We report a retrospective analysis of 128 consecutive patients with high-risk myelodysplastic syndrome (MDS) and AML who received an alemtuzumab-based reduced-intensity conditioning hematopoietic... Show moreWe report a retrospective analysis of 128 consecutive patients with high-risk myelodysplastic syndrome (MDS) and AML who received an alemtuzumab-based reduced-intensity conditioning hematopoietic SCT (RIC HSCT). The median recipient age was 53 years (range 21-72 years). A total of 49 (38%) recipients had a sibling donor and 79 (62%) had a volunteer-unrelated donor. The hematopoietic cell transplantation-specific comorbidity index (HCT-CI) was assigned to all patients with a score of 0 in 40 (31%), of 1-2 in 45 (35%) and >= 3 in 43 (34%) patients. The 3-year non-relapse mortality (NRM) was 31%, disease-free survival (DFS) was 41% and overall survival (OS) was 46%. The 3-year NRM for patients with a HCT-CI score of 0, 1-2 or >= 3 was 16, 24 and 42%, respectively. The 3-year DFS and OS by HCT-CI was 58 and 69% (score 0), 39 and 39% (score 1-2) and 24 and 32% (score >= 3), respectively. On multivariate analysis, HCT-CI was an independent variable affecting 3-year NRM, DFS and OS (P-value = 0.04, 0.01 and < 0.01, respectively). Although the disease stage at the time of transplant was an additional independent predictive variable on transplant outcomes, recipient age (>/<50 years) did not have a significant predictive impact. In MDS or AML patients with advanced disease receiving alemtuzumab-based RIC HSCT, the HCT-CI provides an important means of stratifying patients with a high risk of inferior transplant outcomes. Bone Marrow Transplantation (2010) 45, 633-639; doi:10.1038/bmt.2009.236; published online 21 September 2009 Show less
Michallet, M.; Dreger, P.; Sutton, L.; Brand, R.; Richards, S.; Biezen, A. van; ... ; Milligan, D. 2010
P>From 2002 to 2007, 49 myeloma patients who relapsed following autologous SCT were included in a prospective multicenter trial to determine the efficacy of a reduced melphalan/fludarabine... Show moreP>From 2002 to 2007, 49 myeloma patients who relapsed following autologous SCT were included in a prospective multicenter trial to determine the efficacy of a reduced melphalan/fludarabine regimen followed by allogeneic SCT from unrelated donors. All patients showed leucocyte and platelet engraftment after a median of 15 and 19 d, respectively. Grade II-IV acute graft-versus-host disease (GvHD) occurred in 25% of patients and 35% had chronic GvHD. Overall response rate at day 100 was 95% including 46% complete remission (CR). Cumulative incidence of non-relapse mortality at 1 year was 25% [95% confidence interval (CI): 13-37%] and was significantly lower for human leucocyte antigen (HLA)-matched compared to -mismatched SCT (10% vs. 53%, P = 0 center dot 001). The cumulative incidence of relapse at 3 years was 55% (95% CI: 40-70%). After a median follow up of 43 months, the estimated 5-year progression-free and overall survival rates were 20% and 26% respectively and were significantly better for matched in CR at day 100 (41% vs. 7%, P = 0 center dot 04 and 56% vs. 16%, P = 0 center dot 02). We conclude that optimal donor selection is mandatory for a low non-relapse mortality and high relapse incidence, which remains a major concern, should be improved by including post-transplant strategies to upgrade remission status. Show less
OBJECTIVE: In elective orthopaedic hip- and knee replacement surgery patients, we studied the effect of implementation of a uniform transfusion policy on RBC usage. STUDY DESIGN AND METHODS: A... Show moreOBJECTIVE: In elective orthopaedic hip- and knee replacement surgery patients, we studied the effect of implementation of a uniform transfusion policy on RBC usage. STUDY DESIGN AND METHODS: A randomized, controlled study. A new uniform, restrictive transfusion policy was compared with standard care, which varied among the three participating hospitals. Only prestorage leucocyte-depleted RBC(s) were used. Primary end-point was RBC usage, related to length of hospital stay. Secondary end-points were Hb levels, mobilization delay and postoperative complications. RESULTS: Six hundred and three patients were evaluated. Adherence to the protocol was over 95%. Overall mean RBC usage was 0.78 U/patient in the new policy group and 0.86 U/patient in the standard care policy group (mean difference 0.08;95% CI [-0.3; 0.2]; P = 0.53). In two hospitals, the new transfusion policy resulted in a RBC reduction of 30% (0.58U RBC/patient) (P = 0.17) and 41% (0.29 U RBC/patient) (P = 0.05) respectively. In the third hospital, however, RBC usage increased by 39% (0.31 U RBC/patient) (P = 0.02) with the new policy, due to a more restrictive standard care policy in that hospital. Length of hospital stay was not influenced by either policy. CONCLUSIONS: Implementation of a uniform transfusion protocol for elective lower joint arthroplasty patients is feasible, but does not always lead to a RBC reduction. Length of hospital stay was not affected. Show less
Lim, Z.; Brand, R.; Martino, R.; Biezen, A. van; Finke, J.; Bacigalupo, A.; ... ; Witte, T.M. de 2010
