Browsing by Author "Wilhelm, M."

Background: The aim of the study was to compare the efficacy of empirical antifungals in combination with broad spectrum antibiotics with that of antibiotics atone in high risk febrile neutropenic cancer patients not responding to initial antibacterial therapy. Patients and Methods: A prospective, randomized controlled trial was conducted at 22 cancer centers in Germany. Patients with fever of unknown origin were randomized to either piperacillin (Pip) plus an aminoglycoside (AMG) (arm A) or a third generation cephalosporin (Ceph) plus AMG (arm 13). Patients not responding after 4-6 days were randomized to either imipenem (Imi) plus gtycopeptide (GLP) (arm C), or Imi/GLP plus amphotericin B deoxycholate (AmB) plus 5-flucytosine (5-FC) (arm D), or Imi/GLP plus fluconazote (Fluco) (arm E). A successful outcome was defined as resolution of fever. Results: In arm A, 192 of 373 patients (51.5%) responded as compared to 176 of 344 patients (51.2%) in arm B. The response rates of 155 patients randomized for further empirical treatment were 55.6%, 77.8% and 62.5% in arm C, D and E, respectively. The difference between arm C and D was of borderline statistical significance (p = 0.06) after correction for multiple testing. Conclusion: In neutropenic cancer patients with persistent fever the combination of antibiotics with AmB/5-FC is superior to salvage antibacterial therapy atone. There is no difference in efficacy between Pip and third generation Ceph given as initial empirical therapy in combination with an AMG.

Aluminum (Al) is a well known contaminant of intravenous solutions. The aim of the present study was the estimation of the aluminum load in patients of an intensive care unit (ICU). 15 patients with normal renal function took part. The study period was 15 days. Al was measured in serum, 24h-urine and 132 samples of parenterals. Daily Al doses were recorded. Al balance was calculated on the basis of the iatrogenic Al dose and renal Al excretion. Al analysis was performed by graphite furnace atomic absorption spectrometry (AAS) with Zeeman background correction under careful quality control. solutions with Al levels > 100 mug/l were: calcium salts, additives for parenteral nutrition solutions, antibiotics, acetylcysteine, triflupromazine, catecholamines and colloids. The Al content of solutions for parenteral nutrition ranged from 4.3 to 69 mug/l. Al doses amounted to 46 - 456 (median 119) mug/d, equivalent to 0.7 to 6.5 (median 1.7) mug/kg b.w. RenalAl excretion ranged from 10.5 to 723.1 mug/d (median 53 mug/d). These amounts partly exceeded the maximal dose (2 mug/kg b.w. per day), recommended by ASPEN/ASCN. Despite of the highly elevated renal Al excretion the median serum concentration of Al was only moderately increased (6.1 mug/l; range: <1.5 to 23.6 mug/l). However, calculations on the basis of the iatrogenic Al dose and renalAl excretion resulted in a netAl uptake (median) of 61 mug/d (maximum: 291 mug/d). Al amounts of this magnitude must be considered potentially harmful in ICU patients, especially with impaired renal function. Parenteral therapy resulted in a considerable Al dose with a positive Al balance in ICU patients. Threshold values for Al contamination of parenterally administered drugs and solutions should be established.

The efficacy and toxicity of a combination of fludarabine and cyclophosphamide (FC) was evaluated in patients with B-cell chronic lymphocytic leukaemia (CLL). Between April 1997 and July 1998, 36 patients with. CLL (median age 59 years) received a regimen that consisted of fludarabine 30 mg/m(2) in a 30-min IV infusion, d 1-3, and cyclophosphamide 250 mg/m(2) in a 30-min IV infusion on d 1-3. Cycles were repeated every 28 d. Twenty-one patients had received between one and three different treatment regimens prior to the study, while 15 patients had received no prior therapy. The median Eastern Cooperative Oncology Group performance score was 1. One patient was at Binet stage A, 18 were stage B and 17 patients were, stage C. Objective responses, assessed according to the revised guidelines of the National Cancer Institute-sponsored Working Group, were recorded in 29 out of 32 assessable patients (90.6%). Twenty-four partial remissions and five complete remissions were observed. Two patients showed no change and one patient showed disease progression. At February 2000, three of the responders had relapsed. Severe neutropenia, anaemia and thrombocytopenia (Common Toxicity Criteria grade 3 and 4) were observed in 25, six and six patients (69.4%, 16.7% and 16.7%) respectively. Other side-effects were uncommon. No treatment-related deaths and no grade 3 or 4 infections occurred. We conclude that the combination of fludarabine and cyclophosphamide showed significant activity in patients with CLL. Myelosuppression was the major side-effect. These results warrant further study on the FC combination in randomized trials.

Tyrosine kinase inhibitors represent today's treatment of choice in chronic myeloid leukemia (CML). Allogeneic hematopoietic stem cell transplantation (HSCT) is regarded as salvage therapy. This prospective randomized CML-study IIIA recruited 669 patients with newly diagnosed CML between July 1997 and January 2004 from 143 centers. Of these, 427 patients were considered eligible for HSCT and were randomized by availability of a matched family donor between primary HSCT (group A; N = 166 patients) and best available drug treatment (group B; N = 261). Primary end point was long-term survival. Survival probabilities were not different between groups A and B (10-year survival: 0.76 (95% confidence interval (CI): 0.69-0.82) vs 0.69 (95% CI: 0.61-0.76)), but influenced by disease and transplant risk. Patients with a low transplant risk showed superior survival compared with patients with high( P < 0.001) and non-high-risk disease (P = 0.047) in group B; after entering blast crisis, survival was not different with or without HSCT. Significantly more patients in group A were in molecular remission (56% vs 39%; P = 0.005) and free of drug treatment (56% vs 6%; P < 0.001). Differences in symptoms and Karnofsky score were not significant. In the era of tyrosine kinase inhibitors, HSCT remains a valid option when both disease and transplant risk are considered.