Biomedical subjects

Ronald Brand

Publications and source records attributed to Ronald Brand.

29 records · Page 2Linked to original sources

PubMed2003

Donor CMV serologic status and outcome of CMV-seropositive recipients after unrelated donor stem cell transplantation: an EBMT megafile analysis.

Cytomegalovirus (CMV) has been a major cause of morbidity and mortality after allogeneic stem cell transplantation (SCT). The importance of the recipient's serologic status is paramount. However, the importance of the donor's serologic status in CMV-seropositive recipients is controversial. We analyzed the influence of the donor's CMV status in a large cohort of patients. A total of 7018 patients seropositive for CMV reported to the European Group for Blood and Marrow Transplantation (EBMT) were included; 5910 patients had undergone HLA-identical sibling SCT and 1108 patients had undergone unrelated donor SCT. Univariate and multivariate proportional hazards models were constructed for survival, event-free survival, transplant-related mortality, and relapse incidence. Patients receiving grafts from CMV-seropositive HLA-identical sibling donors had the same survival as patients grafted from seronegative donors (hazard ratio [HR], 1.04; P =.37; 95% confidence interval [CI], 0.95-1.14). However, unrelated donor stem cell (SC) transplant recipients receiving grafts from CMV-seropositive donors had an improved 5-year survival (35% versus 27%; HR = 0.8; P =.006), an improved event-free survival (30% versus 22%; HR = 0.8; P =.01), and a reduced transplant-related mortality (49% versus 62%; HR = 0.7; P <.001). There was no influence on the relapse incidence. The effects of donor CMV status remained in multivariate analyses. The effect of donor status was different among different disease categories. In patients with chronic myelogenous leukemia (CML), T-cell depletion abrogated the beneficial effect of donor status, suggesting that the effect is mediated through transfer of donor immunity. Our data suggest that donor CMV status influences outcome of unrelated SCT. For a CMV-seropositive patient, a seropositive donor might be preferable.

Adolescent↗

PubMed2003

Stem cell transplantation for chronic myeloid leukemia in children.

Hematopoietic stem cell transplantation (SCT) is the only proven cure for chronic myeloid leukemia (CML), a rare disease in childhood. We report outcomes of 314 children with Philadelphia-chromosome-positive (Ph+) CML undergoing SCT from HLA-matched siblings (n = 182) or volunteer-unrelated donors (VUD; n = 132). Three-year overall survival (OS) and leukemia-free survival (LFS) rates were 66% and 55% (n = 314). For 156 children in first chronic phase (CP1) who underwent transplantation from HLA-identical siblings, OS and LFS rates were 75% and 63%. For 97 children who underwent SCT in CP1 from VUD, 3-year OS and LFS rates were 65% and 56%, reflecting higher transplantation-related mortality (TRM) after VUD SCT (35% vs 20%; multivariate hazard ratio [HR], 1.9; 95% confidence interval [CI], 1.0-3.5; P =.05). In a multivariate model for OS and LFS, outcomes were superior in CP1 than in advanced phase (AP/CP1) (OS HR, 2.0; 95% CI, 1.3-3; P =.001; LFS HR, 1.8; 95% CI, 1.2-2.6; P =.003). For relapse, donor source (VUD/sibling) (HR, 0.38; 95% CI, 0.19-0.76; P =.006) and disease stage (AP/CP1) (HR, 2.4; 95% CI, 1.36-4.3; P =.003) were significant. This is the first large series to show that SCT confers long-term LFS in most children with CML and helps assess alternative therapy, including tyrosine kinase inhibitors.

Adolescent↗

PubMed2003

Mortality and neurologic, mental, and psychomotor development at 2 years in infants born less than 27 weeks' gestation: the Leiden follow-up project on prematurity.

