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Cell Dose (cell + dose)
Kinds of Cell Dose Selected AbstractsClinical and experimental uses of umbilical cord bloodINTERNAL MEDICINE JOURNAL, Issue 12 2002I. D. Lewis Abstract Umbilical cord blood (UCB) has been used successfully as an alternative source of haemopoietic stem cells (HSC) in allogeneic stem-cell transplantation for the treatment of acquired and genetic diseases. Advantages of using UCB include: (i) no risk to the donor, (ii) no donor attrition, (iii) minimal risk of viral transmission and (iv) immediate availability. Early results have highlighted differences in engraftment rates and toxicity between UCB and other sources of HSC. These differences relate to the low cell dose in UCB and also to the intrinsic properties of UCB. In this article, the clinical outcome of UCB transplantation (UCBT) will be reviewed with a discussion of the biological characteristics of UCB that may account for some of the clinical outcomes. To overcome the limitations of low cell dose, novel approaches such as ex vivo expansion of HSC are being actively explored, and this will be summarized in the present study. Finally, the success of UCBT has led to the establishment of dedicated UCB banks worldwide and the regulatory issues surrounding this will be briefly discussed. (Intern Med J 2002; 32: 601,609) [source] Granulocyte colony-stimulating factor produces a decrease in IFN, and increase in IL-4 when administrated to healthy donorsJOURNAL OF CLINICAL APHERESIS, Issue 4 2010Octavio Rodríguez-Cortés Abstract Hematopoietic stem cells transplantation (HSCT) is the leading curative therapy for a variety of hematological and hereditary diseases; however, graft versus host disease (GVHD), an immunologic phenomenon that is favored by Th1 cytokines and cytotoxic cells from donors, is present frequently and is one of the most important causes of transplant related mortality. Peripheral blood HSCT is the preferred source of stem cells in almost 100% of the cases of autologous HSCT and in 70% of allogeneic transplants. The best mobilizing agent to get the stem cells out from the bone marrow is the Granulocyte-Colony Stimulating Factor (G-CSF). In this work, our main objective was to study a possible correlation between the graft cell dose and the patient's clinical outcome. We evaluated the immunologic changes produced by G-CSF in the lymphocyte and cytokine profiles in allogeneic HSC donors. HSC from twelve donors were mobilized with G-CSF at 16 ,g/kg/day, for 5 days. Basal Peripheral Blood (BPB), Mobilized Peripheral Blood (MPB), and aphaeresis mononuclear cells (G-MNC) samples were taken from all donors. Using flow cytometry, we quantified CD19+, CD3+, CD3+CD4+, CD3+CD8+, NK, NKT, DC1, and DC2 cells. Cytokines were determined by ELISA in culture supernatants. CD19+ (p = 0.001), DC1 (p < 0.002) and DC2 (p < 0.001) cells were increased in MPB with respect to BPB. An increase in Th2 cytokines such as (IL-4) and a decrease in Th1 cytokines (IFN,, IL-2) were also found in MPB samples. In conclusion, Th1 and Th2 cytokines are relevant in predicting the clinical outcome after allogeneic peripheral blood HSCT. J. Clin. Apheresis 25:181,187, 2010. © 2010 Wiley-Liss, Inc. [source] Mobilization effects of G-CSF, GM-CSF, and darbepoetin-, for allogeneic peripheral blood stem cell transplantationJOURNAL OF CLINICAL APHERESIS, Issue 5 2009Shi Nae Kim Abstract The effects of GM-/G-CSF and darbepoetin-, on stem cell mobilization were investigated. From February 2005 to March 2007, 30 allogeneic sibling donors were randomly assigned to a G-CSF group (5 ,g/kg/day for 5,7 days) or triple group (GM-CSF 10 ,g/kg/day on 1st and 2nd day, G-CSF 5 ,g/kg/day for 5,7 days, and darbepoetin-, 40 mg on 1st day). The MNCs and CD34+ cells were not different between the two groups, although the doses (×108/kg of recipient body weight) of CD3+ cells (3.64 ± 1.75 vs. 2.63 ± 1.36, P = 0.089) and CD8+ cells (1.07 ± 0.53 vs. 0.60 ± 0.30, P = 0.006) were lower in the triple