Distinct forms of tyrosine kinase domain (TKD), juxtamembrane domain, exon 8, and internal tandem duplication (ITD) mutations of c-KIT, were observed in about 46% of core binding factor leukemia (CBFL) patients. To evaluate their prognostic significance, 67 adult patients with CBFL were analyzed to ascertain the c-KIT mutation status. In acute myeloid leukemia (AML) with t(8;21), the presence of c-KIT TKD mutation at codon 816 (TKD 816 ) was associated with a high white blood cell count at diagnosis (median, 29.60 ؋ 10 9 /L) and a higher incidence (33%) of extramedullary leukemia (EML) during the course of the disease. Data also showed that the TKD 816 mutated patients (n ‫؍‬ 12) had a significantly higher incidence of relapse and a lower overall survival (OS) at 24 months, compared with the 17 c-KIT unmutated (c-KIT ؊ ) patients (90% vs 35.3%, P ‫؍‬ .002; 25% vs 76.5%, P ‫؍‬ .006, respectively). No difference in relapse incidence (P ‫؍‬ .126) and OS (P ‫؍‬ .474) was observed between the c-KIT mutated other than TKD 816 (n ‫؍‬ 7) and the c-KIT ؊ patients. These findings indicate that c-KIT TKD 816 mutation has a negative impact on the outcome of AML with

Purpose In patients with myeloma, thalidomide significantly improves outcomes but increases the risk of thromboembolic events. In this randomized, open-label, multicenter trial, we compared aspirin (ASA) or fixed low-dose warfarin (WAR) versus low molecular weight heparin (LMWH) for preventing thromboembolism in patients with myeloma treated with thalidomide-based regimens. Patients and Methods A total of 667 patients with previously untreated myeloma who received thalidomide-containing regimens and had no clinical indication or contraindication for a specific antiplatelet or anticoagulant therapy were randomly assigned to receive ASA (100 mg/d), WAR (1.25 mg/d), or LMWH (enoxaparin 40 mg/d). A composite primary end point included serious thromboembolic events, acute cardiovascular events, or sudden deaths during the first 6 months of treatment. Results Of 659 analyzed patients, 43 (6.5%) had serious thromboembolic events, acute cardiovascular events, or sudden death during the first 6 months (6.4% in the ASA group, 8.2% in the WAR group, and 5.0% in the LMWH group). Compared with LMWH, the absolute differences were +1.3% (95% CI, −3.0% to 5.7%; P = .544) in the ASA group and +3.2% (95% CI, −1.5% to 7.8%; P = .183) in the WAR group. The risk of thromboembolism was 1.38 times higher in patients treated with thalidomide without bortezomib. Three major (0.5%) and 10 minor (1.5%) bleeding episodes were recorded. Conclusion In patients with myeloma treated with thalidomide-based regimens, ASA and WAR showed similar efficacy in reducing serious thromboembolic events, acute cardiovascular events, and sudden deaths compared with LMWH, except in elderly patients where WAR showed less efficacy than LMWH.

Summary The prompt response to bortezomib observed in a 63‐year‐old woman with multiple myeloma was associated with a significant increase in alkaline phosphatase (ALP). After similar elevations were noted in patients responding to bortezomib, thalidomide, dexamethasone combination, ALP levels were analysed in two large bortezomib trials. A statistically significant elevation of ALP from baseline was observed in responding patients (complete and partial responders) within three cycles of therapy. The rise in ALP after bortezomib in three patients was explained by a parallel increase in bone‐specific ALP and parathyroid hormone, suggesting that response to bortezomib in myeloma is closely associated with osteoblastic activation.

Summary Acquired activated protein C resistance (aAPCR), not associated with factor V Leiden, has been described in cancer patients with an increased risk of venous thromboembolism (VTE). APCR was determined in 1178 myeloma patients using an activated partial thromboplastin time‐based resistance assay in the presence of excess of factor V‐deficient plasma; polymerase chain reaction amplification of genomic DNA was used to detect factor V Leiden mutation. A total of 109 patients were found to have abnormal APCR and one‐third of them were carriers for the mutation. With a median follow‐up of 40 months, the presence of aAPCR was associated with a significantly increased risk of thrombosis (P ≤ 0·001). APCR was measured again after treatment in 31 patients with abnormal baseline values and had normalised in 30 of them. This study indicates that aAPCR is the most common single transitory baseline coagulation abnormality associated with VTE in myeloma patients.

Tumor-associated neoangiogenesis has recently become a suitable target for antineoplastic drug development. In this overview, we discuss specific drug-associated hemostatic complications, the already known pathogenetic mechanisms involved, and the effect of varying antithrombotic strategies. Multiple agents with angiogenic inhibitory capacity (thalidomide, lenalidomide, bevacizumab, sunitinib, sorafenib, and sirolimus) have obtained US Food and Drug Administration approval, and many others have entered clinical trials. Arterial and venous thromboembolism and hemorrhage have emerged as significant toxicities associated with the use of angiogenesis inhibitors. We present a detailed analysis of the literature on thrombotic complication of antiangiogenic drugs. Close attention to hemostatic complications during antiangiogenic treatment is warranted. Further studies are required to better understand the pathophysiologic mechanisms involved and to define a safe prophylactic strategy.