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At least 1,477 records · Page 82Linked to original sources
PubMed2005

Circulating bcr-abl-specific CD8+ T cells in chronic myeloid leukemia patients and healthy subjects.

BACKGROUND AND OBJECTIVES: The fusion oncoprotein bcr-abl that characterizes chronic myeloid leukemia (CML) is a leukemia-specific antigen, which may be immunogenic in vivo. KQSSKALQR and GFKQSSKAL, peptide sequences spanning the b3a2 bcr-abl junction, have affinity for HLA-A3 and HLA-B8, respectively, and we have shown the presence of KQSSKALQR on the surface of CML cells. We analyzed the existence of bcr-abl-specific T cells in vivo and correlated their presence to contemporary disease burden. DESIGN AND METHODS: We investigated circulating CD8+ T lymphocytes directed against the bcr-abl junction, using fluorochrome-labeled tetramers of HLA-A3 with KQSSKALQR and of HLA-B8 with GFKQSSKAL, and flow cytometry analysis. Using chromium-release assays and interferon-g ELISPOT assays, we also studied the functionality of these expanded T cells. RESULTS: Eight of 12 b3a2+ HLA-A3+ and/or HLA-B8+ CML patients studied serially on at least three occasions had bcr-abl junction-specific CD8+ T cells. Specific T cells were more likely to be found in patients with a low leukemic burden (p=0.03). Three of 18 HLA-A3+ and/or HLA-B8+ healthy donors had bcr-abl junction-specific T cells, though these were not detected in any of 13 subjects who were HLA-A3- and HLA-B8-. Bcr-abl-specific T cells were expandable in vitro in three of seven healthy donors and five of seven CML patients. INTERPRETATION AND CONCLUSIONS: Bcr-abl-specific T cells are detectable in CML patients, and might contribute to leukemic control. The occurrence of specific CD8+ T cells in some healthy donors might represent an immune response to occult BCR-ABL rearrangements.

Adult↗
PubMed2005

Cirrhosis and trauma: a deadly duo.

It has been previously reported that trauma patients with cirrhosis undergoing emergency abdominal operations exhibit a fourfold increase in mortality independent of their Child's classification. We undertook this review to assess the impact of cirrhosis on trauma patients. We reviewed the records of patients from 1993 to 2003 with documented hepatic cirrhosis and compared them to a 2:1 control population without hepatic cirrhosis and matched for age, sex, Injury Severity Score (ISS), and Glasgow Coma Score (GCS). Demographic, severity of injury, and outcome data were recorded. Student's t test and X2 were used for statistical analysis and a P < 0.05 was significant. Sixty-one patients had documented cirrhosis and were compared to 156 matched controls. Comparing the two groups demonstrates there was no difference in age, ISS, or GCS. Intensive care stay, hospital length of stay, blood requirements in the first 24 hours postinjury, and mortality (33% vs 1%) was significantly greater in the trauma patients with cirrhosis. Fifty-five per cent of deaths in the cirrhosis group was due to sepsis, and, as the Child's class increases, so does the mortality (Child's A, 15%; B, 37%; and C, 63%). In 64 per cent of cirrhotics without an emergent abdominal operation, mortality was 21 per cent. In the 36 per cent of cirrhotics who had emergent abdominal operation, mortality was 55 per cent. Hepatic cirrhosis in trauma patients, regardless of severity of injury or the need for an abdominal intervention, is a poor prognostic indicator. The necessity of an abdominal operative intervention further amplifies this effect. Trauma and cirrhosis is, in fact, a deadly duo.

Abdominal Injuries↗
PubMed2006

Adjuvant chemotherapy for non-small cell lung cancer: a New Zealand perspective.

This article reviews recent developments with the use of adjuvant chemotherapy for resected early-stage non-small cell lung cancer (NSCLC) and the implications of these developments for healthcare in New Zealand (NZ). Non-small cell lung cancer is a major cause of mortality and morbidity in NZ, and is greatly over-represented among Maori and socioeconomically deprived populations. Early-stage NSCLC is potentially curable by surgery, but long-term outcome after surgical resection is limited by disease recurrence locally or at sites distant from the primary disease. Three recent large randomised controlled phase III trials using modern platinum-based combination chemotherapy protocols have shown significant survival benefits for the use of postoperative adjuvant chemotherapy after resection of early-stage NSCLC. Cisplatin plus vinorelbine was used as the adjuvant chemotherapy regimen in two of these trials resulting in improvements in 5-year survival of 51.2% versus 42.6% (p=0.013) and 69% versus 54% (p=0.03), respectively. In NZ, adjuvant chemotherapy for NSCLC is expected to prevent up to 15 lung cancer deaths each year for relatively low drug expenditure and has the potential to benefit Maori and the economically-deprived disproportionately more than other populations. In conclusion, it is the opinion of this group of NZ lung cancer specialists that adjuvant chemotherapy with cisplatin plus vinorelbine should now be adopted as a standard of care for patients with resected stage II and III NSCLC. For this to occur, current PHARMAC policies preventing its use for these eligible patients will need to be revised.

Antineoplastic Agents, Phytogenic↗