Biomedical subjects

R Brand

Publications and source records attributed to R Brand.

At least 19 recordsLinked to original sources

PubMed2006

Autologous stem cell transplantation for therapy-related acute myeloid leukemia and myelodysplastic syndrome.

We report the results of 65 patients with treatment-related myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML) who were transplanted from an autograft and reported to the EBMT. The median age was 39 years (range, 3-69), and stem cell source was bone marrow (n = 31), or peripheral blood progenitor cells (n = 30), or the combination of both (n = 4). The primary disease was solid tumors (n = 37), Hodgkin's disease (n = 13), non-Hodgkin's lymphoma (n = 10), acute lymphoblastic leukemia (n = 2) or myeloproliferative syndromes (n = 3). The types of MDS were as follows: RAEB (n = 1; 2%), RAEB-t (n = 3; 5%), or AML (n = 56; 87%). The median time between diagnosis and transplantation was 5 months (range, 3-86). The Kaplan-Meier estimates of the probability of 3-year overall and disease-free survival were 35% (95% CI: 21-49%) and 32% (95% CI: 18-45%), respectively. The median leukocyte engraftment was faster after transplantation with peripheral blood stem cells than with bone marrow: 12 (range, 9-26) vs 29 (range, 11-67) days (P<0.001). The cumulative incidence of relapse was 58% (95% CI: 44-72%) and of treatment-related mortality 12% (95% CI: 6-38%). Lower relapse rate was seen in patients transplanted in first complete remission (CR1 vs non-CR1: 3 years: 48 vs 89%; P = 0.05). Furthermore, age beyond 40 years resulted in a higher treatment-related mortality (47 vs 7%; P = 0.01). In a multivariate analysis, transplantation in CR1 age as well as their interaction influenced overall survival significantly. Autologous transplantation may cure a substantial number of patients with treatment-related MDS/AML, especially if they are in CR1 and of younger age.

Adolescent↗

PubMed2005

Is attrition bias a problem in neonatal follow-up?

AIM: To assess whether attrition rate influences outcome in the follow-up of very preterm infants. STUDY DESIGN: In a national follow-up study of infants born alive in 1983 in the Netherlands with a gestational age less than 32 weeks and/or a birth weight less than 1500 g, outcome was assessed separately for adolescents who responded early or late to a follow-up invitation at age 14 years. Neonatal data and outcome results of earlier assessments from early and late responders were compared to those of non-responders by univariate and nominal (polytomous logistic) regression analysis. SUBJECTS: There were 723 (76%) early responders, 130 (14%) late responders and 109 (11%) non-responders. RESULTS: We found significantly more non-Dutch origin and more disabilities and school problems at age 10 years in late- and especially in non-responders. At age 14 years, the health utility index was significantly lower in late responders compared to early responders. School outcome did not show difference in relation to the response groups. CONCLUSION: The results suggest that the incidence of adverse outcome in very preterm infants is underestimated when follow-up is incomplete and hence response rate is not a negligible problem in the assessment of late outcome. Therefore, follow-up studies should include a drop-out analysis to enable comparison to other studies.

Adolescent↗

PubMed2005

CONCOR, an initiative towards a national registry and DNA-bank of patients with congenital heart disease in the Netherlands: rationale, design, and first results.

