PCR-detectable nonneoplastic Bcl-2/IgH rearrangements are common in normal subjects and cancer patients at diagnosis but rare in subjects treated with chemotherapy.

PURPOSE: To assess whether nonneoplastic Bcl-2/IgH rearrangements act as a confounding factor in the setting of minimal residual disease analysis by evaluating their incidence in a panel of lymphoma-free subjects, including cancer-free donors and chemotherapy-naive and chemotherapy-treated cancer patients. PATIENTS AND METHODS: A total of 501 nonlymphoma subjects have been assessed: 258 cancer-free patients and 243 patients with malignancies other than lymphoma, 112 of whom were chemotherapy-naive. Patients were primarily assessed by nested polymerase chain reaction (PCR), followed by real-time quantitative PCR if they scored positive. In addition, six initially PCR-positive cancer-free donors were prospectively reassessed by qualitative and quantitative PCR after 30 and 60 days. RESULTS: The overall incidence of Bcl-2/IgH positivity was 9.6%, with a median number of 11 rearrangements per 1,000,000 diploid genomes (range, 0 to 2,845 rearrangements), as assessed by real-time PCR. The incidence was similar in healthy subjects and cancer patients at diagnosis (12% and 12.5%; P = not significant). In contrast, the incidence of this translocation was only 2.3% in chemotherapy-treated patients (P <.001). In addition, three initially PCR-positive cancer-free donors showed persistence of their rearrangements when assessed after 30 and 60 days. CONCLUSION: The low incidence of nonneoplastic Bcl-2/IgH rearrangements following chemotherapy provides further evidence of the prognostic role of persistent PCR-positivity in the posttreatment molecular follow-up of follicular lymphoma patients.

Implementing guidelines for venous thromboembolism prophylaxis in a large Italian teaching hospital: lights and shadows.

BACKGROUND AND OBJECTIVES: Venous thromboembolism (VTE) remains a serious complication in hospitalized patients, in spite of several published guidelines (GL) on its prevention. The objective of this study (part of the TRiPSS-2 project) was to evaluate the impact of a locally adapted GL, supported by a multifaceted implementation strategy, in improving VTE prophylaxis in a large teaching hospital. DESIGN AND METHODS: A before and after controlled study was used to evaluate the impact of the recommendations on the appropriateness of prophylaxis. We evaluated the medical charts of two random samples, each of 250 patients, discharged in the first semester of the years 2000 and 2002. The hospital incidence of VTE (1996-2004) was also monitored, through the discharge summaries. RESULTS: Among high risk patients, appropriateness of prophylaxis increased both in medical (from 25% to 41.7%, p=0.0075) and in surgical patients (from 63.7% to 97.1%, p=0.0004). A parallel sharp increase (by 6-8 times) of consumption of elastic stockings was documented. In both medical and surgical patients the incidence of VTE decreased markedly and sustainedly in 2002-2004, with an adjusted odds ratio of 0.68 (95% confidence interval: 0.62-0.75). However, the use of lower than recommended doses of heparins and the increased use of prophylaxis in low risk patients represent unsolved problems. INTERPRETATION AND CONCLUSIONS: Implementing locally adapted GL may be highly effective in improving appropriateness of prophylaxis and in reducing the incidence of VTE; however a careful evaluation of changes is recommended in order to identify unsolved problems or undesired effects.

Thromboelastogram monitoring in the perioperative period of hepatectomy for adult living liver donation.

Living donor liver transplantation (LDLT) is becoming a widespread procedure. However, the risk of surgical and medical complications in healthy donors is still a major concern. Hypercoagulability contributes to thromboembolic complications after surgery, but alterations of hemostasis after liver resection are difficult to predict. This study aims to define the perioperative coagulation profile of living liver donors by the use of both routine tests and thromboelastogram (TEG). Ten subjects undergoing right hepatectomy for LDLT were studied. A complete coagulation screening was performed before operation. The coagulation profile was evaluated by platelet count, prothrombin time-international normalized ratio (PT-INR), activated partial thromboplastin time (aPTT), and TEG at the beginning and at the end of surgery, and on days 1, 3, 5, and 10 after operation, while the donors were under low molecular weight heparin (LMWH) prophylaxis. At preoperative screening, no subject showed evidence of a prothrombotic state. In all cases, TEG was normal at the beginning of surgery. In the postoperative period, despite decreased platelet counts, increased PT-INR, and normal aPTT values, TEG evidenced the progressive development of hypercoagulability in 4 subjects on day 5 and in 6 subjects on day 10. One donor with a definitely hypercoagulable TEG on day 5 experienced deep venous thrombosis (DVT) on day 8, which was resolved with therapeutic doses of LMWH. In conclusion, despite routine tests suggesting hypocoagulability and LMWH prophylaxis, TEG monitoring showed the unexpected occurrence of hypercoagulability in the majority of the subjects after hepatectomy for LDLT. TEG monitoring could be useful in the perioperative management of donors to guide antithrombotic treatment and increase the safety of the procedure.

Human leukocyte interferon-alpha treatment for chronic HCV-related hepatitis in hemophilic patients previously intolerant to other interferons-alpha.

Thirty patients affected by hemophilia A or B or von-Willebrand's disease and chronic posttransfusional active HCV hepatitis who developed major side effects during the course of a previous treatment with recombinant interferon-alpha (IFN-alpha) were studied. In all patients IFN-alpha therapy had to be discontinued and those who achieved a primary serologic and viral response to HCV relapsed within a few months. After a washout period, patients were retreated with human leukocyte IFN-alpha, 6 MU thrice weekly for 12 months. In about 90% of patients, a primary response, with normal AST and GGT values and undetectable HCV-RNA, was achieved within the third month of treatment and for the entire duration of treatment none of the patients had to discontinue therapy because of severe adverse reactions. During posttherapy follow-up only one patient relapsed. The human leukocyte IFN-alpha regimen looks to be very effective and safe for carriers of inherited clotting disorders who developed major side effects with recombinant IFN-alpha therapy for HCV-related chronic hepatitis.