Single cord blood unit (CBU) predominance is usually established within the first month after double umbilical cord blood transplantation (UCBT). However, the kinetics of engraftment of the... Show moreSingle cord blood unit (CBU) predominance is usually established within the first month after double umbilical cord blood transplantation (UCBT). However, the kinetics of engraftment of the different leukocyte subsets and the mechanism of graft predominance is largely unknown. To investigate whether a differential engraftment might reveal a specific subset that could play a key role in the mechanism of graft predominance, we studied early engraftment kinetics of different leukocyte subpopulations by flow cytometry using human monoclonal antigen-specific human leukocyte antigen antibodies, directed against mismatched human leukocyte antigen-A or -B antigens between recipient and CBUs. Twenty-two patients, who had received a double UCBT preceded by a reduced-intensity conditioning regimen, were evaluated at days +11, +18, +25, and +32 posttransplantation. Single CBU predominance in the various leukocyte subsets was established within 18 days posttransplantation. CD4+ T cells of the dominant CBU showed early peripheral blood expansion. Moreover, chimerism in CD4+ and CD8+ T cell and natural killer cell subsets at day +11 was predictive of ultimate graft predominance. These findings show that engraftment kinetics of the various leukocyte subsets vary considerably after double UCBT and may suggest an important role for CD4+ T cells in a presumed alloreactive graft-versus-graft rejection. Show less
So-Osman, C.; Nelissen, R.; Brand, R.; Faber, F.; Slaa, R. te; Stiggelbout, A.; Brand, A. 2013
BACKGROUND: Peri-operative red blood cell transfusions have been associated with post-operative complications in patients undergoing elective orthopaedic hip or knee replacement surgery. MATERIALS... Show moreBACKGROUND: Peri-operative red blood cell transfusions have been associated with post-operative complications in patients undergoing elective orthopaedic hip or knee replacement surgery. MATERIALS AND METHODS: We performed a post-hoc analysis of data extracted from a randomised study on transfusion triggers using pre-storage leucocyte-depleted red blood cells. Patients who were assigned to the most restrictive transfusion policy ("restrictive group") were compared with patients who were assigned to the most liberal policy ("liberal group"). End-points were red blood cell use, hospital stay, haemoglobin levels, post-operative complications and quality of life scores. RESULTS: Of 603 patients, 26.4% patients in the restrictive group and 39.1% in the liberal group were transfused (P =0.001). The rate of post-operative infections was lower, although not statistically significantly so, in the restrictive group than in the liberal group (5.4% vs 10.2%, respectively) as was the rate of respiratory complications (1.7% vs 4.9%, respectively), whereas hospital stay, cardiovascular complications and mortality rate were not different in the two groups. Quality of life scores were not associated with type of transfusion policy, the number of red blood cell transfusions or the transfusion status. DISCUSSION: A restrictive transfusion protocol was not associated with worse outcome and resulted in a lower transfusion rate compared to the liberal policy. Well-being (quality of life) was not associated with transfusion policy or with red blood cell transfusions. Show less
Wiersum-Osselton, J.C.; Walraven, S.M. van; Bank, I.; Lenselink, A.M.; Fibbe, W.E.; Bom, J.G. van der; Brand, A. 2013
BACKGROUND: Neonates with Rhesus c (Rh c) hemolytic disease of the fetus and newborn (HDFN) are often managed in the same way as neonates with Rhesus D (Rh D) HDFN, although evidence to support... Show moreBACKGROUND: Neonates with Rhesus c (Rh c) hemolytic disease of the fetus and newborn (HDFN) are often managed in the same way as neonates with Rhesus D (Rh D) HDFN, although evidence to support this policy is limited. The objective of this study was to evaluate neonatal outcome in severe Rh c HDFN compared to Rh D HDFN. STUDY DESIGN AND METHODS: A retrospective study of (near-)term neonates with severe Rh c (n = 22) and Rh D HDFN (n = 103; without additional antibodies) admitted to the Leiden University Medical Center between January 2000 and October 2011 was conducted. The need for intrauterine transfusions (IUTs), phototherapy, exchange transfusions (ETs), and top-up transfusions up to 3 months of age were recorded and compared between both groups. RESULTS: Although there was a trend for a slightly more severe antenatal course for Rh D HDFN reflected by an earlier need for and higher number of IUTs (median [interquartile range], 2 [1.5-4] vs. 2 [1-2] in Rh c HDFN; p = 0.070), no significant differences were found for the postnatal course between Rh c and Rh D group in days of phototherapy (mean, Days 4.8 and 4.6, respectively; p = 0.569), need for ET (50% vs. 44%, respectively; p = 0.589), and top-up transfusions (62% vs. 78%, respectively; p = 0.128). CONCLUSION: Postnatal outcome in neonates with severe Rh c HDFN is similar compared to neonates with severe Rh D hemolytic disease in terms of days of phototherapy, need for ET, and need for top-up transfusions. These results justify a similar postnatal management of neonates with Rh D and Rh c HDFN. Show less
BACKGROUND: Women whose fetuses were treated with intrauterine transfusions (IUTs) for alloimmune hemolytic disease are high responders to red blood cell (RBC) antigens. We investigated the risk... Show moreBACKGROUND: Women whose fetuses were treated with intrauterine transfusions (IUTs) for alloimmune hemolytic disease are high responders to red blood cell (RBC) antigens. We investigated the risk for HLA alloimmunization. STUDY DESIGN AND METHODS: Women and their children treated with IUT between 1987 and 2008 were included. Participants were HLA antigen typed and studied for the prevalence of HLA antibodies compared to age-matched parous nontransfused blood donors. Anti-D titer, the formation of new RBC antibodies after IUT, and the degree of fetomaternal HLA mismatches on HLA antibody formation and/or persistence were analyzed. RESULTS: A higher prevalence of HLA Class I antibodies was observed in these women compared to controls (41% vs. 23%). Both a higher anti-D titer (>8000) and formation of new RBC antibodies after IUT were associated with increased HLA immunization. HLA antibody formation was associated with the number of fetomaternal triplet epitope mismatches. Antigens within HLA-Bw4, HLA-B35/51/52/53/18/78-complex and A1/A9, were higher and mismatches within HLA-C were less immunogenic than expected. HLA antibodies against the IUT-treated fetus were more persistent than other antibodies. CONCLUSION: Women whose fetuses were treated with IUT had a high risk of developing and maintain fetal-specific HLA Class I antibodies. Factors associated with increased HLA immunization were a higher amount of fetomaternal HLA triplet mismatches, higher anti-D titer, and additional RBC antibody formation. We presume that the induction of HLA Class I antibodies is the result of increased fetomaternal hemorrhage during IUT, eliciting antibodies in women with an increased susceptibility to alloimmunization. Show less
Transplantation of thrombopoietin (TPO)-expanded cord blood CD34(+) cells accelerates human platelet recovery in NOD/SCID mice. It is unknown which subpopulations of the TPO-expanded cells mediate... Show moreTransplantation of thrombopoietin (TPO)-expanded cord blood CD34(+) cells accelerates human platelet recovery in NOD/SCID mice. It is unknown which subpopulations of the TPO-expanded cells mediate accelerated platelet recovery and bone marrow (BM) engraftment. In this study, the contribution of these subpopulations to human platelet appearance in the blood and BM engraftment was studied in NOD/SCID mice. Following transplantation of CD34(-) /CD61(-)/lineage(-) cells (Lin(-)), human platelets were detected in the blood of recipient mice from day 4. Both time to platelet recovery and blood platelet counts at 6 weeks after transplantation showed Lin(-) dose dependence. The Lin(-) population was virtually negative for lineage marker expression and lacked CD42b expression but was heterogeneous with regard to CD36 and CD38 expression, reflecting a population in transit but not fully committed toward the megakaryocyte (MK) lineage. Although no definitive phenotype could be established of the cells generating prompt platelet production and cells generating platelets 6 weeks after transplantation, this relatively heterogeneous Lin(-) population is prerequisite to accelerate platelet recovery in vivo. The interval to platelet recovery after transplantation of the CD34(+) cells remaining after expansion (rCD34(+)) was similar to mice transplanted with nonexpanded CD34(+) cells, although the total platelet counts and the engraftment levels in the BM were lower. Cobblestone area-forming cell colony-forming cells resided mostly in the rCD34(+) population. The pro-MK CD61(+) cells did not contribute to human platelet recovery or engraftment in the BM. Our study shows that not all expanded cells appear critical for transplantation. These data support that functional characterization of the expanded cell populations is warranted to make future expansion protocols suitable for clinical application. Show less
