Medicine (St Vincent's) - Research Publications

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    Overview of early response assessment in lymphoma with FDG-PET.
    MacManus, MP ; Seymour, JF ; Hicks, RJ (E-MED LTD, 2007)
    Early assessment of response to chemotherapy with fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) is becoming a routine part of management in patients with Hodgkin lymphoma (HL) and histologically aggressive non-Hodgkin lymphoma (NHL). Changes in FDG uptake can occur soon after the initiation of therapy and they precede changes in tumour volume. Recent studies in uniform populations of aggressive lymphomas (predominantly diffuse large B cell lymphomas) and HL have clarified the value of early response assessment with PET. These trials show that PET imaging after 2-3 chemotherapy cycles is far superior to CT-based imaging in predicting progression-free survival and can be at least as reliable as definitive response assessment at the end of therapy. This information is of great potential value to patients, but oncologists should be cautious in the use of early PET response in determining choice of therapy until some critical questions are answered. These include: When is the best time to use PET for response assessment? What is the best methodology, visual or quantitative? (For HL at least, visual reading appears superior to an SUV-based assessment). Can early responders be cured with less intensive therapy? Will survival be better for patients treated more intensively because they have a poor interim metabolic response? In the future, early PET will be crucial in developing response-adapted therapy but without further carefully designed clinical trials, oncologists will remain uncertain how best to use this new information.
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    Lack of evidence of disease contamination in ovarian tissue harvested for cryopreservation from patients with Hodgkin lymphoma and analysis of factors predictive of oocyte yield
    Seshadri, T ; Gook, D ; Lade, S ; Spencer, A ; Grigg, A ; Tiedemann, K ; McKendrick, J ; Mitchell, P ; Stern, C ; Seymour, JF (NATURE PUBLISHING GROUP, 2006-04-10)
    Ovarian cryopreservation is a promising technique to preserve fertility in women with Hodgkin lymphoma (HL) treated with chemotherapy. Thus, the aim of this study was to examine harvested ovarian tissue for subclinical involvement by HL by morphology/immunohistochemistry, and to define patient and treatment factors predictive of oocyte yield. This was a retrospective analysis of 26 ovarian tissue samples harvested for cryopreservation from women with HL. Histology, immunohistochemistry and follicle density (number mm(-3)) was examined. Disease status and preharvest chemotherapy details were obtained on 24 patients. The median age was 22 years (range 13-29). Seven of 24 patients had infradiaphragmatic disease at time of harvest. Nine of 20 patients had received chemotherapy preharvest (ABVD (Adriamycin), Bleomycin, Vinblastine and Dacarbazine) = 7, other regimens = 2). The seven receiving ABVD showed no difference in follicle density compared to patients not receiving treatment (n = 14); (median = 1555 vs 1620 mm3 P = 0.97). Follicle density measurement showed no correlation with patient age (R2 = 0.0001, P = 0.99). There was no evidence of HL involvement in the 26 samples examined (95% CI = 0-11%). In conclusion, subclinical involvement of HL has not been identified in ovarian tissue, even when patients have infradiaphragmatic disease. Furthermore, the quality of tissue harvested does not appear to be adversely affected by patient's age or prior ABVD chemotherapy.
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    An analysis of the utilisation of chemoprophylaxis against Pneumocystis jirovecii pneumonia in patients with malignancy receiving corticosteroid therapy at a cancer hospital
    Worth, LJ ; Dooley, MJ ; Seymour, JF ; Mileshkin, L ; Slavin, MA ; Thursky, KA (NATURE PUBLISHING GROUP, 2005-03-14)
    Pneumocystis jirovecii pneumonia (PCP) is associated with high mortality in immunocompromised patients without human immunodeficiency virus infection. However, chemoprophylaxis is highly effective. In patients with solid tumours or haematologic malignancy, several risk factors for developing PCP have been identified, predominantly corticosteroid therapy. The aims of this study were to identify the potentially preventable cases of PCP in patients receiving corticosteroid therapy at a tertiary care cancer centre and to estimate the frequency of utilisation of chemoprophylaxis in these patients. Two retrospective reviews were performed. Over a 10-year period, 14 cases of PCP were identified: no cases were attributable to failed chemoprophylaxis, drug allergy or intolerance. During a 6-month period, 73 patients received high-dose corticosteroid therapy (> or =25 mg prednisolone or > or =4 mg dexamethasone daily) for > or =4 weeks. Of these, 22 (30%) had haematologic malignancy, and 51 (70%) had solid tumours. Fewer patients with solid tumours received prophylaxis compared to patients with haematologic malignancy (3.9 vs 63.6%, P<0.0001). Guidelines for PCP chemoprophylaxis in patients with haematologic malignancy or solid tumours who receive corticosteroid therapy are proposed. Successful primary prevention of PCP in this population will require a multifaceted approach targeting the suboptimal prescribing patterns for chemoprophylaxis.
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    Negative selection of chronic lymphocytic leukaemia cells using a bifunctional rosette-based antibody cocktail
    Essakali, S ; Carney, D ; Westerman, D ; Gambell, P ; Seymour, JF ; Dobrovic, A (BMC, 2008-01-29)
    BACKGROUND: High purity of tumour samples is a necessity for accurate genetic and expression analysis and is usually achieved by positive selection in chronic lymphocytic leukaemia (CLL). RESULTS: We adapted a bifunctional rosette-based antibody cocktail for negative selection of B-cells for isolating CLL cells from peripheral blood (PB). PB samples from CLL patients were split into aliquots. One aliquot of each sample was enriched by density gradient centrifugation (DGC), while the other aliquot of each sample was incubated with an antibody cocktail for B-cell enrichment prior to DGC (RS+DGC). The purity of CLL cells after DGC averaged 74.1% (range: 15.9 - 97.4%). Using RS+DGC, the purity averaged 93.8% (range: 80.4 - 99.4%) with 23 of 29 (79%) samples showing CLL purities above 90%. RNA extracted from enriched CLL cells was of appropriately high quality for microarray analysis. CONCLUSION: This study confirms the use of a bifunctional rosette-based antibody cocktail as an effective method for the purification of CLL cells from peripheral blood.