group. The engraftments, frequency of RBC transfusions, and hemoglobin recovery were not different between the two groups. The cumulative incidence of overall and Grades II,IV aGVHD was 64.3% vs. 61.1% and 25.9% vs. 27.1% in the G-CSF and triple regimen group, respectively, whereas the cumulative incidence of cGVHD was 20.8 ± 1.3% and 24.4 ± 1.7%, respectively. In conclusion, the triple regimen did not seem to be superior to G-CSF alone in terms of the CD34+ cell dose, hemoglobin recovery, and GVHD. However, the CD8+ cell count was significantly lower in the triple regimen group. The role of a lower CD8+ cell count in the graft may need to be elucidated in the future. J. Clin. Apheresis, 2009. © 2009 Wiley-Liss, Inc. [source] Multiple myeloma patients receiving large volume leukapheresis efficiently yield enough CD34+ cells to allow double transplantsJOURNAL OF CLINICAL APHERESIS, Issue 1 2009A.C. Zubair Abstract Current protocols for myeloma patients require more than one autologous transplant. We performed a retrospective study to determine the cost-effectiveness of large volume leukapheresis (LVL) compared with standard volume leukapheresis (SVL) collection when two transplants are required. We evaluated 87 patients who underwent a cumulative total of 260 LVL and SVL collections. The median product volume per collection was 356 ml for LVL, and this was significantly higher than the median product volume per collection for SVL (median 149.5 ml, P < 0.001). The median total CD34+ cell yield/kg was 6.4 × 106 for LVL and 5.2 × 106 for SVL. This difference was statistically significant (P = 0.005). Because the target CD34+ cell dose for a single transplant was 3 × 106/kg at our institution, overall the LVL yields enough CD34+ cells that could allow for two transplants. Therefore, more patients in the LVL group were able to undergo a potential second transplant. Because of the reserved cells for a second transplant, LVL patients received significantly less CD34+ cell/kg per transplant than the patients in SVL group (P = <0.001). As a result, LVL group had statistically significant but clinically insignificant delay in neutrophil (P = <0.001) and platelet (P = 0.02) engraftments. Additionally, using LVL instead of SVL to collect ,6 × 106/kg CD34+ cells may potentially save $7,497 per patient. We therefore conclude that LVL is the method of choice for collection of multiple myeloma patients when two transplants are anticipated. J. Clin. Apheresis, 2009. © 2009 Wiley-Liss, Inc. [source] Bone marrow transplantation for ,-thalassaemia major by an HLA-mismatched parentJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 3 2002CF Li Abstract: A six-year-old boy was diagnosed with ,-thalassaemia major during infancy. Since then, he required monthly blood transfusion and irregular iron chelation therapy. He had hepatosplenomegaly and elevated liver enzymes; the serum ferritin was up to 3800 ng/mL. An echocardiogram showed left-ventricular enlargement. His one-antigen-mismatched mother was chosen as a bone marrow donor. He was pretreated with intensive red blood cell transfusion and hydroxyurea for 6 weeks prior to conditioning. The conditioning included total body irradiation (300 cGy), busulfan (14 mg/kg), cyclophosphamide (160 mg/kg) and anti-thymocyte globulin (rabbit; 90 mg/kg). Marrow cell dose was 5.4 × 108/kg. Graft versus host disease (GVHD) prophylaxis included cyclosporine A (CSA) and methylprednisolone. Neutrophil engraftment occurred on day 23. Grade II acute GVHD occurred on day 45. The patient developed complications including septicaemia, haemorrhagic cystitis, intracranial haemorrhage and heart failure. He subsequently recovered from the complications without sequelae. The patient remained transfusion-independent at a follow-up examination after 18 months. This case suggested that a mismatched family member may be considered as a bone marrow donor for ,-thalassaemia major. In places where conventional treatment is not feasible, for example, in China, this approach