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Tomasz Szczepanski

Publications and source records attributed to Tomasz Szczepanski.

8 recordsLinked to original sources
PubMed2006

Avascular necrosis--an antineoplastic-treatment-related toxicity: the experiences of two institutions.

Avascular necrosis (avn) is a complication of treatment for malignancies in children and adolescents. The authors present a two-center retrospective of experiences with avn in children treated for acute lymphoblastic leukaemia or non-Hodgkin lymphoma (8 from 191 patients with newly diagnosed disease in total of 19 sites). The median age at diagnosis was 16.6 years. Avn was observed in 4.1% of the group, higher among males than females (7/1), both during and after therapy. Early diagnosis of the process has enabled 7 patients to avoid surgical intervention. The increased incidence of avn, the multimodal character of symptoms, but unknown late consequences of avn showed that prospective studies of early recognition and proper therapy are needed.

Adolescent↗
PubMed2004

Aberrant methylation in promoter-associated CpG islands of multiple genes in relapsed childhood acute lymphoblastic leukemia.

Methylation profile was analyzed in nine cases of relapsed childhood acute lymphoblastic leukemia (ALL) for p14, p15, p16, Rb, MGMT, APC, hMLH1, RARbeta, RIZ, DAPK, and FHIT genes by using methylation specific polymerase chain reaction (MSP) analysis. Frequency of methylation in each gene was: MGMT, 56%; RARbeta, 44%; and p16, 22%, respectively. None of the p14, p15, Rb, APC, hMLH1, RIZ, DAPK, and FHIT genes were hypermethylated. Five (56%) of 9 cases showed methylation of at least one gene. All of the samples with hypermethylation in p16 and MGMT gene at relapse, had already acquired the change at the time of initial diagnosis. Interestingly, three of 4 cases with RARbeta gene methylation at relapse did not have methylation of this gene at the time of initial presentation. These results suggest that hypermethylation might be involved in the relapse of childhood ALL.

Adolescent↗
PubMed2003

Vdelta2-Jalpha rearrangements are frequent in precursor-B-acute lymphoblastic leukemia but rare in normal lymphoid cells.

The frequently occurring T-cell receptor delta (TCRD) deletions in precursor-B-acute lymphoblastic leukemia (precursor-B-ALL) are assumed to be mainly caused by Vdelta2-Jalpha rearrangements. We designed a multiplex polymerase chain reaction tified clonal Vdelta2-Jalpha rearrangements in 141 of 339 (41%) childhood and 8 of 22 (36%) adult precursor-B-ALL. A significant proportion (44%) of Vdelta2-Jalpha rearrangements in childhood precursor-B-ALL were oligoclonal. Sequence analysis showed preferential usage of the Jalpha29 gene segment in 54% of rearrangements. The remaining Vdelta2-Jalpha rearrangements used 26 other Jalpha segments, which included 2 additional clusters, one involving the most upstream Jalpha segments (ie, Jalpha48 to Jalpha61; 23%) and the second cluster located around the Jalpha9 gene segment (7%). Real-time quantitative PCR studies of normal lymphoid cells showed that Vdelta2 rearrangements to upstream Jalpha segments occurred at low levels in the thymus (10(-2) to 10(-3)) and were rare (generally below 10(-3)) in B-cell precursors and mature T cells. Vdelta2-Jalpha29 rearrangements were virtually absent in normal lymphoid cells. The monoclonal Vdelta2-Jalpha rearrangements in precursor-B-ALL may serve as patient-specific targets for detection of minimal residual disease, because they show high sensitivity (10(-4) or less in most cases) and good stability (88% of rearrangements preserved at relapse).

Adolescent↗
PubMed2003

Assessment of chosen parameters of the immune system in children with acute lymphoblastic leukemia.

The immunosuppressive effect of cytostatics, basic therapeutic agents in the treatment of proliferative diseases of the hematopoietic system, and the rising number of children cured from acute leukaemias form together a need to monitor the status of the immune system following cessation of therapy. Surface antigens in lymphocytes from peripheral blood were assessed in 16 children directly after intensive chemotherapy (i.e., after protocol II of the BMF program) and in 25 children 12-13 months following conclusion of acute lymphoblastic leukemia treatment. The results were compared to data obtained from children never afflicted with neoplastic disease. A significant decrease in the average number of lymphocyte subpopulations was noted in the case of the treated children directly after intensive chemotherapy. The average values of lymphocyte subpopulations in children with concluded treatment are within the norm, with the exception of NK and TS lymphocytes.

Adolescent↗
PubMed2003

Assessment of clonal stability of minimal residual disease targets between 1st and 2nd relapse of childhood precursor B-cell acute lymphoblastic leukemia.

BACKGROUND AND OBJECTIVES: Immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements are excellent patient-specific targets for polymerase chain reaction (PCR)-based detection of minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL). Nevertheless, instability of these targets during the course of the disease has important implications for PCR-based MRD monitoring and may lead to false negative results. DESIGN AND METHODS: Several studies have shown that Ig and TCR targets are reasonably stable in ALL between diagnosis and first relapse, but up to now, there are no data on the stability of these targets between first and second relapse. We, therefore, performed a PCR-study on bone marrow samples from 49 children with precursor B-ALL at first and second relapse. Homo-heteroduplex PCR analyses were used for identification of clonal IGH, IGK-Kde, TCRG and TCRD gene rearrangements. Clonal targets were studied by sequencing and/or comparative homo-heteroduplex analysis. RESULTS: In 52% (25/48) of the patients, all PCR targets identified at first relapse were preserved at second relapse; in 92% (44/48) of the patients at least one target and in 73% (35/48) at least two targets remained stable. Best stability was found for IGH and TCRG gene rearrangements. INTERPRETATION AND CONCLUSIONS: Based on these first data about clonal stability of Ig and TCR targets between first and second relapse of childhood precursor B-ALL, we developed a stepwise strategy for appropriate selection of stable PCR targets for MRD monitoring. This strategy was applicable in 84% of the relapsed patients and resulted in at least one stable MRD-PCR target per patient in 98% of these children.

Adolescent↗
PubMed2002

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↗
PubMedDate not supplied

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↗