In vitro sensitivity of leukemic cells to nucleoside derivatives in childhood acute leukemias: good activity in leukemic relapses.

Nucleoside analogues such as fludarabine and cladribine are used in therapy of indolent lymphomas and leukemias in adults, while cytarabine is used mainly in protocols for acute leukemias. Mechanisms of their activity is based on inhibition of enzymes involved in DNA, RNA and protein synthesis. The objective of the study was the analysis of in vitro cellular drug sensitivity in childhood acute lymphoblastic (ALL) and myeloid (AML) leukemia. Isolated leukemic cells obtained from 264 patients, including 152 initial ALL, 45 relapsed ALL, 54 initial AML and 13 relapsed AML were tested for cytotoxicity for fludarabine, cladribine, and cytarabine by the MTT assay. Drug concentration lethal to 50% of tested cells was regarded as a value of drug resistance. Three tested nucleoside analogues showed highest cytotoxicity against initial ALL samples. Samples of relapsed ALL and initial AML were more resistant than ALL de novo ones. Unexpectedly, no differences were observed between initial and relapsed AML samples for all tested drugs, what suggests that nucleoside analogues are active drugs in relapsed AML, which is commonly regarded as a resistant disease. All tested drugs presented significant cross-resistance in each of analyzed subgroups. In summary, tested nucleoside analogues presented relatively good activity against childhood leukemias at relapse stage.

Late cognitive and radiographic changes related to radiotherapy: initial prospective findings.

BACKGROUND: Assumptions about the damaging effects of radiotherapy (XRT) are based on studies in which total dose, dose fraction, treatment volume, degree of malignancy, chemotherapy, tumor recurrence, and neurologic comorbidity interact with XRT effects. This is a prospective, long-term study of XRT effects in adults, in which total dose and dose fraction were constrained and data related to tumor recurrence and neurologic comorbidity (e.g., hypertension) were excluded. METHODS: The effects of XRT on the cognitive and radiographic outcomes of 26 patients with low-grade, supratentorial, brain tumors yearly from baseline (6 weeks after surgery and immediately before XRT) and yearly to 6 years were examined. Radiographic findings were examined regionally. RESULTS: Selective cognitive declines (in visual memory) emerged only at 5 years, whereas ratings of clinical MRI (T2 images) showed mild accumulation of hyperintensities with post-treatment onset from 6 months to 3 years, with no further progression. White matter atrophy and total hyperintensities demonstrated this effect, with subcortical and deep white matter, corpus callosum, cerebellar structures, and pons accounting for these changes over time. About half of the patients demonstrated cognitive decline and treatment-related hyperintensities. CONCLUSIONS: There was no evidence of a general cognitive decline or progression of white matter changes after 3 years. Results argue for limited damage from XRT at this frequently used dose and volume in the absence of other clinical risk factors.

Development and initial validation of an Arabic version of the Expanded Trail Making Test: implications for cross-cultural assessment.

The performances of Sudanese subjects, both normal and brain damaged, on an Arabic version of the Expanded Trail Making Test were compared to those of normal and brain-damaged subjects from the United States, who completed the standard English version of this test. Preliminary psychometric properties of the Arabic version of the Expanded Trail Making Test were defined. Significant intergroup differences in performance were observed. Interestingly, the performances of Sudanese normals were found to be similar to those of U.S. brain-damaged subjects. The results are discussed in terms of reducing neuropsychological diagnostic errors attributable to ethnocultural factors.

Subject-selection procedures in neuropsychological research: a meta-analysis and prospective study.

The present study examined methods of control- and experimental-subject selection in neuropsychological research. Using both meta-analytic and prospective procedures, it was found that varied subject-selection procedures can potentially confound the results of neuropsychological studies and, by extension, can thwart the formulation of laws regarding neuropsychological function. In terms of selecting control subjects, the current findings suggest that individuals who self-report a negative history for neuropathology and psychopathology are adequate, perhaps even preferable, for inclusion. In terms of selecting experimental subjects, it appears preferable, if not essential, to obtain lesion confirmation through relevant neurodiagnostic tests. Based on these findings, it is recommended that subject selection be made on the basis of scientific merit rather than convenience or availability.

