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Mariusz Wysocki

Publications and source records attributed to Mariusz Wysocki.

At least 37 records · Page 2Linked to original sources

Langerhans' cell histiocytosis of the mandible in bone scintigraphy and CT.

UNLABELLED: The authors present a case of a 4-year old boy with a quickly growing tumor of the jaw. The CT examination revealed a destructive tumor in the body of the mandible involving soft tissues. A diagnosis of eosinophilic granuloma of the mandible was confirmed by a biopsy of the tumor. Skeletal scintigraphy showed areas of increased and decreased radiotracer uptake. The fusion of CT and scintigraphy images showed that the "cold" focus corresponds with the osteolytic area and the "hot" focuses are larger than the areas of osseous reconstruction shown in CT. CONCLUSION: In cases of histiocytosis skeletal scintigraphy and CT are complementary methods that enable one to make an assessment of the extent of the disease.

Child, Preschool↗

[Prophylactic use of hematopoietic growth factors (G-CSF, GM-CSF) in prevention of chemotherapy-induced myelosuppression in children].

The study has been evaluated an efficiency of preventive use of hematopoietic cytokines in children with neoplastic diseases. The analysed material consisted of 28 children with neoplastic diseases. They all had 148 incidents of chemotherapy-induced myelosuppression with prophylactic use of GM-CSF or G-CSF 5 micrograms/kg daily. The study showed that the prophylactic use of hematopoietic growth factors after the end of each chemotherapy course significantly shortens the duration of extreme neutropenia, the length of treatment of neutropenia-induced infections, the time of hospital care and decreases the delay between succeeding chemotherapy courses.

Adolescent↗

[Advances in the treatment of children with high risk acute lymphoblastic leukemia (ALL) treated with modified "NEW YORK" protocols between 1987 and 2002].

From 1981 to 1986, in children with ALL and initial WBC > or = 50,000/mm3, over 6-year disease-free survival was significantly lower (33%) than in children with WBC < 50,000/mm3 (60%). In attempt to improve this unsatisfactory results, three modified American protocols named: "New York", "New York I", and "New York II", "New York I", and "New York II" were introduced consecutively in the centers of Polish Pediatric Leukemia Lymphoma Study Group (respectively, in 1987, 1997, and 1999). The treatment results achieved in three consecutive therapeutic groups of children with ALL and initial WBC > or = 50,000/mm3: group I--213 children (1987-1996), group II--58 children (1997-1999), and group III--52 children (1999-2001) are presented. The observation was completed in December 31, 2002. In three evaluated groups the first complete remissions (CRs) were achieved in 90.6%. 94.8%. and 94.2% of patients, respectively. Relapses occurred in 71 patients of group I (37%), in 9 patients of group II (16%), and in 6 patients of group III (12%). The complications of treatment caused death in 7 children of group I, in 1 child of group II, and in 2 children of group III. Eighty-one (38%), 11 (18.9%), and 9 (17.3%) patients, respectively, died due to progression of disease. The event-free survival (EFS) in three evaluated groups did not depend on age of children and WBC. The rates of 2-, 5-, and 10-year event-free survival (EFS) in group I were: 69.9%, 55.3%, and 53.6%, respectively and the rates of 2- and 5-year EFS in group II were: 80.7% and 72.7%, respectively. The rate of 2-year EFS in group III was 71.6%. The analysis of achieved treatment results in three evaluated groups shows the gradual improvement of the prognosis in children with ALL and initial WBC > or = 50,000/mm3 treated with the use of modified protocols "New York" and "New York I" in comparison with patients treated before 1987. Longer observation is needed for evaluation of efficacy and complications of "New York II" protocol.

Child↗

[Efficacy of idarubicin in the treatment of childhood acute non-lymphoblastic leukemia: report of Polish Pediatric Leukemia/Lymphoma Study Group].