INTRODUCTION: Survival of patients with congenital heart disease has dramatically improved after surgical repair became available 40 years ago. Instead of a mortality of 85% during childhood following the natural course, over 85% of these infants are now expected to reach adulthood. However, data on long-term outcome is scarce due to the lack of large, national registries. Moreover, little is known about the genetic basis of congenital heart defects. In 2000, the Interuniversity Cardiology Institute of the Netherlands and the Netherlands Heart Foundation have taken the initiative to develop a national registry and DNA-bank of patients with congenital heart disease in the Netherlands named CONCOR. OBJECTIVES: The aims of the CONCOR project are to facilitate investigation of the prevalence and long-term outcome of specific congenital heart defects and their treatment, to develop an efficient organisational structure for the improvement of healthcare for patients with congenital heart disease, and to allow investigation of the molecular basis of congenital heart defects. METHODS: After informed consent, research nurses enter data of participating patients into the CONCOR database using a web application. Data is transferred over the Internet via a secure connection. About 20 ml blood is withdrawn from the patient, and the DNA is isolated and stored. From each participating patient family history on congenital heart disease is obtained. RESULTS: Within two and a half years more than 4200 patients have agreed to participate. More than 99% of the patients that were asked have given their consent to participate in CONCOR. From 60% of these patients DNA has already been obtained. Mean age of the patients included is 34 years; more than 85% of the patients are younger than 45 years. Late complications occur frequently and the incidence increases with advancing age. 18% of the patients are known with supraventricular or ventricular arrhythmias. 2% of the included patients suffered a cerebrovascular accident, 139 (3%) had endocarditis. 6% of the patients has pulmonary hypertension or Eisenmenger syndrome. More than 15% of the patients reported an affected family member with congenital heart disease in the first, second, or third degree. 6% has an affected first-degree relative, and 4% a second-degree relative. Already 10 research projects have started using the CONCOR data and DNA. CONCLUSION: The population of patients with congenital heart disease is young and rapidly growing. Late complications occur frequently and the incidence increases with advances age. The CONCOR registry and DNA-bank facilitates research on prevalence and long-term outcome and allows investigation of the molecular basis of congenital heart disease.

Academies and Institutes↗

PubMed2005

Stem cell transplantation from identical twins in patients with myelodysplastic syndromes.

In a multicentre retrospective EBMT database study, we analysed factors influencing outcome in 38 patients with MDS/sAML who were transplanted with stem cells from their syngeneic twin and compared those to 1444 patients who were transplanted from an HLA-identical sibling. The median time to leukocyte and platelet engraftment was faster in the twin group: 14 vs 17 (P=0.02) and 16 vs 26 days (P=0.09), respectively. The 5 years cumulative incidence of treatment-related mortality (TRM) was higher in the sibling than in the twin group (38 vs 27%; P=0.05). The 5 year cumulative incidence of relapse was 32% (95% CI: 29-35%) for the siblings and 39% (95% CI: 26-60%; P=0.6) for the twins. A trend for better 5-years disease-free and overall survival was observed in the twin group: 34% (95% CI: 14-54%) vs 28% (95% CI: 25-31%; P=0.2) and 36% (95% CI: 15-57%) vs 32% (95% CI: 29-35%; P=0.09), respectively. In a multivariate analysis, stem cell transplantation from identical twins had a lower TRM: HR: 0.4 (95% CI: 0.2-0.9; P=0.03). The relapse rate was similar for both groups with a HR of 1.2 (95% CI: 0.07-2.1; P=0.5), with a better survival for the twins: HR 0.6 (95% CI: 0.4-1.0; P=0.07). We conclude that twin transplantation in MDS/sAML is associated with a similar relapse risk, a lower TRM and a trend for better overall survival in comparison to transplantation from HLA-identical siblings.

Adolescent↗

PubMed2005

Cause of death after allogeneic haematopoietic stem cell transplantation (HSCT) in early leukaemias: an EBMT analysis of lethal infectious complications and changes over calendar time.

We analysed a large homogeneous group of 14,403 patients transplanted for early leukaemia from an HLA-identical sibling and reported to the EBMT in four time cohorts: 1980-1989 (24%), 1990-1994 (26%), 1995-1998 (30%) and 1999-2001 (20%). We focused on death from infection. End points were survival, death from relapse and transplant-related mortality (TRM), which was subdivided into death from graft-versus-host disease (GvHD) (1315 patients; 25% of deaths), infection (597 patients; 11% of deaths) or 'other' causes (1875 patients; 34% of deaths). Survival increased from 52% at 5 years in the first to 62% in the third cohort (P<0.05) and TRM decreased from 36 to 26% (P<0.05) due to a reduction in death from infection (P<0.001). GvHD, 'other' causes and relapse did not improve. The relative proportions of bacteria (217 patients; 36%), viruses (183 patients; 31%), fungi (166 patients; 28%) or parasites (32 patients; 5%) as cause of infectious death (cumulative incidence of death at 5 years 1.8, 1.6, 1.4 and > or = 0.3%, respectively) and median time to death from infections (3 months (range 0-158 months)) did not change. Death from infections has been reduced significantly, but it still represents an ongoing risk after HSCT and draws attention to the time beyond the initial period of neutropenia.

