Rituximab plus bendamustine or chlorambucil for chronic lymphocytic leukemia: primary analysis of the randomized, open-label MABLE study.

MABLE investigated the efficacy and safety of rituximab plus bendamustine or rituximab plus chlorambucil in fludarabine-ineligible patients with chronic lymphocytic leukemia. Patients received rituximab plus bendamustine or rituximab plus chlorambucil every four weeks for six cycles. Rituximab plus chlorambucil-treated patients without a complete response after Cycle 6 received chlorambucil monotherapy for at least six additional cycles or until complete response. The primary endpoint was complete response rate (confirmed by bone marrow biopsy) after Cycle 6 in first-line patients. Secondary endpoints included progression-free survival, overall survival, minimal residual disease, and safety. Overall, 357 patients were randomized (rituximab plus bendamustine, n=178; rituximab plus chlorambucil, n=179; intent-to-treat population), including 241 first-line patients (n=121 and n=120, respectively); 355 patients received treatment (n=177 and n=178, respectively; safety population). In first-line patients, complete response rate after Cycle 6 (rituximab plus bendamustine, 24%; rituximab plus chlorambucil, 9%; P=0.002) and median progression-free survival (rituximab plus bendamustine, 40 months; rituximab plus chlorambucil, 30 months; P=0.003) were higher with rituximab plus bendamustine than rituximab plus chlorambucil. Overall response rate and overall survival were not different. In first-line patients with a complete response, minimal residual disease-negativity was higher with rituximab plus bendamustine than rituximab plus chlorambucil (66% vs 36%). Overall adverse event incidence was similar (rituximab plus bendamustine, 98%; rituximab plus chlorambucil, 97%). Rituximab plus bendamustine may be a valuable first-line option for fludarabine-ineligible patients with chronic lymphocytic leukemia.

Anxiety and pain during bone marrow aspiration and biopsy.

Background Previously we found that pre-procedural nervousness and tension (translated into English as "anxiety"), assessed on a non-validated five-point scale, correlated with pain intensity of the various stages of bone marrow aspiration and biopsy (BMAB). The fewer the previous BMAB procedures the stronger the pain from a repeated procedure. The primary purpose of the present observational study is to evaluate the state of anxiety just before BMAB and to find out whether it affects the pain experiences during the various stages of the BMAB procedure. We also examined whether first-timers differ from patients with previous BMAB experience in the degree of anxiety and intensity of BMAB procedural pain. Methods A total of 166 adult outpatients undergoing the BMAB from the Helsinki University Hospital were enrolled, 48 of them being first-timers. The level of anxiety was measured with State-Trait Anxiety Inventory (STAI) and the pain experiences associated with the various stages of the procedure were evaluated on the NRS-scale (Numeral Rating Scale 0-10) and using the Finnish pain vocabulary. BMAB was planned to be performed under lidocaine infiltration anaesthesia but, on request, patients were allowed to receive premedication with diazepam orally or alfentanil i.m. If, in spite of supplemental local anaesthetic the patient still felt pain from the sampling needle tip, i.m. alfentanil was administered. Results There was a clear association between anxiety and pain during all stages of the procedure, except during biopsy. The NRS scores varied from 0 to 10 in all the various stages of BMAB. The first-timers did not differ from the more experienced patients with regard to pain experiences; only the pain felt during the local anaesthetic infiltration was milder (P = 0.007) in first-timers than in the others. Procedural pain in those who were given analgesic or sedative premedication was similar (P < 0.05) to that in the non-premedicated patients. The words characterizing the pain of the various stages belonged to a major extent (76-90%) to the sensory class of words. Conclusion Pre-procedural anxiety had a major impact on the pain ratings. The first-timers and patients with previous experience of BMAB had a similar degree of pre-procedural anxiety, as well as of the intensity of procedural pain, except that infiltration of local anaesthetic was less painful in the first-timers. Implications Identification of anxious (fearful) patients prior to BMAB, and premedicating them individually may improve satisfaction in both patient and caregiver.

Comparison of articaine and lidocaine for infiltration anaesthesia in patients undergoing bone marrow aspiration and biopsy.

Infiltration anaesthesia with articaine, a local anaesthetic able to penetrate bone, may relieve procedural pain better than lidocaine in bone marrow aspiration and biopsy. This randomised, double-blind study comprised 150 patients with suspected or known haematologic disease. Either articaine 20mg/ml (50 patients), articaine 40mg/ml (49 patients) or lidocaine 20mg/ml (51 patients), all with adrenaline 5mug/ml, was infiltrated in volume of 6ml (sternal manubrium), 8ml (sternal body) or 10ml (iliac crest) 2min before puncture. Numeral rating scale score (median, range) at injection of local anaesthetic was 3.0 (0-10), at bone puncture 2.0 (0-8), at aspiration 3.5 (0-10) and at biopsy (48 patients) 3.0 (0-10). Pre-procedural anxiety, rated on a verbal scale, correlated significantly with experienced pain (P<0.01). Very anxious patients had fewer previous bone marrow examinations (P<0.01) and they experienced more pain during aspiration (P<0.05). In the post-interview 42 patients reported appearance of pain (median 2.0, range 1-7) after 6.2h, on average, and 15 patients needed oral analgesics. No parameter differed significantly between the groups. In conclusion, the quality of infiltration anaesthesia for bone marrow punctures and aspiration with articaine and lidocaine was similarly poor. Several patients experienced strong pain which correlated with the degree of anxiety.

A randomized, double-blind study comparing Clostridium difficile immune whey and metronidazole for recurrent Clostridium difficile-associated diarrhoea: efficacy and safety data of a prematurely interrupted trial.

A prospective, randomized, double-blind study was designed to compare Clostridium difficile immune whey (CDIW) with metronidazole for treatment of laboratory-confirmed, recurrent, mild to moderate episodes of Clostridium difficile-associated diarrhoea (CDAD). CDIW was manufactured by immunization of cows in their gestation period with inactivated C. difficile vaccine. The resulting colostrum was processed, immunoglubulins were concentrated and the end-product containing high titres of C. difficile immunoglobulin was used as CDIW. 20 patients received metronidazole at a dosage of 400 mg t.i.d. and 18 patients CDIW 200 ml t.i.d. The study was interrupted early because of the bankruptcy of the sponsor. After 14 d of treatment, all 20 (100%) of 20 patients had responded to metronidazole therapy, compared with 16 (89%) of 18 who had received CDIW. 70 d after the beginning of treatment, sustained responses were observed in 11 (55%) of 20 patients receiving metronidazole and 10 (56%) of 18 patients treated with CDIW. In this preliminary study CDIW was as effective as metronidazole in the prevention of CDAD recurrences and it was well tolerated.