Honohan, A.; Tomson, B.; Bom, J. van der; Vries, R. de; Brand, A. 2012
OBJECTIVE To determine the incidence and risk factors for neurodevelopmental impairment (NDI) in children with hemolytic disease of the fetus/newborn treated with intrauterine transfusion (IUT).... Show moreOBJECTIVE To determine the incidence and risk factors for neurodevelopmental impairment (NDI) in children with hemolytic disease of the fetus/newborn treated with intrauterine transfusion (IUT). STUDY DESIGN Neurodevelopmental outcome in children at least 2 years of age was assessed using standardized tests, including the Bayley Scales of Infant Development, the Wechsler Preschool and Primary Scale of Intelligence, and the Wechsler Intelligence Scale for Children, according to the children's age. Primary outcome was the incidence of neurodevelopmental impairment defined as at least one of the following: cerebral palsy, severe developmental delay, bilateral deafness, and/or blindness. RESULTS A total of 291 children were evaluated at a median age of 8.2 years (range, 2-17 years). Cerebral palsy was detected in 6 (2.1%) children, severe developmental delay in 9 (3.1%) children, and bilateral deafness in 3 (1.0%) children. The overall incidence of neurodevelopmental impairment was 4.8% (14/291). In a multivariate regression analysis including only preoperative risk factors, severe hydrops was independently associated with neurodevelopmental impairment (odds ratio, 11.2; 95% confidence interval, 1.7-92.7). CONCLUSION Incidence of neurodevelopmental impairment in children treated with intrauterine transfusion for fetal alloimmune anemia is low (4.8%). Prevention of fetal hydrops, the strongest preoperative predictor for impaired neurodevelopment, by timely detection, referral and treatment may improve long-term outcome. Show less
Bilgin, Y.M.; Watering, L.M.G. van de; Versteegh, M.I.M.; Oers, M.H.J. van; Vamvakas, E.C.; Brand, A. 2011
BACKGROUND Studies in cardiac surgery have reported increased postoperative morbidity and mortality after allogeneic red blood cell (RBC) transfusions. Whether platelet (PLT) and/or plasma... Show moreBACKGROUND Studies in cardiac surgery have reported increased postoperative morbidity and mortality after allogeneic red blood cell (RBC) transfusions. Whether platelet (PLT) and/or plasma transfusions are a marker for more concomitant RBC transfusions or are independently associated with complications after cardiac surgery is unknown. STUDY DESIGN AND METHODS Data from two randomized controlled studies were combined to analyze the effects of PLT and/or plasma transfusions on postoperative infections, length of stay in the intensive care unit (ICU), all-cause mortality, and mortality in the presence or absence of infections in the postoperative period. RESULTS After adjusting for confounding factors, plasma units and not RBC transfusions were associated with all-cause mortality. White blood cell (WBC)-containing RBC transfusions and PLT transfusions were associated with mortality occurring in the presence of or after infections. The number of (WBC-containing) RBC transfusions was also significantly associated with postoperative infections and with ICU stay for 4 or more days. CONCLUSION Although it is difficult to separate the effects of blood components, we found that in cardiac surgery, perioperative plasma transfusions are independently associated with all-cause mortality. WBC-containing RBC transfusions and PLT transfusions are independently associated with mortality in the presence of infections in the postoperative period. Future transfusion studies in cardiac surgery should concomitantly consider the possible adverse effects of all the various transfused blood components. Show less
Bilgin, Y.M.; Watering, L.M.G. van de; Versteegh, M.I.M.; Oers, M.H.J. van; Vamvakas, E.C.; Brand, A. 2011
