 patients (27%), mostly boys. After the treatment 9 children were permanently obese. Body mass deficiency was found at 5 patients during the treatment and was the same when the treatment protocol was completed.
English Abstract↗
Incidental neuroblastoma.
The diagnosis of neuroblastoma in its early stage, especially in asymptomatic children, with the so-called incidentally diagnosed disease, may be associated with a good prognosis. The aim of this study is an attempt at analyzing this problem. Between 1 January 1993 and 30 April 1998, 40 children with newly diagnosed neuroblastoma started therapy at the authors' department. The disease was diagnosed incidentally in 5 (12.5%) patients. In no incidentally diagnosed child was stage IV disease detected, while in the remaining patients its incidence was 71%. All the children (median age 2 months) with incidental diagnosis have remained alive (median 39 months) in continuous remission without treatment. Among 35 children (median age 2 years and 7 months) with overt neuroblastoma, 18 died (median survival time 14.5 months). Seventeen patients have remained alive (median 45 months). The results show that children with incidentally diagnosed neuroblastoma are characterized by a more favorable prognosis than children with clinical disease.
Humans↗
[Polish Paediatric Leukaemia/Lymphoma Study Group - 25 years of activity].
In 1974, Professor Jerzy Armata initiated the organization of a multicentre cooperative group, which later became known as the Polish Paediatric Leukaemia/Lymphoma Study Group (PPL/LSG). At first the Group included three centres headed by Professor J. Armata (Cracow), Professor U. Radwanska (Poznan) and Professor J. Boguslawska-Jaworska (Wroclaw), but gradually it extended to nine university departments of paediatric hematologic oncology. Within the past 25 years, the introduction and employment of standardized, common treatment regimens based on our experience, as well as on the results of other oncological groups in Europe and the United States, resulted in a significant improvement of therapeutic results in childhood cancer, especially of the lymphatic and haematopoetic systems. The improvement in the recovery rates was as follows: in acute lymphoblastic leukaemia: from 25% to 84%, in non-Hodgkin's lymphoma recovery: from 28% to 82%, in Hodgkin's disease: from 80% to 90%. In acute non-lymphoblastic leukaemia the improvement in treatment results (from 15% to 40%) was also significant but still unsatisfactory.
Child↗
[Intermediate doses of cytosine arabinoside in the treatment of acute non-lymphoblastic leukaemia in children].
Between 1995-1997, at 7 centres of the Polish Paediatric Leukaemia/Lymphoma Study Group (PPLLSG) treatment was started in 102 children with acute non-lymphoblastic leukaemia. Sixty-two children treated according to the new protocol adjusted for risk factors were evaluated. Thirty-one patients belonged to standard risk and 23 to high risk group. Eight children were not evaluated due to early death. Out of 62 children, 44 (70,9%) achieved remission; in standard and high risk groups the rates of remission were 87,5% and 73%, respectively. Four-year event-free survival (EFS), relapse-free survival (RFS) and overall survival (OS) probability in all patients were: 40,2%, 42% and 59% respectively, in standard risk group: 49,5%, 52,5%, 59,1%; in high risk group: 42%, 43,4% and 57,8%. In comparison with the previous period (1983-1994) EFS increased from 30% to 42%, which was statistically insignificant.
Adolescent↗
[Preliminary results of BFM 96 protocol in treatment of childhood ALL relapse in the experience of the Polish Paediatric Leukaemia /Lymphoma Study Group].
Between 1998 and 1999, 36 children aged from 3 months to 18 years (10 girls and 26 boys) with first relapse of acute lymphoblastic leukaemia were included in the study. The children were treated according to the BFM 96 relapse protocol. There were 24 cases with early (including 9 children with very early) and 12 cases with late relapse ( BM-20, local extra BM-6, combined 10). The overall second complete remission (CR) rate was 83,33%. The probability of overall EFS after 2 years was 73,3%. The results obtained with BFM 96 chemotherapy in children with first late relapse are acceptable. For children with early relapses, megachemotherapy with BMT in second remission should be used.
Adolescent↗
[Adverse reactions associated with the use of L-asparaginase during therapy of patients with nB non-Hodgkin's lymphoma. Report of the Polish Paediatric LeuKaemia/Lymphoma Study Group].
The aim of the study was to determine the side effects of asparaginase administration during treatment protocol for childhood non-Hodgkin's lymphoma (NHL). Drug adverse reactions occurred in 20/66 of patients (30,3%) treated in 9 centres in Poland between 1993 and 1998. The most common side effects were coagulation disturbances in 12/66 of the children (18,2%), which occurred due to reduced production of important coagulation factors. Six patients (9,1%) developed impairment of liver function (9,1%). Drug toxicity caused the modifications of treatment protocol in 12/66 (18,2%) of patients, mainly in the induction phase; 3 children died due to relapse of disease.
