Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMG-HD4 trial.

The Dutch-Belgian Cooperative Trial Group for Hematology Oncology Group-65/German-speaking Myeloma Multicenter Group-HD4 (HOVON-65/GMMG-HD4) phase III trial compared bortezomib (BTZ) before and after high-dose melphalan and autologous stem cell transplantation (HDM, PAD arm) compared with classical cytotoxic agents prior and thalidomide after HDM (VAD arm) in multiple myeloma (MM) patients aged 18-65 years. Here, the long-term follow-up and data on second primary malignancies (SPM) are presented. After a median follow-up of 96 months, progression-free survival (censored at allogeneic transplantation, PFS) remained significantly prolonged in the PAD versus VAD arm (hazard ratio (HR)=0.76, 95% confidence interval (95% CI) of 0.65-0.89, P=0.001). Overall survival (OS) was similar in the PAD versus VAD arm (HR=0.89, 95% CI: 0.74-1.08, P=0.24). The incidence of SPM were similar between the two arms (7% each, P=0.73). The negative prognostic effects of the cytogenetic aberration deletion 17p13 (clone size ⩾10%) and renal impairment at baseline (serum creatinine >2 mg dl-1) on PFS and OS remained abrogated in the PAD but not VAD arm. OS from first relapse/progression was similar between the study arms (HR=1.02, P=0.85). In conclusion, the survival benefit with BTZ induction/maintenance compared with classical cytotoxic agents and thalidomide maintenance is maintained without an increased risk of SPM.

Injury severity of restrained front seat occupants in car-to-car side impacts.

The influence of a number of factors, including age and particularly seating position, on the injury severity of restrained occupants was examined for 41 front-seat occupants seated adjacent to the impact (near side) and 38 sitting opposite the impacted side (far side) in car-to-car side collisions (center of impact: front door and B-pillar). Above an energy equivalent speed of 40 km/h all near-side occupants and about half of the far-side occupants sustained severe injuries. A logistic regression analysis showed that within range of 30-60 km/h (delta v 20-60 km/h) the probability of severe injuries increased dramatically from approximately 20% to more than 90%; in these cases, far-side occupants had the same injury probability as near-side occupants only when the speed was 10 km/h higher. The main cause of death for 27 occupants seated on both sides was polytrauma, this was accompanied in two-thirds of the cases by serious head injuries. The second most frequent cause of death was head injury.

Influencing factors on the injury severity of restrained front seat occupants in car-to-car head-on collisions.

The results of 319 cases of belt-restrained front seat car occupants (234 drivers and 85 passengers) from 241 vehicles in car-to-car head-on collisions were examined. Ninety-five occupants were uninjured, 195 sustained a total injury severity of Maximum Abbreviated Injury Score (MAIS) 1-3 and 29, MAIS 4-6. There were 27 fatalities, and the main causes of death were polytrauma and hemorrhage. The main factors influencing occupant injury severity were: the energy equivalent speed (EES); the change of velocity (delta upsilon); the maximum deformation depth; and the collision angle. With an EES > 50 km/h fatal injuries can be expected, and above 60 km/h no occupant remained uninjured. The results of a multivariate analysis were: EES influenced the injury severity at all body locations except the spinal cord; occupant position effected only head injury severity, with drivers being more severely injured; occupant age influenced the injury severity at the thorax, abdomen, and extremities and MAIS as well. Age was a further factor influencing injury severity, e.g. with an EES of 50 km/h the probability of being fatally injured was 30%-45% higher for occupants over 59 years than those under 20.

Increased risk of catheter colonization and catheter-related infections in severe immunocompromized patients with multiple myeloma undergoing high-dose glucocorticoid treatment.