UNLABELLED: Results of treatment of childhood ANLL remained unsatisfactory for a long time, and introduction of a new drug seemed justified as the EFS achieved in this disease between 1993-97 was 42%. In 1998 a new protocol containing idarubicine in dose 12 mg/m2 (each dose regardless of treatment phase) was introduced. Between 1998 and 2001, 137 children with ANLL were referred to nine participating centers of PPLLSG. Thirty nine were uneligible, so 98 were evaluated. Among them 56 were qualified to standard risk group (SRG) and 35 to high risk group (HRG). In 7 children the risk group was not established due to early death. Remission rate was 79% in the whole group and 98% and 63% in SRG and HRG, respectively. The actuarial 3-year overall survival (OS), 3-year event-free survival (EFS) and 3-year event-free interval (EFI) are respectively: In the whole group 61%, 54% and 67%; in SRG 81%, 70% and 71%; in HRG 40%, 40%, and 53%. CONCLUSIONS: Due to introduction if idarubicine significant improvement of the results was achieved in SRG (better OS, EFS and EFI). Better new treatment methods are required in HRG.

Adolescent↗

Ex vivo drug resistance profile in childhood acute myelogenous leukemia: no drug is more effective in comparison to acute lymphoblastic leukemia.

Therapy results in childhood acute myelogenous leukemia (AML) differ from those of acute lymphoblastic leukemia (ALL). Cellular drug resistance might be one of the reasons of therapy failure in AML. The aim of the study was the analysis of ex vivo drug resistance profile in childhood initial and relapsed AML in comparison to initial ALL. Fifty-three AML samples were tested for chemosensitivity and results were compared with those of 106 initial ALL samples. Ex vivo drug resistance was tested by means of the MTT assay. Up to 29 cytotoxic drugs were tested for each patient. When compared to de nova ALL samples, myeloblasts from initial AML samples were significantly more resistant to most tested drugs, except cytarabine, mercaptopurine and thioguanine. Relapsed AML samples, in relation to initial AML samples, showed comparable sensitivity to cytarabine, idarubicin, fludarabine and cladribine. Patients, who have died due to refractory or relapsing disease, were already on first diagnosis 2-fold more resistant to cytarabine, 6.4-fold more resistant to cisplatin and 3-fold more resistant to carboplatin, when compared to those who stay in remission. Resistance to prednisolone was observed in 85% initial and all relapsed AML samples, in comparison to 33% of ALL samples. Resistance to cytarabine occurred in 2.1% of ALL and 12% of AML cases while a patient with Down syndrome presented the most sensitive drug resistance profile. In conclusion this study shows that no drug was found which, on average, was more effective in AML than in ALL samples. The sensitivity of myeloblasts to platinum derivatives might have prognostic value.

Carboplatin↗

In vitro drug resistance profiles of adult acute lymphoblastic leukemia: possible explanation for difference in outcome to similar therapeutic regimens.

Age has important prognostic impact in acute lymphoblastic leukemia (ALL). Adults with ALL have a worse prognosis compared to children. This may be due to different, unfavorable biology, poor treatment tolerance, drug resistance, higher expression of drug resistance related proteins. The lymphoblasts from adult ALL show an increased in vitro resistance to cytotoxic drugs, including prednisolone, dexamethasone, cytosine arabinoside, daunorubicin, L-asparaginase and methotrexate. Glucocorticoid resistance may be a fundamental difference between children, adolescents and adults with ALL, which may underlie different biological aspects and also explain the difference in prognosis. It seems that in vitro resistance to prednisolone with respect to the age might be a continuous variable in ALL patients, except infants. The greater the age, the higher the in vitro resistance to prednisolone. This may be due to induction of various defense mechanisms, such as an activation of P-glycoprotein, which develops throughout the life and protect the human against xenobiotics. Among a number of various drug resistance mechanisms, only several weak differences between adults and children with ALL have been reported including higher P-glycoprotein expression, lower methotrexate polyglutamate accumulation and possibly more often p53 gene mutations in adults. Intrinsic resistance, induction of drug resistance proteins expression during chemotherapy and co-existence of various mechanisms are common phenomena in adult ALL. It seems that age itself, more than drug resistance profile, reflects factors which have direct effect on chemotherapy response in adult ALL.

