Tailoring New Myeloma Therapies: How Are They Best Used?

not received at time of going to print Tuesday 16 ABSTRACTS ABSTRACTS Tuesday 16 A180 Tuesday 16 October 1530-1630 ASTH Symposium: Oral Anticoagulation Control Central Room C 1530 Oral Anticoagulant Control in Lupus Anticoagulant Patients Ian Mackie Haemostasis Research Unit, Haematology Department, University College London, UK The incidence of thrombosis in patients with antiphospholipid syndrome (APS) is increased and some reports have recommended a higher intensity of warfarin treatment. However, later studies have shown that higher INR values give no reduction in thrombosis incidence while te bleeding risk is greater. A target INR of 2.5 is generally considered appropriate for venous thrombosis. Other studies have suggested higher target ranges because the PT/INR system may be falsely increased by interference of lupus anticoagulant (LA) with the phospholipid component of the PT reagent, particularly where recombinant tissue factor is employed. The majority of patients (>95%) with APS have a normal PT in the absence of other coagulopathies. When the PT is prolonged, it is often due to hypoprothrombinaemia, resulting from high affinity antibodies and immune depletion. These antibodies differ from those commonly seen in APS, which have low affinity and cause no prothrombin depletion. Certain reagents are more sensitive to LA and indeed have been utilised in LA detection systems. However, the perceived between reagent differences in INR in LA patients mostly disappear when instrument and reagent specific INR/ISI calibration is performed. All patients should have a baseline PT and where this is elevated, alternative PT reagents may be employed. In the rare patients with significant prolongation of the baseline PT and difficulty in establishing the true degree of anticoagulation, amidolytic factor X assays may be helpful. It is possible that some of these patients may also have antibodies directed against factor VII or tissue factor. Activation marker assays (D-dimer, TAT , F1.2) have been employed by some, to assess ongoing thrombin generation and efficacy of warfarin prophylaxis, but there are no well controlled studies. The use of point of care devices for INR in APS should be performed with caution. Some devices are very sensitive to LA and most manufacturers list this as a specific exclusion to their use. Tuesday 16 ABSTRACTS ABSTRACTS Tuesday 16 A181 Tuesday 16 October 1530-1630 ASTH Symposium: Oral Anticoagulation Control Central Room C 1600 Point of Care INR Michael Ray Pathology Queensland, Brisbane, Australia Objective Point of Care (POC) monitoring of oral anticoagulant therapy is providing improved outcomes for both selected patients who can adequately self-monitor and those patients who do not have easy access to routine laboratory testing. This presentation will describe the home monitor, the CoaguChek and its successor, the CoaguChek XS and the use of the latter for patients requiring ventricular assist devices (VAD) and who are able to go home. It will also describe the implementation of INR testing across Queensland on a different class of point-of-care analyser, the i-STAT 1. Methods Each of the three analysers was evaluated individually at different times as they became commercially available. Patients being routinely monitored for oral anticoagulant therapy at our hospital were selected. The phlebotomists were trained in the use of the instruments and performed POC INR determinations at the bedside using fingerprick blood at the same time as drawing venous samples for laboratory INR testing. Results The CoaguChek was considered suitably accurate for use in the hospital’s paediatric ward, but only up to an INR of 3.0. It was in use successfully for 5 years. The improved agreement of the CoaguChek XS with the laboratory results made it possible for VAD patients to self-monitor at home. The excellent accuracy of the i-STAT INR led to its routine use in 40 sites around Queensland. Discussion Pathology Queensland are responsible for quality assurance of POC instruments, training of medical and nursing staff in their use, and storage of the data. The i-STAT has facilitated this process. Group co-ordinating laboratories in the larger hospitals manage the procurement, quality assurance and distribution of test cartridges. In the last year 2830 INRs were performed on the iSTAT throughout Queensland in a timely and controlled manner. Tuesday 16 ABSTRACTS ABSTRACTS Tuesday 16 A182 Tuesday 16 October 1530-1630 Diagnostic Laboratory Science: New Laboratory Tests and Techniques Meeting Room 5 1530 Monitoring Human Cytomegalovirus-Specific Cellular Immunity Using Quantiferon®-CMV Tania Crough, Susan Walker, Stephen Jones and Rajiv Khanna 1 Australian Centre for Vaccine Development, Queensland Institute of Medical Research, Brisbane, Australia 2 Cellestis Inc., Melbourne, Australia We have longitudinally analyzed HCMV-specific CD8 + T-cell responses in a cohort of