Catheter-related infections (CRI) are an important problem in medicine because of major consequences for treatment, prolongation of hospitalization and increasing therapy costs. Malignancies, immunodeficiency, severe burns and malnutrition compromise host defense. Studies to quantify the increased risk of CRI in immunocompromised patients are required. We analyzed the influence of immunoglobulin deficiency and high-dose glucocorticoid treatment in patients with multiple myeloma with regard to catheter colonization and CRI. In patients with multiple myeloma, central venous catheters (CVC) were significantly more frequently colonized (> 15 CFU) as compared to patients with other malignancies undergoing chemotherapy. We found a tendency towards a higher CRI rate in the myeloma patient group. Interestingly, despite of the significantly higher incidence of catheter colonization and a tendency towards higher CRI rates in severely immunocompromised patients, the incidence of signs of local (redness of the entry site) and systemic (fever) host reactions is reduced in myeloma patients. To decrease the CRI rate in myeloma patients during chemotherapy which includes high-dose glucocorticoids, we use antibacterial (silver-coated) catheters.

Prevention of catheter-related infections by silver coated central venous catheters in oncological patients.

Catheter-related infection (CRI) is a serious complication of central venous catheterization. We have investigated the efficacy of a silver-coated polyurethane catheter (Pellethane, Fresenius AG, Germany) in preventing CRI in oncological patients receiving chemotherapy in a phase II study. From November 1992 through April 1994, 266 patients were assigned to receive single lumen catheters, either standard uncoated catheters (UC, n = 113) or silver-coated ones (SC, n = 120). Catheters were inserted into the internal jugular vein after institutional approval and informed consent. Duration of catheterization (UC vs. SC = 13.3 vs. 12.7 days) and leukopenia (< 1.0 x 10(9) WBC/l; 4.3 vs. 3.6 days) were similar in both groups demonstrating a comparable risk for infections. Skin reactions at the catheter entry site were recorded daily. CRI and colonization rates were studied by semiquantitatively culturing intradermal and intravascular segments. CRI were confirmed by blood cultures obtained via catheter and from peripheral veins in cases of suspected sepsis or at the end of catheterization. No adverse effects from the silver-coated catheter could be observed. The bacteriological results showed that SC were colonized (> 15 CFU) in 45.1% and UC in 44.2%. CRI developed in 21.2% of the UC patients but only in 10.2% of the SC patients (p = 0.011). We conclude that this new silver-coated central venous catheter is biocompatible and effective in reducing the incidence of catheter-related infections in oncological patients.

Technical parameters influencing the severity of injury of front-seat, belt-protected car passengers on the impact side in car-to-car side collisions with the main impact between the front and rear seats (B-pillars).

Authentic car-to-car side collisions (n = 30) with the main impact area at the B-pillar were analyzed to find technical parameters corresponding with the injury severities of the front seat, belt-protected car passengers on the impact side. EES (Energy Equivalent Speed) and delta v (delta v, change in velocity) were highly significant predictors of the severity of thoracic and abdominal injuries and total injury severity coded according to the Abbreviated Injury Scale (AIS). At an EES or delta v greater than or equal to 40 km/h all front-seat car passengers on the impact side sustained a total injury severity of Maximum AIS (MAIS) greater than or equal to 4 and died. Although a passenger could survive the crash without injury to one or more body regions up to the highest EES- and delta v-values, at EES or delta v greater than or equal to 40 km/h fatal injuries were sustained in at least one body region. At an EES greater than or equal to 35 km/h or a delta v greater than or equal to 15 km/h no front-seat car passenger on the impact side remained uninjured.

Liver and spleen ruptures in authentic car-to-car side collisions with main impact at front door or B-pillar.

Seventy-nine belt-protected front seat occupants sustained authentic car-to-car side collisions with impact at front door or B-pillar in which energy equivalent speed (EES) and delta V had a highly significant influence on the occurrence of liver and spleen ruptures. From an EES greater than or equal to 40 km/h the risk of suffering liver and spleen injuries proved to be much higher for occupants on the impact side. Drivers on the impact side often had combined liver and spleen ruptures, front seat passengers had only liver ruptures and combined liver and spleen ruptures. The number of rib fractures on the left or right had a highly significant influence on the occurrence of liver and spleen ruptures. Liver ruptures and combined liver and spleen ruptures were often combined with pelvic ruptures.