Adult↗

Course of viral hepatitis B and combined B and C hepatitis in children treated for neoplastic diseases.

BACKGROUND: Viral hepatitis C in children is milder than in adults. Patients with tumors, because of immune deficits, seem to be at risk of rapid liver disease progression. Little is known about the course of HCV and dual HBV-HCV infections in such patients. MATERIAL/METHODS: The study assessed clinical courses of HCV and dual HBV-HCV infections in 249 children with tumors aged 1-18 years, divided into four groups: with HCV infection - 53, HBV-HCV infection - 53, HBV only - 33 and infection-free - 110. RESULTS: Hepatitis C was often chronic - in 83.3% of patients with HCV and 77.3% of those with dual infection. Over 80% had no jaundice. Mean AlAT activity was the highest in the HCV group (149.2I202.7 IU/l), lower in the dual infection group (123.3I148.1 IU/l; p<0.02), and the lowest in HBV (92.7I152.9 IU/l). Transaminasemia course in patients with HCV and dual HBV-HCV infections was most frequently fluctuating (50.9% and 45.3%, respectively). 52.8% of children with HCV demonstrated no advanced inflammatory lesions with invasion of the lamina limitans, no marked fibrosis, and minimum changes in descriptive classification. In 92.3% of children with dual infections, inflammatory activity was mild or mean, with no fibrosis in 61.5%, and persistent chronic inflammation predominant in descriptive classification (46.1%). CONCLUSIONS: HCV and HBV-HCV infections in children with neoplastic diseases tend to take chronic forms, but their clinical course is mild with signs of severe inflammatory activity or hepatic stroma remodeling observed on histopathology.

Adolescent↗

In vitro activity of oxazaphosphorines in childhood acute leukemia: preliminary report.

Glufosfamide (beta-D-glucosyl-ifosfamide mustard) is a new agent for cancer chemotherapy. Its pharmacology is similar to commonly used oxazaphosphorines, but it does not require activation by hepatic cytochrome P-450 and preclinically demonstrates lower nephrotoxicity and myelosuppression than ifosfamide. The aim of the study was a comparison of the drug resistance profiles of glufosfamide and other oxazaphosphorines in childhood acute leukemias. Leukemic cells, taken from children with ALL on diagnosis (n = 41), ALL on relapse (n = 12) and AML on diagnosis (n = 13) were analyzed by means of the MTT assay. The following drugs were tested: glufosfamide (GLU), 4-HOO-ifosfamide (IFO), 4-HOO-cyclophosphamide (CYC) and mafosfamide cyclohexylamine salt (MAF). In the group of initial ALL samples median cytotoxicity values for GLU, IFO, CYC and MAF were 15.5, 33.8, 15.7 and 7.8 microM, respectively. In comparison with initial ALL samples, the relative resistance for GLU and IFO in relapsed ALL samples was 1.9 (p = 0.049) and 1.3 (ns), and in initial AML samples 31 (p < 0.001) and 5 (p = 0.001), respectively. All oxazaphosphorines presented highly significant cross-resistance. Glufosfamide presented high activity against lymphoblasts both on diagnosis and on relapse.

Adolescent↗

Cross-resistance to five glucocorticoids in childhood acute lymphoblastic and non-lymphoblastic leukemia samples tested by the MTT assay: preliminary report.