OBJECTIVE: To determine the outcome of infants with a gestational age (GA) <27 weeks, born in the mid-1990s. DESIGN: Regional, prospective study; part of the Leiden Follow-Up Project on Prematurity. SETTING: Three health regions in The Netherlands. PATIENTS: A total of 266 live born infants (1996/1997) with GA <32 weeks; 46 infants were <27 weeks. MAIN OUTCOME MEASURES: Neurologic examination (according to Hempel) and assessment of mental and psychomotor development using the Bayley Scales of Infant Development I, at the corrected age of 2 years. RESULTS: Mortality was 35% (16 of 46) <27 weeks, compared with 6% (14 of 220) in infants with GA 27 to 32 weeks; withdrawal of treatment in 60% and 43%, respectively. Below 27 weeks mortality was higher after extra-uterine transport and pregnancy induction. Neonatal morbidity was higher in infants <27 weeks compared with infants 27 to 32 weeks. Below 27 weeks postnatal use of dexamethasone and being hospitalized at term were associated with abnormal neurologic outcome; there was a higher incidence in (mild) mental developmental delay compared with the older infants. Adverse outcome (dead or abnormal neurologic, psychomotor, or mental development) in infants 23 to 24, 25, 26, and 27 to 32 weeks GA was, respectively, 92% (11 of 12), 64% (7 of 11), 35% (8 of 23), and 18% (40 of 220). CONCLUSIONS: Mortality and neonatal morbidity were higher in infants with GA <27 weeks compared with infants born between 27 and 32 weeks. The high adverse outcome of infants <25 weeks suggests that one should carefully weigh whether or not to aggressively resuscitate and treat these extremely premature infants.

Child Development↗

PubMed2003

Term breech presentation in The Netherlands from 1995 to 1999: mortality and morbidity in relation to the mode of delivery of 33824 infants.

OBJECTIVE: To analyse neonatal mortality and morbidity in term infants born in breech presentation in relation to the mode of delivery (planned caesarean section, emergency caesarean section or vaginal delivery) and to compare these findings with those of the Term Breech Trial Collaborative Group [Hannah et al. Lancet 2000; October]. DESIGN: Retrospective observational study. SETTING: The Netherlands. POPULATION: Infants (n = 33824) born at term in breech presentation in the Netherlands between 1995 and 1999. Multiple pregnancies, antenatal death and major congenital malformations were excluded. METHODS: Data derived from the Dutch Perinatal Database were used to compare neonatal outcome of infants born in breech presentation in relation to the different modes of delivery (i.e. planned caesarean section, emergency caesarean section and vaginal delivery). Correction was made for differences in parity, duration of gestation and birthweight, using logistic regression. MAIN OUTCOME MEASURES: Intrapartum and first-week neonatal death, 5 minute Apgar score and birth trauma. Vaginal delivery and emergency caesarean section resulted in a sevenfold increase in low Apgar score, a threefold increase in birth trauma and a twofold increase in perinatal mortality when compared with the results of planned caesarean section. CONCLUSIONS: This study confirms the data found by Hannah et al. on an increase in early neonatal morbidity and mortality, following a trial of labour in cases of term breech presentation. These data require carefully weighed consideration against increased maternal (long term) risks due to a rise in caesarean sections.

Breech Presentation↗

PubMed2002

Graft-versus-host disease and outcome in HLA-identical sibling transplantations for chronic myeloid leukemia.

Graft-versus-host disease in its acute (aGvHD) or chronic form (cGvHD) remains the most important posttransplantation factor influencing outcome after allogeneic hematopoietic stem cell transplantation (HSCT). It increases transplantation-related mortality (TRM) but reduces risk of relapse. The net effect of these 2 discordant effects determines survival. In view of current interests to exploit graft-versus-leukemia (GVL) effects, we analyzed 4174 HLA-identical sibling transplantations for chronic myeloid leukemia in first chronic phase, depending on the presence or absence and severity of GvHD with a landmark analysis. During the first 100 days, only aGvHD grades III and IV had an impact on TRM. During the time period day 100 to 3 years increasing severity of aGvHD is associated with increased TRM and decreased relapse incidence (RI) with hazard ratios (HRs) for TRM as follows: grade 0, HR = 1.0; grade I, HR = 1.52 (1.19-1.96); grade II, HR = 2.48 (1.95-3.14); grade III, HR = 5.76 (4.44-7.48); grade IV, HR = 14.7 (10.9-19.9) and likewise for RI: grade I versus 0, HR = 0.94 (0.76-1.16); grade II, HR = 0.60 (0.46-0.77); grade III, HR = 0.48 (0.29-0.81); grade IV, HR = 0.14 (0.02-0.99). Beyond 3 years, TRM and RI are determined by cGvHD. Limited cGvHD reduces RI to the same extent as extensive cGvHD but has no impact on TRM and, hence, results in best survival with an HR = 0.48 (0.32-0.71). aGvHD grade I has the highest likelihood of subsequent limited cGvHD, which results in cumulative incidence estimates of survival at 10 years being best for patients with initial aGvHD grade I: survival at 10 years grade 0 = 59%, I = 63%, II = 56%, III = 26%, IV = not applicable. These data clarify the role of GvHD in posttransplantation outcome. Considerations for long-term outcome are essential when short-term data of interventions on GvHD are analyzed.

