Corinna Hahn-Ast

A systematic review of phase II trials of thalidomide/dexamethasone combination therapy in patients with relapsed or refractory multiple myeloma

Thalidomide monotherapy in relapsed/refractory multiple myeloma (MM) has a response rate of 30%. The combination of thalidomide with dexamethasone (Thal/Dex) is expected to improve responses, but it is unknown if the combination increases the rate of adverse events. Here, we conducted a systematic review of studies evaluating Thal/Dex in relapsed/refractory MM. Twelve studies were included, comprising 451 patients. The response rate (CR and PR) was 46% (95% CI 42–51%). Therapy‐related toxicity was comparable to thalidomide monotherapy and included somnolence (26%, 95% CI 22–31%), constipation (37%, 95% CI 32–42%) and peripheral neuropathy (27%, 95% CI 23–32%). Only venous thromboembolism appeared to occur more often with Thal/Dex (5%, 95% CI 3–8%). Thus, using Thal/Dex results in an improved response rate in relapsed/refractory MM, with a toxicity rate comparable to thalidomide monotherapy.

False positivity of the Aspergillus galactomannan Platelia ELISA because of piperacillin/tazobactam treatment: does it represent a clinical problem?

OBJECTIVES False-positive results of the galactomannan (GM) ELISA caused by concurrent administration of piperacillin/tazobactam have been reported in patients with febrile neutropenia. PATIENTS AND METHODS This prospective study investigated different sampling times in 30 patients receiving piperacillin/tazobactam for febrile neutropenia. RESULTS Prior to the first piperacillin/tazobactam infusion, a median GM index of 0.2 [interquartile range (IQR) 0.1-0.3] was noted; in two patients (7%) the index was 0.5. Immediately after piperacillin/tazobactam infusion, the median index increased to 0.3 (IQR 0.2-0.4, P = 0.002) leading to 21% (7/30) false-positive results, if > or = 0.5 is assumed as the cut-off level. GM indices before the next piperacillin/tazobactam infusion were not increased (median 0.2, IQR 0.2-0.35, P > 0.05), but 10% (3/30) were still > or = 0.5. With a cut-off level of > 0.7, no false-positive results were noted at any sampling time point. CONCLUSIONS We conclude that the clinical relevance of false-positive GM results during piperacillin/tazobactam treatment is small if samples are collected prior to infusion and if a cut-off level of > 0.7 is used.

Successful Treatment of Patients With Multiple Myeloma and Impaired Renal Function With Lenalidomide: Results of 4 German Centers

UNLABELLED Retrospective multicenter analysis of 26 patients with multiple myeloma to assess the efficacy and toxicity of relapse treatment with lenalidomide/dexamethasone in renal-function impairment. Analysis showed myeloma overall response rate of 84%, with 42% of patients with improvement of renal function. Lenalidomide/dexamethasone is highly effective, with acceptable toxicity in the renally impaired patient group. PURPOSE Renal impairment is one of the main complications of multiple myeloma associated with unfavorable prognosis. Lenalidomide in combination with dexamethasone is an effective treatment of relapsed and/or refractory multiple myeloma and may be used in patients with myeloma and with renal insufficiency with appropriate dose adaption according to creatinine clearance (CLCr). However, there are limited data on the use of this regimen in patients with myeloma and with impaired renal function. PATIENTS AND METHODS We report on 26 patients, in 4 German centers, with impaired renal function and relapsed and/or refractory multiple myeloma who were treated with lenalidomide/dexamethasone-based regimens; we retrospectively analyzed their data. RESULTS All 26 patients had a CLCr < 60 mL/min. Six patients were permanently or temporarily dialysis dependent. Overall response rate (ie, at least a partial response) was 84%. The rate of renal response (at least minor renal response) was 42%, with 6 patients achieving a complete renal response. A median time of 28 days was documented until first response. Six patients had grade 3/4 thromboembolic events; all but one of these patients received prophylaxis with acetylsalicylic acid. CONCLUSION Lenalidomide-based treatment is highly effective and is an attractive treatment option in patients with multiple myeloma with impaired renal function. In this analysis, renal function was improved in a substantial proportion of patients.

An Audit of Efficacy and Toxicity of Teicoplanin Versus Vancomycin in Febrile Neutropenia: Is the Different Toxicity Profile Clinically Relevant?

Background:Glycopeptides are often used for persistent fever in neutropenic patients. This study compares efficacy and toxicity of teicoplanin and vancomycin.Patients and Methods:Hundred consecutive neutropenic patients with hematological malignancies and persistent fever after 72 h of first-line antibiotic therapy (91% piperacillin/tazobactam) were treated with teicoplanin (800 mg on day 1, then 400 mg/day) + piperacillin/tazobactam + gentamicin from 08/96 to 09/00 (group T) or with vancomycin (2 g/day) + meropenem + levofloxacin from 10/00 to 04/02 (group V). Success was defervescence (≥ 7 days) in absence of any sign of continuing infection. Nephrotoxicity was monitored daily as increase in serum creatinine.Results:Fifty patients were analyzed in each group. Efficacy was evaluated in patients with piperacillin/tazobactam as first-line therapy only. Treatment was successful in 76% in group T (n = 42) and 59% in group V (n = 49), p = 0.118. Toxicity was evaluated in all patients. The median increase of creatinine was 11% (interquartile range 0%–30%) in group T and 17% (0%–74%) in group V, p = 0.062. In patients who received concomitant amphotericin B (given for 7 days and 6 days, respectively, p = 0.525), median creatinine increased from 0.9 mg/dl (0.8–1.1) to 1.2 mg/dl (0.9–1.5) in group T and from 0.9 mg/dl (0.8–1.08) to 1.55 mg/dl (1.33–2.23) in group V (p < 0.001). This led to a doubling of creatinine in 2/23 (9%) patients of group T and in 9/16 (56%) patients of group V (p = 0.003). A multivariate analysis revealed that concomitant use of amphotericin B (p < 0.001) and treatment with vancomycin (p = 0.002) were independently associated with nephrotoxicity.Conclusion:Teicoplanin and vancomycin were comparably effective in patients with neutropenia and persistent fever, but – if combined with amphotericin B – vancomycin was significantly more nephrotoxic than teicoplanin.