In vitro antileukemic activity of five glucocorticoids and their cross-resistance pattern in childhood acute lymphoblastic and non-lymphoblastic leukemia were determined by means of the MTT assay in 25 leukemia cell samples of childhood acute leukemias. The equivalent antileukemic concentrations of the drugs tested were: 34 microM hydrocortisone (HC), 8 microM prednisolone (PRE), 1.5 microM methylprednisolone (MPR), 0.44 microM dexamethasone (DX) and 0.22 microM betamethasone (BET). In comparison with initial ALL cell samples, the relapsed ALL group was more resistant to PRE (38-fold, p = 0.044), DX (> 34-fold, p = 0.04), MPR (38-fold), BET (45-fold) and HC (33-fold). The AML cell samples were even more resistant to: PRE (> 85-fold, p = 0.001), DX (> 34-fold, p = 0.004), MPR (> 69-fold, p = 0.036), BET (> 69-fold, p = 0.038) and HC (54-fold, p = 0.059) when compared with ALL on initial diagnosis. A significant cross-resistance among all the glucocorticoids used was found. Only in some individual cases the cross-resistance was less pronounced.

Adolescent↗

The influence of intracellular idarubicin and daunorubicin levels on drug cytotoxicity in childhood acute leukemia.

Uptake and efflux of two anthracyclines, idarubicin (IDA) and daunorubicin (DNR), was studied in childhood acute leukemia samples. A comparison of IDA and DNR transport phenomena in relation to drug cytotoxicity and expression of P-glycoprotein (PGP) was made. Intracellular content of IDA/DNR was determined by flow cytometry using the fluorescent properties of the drugs. In vitro drug cytotoxicity was measured by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay. PGP expression was analysed by flow cytometry. The uptake and efflux rates were non-significantly higher for IDA than DNR. There were no differences between three types of leukemia with respect to drug content during accumulation and retention. After correction for the cell volume, intracellular concentration of both drugs in each moment of uptake and efflux was significantly lower in relapsed ALL and AML samples in comparison with initial ALL cells. Efflux, but not uptake, of both drugs was inversely correlated with PGP expression and IDA, but not DNR, cytotoxicity. The cytotoxicity was correlated with drug accumulation for both drugs and with drug retention for IDA. In conclusion, it seems that (1) intracellular content was related to the lipophilic properties of the drugs rather than to the type of leukemia, (2) decreased intracellular concentration of both drugs might have an impact on compromised therapy results in AML and relapsed ALL children, (3) IDA presents higher cytotoxicity, which possibly might be decreased by the presence of PGP. These results might have a practical impact on the rational design of new chemotherapy protocols.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Flow cytometric analysis of peripheral blood lymphocytes in children with chronic gastroduodenitis with and without Helicobacter pylori infection].

The immune system plays an important role in chronic gastroduodenitis. A group of 70 children with chronic gastroduodenitis were subjected to examinations, including 42 children with H. pylori infection (group I) and 28 children without H. pylori infection (group II). Applying the method of flow cytometry, the per cent values of peripheral blood lymphocytic subpopulations were determined before and after treatment. The obtained results of examinations in group I were compared with those obtained in group II and were also compared with the standards given by Zeman for healthy children. On the basis of analysis of own material it was found that in both studied groups before and after the treatment lower per cent values were observed of CD3 and CD8 T-cells, NK CD56 cells and higher value of CD4 to CD8 T-cell ratio was disclosed as compared to healthy children. Comparing the per cent values of lymphocytic subpopulations in children with and without H. pylori infection it was found that in group I a higher per cent of CD4 T-cells, lower per cent of CD8 T-cells and, therefore, higher value of CD4 to CD8 T-cell ratio were present.

Adolescent↗

Differences in significance of drug resistance mechanisms between adult and childhood acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is now curable in 60-80% of children. In adults, in spite of adopting treatment protocols based on therapy for childhood ALL, the disease is still curable in 30-40% of patients only. These worse results of therapy may be due to the induction of various cell defence mechanisms, such as activation of P-glycoprotein, which protects man against xenobiotics. Among a number of various multi-drug resistance mechanisms, differences between adults and children with ALL have been found only for higher P-glycoprotein expression and possibly more often p53 gene mutations in adults. Induction of expression of drug resistance proteins during chemotherapy and co-existence of various mechanisms are common phenomena in adult ALL. Differences in resistance to different drugs might contribute to the impact of age on the outcome of ALL. The underlying mechanisms for these differences are still largely unknown; however, knowledge about drug resistance mechanisms can lead to new therapeutic options.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

In vitro activity of glufosfamide in childhood acute leukemia.

