[Allelic variants of TPMT and the risk of leucopenia and neutropenia in patients treated for acute leukaemia]. / Warianty alleliczne TPMT a ryzyko leukopenii i neutropenii u pacjentów leczonych z powodu ostrej bialaczki.

AIM: The objective of this study was to analyse the influence of TPMT genetic polymorphism on the occurrence of therapeutical adverse effects such as hematological disorders, leucopenia and neutropenia after thiopurines administration. MATERIAL AND METHODS: The examined group consisted of 210 patients (121 boys, 89 girls) aged between 1 and 18 (median age 7 years, average age 8 years, SD+/-5.32) treated for leukaemia (acute lymphoblastic leukaemia ALL: n=167; acute myeloblastic leukaemia AML: n=43). Analysis of treatment adverse reactions in every child was performed according to the WHO toxicity scale, during the entire length of observation period and in particular stages (6 stages). RESULTS: Analysis of changes in selected blood count parameters in the whole treatment period in the acute leukaemia group indicated that in the TPMT *2, *3A or *3C polymorphism carriers' group there is a statistically significant decrease in the white blood cell count (p=0.0025) and in the neutrophil count (p=0.019). Detailed assessment in particular treatment periods indicated that increased leukopenia in TPMT heterozygotes occurred significantly more frequently only in early re-induction period (p=0.012). CONCLUSION: Thiopurines administration is related to the increase in hemato-oncological treatment toxicity in TPMT heterozygotes.

[Evaluation of selected endocrine complications in patients treated with auto- and allo-haematopoietic stem cell transplantation]. / Ocena wybranych powiklan endokrynologicznych u pacjentów po autologicznym i allogenicznym przeszczepie krwiotwórczych komórek macierzystych.

AIM: The aim of this study was to evaluate the endocrine complications, in particular disorders of growth and thyroid function and glucose metabolism dysfunctions in patients treated with allo- and auto-haematopoietic stem cell transplantation (HSCT). MATERIAL AND METHODS: The investigated group consisted of: I. 16 patients after auto-HSCT (6 girls, 10 boys) aged 3-20 years (average 10,8+/-) because of acute myelogenous leukaemia (n=5), non Hodgkin lymphoma (n=3), neuroblastoma (n=3), embryonal cancer (n=2), medulloblastoma (n=1), Ewing's sarcoma/PNET (n=1), hyper eosinophilic syndrome (n=1). High dose chemiotherapy (HDC/T) included: BU/MEL (busulfan/melfalan) (n=7), BEAM (carmustine, eteposide, cytosine arabinose, melfalan) (n=3). II. 30 patients after allo-HSCT (20 girls, 10 boys) aged 3-17 years (average 9,56). Indication for HSCT was acute lymphoblastic leukaemia (n=11), acute myelogenous leukaemia (n=5), chronic myeloid leukaemia-CML (n=6), myelodysplastic syndromes (n=2), non Hodgkin lymphoma (n=1), juvenile myelomonocytic leukemia (n=1), severe aplastic anaemia (n=1), Blackfan-Diamond anaemia (n=1), severe combined immune deficiency (n=1), rhabdomyosarcoma (n=1). The patients underwent the following types of transplantation: HSCT of matched sibling donor (n=13), HSCT of matched unrelated donor (n=11) and HLA-mismatched related donor (n=6). The preparative regimens consisted of HDC/T usually BU/MEL (n=3); BU/CY/VP (busulfan, cyclophosphamide, etoposide) (6); BU/CY/ATG (anti-thymocyte globulin) (n=5), VP/ATG/TBI (total body irradiation) (n=3). 19 children received CI (cranial irradiation) prior to grafting: auto-HSCT (n=6) and allo-HSCT (n=13) and 6 patients underwent TBI. 18 children received high steroid doses at least 28 days before transplant, 4 patients in the auto-HSCT group, and in the allo-HSCT group 14 patients before and 20 after HSCT procedure. The analysis of thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3), hemoglobin A1c (HbA1c), prolactine (PRL), oral glucose tolerance test, growth hormone (GH test) and thyrotropin releasing hormone (TRH) test was performed in each case. RESULTS: Hypothyroidism was found in 5 patients (3 after allo-HSCT, 2 after auto-HSCT). Thyroid hormone substitution was applied. No case of hyperthyroidism was diagnosed. Growth deficit was found in 8 patients (6 girls, 2 boys) between 13 to 70 months after allo-transplantation (average 36 months). Three children from the above group received CI. Growth hormone substitution was applied in 1 girl (ALL, HLA MM REL, CI). An impaired excretion of GH after stimulation was diagnosed in 14 pts (10 after allo-HSCT, 4 after auto-HSCT). The growth process should still be observed in this subgroup. Glucose intolerance was found in 7 patients: in 4 treated with auto-HSCT and in 3 after allo-HSCT. Diabetes mellitus was diagnosed in none of them. An impaired glucose tolerance curve with increased excretion of insulin was diagnosed in 12 children. CONCLUSIONS: Early endocrinological care is necessary in patients treated both with auto-HSCT and allo-HSCT due to high risk of hormonal disorders.

