Genetic polymorphisms of biotransformation enzymes in patients with Hodgkin's and non-Hodgkin's lymphomas.

OBJECTIVE: Considering the role in the metabolism of chemicals played by biotransformation enzymes, we aimed at determining whether any association exists between genetic polymorphisms in cytochromes p450 (CYP1A1 and CYP2E1), epoxide hydrolase (EPHX1), NAD(P)H: quinone oxidoreductase (NQO1), glutathione S-transferases (GSTs M1/P1/T1) and individual susceptibility to lymphomas. METHODS: Genotyping assays based on polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were used to determine the frequency of polymorphisms in CYP1A1 (3'-flanking region), CYP2E1 (5'-flanking region and intron 6), EPHX1 (exon 3 and exon 4), NQO1 (exon 6), GSTM1 (deletion), GSTP1 (exon 5), and GSTT1 (deletion) in a case-control study composed of 219 patients with morbus Hodgkin (MH) and non-Hodgkin's lymphomas (NHL) and 455 age- and gender-matched healthy individuals. RESULTS: Grading of NHL seemed to be associated with polymorphism in CYP2E1-intron 6 ( P=0.041). The EPHX1-exon 3 genotype distribution was significantly different between male controls and male patients with both kinds of lymphomas ( P=0.01) or with NHL ( P=0.019). The genotype GSTP1*2/*2 was prevalent in all MH (odds ratio (OR) =2.08, 95% confidence interval (CI) =1.05-4.14, P=0.035) and this difference was particularly evident in female subjects (OR=2.97, 95% CI=1.16-7.61, P=0.023). A significant difference in the distribution of GSTP1-exon 5 genotypes was found between NHL tumors larger vs. smaller than 5 cm ( P=0.03). CONCLUSIONS: The results suggest that genetic polymorphisms of biotransformation enzymes may play a significant role in the development and progression of lymphoid malignancies.

[Intensive therapy with paclitaxel (Taxol) and cyclophosphamide followed by administration of G-CSF as a mobilization regimen in patients with breast carcinoma and indications for autologous hematopoietic cell transplantation]. / Intenzifikovaná terapie paclitaxelem (Taxol) a cyklofosfamidem s následným podáváním G-CSF jako mobilizacní rezim u nemocných s karcinomem prsu indikovaných k autologní transplantaci krvetvorných bunek.

Cyclophosphamide (4 g/m2) and paclitaxel (Taxol) (175, 200 or 250 mg/m2) therapy with subsequent administration of G-CSF (10 micrograms/kg) has been used as intensification and as mobilization therapy for patients with breast cancer. This regimen was used in 19 patients, as part of adjuvant therapy in 14 and as part of therapy of metastatic disease in five. Median number of collected CD34+ cells was 17.5 x 10(6)/kg (2.9-48.1). All patients except one (94.7%) reached minimal required number of CD34+ cells (> or = 3 x 10(6)/kg). Median number of leukapheresis was two. The required number of cells (> or = 3 x 10(6)/kg) was collected in one leukapheresis in 17 out of 19 patients (89.5%) and more than five and 10 x 10(6)/kg CD34+ cells respectively were collected in 14 (73.7%) and 11 (57.9%) patients respectively. No factor significantly influencing the amount of collected cells (except the trend in favour of later year of therapy and large-volume leukapheresis) was identified. Leukopenia gr. 4 was observed in 88.9% of treated patients and febrile neutropenia developed in 46.2% patients. Although the antitumour activity of this chemotherapy was not possible to assess it seems that this intensification could be successfully used as a therapy and as very potent mobilization regimen.

[Administration of interferon alpha as post-transplantation immunotherapy in malignant lymphoma. Case control study]. / Podávání interferonu alfa jako potransplantacní imunoterapie u maligních lymfomu. Párovaná studie.

BACKGROUND: A possible cause of relapses in patients with malignant lymphomas after autologous transplantation of haematopoietic cells is among others the absence of an immune reaction. The objective of the present study was to assess the effect of long-term interferon alpha administration after autologous transplantation in malignant lymphomas. METHODS AND RESULTS: A total of 16 patients were followed up (9 men and 6 women, mean age 44 years) 14 with non-Hodgkin's lymphoma and two with Hodgkin's disease where after high-dose transplantation with autologous transplantation of haematopoietic cells immunotherapy was started by administration of IFN alpha 3 MU three time per week. The treatment was well tolerated, only in two patients (12.5%) the doses had to be reduced or temporarily discontinued. The results were compared with a control group (16 subjects, 12 men, 4 women, mean age 43 years and similar other characteristics as the followed up group) who were not given IFN alpha after transplantation. The controls were paired with regard to the condition after transplantation, grade of pretreatment, diagnosis and age. In the group treated with IFN alpha five relapses developed and two deaths occurred, in the control group four relapses and three deaths. The probability of survival without signs of progression (PFS) and total survival (OS) within 18 months is in the treated group 67.4% and 88.9%, in the control group 86.5% and 93.8%. The results are not statistically significant. CONCLUSIONS: The authors confirmed in their study the feasibility of long-term administration of IFN alpha after transplantation. On a preliminary basis it may be stated that the results did not differ in the treated and not treated patients, nevertheless the impact of this type of immunotherapy or its modification will have to be evaluated in a randomized study.