Summary. The last four decades have seen a significant increase in the incidence of non-Hodgkin's lymphoma (NHL) as a possible result of increasing environmental carcinogen exposure, particularly pesticides and solvents. Based on the increasing evidence for an association between carcinogen exposure-related cancer risk and xenobiotic gene polymorphisms, we have undertaken a case-control study of xenobiotic gene polymorphisms in individuals with a diagnosis of NHL. Polymorphisms of six xenobiotic genes (CYP1A1, GSTT1, GSTM1, PON1, NAT1, NAT2) were characterized in 169 individuals with NHL and 205 normal controls using polymerase chain reaction-based methods. Polymorphic frequencies were compared using Fisher's exact tests, and odds ratios for NHL risk were calculated. Among the NHL group, the incidence of GSTT1 null and PON1 BB genotypes were significantly increased compared with controls, 34% vs 14%, and 24% vs 11% respectively.Adjusted odds ratios calculated from multivariate analyses demonstrated that GSTT1 null conferred a fourfold increase in NHL risk (OR ¼ 4AE27; 95% CI, 2AE40-7AE61, P < 0AE001) and PON1 BB a 2AE9-fold increase (OR ¼ 2AE92; 95% CI, 1AE49-5AE72, P ¼ 0AE002). Furthermore, GSTT1 null combined with PON1 BB or GSTM1 null conferred an additional risk of NHL. This is the first time that a PON1 gene polymorphism has been shown to be associated with cancer risk. We conclude that the two polymorphisms, GSTT1 null and PON1 BB, are common genetic traits that pose low individual risk but may be important determinants of overall population NHL risk, particularly among groups exposed to NHL-related carcinogens.
SummaryAn automated cartridge-based detection system (GeneXpert; Cepheid) is being widely adopted in low throughput laboratories for monitoring BCR-ABL1 transcript in chronic myelogenous leukaemia. This Australian study evaluated the longitudinal performance specific characteristics of the automated system.The automated cartridge-based system was compared prospectively with the manual qRT-PCR-based reference method at SA Pathology, Adelaide, over a period of 2.5 years. A conversion factor determination was followed by four re-validations. Peripheral blood samples (n = 129) with international scale (IS) values within detectable range were selected for assessment. The mean bias, proportion of results within specified fold difference (2-, 3- and 5-fold), the concordance rate of major molecular remission (MMR) and concordance across a range of IS values on paired samples were evaluated.The initial conversion factor for the automated system was determined as 0.43. Except for the second re-validation, where a negative bias of 1.9-fold was detected, all other biases fell within desirable limits. A cartridge-specific conversion factor and efficiency value was introduced and the conversion factor was confirmed to be stable in subsequent re-validation cycles. Concordance with the reference method/laboratory at >0.1–≤10 IS was 78.2% and at ≤0.001 was 80%, compared to 86.8% in the >0.01–≤0.1 IS range. The overall and MMR concordance were 85.7% and 94% respectively, for samples that fell within ± 5-fold of the reference laboratory value over the entire period of study.Conversion factor and performance specific characteristics for the automated system were longitudinally stable in the clinically relevant range, following introduction by the manufacturer of lot specific efficiency values.
Summary:A 47-year-old man with a 2-year history of Philadelphia chromosome-positive chronic phase (CP) chronic myeloid leukaemia (CML) underwent autologous PBSCT. During the period of haemopoietic reconstitution he underwent five leucapheretic (LP) harvests yielding a total of 2.6 ؋ 10 6 /kg CD34 + cells. Cytogenetic analyses revealed 94, 83, 83, 96 and 85% Ph negativity respectively for the five harvests. RT-PCR analyses for BCR-ABL performed on randomly picked CFU-GM from the five LP products were negative in all cases. These observations suggest that the majority of harvested cells, including the more primitive clonogenic cells, were BCR-ABL (Ph) negative and presumably were not part of the leukaemic clone. These findings support the notion that autologous PBSCT in CML whilst serving as a therapeutic manoeuvre may also facilitate the collection of non-leukaemic progenitor cells for further transplantation procedures. Keywords: CML; PBSCT; leucapheresis; purging Potentially curative alloSCT is presently unavailable to the majority of CML patients because of patient age and/or the lack of availability of a suitably matched donor.1 Interferon is reported in some multicentre randomised studies to be associated with a prolongation of survival when compared to chemotherapy, 2,3 however, no discernible plateauing of survival curves has been demonstrated, thus suggesting that IFN is unlikely to be curative. Comparison with historical controls suggests that autologous PBSCT may be associated with a prolongation of survival for CP CML patients and in instances can result in prolonged periods of Philadelphia chromosome-negative haemopoiesis.4 Thus, the demonstration that significant numbers of Ph-negative peripheral blood MNC could be obtained by LP after the administration of high-dose chemotherapy 5 has led to the development of numerous therapeutic strategies based on Correspondence: Dr A Spencer, Hunter Haematology Unit, Locked Bag 7, Hunter Region Mail Centre, NSW 2310, Australia Received 8 July 1997; accepted 2 September 1997 this perceived in vivo purging effect. Whether PBSCT following in vivo purging is more beneficial when compared to the use of unmanipulated PBSC is uncertain but theoretically it is a more attractive approach. Based on these observations we chose to examine whether sufficient numbers of PBSC could be obtained during the recovery phase from PBSCT to enable a second autografting procedure, thus combining a potential therapeutic benefit with high-dose chemotherapy in vivo purging and subsequent progenitor cell collection. Case reportIn March 1995, a 47-year-old male was incidentally found to have a total leucocyte count of 97 ϫ 10 9 /l with a normal haemoglobin and platelet count. The peripheral blood features were consistent with CP CML. Bone marrow aspirate confirmed the diagnosis with 100% of metaphases showing t(9;22)(q34;q11). RT-PCR revealed b2a2 BCR-ABL transcripts. Initial disease control was achieved with hydroxyurea. He was then started on daily alpha-interferon (IFN) and received subc...
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