[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]. / Objawy niepozadane leczenia preparatami L-asparaginazy u chorych z nieziarniczym chloniakiem zlosliwym typu NB w oparciu o material Polskiej Pediatrycznej Grupy ds. Leczenia Bialaczek i Chloniaków Zlosliwych u dzieci.

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.

[Abdominal presentation of B-cell non-Hodgkin's lymphoma (B-NHL) - surgical treatment and its results. Report of the Polish Paediatric Leukaemia/Lymphoma Study Group]. / Manifestacja brzuszna chloniaka B-komórkowego u dzieci - interwencja chirurgiczna i wyniki leczenia. Raport PPGLBC.

The aim of this study was to analyse the effect of LMB-89 protocol and surgical procedure at initial laparotomy on the outcome in children with abdominal B-cell NHL. The initial surgery intervention was: complete resection (20% pts), subtotal resection (20%), partial resection (4%), biopsy (36%). Postoperative complications occurred in 5 children. Complete recovery (CR) was achieved in 92% pts. There were 4% non responder patients. Two patients died before CR evaluation (tumour lysis syndrome; bleeding and multi organ failure after initial surgery). One patient died in CCR from sepsis probably influenced by the previous local operation. 10.8% patients relapsed. The estimate EFS for all patients with AB-NHL is 81%, 85% for stage III and 73% for stage IV. Major surgery in advanced stages is not recommended since it delays chemotherapy and fails to improve overall survival.

[G-CSF and GM-CSF in treatment of neutropaenia after chemotherapy in children with neoplasms]. / G-CSF i GM-CSF w leczeniu neutropenii po chemioterapii nowotworów u dzieci.

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.

[The analysis of failures in the treatment of children with non-B non-Hodgkin's lymphoma. Polish pediatric leukemia/lymphoma study group report]. / Analiza niepowodzen w leczeniu dzieci z nieziarniczym chloniakiem zlosliwym typu NB. Raport Polskiej Pediatrycznej Grupy ds. Leczenia Bialaczek i Chloniaków zlosliwych u dzieci.

The aim of the study was to evaluate the results of treatment of 46 children with non B non-Hodgkin's Lymphoma registered in 7 centers of Polish Paediatric Leukaemia/Lymphoma Study Group from 1993 to 1998. The patients were treated according to BFM-90 protocol based on German regimen. The overall probability of event-free survival for the all children after 4 years of follow-up was 71%, for patients in stage III--65%, stage IV--70%. The achieved results were not as positive as in the BFM Study Group, what was related to: the great number of children with advanced stage of disease (54.3%), the late final diagnosis, the great number of recurrences (22.5%) and deaths caused by the toxicity of medication (6.5%) (infections, drug toxicity).

[The efficacy of G-CSF and GM-CSF in the adjunctive treatment of infections complicating chemotherapy of solid tumors in children. Report of Polish Pediatric Leukemia/Lymphoma Treatment Group]. / Skutecznosc G-CSF i GM-CSF w leczeniu wspomagajacym zakazen wiklajacych chemioterapie guzów litych u dzieci. Raport PPG/LBC.

Total number of 306 cycles of GM-CSF-Leucomax Sandoz (5 mg/kg/day s.c.) and/or G-CSF Filgrastim Hoffmann-La Roche (5-10 mg/kg/day s.c.) was applied in 146 children aged from 0.5-18 years during neutropenia associated with chemotherapy of solid tumours. Seventeen children with malignancies served as a historical control group. Our study have demonstrated after both G- and GM-CSF therapy shorter period of neutropenia, reduction of the number of febrile days and a decreased frequency of infectious complications and infection's duration.