Adolescent↗

PubMed2005

Reduced-intensity conditioning lowers treatment-related mortality of allogeneic stem cell transplantation for chronic lymphocytic leukemia: a population-matched analysis.

To elucidate whether reduced-intensity conditioning (RIC) decreases treatment-related mortality (TRM) after allogeneic stem cell transplantation (allo-SCT) for chronic lymphocytic leukemia (CLL), we retrospectively compared 73 RIC cases from a recent EBMT survey with 82 patients from the EBMT database who had undergone standard myeloablative conditioning (MC) for CLL during the same time period. The two populations were matched by adjusting the primary risk factor, the conditioning regimen, in a series of Cox models for age, sex, donor type, remission status at transplant and analyzed for its effect on TRM, relapse incidence, event-free (EFS) and overall survival (OS). After adjustment, a significant reduction of TRM became evident for the RIC population (hazard ratio (HR) 0.4 (95% confidence interval 0.18-0.9); P=0.03). On the other hand, RIC was associated with an increased relapse incidence (HR 2.65 (0.98-7.12); P=0.054). There was no significant difference between RIC and MC in terms of EFS (HR 0.69 (0.38-1.25); P=0.22) and OS (HR 0.65 (0.33-1.28); P=0.21). We conclude that RIC appears to favorably influence TRM after allo-SCT for CLL. This observation, as well as possible detrimental effects of RIC on relapse risk, should be confirmed by prospective studies.

Adult↗

PubMed2005

Epidiaphyseal versus other intercalary allografts for tumors of the lower limb.

Epidiaphyseal intercalary reconstruction has become possible for bone tumors that extend into the epiphysis because advances in magnetic resonance imaging and chemotherapy allow close resection while sparing the juxtaarticular bone and joint. In a retrospective study, we questioned whether epidiaphyseal reconstructions around the knee had a clinical outcome (measured as long-term survival, complication rate, and functional score) comparable with metadiaphyseal and diaphyseal reconstructions. Between 1988 and 1999, 14 epidiaphyseal, nine metaphyseal, and 12 diaphyseal reconstructions were done, and the median followup was 7.2 years. Kaplan-Meier analysis showed a 10-year survival rate of 79% for epidiaphyseal reconstructions, which did not differ from an 89% rate for metadiaphyseal and a 75% rate for diaphyseal reconstructions. Epidiaphyseal complications included two infections, five fractures, and three nonunion treatments. Complications for all 35 grafts included three infections, 12 fractures, and nine nonunion treatments. Ultimately, six grafts failed, with infection and length of resection as predisposing factors. All epiphyseal osteotomies had tumor-free margins and no local recurrences. The mean Musculoskeletal Tumor Society score for each type of intercalary reconstruction was between 23 and 24. Because the epidiaphyseal reconstruction avoids complications associated with joint reconstruction and the results are comparable with those of other types of intercalary grafts, these reconstructions should be considered if at least 1 cm of tumor-free juxtaarticular bone can be maintained.

Adolescent↗

PubMed2005

Ethnic differences in congenital malformations in the Netherlands: analyses of a 5-year birth cohort.

Congenital malformations are among the major causes of perinatal mortality and morbidity at present. Research into the ethnic diversity of congenital malformations can form a basis both for aetiological studies and for health care advice and planning. This study compared the overall prevalence of congenital malformations, the prevalence in different organ systems and of several specific malformations between different maternal ethnic groups in the Netherlands using a 5-year national birth cohort (1996-2000) containing 881 800 births. Maternal ethnic groups considered were Dutch; Mediterranean (Moroccan/Turkish); other European; Black; Hindu and Asian. Mediterranean women had a 20% higher risk of having a child with a congenital malformation than Dutch women (age-adjusted OR = 1.21 [95% CI 1.16, 1.27]). They showed an increased risk of malformations in several organ systems such as the central nervous system and sensory organs, the urogenital system and skin and abdominal wall. Further, they had an increased risk of the group of chromosomal malformations/multiple malformations/syndromes. For the specific group of multiple malformations the maternal age adjusted OR was 1.80 [95% CI 1.47, 2.20]. The Black group showed a significantly increased risk of skeletal and muscular malformations (age adjusted OR = 1.76 [95% CI 1.53, 2.02]) with a sixfold increased risk of polydactyly compared with the Dutch group. For Mediterranean women, the largest and fastest growing group of immigrants in the Netherlands, this study demonstrated an increased risk of congenital malformations.