Adolescent↗

PubMed2002

Prospective study of renal insufficiency after bone marrow transplantation.

Since more and more children survive allogeneic bone marrow transplantation (BMT), knowledge of acute and late complications becomes increasingly important. Besides the major complications [(opportunistic) infections, veno-occlusive disease, graft versus host disease, and recurrence of primary disease], acute and chronic renal insufficiency are significant post-transplant complications that may contribute to transplant-related mortality. To elucidate risk factors for acute and chronic renal insufficiency post BMT, we performed a prospective study of all 66 children who received a BMT in a 2-year period at our institution; 21% had acute renal insufficiency post BMT. Risk factors for acute renal insufficiency were veno-occlusive disease, high cyclosporin serum levels, and foscarnet therapy. Of surviving patients, 11% developed chronic renal insufficiency 1 year post BMT. Acute renal insufficiency was the sole predictor of chronic renal insufficiency. In contrast to studies in adults, we did not find total body irradiation to be a risk factor for chronic renal insufficiency. Future long-term studies are needed to assess incidence and morbidity of chronic renal insufficiency in children following allogeneic BMT.

Acute Kidney Injury↗

PubMed2002

Donor lymphocyte infusion for relapsed chronic myelogenous leukemia: prognostic relevance of the initial cell dose.

Donor lymphocyte infusion (DLI) can produce durable remissions in patients with chronic myelogenous leukemia (CML) who have a relapse after an allogeneic stem cell transplantation. However, the best modality to administer DLI is still unclear. The effect of the initial cell dose (ICD; ie, mononuclear cells x 10(8)/kg received in the first instance) on outcome was retrospectively analyzed in 298 of 344 patients treated with DLI at 51 centers. Patients were classified into 3 groups according to the ICD: 98 in group A ( 2.0). Additional infusions were given to 62%, 20%, and 5% of patients in groups A, B, and C, respectively. A lower ICD was associated with less graft-versus-host disease (GVHD; A, 26%; B, 53%; C, 62%; P <.001), less myelosuppression (A, 10%; B, 23%; C, 24%; P =.01), and similar response rate (A, 78%; B, 73%; C, 70%; P =.48). Nonadjusted estimates of 3-year survival, failure-free survival, and DLI-related mortality were 84%, 66%, and 5% respectively, in group A; 63%, 57%, and 20% in group B; and 58%, 45%, and 22% in group C. Outcome analysis was adjusted for patient age, donor type, sex of donor, sex mismatch, disease phase at transplantation, T-cell depletion, interval from transplantation to DLI, GVHD prior to relapse, relapse type, and date of DLI. After adjustment, lower ICD was associated with less GVHD, less myelosuppression, same response rate, better survival, better failure-free survival, and less DLI-related mortality. Our results suggest that the first DLI dose should not exceed 0.2 x 10(8) mononuclear cells/kg.

Adult↗

PubMed2002

Retrospective comparison of bone marrow and granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells for allogeneic stem cell transplantation using HLA identical sibling donors in myelodysplastic syndromes.