[The efficacy of G-CSF and GM-CSF in the adjunctive treatment of infections complicating chemotherapy of acute leukemia in children]. / Skutecznosc G-CSF i GM-CSF w leczeniu wspomagajacym zakazen wiklajacych chemioterapie ostrych bialaczek u dzieci.

Growth factors (G-CSF Neupogen Roche i GM-CSF Leucomax Sandoz) have been applied in 133 therapeutic and prophylactic cycles in 88 children with acute leukaemias. GM-CSF and G-CSF were administered subcutaneously or intravenously at a dose of 2 to 8 micrograms/kg for 2 to 28 days. 45 prophylactic cycles had been administered in children with acute lymphoblastic leukaemia in high risk group and in relapses, which caused significant reduction in the number of infections, time of neutropenia and fever. Therapeutic cytokines cycles were applied when the absolute neutrophil count have fallen below 0.5 x 109/l. We observed significant reduction in duration of neutropenia in these cycles. Tolerance of GM-CSF and G-CSF was good. Side effects were not observed.

[The effectiveness of G-CSF and GM-CSF in the adjunctive treatment of infections complicating chemotherapy of non-Hodgkin's lymphoma in children. Report of Polish Pediatric Leukemia/Lymphoma Treatment Group]. / Skutecznosc G-CSF i GM-CSF w leczeniu wspomagajacym zakazen wiklajacych chemioterapie nieziarniczych chloniaków zlosliwych u dzieci. Raport PPG/LBC.

Total number of 252 cycles of GM-CSF-Leucomax Sandoz (5 mg/kg/day s.c.) and/or G-CSF Filgrastim Hoffmann-La Roche (5-10 mg/kg/day s.c.) was applied in 124 children aged from 0.5-20 years during neutropenia associated with chemotherapy of non-Hodgkin's lymphoma (NHL). Twenty four children with NHL treated according to the same chemotherapy protocol but without G-CSF and GM-CSF served as a control group. Our study have demonstrated the good efficacy of both G-CSF and GM-CSF therapy. They shortened the period of neutropenia, reduced the number of febrile days, infection's duration and decreased the frequency of infectious complications.

[Amifostine (ethyol) in the adjunctive treatment of children with acute lymphoblastic leukemia]. / Amifostyna (Ethyol) w leczeniu wspomagajacym dzieci chorych na ostra bialaczke limfoblastyczna.

Myelosuppression is one of the most common side effects during chemotherapy in children with leukemia and lymphoma. That is why the protection of patients against the acute and chronic toxicity of antineoplastic therapy has become a major concern of oncology centers. Amifostine (Ethyol--Schering-Plough) represents a new adjunct for the management of cancer patients receiving chemotherapy. It has the ability to protect selectively a range of tissues and bone marrow against acute and cumulative toxicity of chemotherapy. Because solid tumors tend to be hypovascular and more acid than normal tissue, amifostine may protect selectively normal tissue. Amifostine is believed to scavenge free radicals, repair radicals on essential molecules and from mixed disulfides to protect normal cells. In this trial we demonstrate how amifostine protects granulocytes, erythrocytes and platelets against toxicity of chemotherapy.

[Duration of second remission of Hodgkin's disease in children. Results of treatment achieved by the Polish Leukemia and Malignant Lymphoma Therapy in Children Group]. / Trwalosc drugiej remisji w chorobie Hodgkina u dzieci. Wyniki leczenia Polskiej Grupy ds. Leczenia Bialaczki i Chloniaków Zlosliwych u Dzieci.

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.

[Results of treatment of Hodgkin's disease in children. Observation of 203 cases treated with modified MVPP regimen combined with local radiotherapy]. / Wyniki leczenia choroby Hodgkina u dzieci. Obserwacja 203 przypadków leczonych zmodyfikowana chemioterapia MVPP skojarzona z miejscowym napromienianiem.

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.