The response rate of 48% with IDEC-C2B8 is comparable to results with single-agent cytotoxic chemotherapy. Toxicity was mild. Attention needs to be paid to the rate of antibody infusion, with titration according to toxicity. Further investigation of this agent is warranted, including its use in conjunction with standard chemotherapy.

This study investigated the efficacy, safety, and clinical benefit of alemtuzumab (Campath-1H) for patients with relapsed or refractory B-cell chronic lymphocytic leukemia exposed to alkylating agents and having failed fludarabine therapy. Ninety-three patients received alemtuzumab in 21 centers worldwide, with the aim to obtain an overall response rate of at least 20%. Dosage was increased gradually (target 30 mg, 3 times weekly, for a maximum of 12 weeks). Infection prophylaxis was mandatory, beginning on day 8, and continuing for a minimum of 2 months after treatment. Responses were assessed at weeks 4, 8, and 12, and patients were followed for 34 months. Overall objective response in the intent-to-treat population (n ‫؍‬ 93) was 33% (CR 2%, PR 31%). Median time to response was 1.5 months (range, 0.4-3.7 months). Median time to progression was 4.7 months overall, 9.5 months for responders. At data cut-off, 27 patients (29%) were alive; overall median survival was 16 months (95% CI: 11.8-21.9) and 32 months for responders. Nineteen responders survived more than 21 months. Clinical benefit was observed both in responders and in patients with stable disease. The most common adverse events were related to infusion, generally grade 1 or 2 in severity, occurring mainly in the first week. Grade 3 or 4 infections were reported in 25 patients (26.9%). However, only 3 (9.7%) of 31 patients who responded to alemtuzumab treatment developed grade 3 or 4 infections on the study. Alemtuzumab induced significant responses in these patients with clinical benefit in the majority and with acceptable toxicity in a high-risk group. (Blood. 2002; 99:3554-3561)

No abstract

(131)I tositumomab is effective in CD20-positive lymphoma progressive after rituximab, with a 65% OR rate and median PFS of 24.5 months for responders. Patients with follicular grade 1 or 2 histology and tumors < or = 7 cm achieved very high OR and CR rates, with 48% PFS at 3 years.

FLT3 mutations are prevalent in AML patients and confer poor prognosis. Crenolanib, a potent type I pan-FLT3 inhibitor, is effective against both internal tandem duplications and resistance-conferring tyrosine kinase domain mutations. While crenolanib monotherapy has demonstrated clinical benefit in heavily pretreated relapsed/refractory AML patients, responses are transient and relapse eventually occurs. Here, to investigate the mechanisms of crenolanib resistance, we perform whole exome sequencing of AML patient samples before and after crenolanib treatment. Unlike other FLT3 inhibitors, crenolanib does not induce FLT3 secondary mutations, and mutations of the FLT3 gatekeeper residue are infrequent. Instead, mutations of NRAS and IDH2 arise, mostly as FLT3-independent subclones, while TET2 and IDH1 predominantly co-occur with FLT3-mutant clones and are enriched in crenolanib poor-responders. The remaining patients exhibit post-crenolanib expansion of mutations associated with epigenetic regulators, transcription factors, and cohesion factors, suggesting diverse genetic/epigenetic mechanisms of crenolanib resistance. Drug combinations in experimental models restore crenolanib sensitivity.

No abstract

Background: Deep vein thrombosis (DVT) is one of the most common complications of total hip (THA) and total knee arthroplasty (TKA). Though the reported incidence of DVT is very high, that of proximal DVT is low and that of fatal thromboembolism is very low. Hence the issue of prophylaxis for DVT remains controversial.The incidence of DVT is based on various studies in European and American populations. The Asian population is genetically and socially quite different from American and European populations, and the incidence of DVT can be quite different. Therefore a prospective study was initiated at our centre to determine incidence of DVT after THA and TKA in Indian patients. Methods: A prospective study was conducted on 60 hips in 45 patients and 46 knees in 26 patients who underwent THA and TKA respectively, without any known risk factors for thromboembolic disease. DVT was studied by preoperative and postoperative serial colour Doppler ultrasonography. No prophylaxis was given to any of the patients. Results: DVT was found in two patients who had undergone THA. No case of DVT was detected in any patient who had undergone TKA. Conclusion: These results suggest that the incidence of DVT in Indian patients is very low and is not comparable with American and European populations. It is therefore not cost effective to advise prophylaxis in Indian patients undergoing THA/TKA who have no known risk factors for DVT.

In dental research, bite force serves as a valuable parameter to evaluate the efficacy of masticatory system. A variety of devices with different design and working principle have been used to record bite force, but no single device is capable to record all the required forces. One may find it difficult to choose a device that will fulfil the purpose of recording bite force for research. So, the present review aims to report and compare the wide range of devices and will help in describing their uses for recording bite force.