Abdominal Wall↗

PubMed2005

Nonresponse bias in a follow-up study of 19-year-old adolescents born as preterm infants.

OBJECTIVE: To assess the effect of demographic and neonatal risk factors and outcome at the last available assessment on the probability of full responders, postal responders (those who only responded to the mailed questionnaire), or nonresponders in a follow-up study of 19-year-old adolescents who were born as preterm infants. DESIGN: The 19-year follow-up program was part of a large ongoing collaborative study in The Netherlands on the long-term effect of prematurity and dysmaturity on various medical, psychological, and social parameters. In the original cohort, 1338 infants (94%) with a gestational age of < 32 weeks and/or a birth weight of < 1500 g were enrolled. Neonatal mortality was 23% (n = 312), and another 67 children had died between the ages of 28 days and 19 years, leaving 959 survivors (72% of the original cohort) for follow-up at the present assessment. To study the effect of nonresponse, we divided the 959 survivors into 3 groups: full responders (596 [62.1%]), postal responders (109 [11.4%]), and nonresponders (254 [26.5%]). In the 3 groups we compared demographic and neonatal data, as well as outcome at the last available assessment. RESULTS: The odds ratios (ORs) for male versus female for the probabilities of nonresponse and postal response were statistically significant: 2.7 (95% CI: 1.9-3.9) and 1.6 (95% CI: 1.0-2.5), respectively. The same holds for the ORs for non-Dutch versus Dutch and low versus high maternal education for nonresponse: 2.0 (95% CI: 1.3-3.2) and 3.7 (95% CI: 2.0-6.7), respectively. Special education and severe handicap showed a statistically significant influence on nonresponse (OR: 1.6; 95% CI: 1.1-2.4 and OR: 2.6; 95% CI: 1.3-5.2) and postal response (OR: 2.0; 95% CI: 1.2-3.3 and OR: 4.4; 95% CI: 2.0-9.9), respectively. At the age of 19 years, primary school and special education were found significantly more frequent in the postal responders than in the full-response group (20% and 21% vs 6% and 12%). The full responders, on the other hand, were higher educated than were the postal responders. CONCLUSIONS: In this follow-up study at the age of 19 years, boys, non-Dutch adolescents, and low maternal education were overrepresented in the nonresponse and postal-response groups. Nonresponse decreased the proportion of infants with adverse outcome in assessed children. To be able to present reliable results for the total group of survivors in long-term follow-up studies, the nonresponse bias needs to be quantified. Therefore, it is evident that more research using statistical methods such as imputation of missing data is needed.

Adolescent↗

PubMed2004

Differences between participants and nonparticipants in an exercise trial for adults with rheumatoid arthritis.

OBJECTIVE: To investigate the generalizability of the results of a randomized controlled trial on the effectiveness of long-term, high-intensity exercises in the rheumatoid arthritis patients in training (RAPIT) trial by comparing the characteristics of the participants with the nonparticipants. METHODS: Participants and nonparticipants were mailed questionnaires on sociodemographic characteristics, health status, reasons not to participate, and attitudes toward intensive exercise. RESULTS: The questionnaires from 892 (75%) nonparticipants and 299 (97%) participants were collected. The nonparticipants were slightly older, more often male, and had longer disease duration than the participants. The nonparticipants perceived their disease as more serious, used fewer disease-modifying antirheumatic drugs, had a lower level of education, and a more negative attitude toward intensive exercise. CONCLUSION: The results of the RAPIT trial might not be generalizable to the entire target population. To promote participation in long-term, high-intensity exercises, health professionals should more actively discuss the potential benefits of exercise with their RA patients while taking into consideration specific factors related to participation.