Adolescent↗
[The incidence and treatment of the first relapse in children with Hodgkin's disease].
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.
Adolescent↗
[Results of the treatment of myelodysplastic syndrome (MDS)obtained by the Polish Paediatric Leukaemia /Lymphoma Study Group].
Sixty children with MDS treated in six centres of the Polish Paediatric Leukaemia/Lymphoma Study Group in the period 1975-1999 were included in the study. In 20 children RAEB-T, in 13 RA, in 21 RAEB and in 6 CMML were diagnosed. Our own and literature data showed that BMT is the best therapy for children with MDS. We need a new comprehensive protocol for the diagnosis and treatment of children with MDS in Poland.
Adolescent↗
[G-CSF and GM-CSF in treatment of neutropaenia after chemotherapy in children with neoplasms].
A total number of 608 cycles of G-CSF and/or GM-CSF was applied in 280 patients aged from 6 months to 20 years during neutropaenia associated with chemotherapy of children's neoplasms (NHL-124, NBL-42, RMS-36, Nephroblastoma-18, Osteosarcoma-17, Ewing's Sarcoma-14, Hepatoblastoma-6, Neurofibrosarcoma-6, PNET-5, Medulloblastoma-3, Fibrohistiocytoma-3, Angiosarcoma-2, other - 4). G-CSF - Neupogen (Filgastrim, Hoffman La Roche - 492 cycles) and GM-CSF - Leucomax (Molgramostim, Shering Plough - 116 cycles) were administered 5 mg/kg/day s.c. Forty one children with malignancies (NHL -21 cases, solid tumours -17) treated before cytokines were in use served as a control group. Our study demonstrated that G-CSF and GM-CSF therapy, gives a shorter period of neutropaenia, reduction of the number of febrile days, decreased frequency of infection and shortened its duration.
Adolescent↗
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.
Adolescent↗
Tumour necrosis factor alpha (TNF alpha) and leukaemic cells: secretion and response.
Leukaemic cells from various types (ALL-O, ALL-proB, ALL-common [cALL], ALL-T) of acute lymphoblastic leukaemia (ALL) and non-lymphoblastic leukaemia (ANLL) were studied for their ability to produce tumour necrosis factor alpha (TNF). The role of exogenous and endogenous TNF in proliferation in vitro of leukaemic cells was also assessed. Leukaemic cells from different types of acute leukaemia were found to show major differences in their ability to proliferate in vitro. High production of TNF was observed mainly in ALL-T and ANLL but in ALL-T it was not associated with the proliferation rate of leukaemic cells. In most instances no bioactive TNF was detected. The variable response of leukaemic cells (inhibition or stimulation of proliferation) to exogenous human recombinant (rTNF) was assessed. The role of endogenous TNF as a growth factor or agent associated with resistance to exogenous TNF was excluded as judged by a lack of effect of the TNF synthesis inhibitor pentoxifylline (PTX) and of anti-TNF antibody and PTX/rTNF. There was no association of the effect of rTNF on proliferation of leukaemic cells with their immunophenotype, spontaneous release of TNF or proliferation rate. Hence, this study does not provide evidence for the role of TNF as a growth factor for leukaemic cells or for its role in the inhibition of proliferation of leukaemic cells.
Adolescent↗
[Does residual mediastinal mass in children with completed treatment of Hodgkin's disease affect the incidence of relapses?].
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.
Adolescent↗
[The efficacy of BFM-90 program in the treatment of acute lymphoblastic leukemia in children in the studies of Polish pediatric leukemia/lymphoma group].
Between years 1993 and 1998, 113 children aged from 6 months to 18 years (41 girls and 72 boys) with first relapse of acute lymphoblastic leukaemia (ALL) were included in the study. All children were treated according to BFM-90 relapse protocol. Thirty-two cases were classified as very early relapses, 56 as early and 25 as late relapses. Sixty-one children had isolated bone marrow relapse, in 30 children extramedullary relapse occurred (in 21 children in central nervous system and in 16 children in testes). There were 23 combined relapses. Remission was achieved in 12 children with very early relapse (78.12%), 32 children with early relapse (85.71) and 19 children with late relapse (96%). Event-free survival in 30 months of follow-up was 29.2%, 59.0% and 73.2% for very early, early and late relapses, respectively. Sixteen children with relapsed ALL after chemotherapy according to BFM-90 relapse protocol underwent high-dose therapy with hematopoietic stem cell transplantation (in 3 cases autologous and in 13 cases allogeneic). In 6 children isolated bone marrow relapse occurred after transplantation, all of them died during subsequent chemotherapy. Ten children is alive and well from 2 to 43 months after transplantation. The results obtained with BFM-90 chemotherapy in children with first early relapses are not acceptable. Such patients require high-dose chemotherapy and transplantation of hematopoietic progenitor cells.
Adolescent↗