CD160 is a human natural killer (NK)-cell–activating receptor that is also expressed on T-cell subsets. In the present study, we examined 811 consecutive cases of B-cell lymphoproliferative disorders (B-LPDs), and demonstrated CD160 expression in 98% (590 of 600) of chronic lymphocytic leukemia (CLL) cases, 100% (32 of 32) of hairy cell leukemia (HCL) cases, 15% (5 of 34) of mantle cell lymphoma (MCL) in the leukemic phase, and 16% (23 of 145) of other B-LPD cases. CD160 transcript and protein were absent in the normal B-cell hierarchy, from stem cells, B-cell precursors, maturing B cells in the germinal center, and circulating B cells, including CD5⁺CD19⁺ B1 cells in umbilical cord. CD160 positivity was significantly higher in CLL and HCL in terms of percentage (65.9% and 67.8%, respectively, P < .0001) and median fluorescence intensity (552 and 857, respectively, P < .0001) compared with all other B-LPD cases. Lymph node CLL samples were also CD160⁺. Using the disease-specific expression of CD5, CD23, and CD160, a score of 3 characterized CLL (diagnostic odds ratio, 1430); a score of 0 excluded CLL, MCL, and HCL; and the CD23/CD5 ratio differentiated CLL from leukemic CD23⁺ MCL. In the B-cell lineage, CD160 is a tumor-specific antigen known to mediate cellular activation signals in CLL, and is a novel target for therapeutic manipulation and monitoring of minimal residual disease.

Objectives. Clinical experience of the impact of serum biomarkers for invasive fungal disease (IFD) varies markedly in haemato-oncology. Invasive pulmonary aspergillosis (IPA) is the commonest manifestation, so we evaluated biomarkers in broncho-alveolar lavage fluid (BAL). Methods. Aspergillus-specific lateral flow device (LFD), qPCR and galactomannan (GM) tests were used with 32 BAL fluid samples from 32 patients at risk of IPA. Eight patients had proven, 3 probable, 6 possible and 15 patients no IPA by EORTC/MSG criteria. Diagnostic accuracies of the tests were evaluated and pair-wise agreement between biomarkers was calculated. The diagnostic performance of the EORTC/MSG criteria was evaluated against the test(s) identified as most useful in IPA diagnosis. Results. Using EORTC/MSG criteria, sensitivities of qPCR and LFD were 100%, GM was 87.5% (cut-off, GM > 0.8), with specificities between 66.7 and 86.7%. The agreement between the qPCR and LFD was almost perfect (Cohen's kappa = 0.93, 95% CI: 0.81 – 1.00). Combined LFD+qPCR had a sensitivity of 100% and specificity of 85.7%. Calcofluor staining and culture of all BAL samples was negative for fungal infection. The median time from starting mould-active antifungal therapy to obtaining BAL was 6 days. Reversing roles, and using LFD+qPCR dual testing to classify cases, the EORTC/MSG criteria had a sensitivity of 83.3%. Conclusions. All three tests are useful for diagnosis of IPA in BAL samples. Despite the significant delays between starting antifungal therapy and bronchoscopy, unlike microscopy and culture, the biomarkers remain informative. In particular, the combination of LFD+qPCR allows sensitive and specific detection of IPA.

We describe an integrated care pathway (ICP) for the optimal management of invasive mould disease (IMD). The ICP is for use by health professionals involved in the care of patients with haematological malignancies and haematopoietic stem cell transplant recipients who are at increased risk of IMD. The ICP is not intended for use in other patient groups where the evidence base is more limited. The ICP involves the patient and their carers, as well as describing the roles and the complex interaction of healthcare professionals in different departments. Therefore, the management of IMD as described in the ICP must be appropriate for the overall organization, and will be dependent on the facilities [e.g. high-efficiency particulate air (HEPA) filtration] and services available. The ICP deals with risk stratification, diagnostic tests, prophylactic and treatment strategies and how to incorporate these into the ICP. Outpatient drug management after hospital discharge and cessation of therapy are outlined. Local implementation of this ICP will vary from centre to centre: the ICP is a generic template for guidance indicating the requirements for optimal IMD management and as such provides a standard against which local practice can be audited. For clinical governance, to minimize variation in practice and, ultimately, to improve patient outcomes, each centre should regularly monitor and document compliance with the local ICP, from provision of patient information, appropriate prescribing and diagnostic investigation to clinical outcomes.

Objective: To determine direct costs associated with a blood transfusion session in two hospital settings.Research design and methods: The study was conducted in two United Kingdom hospital sites during April 2004. Transfusion sessions for patients receiving units of red blood cells within either haematology or oncology departments were followed using time and motion techniques to measure the direct costs. Other data were collected from the centres to calculate the cost of disposables, blood wastage and blood bank machines.Results: Total mean staff cost per transfusion of 2 units was £37.24 (£9.68 for blood bank and £27.56 for ward procedures). The mean cost of disposables was £13.25 and the mean cost for blood products was £287.56. The mean cost of wastage was £11.86 per transfusion. After including other derived costs, such as hospital stay, the mean cost for a transfusion of 2 units of blood was estimated to be £546.12.Conclusion: This study estimates the cost of an average blood transfusion of...

Many biologic markers are associated with poor prognosis in chronic lymphocytic leukemia (CLL), but their mechanistic role remains unclear. Bax is an essential proapoptotic protein and decreased levels in malignant cells lead to resistance to apoptosis. Using a Bax degradation activity (BDA) assay, CLL cells were found to show variable Bax instability. However, BDA did not correlate with Bax protein levels: BDA positive and negative cases had high and low baseline Bax levels. BDA positive cases showed a marked accumulation of poor prognostic markers—unmutated immunoglobulin heavy chain variable genes, ZAP-70/CD38 positivity, 11q22/17p13 deletion, and short lymphocyte doubling time. Patients with BDA positive cells had a shorter median overall survival (OS; 126 months vs not reached, P = .011) and time to first treatment (16 vs 156 months, P = .029) than BDA negative cases. Dual BDA and ZAP-70 positivity had a median OS of 84 months (P = .012). The BDA assay measures the intrinsic ubiquitin/proteasome activity of CLL cells and dynamic changes in Bax protein levels over time. Mechanistically, Bax instability may represent a final common pathway for disparate prognostic markers, as well as being itself an indicator of poor prognosis.

In chronic lymphocytic leukemia (CLL), the detection of minimal residual disease (MRD) correlates with outcome in the trial setting. However, MRD assessment does not guide routine clinical management and its assessment remains complex. We incorporated detection of the B cell, tumor-specific antigen CD160 to develop a single-tube, flow cytometry assay (CD160FCA) for CLL MRD to a threshold of 10⁻⁴ to 10⁻⁵. One hundred and eighty-seven patients treated for CLL were enrolled. Utilizing the CD160FCA methodology, there was a high level of comparison between blood and bone marrow (R=0.87, P<0.001). In a validation cohort, CD160FCA and the international standardised approach of the European Research Initiative on CLL group demonstrated high concordance (R=0.91, P<0.01). Patients in complete remission (CR) and CD160FCA negative had longer event-free survival (EFS) (63 vs 16 months, P<0.01) and prolonged time to next treatment (60 vs 15 months, P<0.001) vs MRD positive patients; with a median time to MRD positivity of 36 months. In multivariate analysis, CD160FCA MRD detection was independently predictive of EFS in patients in CR and even predicted EFS in the good-risk cytogenetic subgroup. CD160FCA offers a simple assay for MRD detection in CLL and gives prognostic information across different CLL risk groups.