Adult↗

PubMed2004

Double-blind, randomized controlled trial on the effect of leukocyte-depleted erythrocyte transfusions in cardiac valve surgery.

BACKGROUND: Leukocytes in allogeneic blood transfusions are believed to be the cause of immunomodulatory events. A few trials on leukocyte removal from transfusions in cardiac surgery have been conducted, and they showed inconclusive results. We found in a previous study a decrease in mortality rates and number of infections in a subgroup of more heavily transfused patients. METHODS AND RESULTS: Patients (n=496) undergoing valve surgery (with or without CABG) were randomly assigned in a double-blind fashion to receive standard buffy coat-depleted (PC) or prestorage, by filtration, leukocyte-depleted erythrocytes (LD). The primary end point was mortality at 90 days, and secondary end points were in-hospital mortality, multiple organ dysfunction syndrome, infections, intensive care unit stay, and hospital stay. The difference in mortality at 90 days was not significant (PC 12.7% versus LD 8.4%; odds ratio [OR], 1.52; 95% confidence interval [CI], 0.84 to 2.73). The in-hospital mortality rate was almost twice as high in the PC group (10.1% versus 5.5% in the LD group; OR, 1.99; 95% CI, 0.99 to 4.00). The incidence of multiple organ dysfunction syndrome in both groups was similar, although more patients with multiple organ dysfunction syndrome died in the PC group. LD was associated with a significantly reduced infection rate (PC 31.6% versus LD 21.6%; OR, 1.64; 95% CI, 1.08 to 2.49). In both groups, intensive care unit stay and hospital stay were similar, and postoperative complications increased with the number of transfused units. CONCLUSIONS: Mortality at 90 days was not significantly different; however, a beneficial effect of LD in valve surgery was found for the secondary end points of in-hospital mortality and infections.

Aged↗

PubMed2004

Benefit and timing of second transplantations in multiple myeloma: clinical findings and methodological limitations in a European Group for Blood and Marrow Transplantation registry study.

PURPOSE: To use European Group for Blood and Marrow Transplantation registry data to assess the benefit and optimal timing of a double-autologous transplantation strategy for patients with myeloma. PATIENTS AND METHODS: 7,452 transplantation patients described as being either in a multiple graft program ("planned") or not, were analyzed on an intention-to-treat basis. Subsequent multivariate analyses concentrated on the real occurrence of second transplantation, survival, relapse, and transplant-related mortality. RESULTS: Although the transplantation rate in the planned group failed to reach 60%, the median survival from transplantation is 60 months for the planned, compared with 51 months for the remainder group. While the hazard ratio of the planned group is 0.89 (95% CI, 0.79 to 1.00; P =.05) before approximately 70 months, this "effect" is reversed after 70 months, with the hazard ratio estimated as 3.01 (95% CI, 1.07 to 8.46; P =.04). A time-dependent multivariate Cox analysis shows that, taking patients without a second transplantation as a reference group, those receiving a second transplantation in first remission (ie, before relapse) show an increased probability of transplant-related mortality, especially if the transplantation is performed more than 12 months after the first, and the reduction of the risk of relapse is less than when the transplantation is performed earlier. Performing a second transplantation after relapse does not seem to prolong survival, though a second transplantation before relapse is associated with a higher probability of mortality. CONCLUSION: To improve survival of tandem autologous transplantation in multiple myeloma, the second transplantation should preferably be performed before relapse and within 6 to 12 months of the first transplantation.

Female↗

PubMed2004

BCR-ABL transcripts are early predictors for hematological relapse in chronic myeloid leukemia after hematopoietic cell transplantation with reduced intensity conditioning.