Glufosfamide is a new agent for cancer chemotherapy. The objective of the study was the comparison of the in vitro drug resistance profile of glufosfamide with other oxazaphosphorines in 106 samples of childhood acute leukemia by means of the MTT assay. The following drugs were tested: glufosfamide, 4-HOO-ifosfamide, 4-HOO-cyclophosphamide, mafosfamide cyclohexylamine salt, prednisolone, vincristine, L-asparaginase, daunorubicin and cytarabine. In the group of initial Acute Lymphoblastic Leukemia (ALL) samples, equivalent cytotoxicity values for glufosfamide, 4-HOO-ifosfamide, 4-HOO-cyclophosphamide and mafosfamide were 5.95, 9.92, 4.60 and 3.90 microg/ml, respectively. In comparison to initial ALL samples, the relative resistance for glufosfamide and 4-HOO-ifosfamide in relapsed ALL samples were 1.9 (p=0.049) and 1.3 (ns), and in initial Acute Myeloblastic Leukemia (AML) samples, respectively, 31 (p<0.001) and 5 (p=0.001). All oxazaphosphorines showed highly significant cross-resistance. In conclusion, in vitro activity of glufosfamide is comparable to ifosfamide. Glufosfamide shows high activity against lymphoblasts both on diagnosis and on relapse, however it cannot circumvent resistance to other oxazaphosphorines.

Adolescent↗

[Bilateral Wilms' tumour. Results of treatment in 29 children].

Retrospective analysis of 29 children with bilateral Wilms' Tumour, 14 boys and 15 girls, aged 4m-5 years, from regional centres of paediatric oncology in Poland, treated according to the O1-92 PPGL Protocol of Wilms' tumour, was performed. All patients were treated with two (ACT + VCR) or three (ACT, VCR, DOX) cytostatic drugs preoperatively, and 26 were operated upon after cytoreductive pretreatment. In 12 children nephrectomy was performed. In 28, kidney sparing surgery was possible and made with success. 2 patients who presented disseminated disease and 1 with nephroblastomatosis were given chemotherapy. 19 out of 29 (65.5%) are alive including 1 patient with nephroblastoma. EFS calculated according to Kaplan-Meier analysis for this group, was 58% at 67 months.

Antineoplastic Combined Chemotherapy Protocols↗

[Malignant vascular tumours in children -- report from the Polish Pediatric Rare Tumors Study].

UNLABELLED: Malignant vascular tumours represent a rare group of neoplasms, usually treated according to protocols for soft tissue sarcomas. THE AIM OF THE STUDY: To assess the clinical characteristics, disease course and outcome in Polish children with malignant vascular neoplasms. MATERIAL AND METHODS: The Polish Paediatric Rare Tumours Study retrospectively analysed multicentre data on 32 children with vascular tumours, registered between 1992 and 2002. On the basis of the histological type of the neoplasm these patients have been divided into three groups: group I -- 10 patients with angiosarcoma (ASA), group II -- 7 children with haemangioendothelioma (HE) and group III- 15 patients with haemangiopericytoma (HP), of both infantile (7 children) and adult-types (8 patients). RESULTS: Group I: 5 patients presented with local, 3 with systemic and 2 with regional disease. Primary complete resection (PRC) was performed in 7 patients, not resulting in local control in any of them. Radiotherapy (RTX) was administered in 5 patients, chemotherapy (CHT) in all. 7 patients relapsed, 3 never entered clinical remission. 9 of the 10 patients of group I, died of disease progression. Group II: PRC was performed in 5 patients and led to local control in 2. Adjuvant RTX was used in 2 and CHT in 4 patients. 2 children relapsed and died of the disease. Infantile HP: PRC was performed in 3 children, remaining 4 patients received adjuvant CHT All children entered complete remission and are disease-free. Adult-type HP: PRC was performed in 5 patients, resulting in local control in 4. Five children were given adjuvant RTX and six CHT Three patients relapsed and died of disease progression. CONCLUSIONS: The effectiveness of primary complete resection in all groups was doubtful. The high rate of metastatic relapses suggests that the currently given systemic therapy is not satisfactory. The only tumour with excellent prognosis was infantile type HP (all patients are alive and free of disease). Adequate treatment for children with angiosarcoma remains still unknown -- 9 of 10 patients died of disease progression. Prognosis in patients with haemangioendothelioma is intermediate, however the role of immunotherapy should be further investigated.