[Analysis of selected undesirable effects of cytostatic drugs in treatment of the central nervous system tumours in children. Preliminary report]. / Analiza wybranych niepozadanych dzialan cytostatyków w trakcie leczenia dzieci z nowotworami osrodkowego ukladu nerwowego.

INTRODUCTION: During treatment of children with brain tumours there is a large risk of occurrence of side effects related to the narrow therapeutic range of cytostatic drugs and irradiation of the central nervous system. AIM: Determination of the patients' risk of undesirable effects and determination of intensification of myelosuppression and hepatocellular damage during treatment of central nervous system tumours, depending on the used therapeutic protocol and the time of chemotherapy. MATERIAL AND METHODS: The investigated group consisted of 17 patients (5 girls, 12 boys) aged 1.5-16 yrs, treated for primary brain tumour. The patients were treated according to different protocols. Protocol I (vincristine, etoposide, carboplatin, cyclophosphamide, ifosfamide and cisplatin) in 4 children with medulloblastoma and with PNET. Protocol II (etoposide, ifosfamide, adriamycin) in 4 children with glioblastoma multiformae, astrocytoma anaplasticum and ependymoma. Protocol III (carboplatin and vincristine) in 3 children with medulloblastoma, ependymoma and glioblastoma multiformae. Protocol IV (vincristine and carboplatin) in 4 children with astrocytoma fibrillare and astrocytoma pilocyticum. 10 patients were given radiotherapy. Frequency of occurrence and intensification of undesirable effects were valuated according to the WHO classification after each cycle of chemotherapy (average 8 cycles) during the whole treatment period (average 8 months): 1. Leucopenia (mm3): 0 grade [gr] (>4.000), 1 gr. (3.000-3.900), 2 gr. (2.000-2.900), 3 gr. (1.000-1.900), 4gr. ( 100000), 1 gr. (75-99000), 2 gr. (50-74000), 3 gr. (25-49000), 4 gr. (<25000) 3. Anaemia (g/dl): 0 gr. (N), 1 gr. (>10), 2 gr. (8-10), 3 gr. (6.5-7.9), 4 gr. (<6.5) 4. Hepatocellular damage (GPT, GOT/bilirubin): 0 gr. (N/N), 1 gr. (2.5xN/-), 2 gr. (2.6-5xN/1.5xN), 3 gr. (5.1-20xN/1.5-3xN), 4 gr. (>20xN/>3xN). RESULTS: In patients treated in accordance with the therapeutic protocols there was no appearance or exacerbation of undesirable side effects. During receiving adriamycin mild hyperbilirubinemia (R=0.53; p<0.05 bilirubin 1 degree) occurred statistically significantly more often. Correlation between usage of temodal and the activity of hepatic enzymes was noticed, meeting the requirements of 1st degree of toxicity according to WHO rates (R-0.66). Consequently, after the usage of temodal, more frequent abnormalities in liver function were shown. During treatment with cyclophosphamide, iphosphamide, etoposide, carboplatin, lomustine and vincristine, complications such as myelotoxicity and hepatotoxicity were not more frequent by statistical significance methods. CONCLUSIONS: Current results of treatment of central nervous system tumours in children showed, that patients tolerated cytostatic therapy relatively well. The observed undesirable effects were abnormal liver enzyme activity and bilirubin levels, higher after adriamycin and temodal therapy. Due to the small group of patients, these results are of preliminary significance. In future, a more in depth analysis of early and late effects of oncological treatment in children with cns tumours is needed.