Kinetics of BCR-ABL transcript elimination and its prognostic implications on relapse were analyzed in patients with chronic myeloid leukemia (CML) after reduced intensity hematopoietic cell transplantation (HCT). In all, 19 CML patients were conditioned with 2 Gy total-body irradiation in combination with (n=14) or without (n=3) fludarabine 3 x 30 mg/m(2) (Flu) or 4.5 Gy total lymphoid irradiation (TLI) with Flu and OKT3 3 x 5 mg (n=2) and were treated with cyclosporine (CSP) and mycophenolate mofetil after allogeneic HCT. BCR-ABL transcripts were analyzed by nested RT-PCR and Taqman((R)) RT-PCR on days +28, +56 and +84 after HCT and were evaluated for their association with relapse. Of the 19 patients, 14 achieved sustained remissions of which six had a negative RT-PCR 28 days after HCT. Five patients relapsed +41, +54, +57, +136 and +234 days after HCT. Predictors for relapse were advanced disease stage (P=0.02) and slow reduction of BCR-ABL transcripts at day 28 (P=0.006) and day 56 (P=0.047) post-transplant. We conclude that a complete clearance of BCR-ABL transcripts is achievable within 4 weeks from HCT even after minimal conditioning and that early kinetics of BCR-ABL transcripts significantly correlate with the probability of hematological relapse.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2004

Non-protein bound iron release during chemotherapy in cancer patients.

Non-protein bound iron (NPBI) is able to catalyse oxidative reactions, causing damage to vital structures. Adverse effects induced by cisplatin seem, in part, to be mediated by free radicals. In the present study, we have measured plasma NPBI, various other iron parameters and antioxidants in 28 cancer patients undergoing cisplatin-based chemotherapy at various time points before and during chemotherapy. No NPBI was present prior to therapy, but within 1-4 days following the first administration of chemotherapy, mean NPBI rose significantly to 10.6+/-6.6 micromol/l (range, 0.6-21.3 micromol/l) in 18 (64.3%) of the 28 patients measured. The rise in NPBI was accompanied by a significant rise in total plasma iron and ferritin and a marked decrease in the latent iron-binding capacity. Concomitantly, plasma vitamins C and E decreased significantly, indicating consumption of antioxidants. Similar observations were also made during the fourth chemotherapy cycle. The increase in NPBI preceded and correlated significantly with chemotherapy toxicity, such as a decrease in leucocyte count and haemoglobin, with a transient rise in various liver enzymes and with known cisplatin-related toxicity, i.e. the loss of renal and hearing function. In conclusion, cisplatin chemotherapy induces oxidative damage which rapidly leads to release of iron from intracellular proteins and the appearance of NPBI. Bone marrow, red blood cells, liver and kidney seem to be a likely source of NPBI. The observed high levels of NPBI may be a major causative determinant in chemotherapy-induced toxicity.

Adolescent↗

PubMed2004

Sudden infant death syndrome in child care settings in the Netherlands.

BACKGROUND: In the Netherlands, there is a very low incidence of sudden infant death syndrome (SIDS) due to effective preventive campaigns. METHODS: During the period September 1996 to August 2002, nationwide 161 deaths from SIDS (about 85% of all cases of SIDS during that time) were investigated by the Cot Death Committee of the Dutch Paediatric Association. RESULTS AND DISCUSSION: Over 10% of cases of SIDS took place during some type of child care. From a national survey carried out in 2000/01 information was available on the child care attendance of 2000 Dutch infants aged 3-6 months. Based on the hours usually spent in child care by these infants, the number of similarly aged infants that died from SIDS while attending child care was 4.2 times higher than expected. Remarkably, the prevalence of known risk factors for SIDS, such as sleeping position and parental smoking, was favourable in the SIDS cases in child care settings. The adherence of child care facilities to the safe sleeping recommendations is high in the Netherlands, and no explanation as to why child care settings may be associated with an increased risk of SIDS is apparent. The possibility of other explanations, such as stress and change in routine care, is hypothesised.

Female↗

PubMed2004

The prognosis following acute primary glenohumeral dislocation.

We have studied 105 patients with 107 acute, primary, dislocations of the glenohumeral joint seen between January 1, 1991 and July 1, 1994. The mean time of follow-up was 71 months (46 to 91). In 34% the injury occurred during a sports activity and in 28% at home. The bias toward sport was even greater in patients less than 40 years of age, and in men. In patients older than 40 years of age, and in women, the dislocation occurred more often at home. The overall probability of recurrence within four years was 26%. Age was the most significant prognostic factor in recurrence which took place in 64% of patients less than 20 years of age and in 6% of those older than 40 years. Statistically, there was no difference between the rates of recurrence in patients who were active in sport and those who were not. The mean Rowe score for the whole group was 87 (15 to 100). Associated fractures were found in 20 patients (19%) and nerve injuries in 22 (21%). None of those in whom a fracture of the greater tuberosity was seen subsequently suffered a recurrent dislocation. At follow-up we found that 36 patients (34%) had not returned to their former employment but in only 2% was this owing to the injured shoulder.