heart and/or lung transplant patients. The detection of active virus replication correlated with a reduced IFNexpression by HCMV-specific CD8 + T-cells and an up-regulation of CD38 expression on the surface of virus-specific CD8 + T-cells, although there was no significant change in the number of virus-specific cells. Most importantly, analysis of IFNproduction by virus-specific CD8 + T-cells in patients with HCMV disease suggested that disease was associated with a reduction in CD8 + T-cell responsiveness to both structural and immediate-early antigens. Based on these results, we have developed a novel diagnostic technology to monitor the HCMV-specific CD8 + T-cell responses referred to as QuantiFERON ® -CMV. Evaluation of QuantiFERON ® -CMV in healthy individuals and solid organ transplant patients revealed that this technology was at least as sensitive and with some HCMV epitopes more sensitive than the ELISPOT for detecting ex vivo IFN. Results from QuantiFERON ® -CMV assays showed 97% (36/37 individuals) agreement with the anti-HCMV serology test in healthy individuals. Taken together, this study indicates a pivotal role for IFNproducing virus-specific CD8 + T-cells in protecting transplant patients from HCMV disease, and this protection is dependent on a broadly focused T cell responses rather than a response directed towards any one single antigen. Furthermore, QuantiFERON ® -CMV is a simple, reproducible and reliable test for the detection of IFNin response to HCMV CD8 + T-cell epitopes, and may be a valuable diagnostic test for the detection of HCMV infection and as a useful clinical tool for monitoring the immune response in immunosuppressed patients during therapy. Tuesday 16 ABSTRACTS ABSTRACTS Tuesday 16 A183 Tuesday 16 October 1530-1630 Diagnostic Laboratory Science: New Laboratory Tests and Techniques Meeting Room 5 1545 Serum Free Light Chain Assay Jill Tate Chemical Pathology, Pathology Queensland, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia Clinical Utility Measurement of serum free light chains (FLC) is useful for the diagnosis and monitoring of monoclonal light chain diseases in particular non-secretory and light chain myeloma, and AL amyloidosis. The FLC assay may also have a role in monitoring intact immunoglobulin myeloma where disease response to treatment may be detected earlier by serum FLC than standard protein electrophoresis due to the shorter half-life of kappa and lambda light chains compared with the intact immunoglobulin molecule. From the point of view of clinical validation of FLC, the major studies have been performed in the diagnostic, not monitoring, setting. Analytical Issues The use of polyclonal anti-human FLC antibodies in immunoassay methods for measurement of monoclonal free light chains raises the question of adequate specificity and affinity to bind to individual monoclonal FLC. Given there may be differences in immunoreactivity between monoclonal and polyclonal proteins, there is the possibility of either overestimation or underestimation of serum FLC. At diagnosis and particularly, for long-term monitoring of monoclonal light-chain disease, reproducible and accurate assay performance is required. Laboratory staff and clinicians should be aware of the potential for non-reactivity of individual monoclonal FLC, the effect that dilution has on FLC measurement, and an appreciation of the impact of assay imprecision on result interpretation. Some monoclonal light chains (particularly kappa FLC) do not dilute in a linear fashion and may be underestimated in the absence of additional off-line dilutions and assay imprecision, especially with different lots of FLC reagent, may have a significant effect on changes in the FLC concentration and the calculated kappa/lambda ratio. These issues, if not adequately appreciated, have the potential to mislead clinical diagnosis and assessment of response to therapy. Tuesday 16 ABSTRACTS ABSTRACTS Tuesday 16 A184 Tuesday 16 October 1530-1630 Diagnostic Laboratory Science: New Laboratory Tests and Techniques Meeting Room 5 1600 Rationale for International Harmonisation of BCR-ABL Monitoring by RTPCR David Ross, Timothy Hughes, Susan Branford Institute of Medical & Veterinary Science, Adelaide, SA, Australia Real-time quantitative reverse transcriptase PCR for BCR-ABL (RQ-PCR) is used to monitor treatment of CML patients. A major molecular response (MMR) has prognostic significance and guides therapeutic decisions. Various RQ-PCR methods are used, and the value representing MMR varies between labs. To overcome this problem an international reporting scale (IS) was proposed, standardizing the absolute value representing MMR as 0.10%. Conversion to the IS uses laboratory (lab)-specific conversion factors (CFs). Thirty-four labs from 13 countries sent 615 patient samples to the reference lab in Adelaide to determine their specific CF. RQ-PCR methods varied by control gene (ABL n=17, BCR n=12, GUSB n=4, other n=4), primers and probes, instruments, an