Summary The activity of thalidomide in relapsed or refractory multiple myeloma is widely accepted but not yet demonstrated in a randomised‐controlled trial. A systematic review of the published clinical trials of these patients could reduce the possible bias of single phase‐II studies. A systematic search identified 42 communications reporting on 1674 patients. Thirty‐two trials used an escalating dosing regimen and four a fixed dose regimen (one dose with 50 mg/d, three doses with 200 mg/d). The target dose in the dose escalating trials was 800 mg/d in 17 trials, 400–600 mg/d in 10 and 200 mg/d in one trial. The intention‐to‐treat population for efficacy was 1629 patients with a median age of 62 years. The complete and partial (>50% reduction in monoclonal protein) response rate was 29·4% (95%‐confidence interval, 27–32%). The rates for minor responses or stable disease were 13·8% (12–16%) and 11·0% (9–13%). Progressive disease was reported in 9·9% (8–11%). The median overall survival from all trials was reported at 14 months. Severe adverse events (grade III–IV) included somnolence 11%, constipation 16%, neuropathy 6%, rash 3%, thrombo‐embolism 3%, cardiac 2%. In conclusion, thalidomide monotherapy achieved complete and partial responses in 29·4% of patients with relapsed or refractory multiple myeloma.

Infection is the main treatment-related cause of mortality in cancer patients. Rapid and accurate diagnosis to facilitate specific therapy of febrile neutropenia is therefore urgently warranted. Here, we evaluated a commercial PCR-based kit to detect the DNA of 20 different pathogens (SeptiFast) in the setting of febrile neutropenia after chemotherapy. Seven hundred eighty-four serum samples of 119 febrile neutropenic episodes (FNEs) in 70 patients with hematological malignancies were analyzed and compared with clinical, microbiological, and biochemical findings. In the antibiotic-naïve setting, bacteremia was diagnosed in 34 FNEs and 11 of them yielded the same result in the PCR. Seventy-three FNEs were negative in both systems, leading to an overall agreement in 84 of 119 FNEs (71%). During antibiotic therapy, positivity in blood culture occurred only in 3% of cases, but the PCR yielded a positive result in 15% of cases. In six cases the PCR during antibiotic treatment detected a new pathogen repetitively; this was accompanied by a significant rise in procalcitonin levels, suggestive of a true detection of infection. All patients with probable invasive fungal infection (IFI; n ‫؍‬ 3) according to the standards of the European Organization for Research and Treatment of Cancer had a positive PCR result for Aspergillus fumigatus; in contrast there was only one positive result for Aspergillus fumigatus in an episode without signs and symptoms of IFI. Our results demonstrate that the SeptiFast kit cannot replace blood cultures in the diagnostic workup of FNEs. However, it might be helpful in situations where blood cultures remain negative (e.g., during antimicrobial therapy or in IFI).While systemic infection is the most common cause of a febrile neutropenia episode (FNE) with significant effects on morbidity and mortality, only 30% of blood cultures taken at the onset of fever are positive (11,15). Nonetheless, patients with FNEs are treated with broad-spectrum antimicrobial agents regardless of the result of their blood culture (7) because potentially life-threatening infections need early treatment to ensure better clinical outcome. Noninfective causes of a systemic reaction culminating in a rise in temperature such as tumor fever, drug fever, or transfusion reactions complicate the diagnostic challenge in cancer patients. In addition, the etiology of a deterioration of an FNE during antimicrobial therapy is often difficult to elucidate, since blood cultures are infrequently positive once effective antimicrobial therapy has started (4). Pathogens such as molds which are rarely found in blood cultures are not uncommon in patients with FNEs, particularly if they suffer from hematological malignancies. For these reasons, FNE is one of the conditions where new diagnostic tools to distinguish an infection from a nonmicrobial cause for fever or to identify rare pathogens are most urgently needed. In the past, raised levels of indirect markers such as procalcitonin (PCT) and interleukin 6 (3, 16) have been shown to be ...

This open case study of severely ill patients with invasive fungal infections demonstrates both excellent efficacy and very low toxicity of caspofungin.

We designed a multicenter Phase II trial to prospectively evaluate the efficacy and safety of the combination of rituximab with the DHAP regimen (dexamethasone, high-dose cytarabine, cisplatin) in patients who relapsed after or were resistant to a CHOP-like regimen. A total of 53 patients with relapsed or resistant aggressive B-cell NHL were analyzed. The overall response rate was 62.3 percent. With a median follow-up of 24.9 months, median overall and progression-free survivals were 8.5 and 6.7 months, respectively. Immunochemotherapy with rituximab and DHAP proved to be feasible and effective in this patient population.

The addition of rituximab to chemotherapy in patients with diffuse large B-cell lymphoma (DLBCL) has been shown to improve outcome in first-line therapy. However, in patients with relapsed or refractory disease, the value of adding rituximab to salvage chemotherapy is less clearly defined. This study performed a matched-pair analysis of patients with relapsed or refractory DLBCL by comparing the combination of dexamethasone, high-dose cytarabine and cisplatin (DHAP) with rituximab to DHAP alone. Sixty-seven patients with relapsed or refractory DLBCL were collected from two prospective phase II trials from Germany and Italy. Twenty-three patient pairs treated with either DHAP in combination with rituximab or DHAP alone could be analysed after matching for important prognostic factors. The addition of rituximab to the DHAP regimen led to higher complete and similar overall remission rates. However, differences with regard to complete remission rates failed to reach statistical significance, thereby necessitating further evaluation of the role of combined immunochemotherapy in this patient population.