Accidents, Home↗

PubMed2003

Treatment-related mortality and graft-versus-leukemia activity after allogeneic stem cell transplantation for chronic lymphocytic leukemia using intensity-reduced conditioning.

Allogeneic stem cell transplantation (SCT) using reduced-intensity conditioning (RIC) has potential to be a promising treatment of aggressive chronic lymphocytic leukemia (CLL). Since available clinical data obtained with this novel approach are very limited, we have performed a survey on this issue. Data of 77 patients were collected from 29 European Group for Blood and Marrow Transplantation centers. Median age was 54 (30-66) years, and the median number of previous chemotherapy regimens was 3 (0-8). HLA-identical sibling donors were used in 81% of the cases. Moderate conditioning regimens (mainly low-dose total body irradiation (TBI) or fludarabine-cyclophosphamide combinations) were administered to 56% of the patients, whereas the remainder received more intense conditioning consisting of fludarabine-busulfan or high-dose melphalan combinations. In 40% of the patients, in vivo T-cell depletion (TCD) with anti-thymocyte globulin or CAMPATH-1H was part of the conditioning regimen. Cumulative treatment-related mortality (TRM) was 18% (95% CI 9; 27) after 12 months. Complete chimerism as well as best response was not achieved immediately post-transplant but took a median of 3 months to develop. The 2-year probability of relapse was 31% (95% CI 18; 44), with no event occurring later than 12 months post transplant in the absence of TCD. With one exception, relapses were not observed after onset of chronic graft-versus-host disease. Event-free and overall survival at 24 months were 56% (95% CI 43; 69) and 72% (95% CI 61; 83), respectively. The median follow-up was 18 (1-44) months. Donor lymphocyte infusions or secondary transplants were performed in 19 patients with insufficient disease control and/or incomplete donor chimerism post-transplant, leading to a response in seven patients (37%). Preliminary multivariate analysis identified less than PR at transplant (hazard ratio (HR) 3.5; P&<0.01) and alternative donor (HR 3.1; P=0.02) as significant risk factors for relapse, whereas number of previous regimens >2 (HR 5.4; P=0.03), TBI (HR 2.5; P=0.05), and alternative donor (HR 2.3; P=0.08) were risk factors for survival. We conclude that RIC might favorably influence the outcome after allogeneic SCT for CLL by reducing TRM while preserving graft-versus leukemia activity.

Adult↗

PubMed2003

Development and evaluation of a follow up assessment of preterm infants at 5 years of age.

BACKGROUND: Long term follow up shows a high frequency of developmental disturbances in preterm survivors of neonatal intensive care formerly considered non-disabled. AIMS: To develop and validate an assessment tool that can help paediatricians to identify before 6 years of age which survivors have developmental disturbances that may interfere with normal education and normal life. METHODS: A total of 431 very premature infants, mean gestational age 30.2 weeks, mean birth weight 1276 g, were studied at age 5 years. Children with severe handicaps were excluded. The percentage of children with a correctly identified developmental disturbance in the domains cognition, speech and language development, neuromotor development, and behaviour were determined. RESULTS: The follow up instrument classified 67% as optimal and 33% as at risk or abnormal. Of the children classified as at risk or abnormal, 60% had not been identified at earlier follow up assessments. The combined set of standardised tests identified a further 30% with mild motor, cognitive, or behavioural disturbances. The paediatrician's assessment had a specificity of 88% (95% CI 83-93%), a sensitivity of 48% (95% CI 42-58%), a positive predictive value of 85% (95% CI 78-91%), and a negative predictive value of 55% (95% CI 49-61%). CONCLUSIONS: Even after standardised and thorough assessment, paediatricians may overlook impairments for cognitive, motor, and behavioural development. Long term follow up studies that do not include detailed standardised tests for multiple domains, especially fine motor domain, may underestimate developmental problems.

Child, Preschool↗