In this multicenter retrospective study, the outcomes of 234 patients with myelodysplastic syndrome (MDS) who underwent transplantation between 1995 and 1999 from HLA-identical siblings were analyzed according to the hematopoietic stem cell source used, that is, bone marrow (BM, n = 132) or granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells (PBPCs, n = 102). There were 69 cases of refractory anemia (RA), 86 RA with excess blasts (RAEB), 75 RAEB in transformation (RAEB-t), and 4 unclassified MDS at diagnosis. The International Prognostic Scoring System was intermediate-2 or high in 104 of the 158 available scores. Multivariate analyses focused on transplantation-related mortality (TRM), 2-year treatment failure incidence, and survival. Use of PBPCs reduced the median duration of neutropenia and thrombocytopenia by 4 and 12 days, respectively. The incidence of acute GVHD was similar whatever the graft type used. Chronic GVHD was more likely to have occurred with PBPCs (odds ratio [OR], 1.62; 95% confidence interval [CI], 0.87-3.02). Two-year TRM was significantly reduced with PBPCs (relative risk [RR], 0.33; 95% CI, 0.15-0.73; P <.007), except for patients who had either RA or high-risk cytogenetics. The 2-year treatment failure incidence was significantly decreased with PBPCs, from 38% to 13% (RR, 0.22; 95% CI, 0.10-0.48; P <.001). Estimate of the 2-year event-free survival was 50% with PBPCs versus 39% with BM. In multivariate analysis, the outcome was significantly improved with PBPCs (RR, 0.27; 95% CI, 0.13-0.52; P <.001), except for patients with either RA or high-risk cytogenetics. In conclusion, PBPCs might be preferred for allogeneic transplantation in MDS patients at high risk for relapse on the basis of morphologic criteria because the use of this hematopoietic stem cell was associated with lower treatment failure incidence and improved survival.

Adolescent↗

PubMed2002

Factors associated with excessive migration in bone impaction hip revision surgery: a radiostereometric analysis study.

A prospective radiostereometric analysis (RSA) study of 18 patients with cemented revision hip surgery and impaction grafting with an Exeter stem was done with a follow-up of 2 years for all patients. All factors that could influence migration (ie, micromotion) of the stem were analyzed with a repeated measurements analysis of variance. Two groups could be identified: a stable group and a continuous migrating group. Two factors significantly influenced micromotion during the follow-up measurements. The first factor was the Paprosky classification (the bigger the defect, the higher the micromotion). The second factor was cement mantle defects in > or =1 Gruen zones. The migrating hip stems had more Gruen zones with cement mantle defects (45%) compared with the stable prostheses (21%). The effect of the first factor on micromotion was limited and probably clinically less relevant. Because the cement mantle defects found in this study were caused by poor instrumentation, the second factor stresses the importance of good instrumentation, which is essential to make this technically demanding technique effective in creating a stable stem-allograft construct in the defective femoral canal.

Aged↗

PubMed2002

Bacterial contamination in postmortem bone donors.

We analyzed factors influencing the contamination rate of allografts and blood samples obtained from postmortem bone donors. 5,710 allografts were harvested, from 550 donors of which 3,164 (55%) were swab culture negative. Blood cultures were positive in 140 donors (26%). The risk of graft contamination increased with each extra team member (Odds Ratio 1.9). It was also higher with organisms of greater virulence in donors with a positive blood culture (OR 3.5). The risk of blood contamination increased per hour postmortem (OR 1.1) and the same increase was seen with organisms of high virulence. In donors with multiple trauma, the risk of blood contamination with organisms of high virulence was greater (OR 8.2), but smaller in donors with preceding organ procurement (OR 0.1). To minimize the bacterial load, donors should be obtained in operating rooms, using aseptic techniques with only a few personnel for procurement. The postmortem time should be kept to a minimum. The procurement cultures from donors with multiple trauma should be carefully interpreted. Blood cultures should be taken into account, since these can help to find contamination not detected by swab cultures.

Bacterial Infections↗

PubMedDate not supplied

A prospective arthroscopic study of acute first-time anterior shoulder dislocation in the young: a five-year follow-up study.

A prospective arthroscopic study was conducted on 31 patients with an acute first-time anterior shoulder dislocation (AFASD). The patients were aged between 16 and 39 years. The mean age was 24 years. None had a history of shoulder problems. All were evaluated after 1, 2, and 5 years. The Constant score, Rowe score, recurrence rate, and instability rate were evaluated, as well as patient satisfaction and sports participation. We conclude that after a prolonged follow-up, an increase in the instability rate in young patients with AFASD may become apparent. The overall instability rate was 55% (17/31) after 5-year follow-up. In patients aged younger than 18 years the instability rate was 71% (5/7). Age was the only predictive factor in shoulder instability. The mean Rowe score was 87 (range, 57-100; SD, 14). Three patients had undergone a stabilization operation at the 5-year follow-up. The intraarticular pathology found at arthroscopy was not predictive of shoulder instability. We could not find a correlation between sporting activities and shoulder instability. On the basis of our results, it appears unlikely that arthroscopic lavage reduces redislocation rates after AFASD in the young patient.

Adolescent↗