Purpose This study was performed to examine the characteristics of transplant activity for patients with myelodysplastic syndromes (MDS) older than 50 years within the European Group for Blood and... Show morePurpose This study was performed to examine the characteristics of transplant activity for patients with myelodysplastic syndromes (MDS) older than 50 years within the European Group for Blood and Marrow Transplantation, and to evaluate the factors predicting outcome within this group of patients. Patients and Methods We performed a retrospective multicenter analysis of 1,333 MDS patients age 50 years or older who received transplantation within the EBMT since 1998. The median recipient age was 56 years, with 884 patients (66%) age 50 to 60 years and 449 (34%) patients older than 60 years. There were 811 HLA-matched sibling (61%) and 522 (39%) unrelated donor transplants. Five hundred patients (38%) received standard myeloablative conditioning (SMC), and 833 (62%) received reduced intensity conditioning (RIC). Results The 4-year estimate for overall survival of the whole cohort was 31%. On multivariate analysis, use of RIC (hazard ratio [HR], 1.44; 95% CI, 1.13 to 1.84; P < .01) and advanced disease stage at transplantation (HR, 1.51; 95% CI, 1.18 to 1.93; P < .01) were associated with an increased relapse rate. In contrast, advanced disease stage at transplantation (HR, 1.43; 95% CI, 1.13 to 1.79; P = .01), use of an unrelated donor (P = .03), and RIC (HR, 0.79; 95% CI, 0.65 to 0.97; P = .03) were independent variables associated with nonrelapse mortality. Advanced disease stage at transplantation (HR, 1.55; 95% CI, 1.32 to 1.83; P < .01) was the major independent variable associated with an inferior 4-year overall survival. Conclusion Allogeneic hematopoietic stem-cell transplantation remains a potential curative therapeutic option for many older patients with MDS. In this analysis, disease stage at time of transplantation, but not recipient age or the intensity of the conditioning regimens, was the most important factor influencing outcomes. Show less
Kroger, N.; Zabelina, T.; Biezen, A. van; Brand, R.; Niederwieser, D.; Martino, R.; ... ; European Grp Blood Marrow 2010
Background Tubular discectomy compared with conventional microdiscectomy has been introduced to speed up the rate of recovery in patients with lumbar disc related sciatica, although similar... Show moreBackground Tubular discectomy compared with conventional microdiscectomy has been introduced to speed up the rate of recovery in patients with lumbar disc related sciatica, although similar results have been shown. The authors performed a subgroup analysis to investigate whether certain patients might benefit more from either two surgical treatments. Methods A double-blinded randomised trial was performed to compare the rate of recovery and outcome at 1 year between tubular discectomy and conventional microdiscectomy. Complete and nearly complete recovery, documented on the patient’s global perceived recovery, were defined as a good outcome. The effect modification of the allocated treatment strategy by predefined variables on the rate of recovery and outcome at 1 year was analysed by Cox proportional hazard analyses and logistic regression analyses, respectively. Results With respect to the outcome rate of recovery, interaction with treatment effect was present for the variable gender and type of disc herniation. Patients with a contained disc herniation (HR 0.73; 95% CI 0.49 to 1.09) and women (HR 0.75; 95% CI 0.54 to 1.06) had slower rates of recovery when treated with tubular discectomy. Variables correlated with good outcome at 1 year were the level of education and Slump test. Higher educated patients (OR 0.18; 95% CI 0.06 to 0.59) and patients with a negative Slump (OR 0.24; 95% CI 0.06 to 0.92) fared worse at 1 year when they underwent tubular discectomy. Conclusions Superiority of tubular discectomy compared with conventional microdiscectomy was not demonstrated. Subgroup analyses identified only a few variables that were associated with more or less benefit from one of the allocated treatments. Show less
Objective: To determine whether the faster recovery after early surgery for sciatica compared with prolonged conservative care is attained at reasonable costs. Design: Cost utility analysis... Show moreObjective: To determine whether the faster recovery after early surgery for sciatica compared with prolonged conservative care is attained at reasonable costs. Design: Cost utility analysis alongside a randomised controlled trial. Setting: Nine Dutch hospitals. Participants: 283 patients with sciatica for 6-12 weeks, caused by lumbar disc herniation. Interventions: Six months of prolonged conservative care compared with early surgery. Main outcome measures: Quality adjusted life years (QALYs) at one year and societal costs, estimated from patient reported utilities (UK and US EuroQol, SF-6D, and visual analogue scale) and diaries on costs (healthcare, patient's costs, and productivity). Results: Compared with prolonged conservative care, early surgery provided faster recovery, with a gain in QALYs according to the UK EuroQol of 0.044 (95% confidence interval 0.005 to 0.083), the US EuroQol of 0.032 (0.005 to 0.059), the SF-6D of 0.024 (0.003 to 0.046), and the visual analogue scale of 0.032 (-0.003 to 0.066). From the healthcare perspective, early surgery resulted in higher costs (difference euro1819 (pound1449; $2832), 95% confidence interval euro842 to euro2790), with a cost utility ratio per QALY of euro41 000 (euro14,000 to euro430 000). From the societal perspective, savings on productivity costs led to a negligible total difference in cost (euro-12, euro-4029 to euro4006). Conclusions: Faster recovery from sciatica makes early surgery likely to be cost effective compared with prolonged conservative care. The estimated difference in healthcare costs was acceptable and was compensated for by the difference in absenteeism from work. For a willingness to pay of euro40,000 or more per QALY, early surgery need not be withheld for economic reasons. Trial registration Current Controlled Trials ISRCTN 26872154. Show less