Adolescent↗

[Soft tissue sarcoma of the bladder and prostate. A report of the Polish Paediatric Solid Tumour Group (PPSTG)].

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children younger then 15 years of age. The treatment of RMS localized in bladder or prostate still remains controversial. The aim of this study was analysis of treatment results in children with soft tissue sarcoma of bladder and prostate. From 1993 to 2001 the PPSTG has used three protocols to treat soft tissue sarcomas in children. The CWS-91 regimen has been served to treat stage I-III and SIOP-IV Intergroup study in stage IV. Since 1996 the CWS-96 protocol for all patients in stage I-IV has been used. After biopsy confirmation of the diagnosis patients were treated with chemotherapy and subsequent surgery. Radiotherapy was administrated with total dose 32Gy v 44.5Gy v 48Gy. The group of 19 patients aged from 3 months to 18 years with median age 6 y 4 m were evaluated. The median follow-up time was 42 months. RMS-embryonal was diagnosed in 11 patients, RMS-alveolare in 4 and others types in 4. Sixteen patients presented clinical stage III and 3 stage IV The tumours were primarily localised in bladder in 16 patients and prostate in 3. Eight were tumours of volume bigger than 10 cm. After induction chemotherapy two patients received partial cystectomy, 5 complete cystectomy and 3 complete cystectomy with genitourinary reconstructive. Eight patients did not receive surgery. The most common treatment failure was isolated, local relapse in 8 children particularly in patients with any second surgery. The EFS for all patients was 52% and for patients with localised RMS tumours 65%. Significant prognostic factors are the initial tumours volume, the lymph nodes infiltration and the response to the first chemotherapy cycle. Surgery is the most important procedure in local control of soft tissue sarcoma. Reconstructive options in poor and non responder patients can improve the EFS and life quality of those patients.

Adolescent↗

Cytotoxicity of cortivazol in childhood acute lymphoblastic leukemia.

BACKGROUND: Glucocorticoids are the most important group of drugs used in the treatment of childhood acute lymphoblastic leukemia (ALL), however, resistance to this group remains the main obstacle in curing the disease. One of the possibilities to circumvent glucocorticoid resistance is the use of new compounds, such as cortivazol (CVZ), which has two binding sites for the glucocorticoid receptor. AIM: Analysis of ex vivo sensitivity to cortivazol and other glucocorticoids in childhood acute lymphoblastic leukemia, as well as the relationship to anticancer therapy outcome. PATIENTS AND METHODS: Leukemic samples from 60 children with ALL were tested by the M7T assay for glucocorticoid resistance. Cell cycle before and after ex vivo glucocorticoid treatment was analyzed by flow cytometry. RESULTS: Although all tested glucocorticoids presented significant cross-resistance, CVZ showed high antileukemic activity. The equivalent activity of CVZ was 165-fold higher than prednisolone, 7.ZS5-fold higher than dexamethasone and 2.8-fold higher than betamethasone. CVZ showed relatively better cytotoxicity than other glucocorticoids in prednisolone-poor-responders. CVZ, like other glucocorticoids, caused cell cycle arrest in the GI-phase, and increased the percentage of apoptotic cells to a greater extent than other glucocorticoids. The results of antileukemic therapy were strongly related to the ex vivo resistance to all tested glucocorticoids. CONCLUSION: Cortivazol has potent antileukemic activity in childhood ALL. Its activity is related to cell cycle arrest and induction of apoptosis.

Adolescent↗