Maintenance rituximab following induction chemoimmunotherapy may prolong progression-free survival in mantle cell lymphoma: a pilot study from the Wisconsin Oncology Network.

BACKGROUND: There is no standard first line treatment for mantle cell lymphoma. PATIENTS AND METHODS: This was a multicenter phase II pilot study of rituximab and modified hyper-fractionated cyclophosphamide, vincristine doxorubicin, dexamethasone (modified R-hyperCVAD) administered every 28 days for four to six cycles followed by rituximab maintenance therapy consisting of four weekly doses every 6 months for 2 years. Unlike traditional hyperCVAD regimens, no methotrexate or cytarabine was administered. RESULTS: Of 22 patients, the overall response rate was 77% and the complete response rate was 64%. With a median follow-up time of 37 months in surviving patients, the median PFS was 37 months and the median OS was not reached. The achievement of a molecular remission did not correlate with improved outcome. The major toxicity was expected myelosuppression. Two patients died during induction treatment. There were no major adverse effects during maintenance therapy. CONCLUSION: In a multicenter trial, modified R-hyperCVAD was tolerable and effective induction therapy for untreated MCL. Maintenance rituximab appeared to prolong PFS without increasing toxicity.

Effects of the Berlin Heart biventricular assist device on microvascular responses in pre-transplant patients.

Microcirculatory forearm cutaneous blood flow was monitored continuously and noninvasively by laser doppler flow-metry (LDF) in 15 patients treated with the Berlin Heart biventricular assist device system (BVAD) for end-stage heart failure under stable hemodynamic states (BVAD pts, n = 10) and norepinephrine therapy (BVAD nor pts, n = 5). Ten healthy human subjects served as controls (C). Cutaneous blood flow was measured before, during, and after external brachial artery occlusion to evaluate the post-occlusive reactive hyperemia (PORH) as a standardized response. To examine microvascular responses to macrohemodynamic changes, the cardiac output (CO) was decreased by a 20% reduction in BVAD pump rate. No significant differences in baseline LDF measurements (in millivolts) were observed among the three groups (C, 470.7 mV +/- 177.3; BVAD pts, 328.0 mV +/- 122.7; BVAD nor pts, 360.0 mV +/- 160.0). After cuff pressure release (1 min later), a significant (p < 0.004) three-fold to four-fold blood flow increase (PORH) occurred in each group (C, 1113.6 mV +/- 469.2; BVAD pts, 813.0 mV +/- 190.1; BVAD nor pts, 498.0 mV +/- 191.8). The difference in PORH between the BVAD pts and BVAD nor pts was significant (p < 0.01), and the time to peak PORH values was different (p < 0.05) among the three groups (C, 22.2 s +/- 10.7; BVAD pts, 11.3 s +/- 12.5; BVAD nor pts, 7.0 s +/- 5.8). A markedly delayed return to baseline occurred in the BVAD pts. The 20% reduction in BVAD pump rate decreased CO significantly (p < 0.05) and increased (p < 0.01) systemic vascular resistance (SVR).(ABSTRACT TRUNCATED AT 250 WORDS)

Recovery of end-organ failure during mechanical circulatory support.

To evaluate organ recovery during mechanical assistance, respiratory, hepatic and renal function parameters of 40 patients who underwent bridge-to-transplant procedures were reviewed retrospectively. Mechanical circulatory support was indicated if the hemodynamic and clinical status deteriorated despite pharmacotherapy with catecholamines, vasodilators, and intravenous use of the phosphodiesterase inhibitor enoximone. Sequelae of cardiogenic shock such as renal, hepatic and respiratory insufficiency were not considered a contraindication for mechanical support. The analysis of preimplant data such as serum creatinine, liver enzymes and pulmonary gas exchange did not identify any predictive indicator of irreversible organ damage. Functional recovery of preexisting respiratory, hepatic and renal dysfunction was found in 91%, 90%, and 85%, respectively. Subsequent transplantation, however, was affected by the number of failing organs prior to mechanical support. Of 17 patients with isolated organ failure prior to assist, 14 (82%) were transplanted. By contrast, 9 (75%) of 12 with combined failure of two organs, and only 6 (54%) of 11 patients with clinical patterns of three failing organ systems received transplants. In all patients who underwent successful transplantation, transplantability was associated with rapid organ recovery within 10 to 15 days after initiating mechanical assistance.

Comparative effects of cefoxitin and cefotetan on vitamin K metabolism.

The effects of cefoxitin and cefotetan on vitamin K metabolism and clotting parameters in five healthy subjects were investigated. No changes in prothrombin time or in the formation of abnormal prothrombin were seen either during or following the cefoxitin or cefotetan phase. However, when phytonadione (10 mg) (vitamin K1) was administered at the completion of each course of antibiotics, formation of vitamin K 2,3-epoxide was observed only during the cefotetan phase. It is probable, therefore, that cefotetan, a cephamycin antibiotic containing the N-methylthiotetrazole side chain, inhibits hepatic vitamin K 2,3-epoxide reductase. While hypoprothrombinemia and formation of abnormal prothrombin were not seen in healthy subjects, the effect of cefotetan on the coagulation status of vitamin K-depleted patients may be adverse.