may be an alternative option. A more intensive immunosuppressive regimen and a higher marrow cell dose may be important for successful engraftment. High-dose anti-thymocyte globulin may also prevent severe GVHD. [source] The impact of CD34+ cell dose on platelet engraftment in pediatric patients following unmanipulated haploidentical blood and marrow transplantation,PEDIATRIC BLOOD & CANCER, Issue 6 2009Ying-Jun Chang PhD Abstract Objective Unmanipulated haploidentical blood and marrow transplantation has been developed as an alternative transplant strategy for pediatric patients with hematological diseases. The aim of this study was to investigate the effects of donor and recipient characteristics on hematopoietic recovery in pediatric patients following unmanipulated haploidentical transplantation. Methods Factors correlating with hematopoietic recovery in 133 pediatric patients after unmanipulated haploidentical transplantation were analyzed retrospectively. Results All patients reached an absolute neutrophil count of 500/µl in a median of 12 days (range, 9,49 days). One hundred thirty-three patients reached an untransfused platelet count of more than 20,000/µl in a median of 15 days (range, 7,180 days). Univariate analysis showed five factors associated with platelet engraftment. These were time to transplantation after diagnosis (P,=,0.072), infused nuclear cells/kg of recipient weight (P,=,0.028), CD3+ cells/kg of recipient weight (P,=,0.082), CD4+ cells/kg of recipient weight (P,=,0.083), and CD34+ cells/kg of recipient weight (P,=,0.012). Multivariate analysis showed that infused CD34+ cells/kg of recipient weight (CD34+ cells more than 2.42,×,106/kg vs. less than or equal to 2.42,×,106/kg, HR,=,1.733; 95% CI 1.222,2.549; P,=,0.002) were significantly associated with an increased risk of platelet engraftment. Patients receiving a CD34+ cell dose more than 2.42,×,106/kg had a short time [12 days (range, 7,176 days)] to achieve an untransfused platelet engraftment, compared to 18 days (range, 7,180 days) in patients receiving a lower dose (P,<,0.001). Conclusions Our results suggest that low number of CD34+ cells in allografts is a critical factor associated with delayed platelet engraftment after unmanipulated haploidentical transplantation in pediatric patients. Pediatr Blood Cancer 2009;53:1100,1106. © 2009 Wiley-Liss, Inc. [source] Clinical outcomes and graft characteristics in pediatric matched sibling donor transplants using granulocyte colony-stimulating factor-primed bone marrow and steady-state bone marrowPEDIATRIC TRANSPLANTATION, Issue 3 2007Kuang-Yueh Chiang Abstract:, Matched sibling donor (MSD) transplant is a life-saving procedure for children with various hematological malignancies and non-malignancies. Traditionally, steady-state bone marrow (S-BM) has been used as the source of stem cells. More recently, peripheral blood stem cell (PBSC) after granulocyte-colony stimulating factor (G-CSF) mobilization has gained popularity. Adult studies of G-CSF-primed BM (G-BM) have shown that it produces rapid white blood cell engraftment like PBSC, but with less chronic graft-vs.-host disease. No such study has been published in pediatric patients. We conducted a pilot clinical trial of G-BM for pediatric patients. Ten patients were enrolled and were compared to a contemporaneous group of 12 patients who received S-BM. Patients in the G-BM group received a higher dose of total nucleated cells/kg (7.01 vs. 3.76 × 108, p = 0.0009), higher granulocyte,macrophage colony-forming units (CFU-GM)/kg (7.19 vs. 3.53 × 105, p = 0.01) and had shorter inpatient length of stay (28 vs. 40 days, p = 0.04). The engraftment, transfusion requirement and disease-free survival between the two groups were similar. We concluded that G-BM should be considered as an alternative graft source to S-BM, with the benefits of larger graft cell dose, higher CFU-GM dose and shorter length of stay. [source] ORIGINAL ARTICLE: Cell-Surface CD200 May Predict Efficacy of Paternal Mononuclear Leukocyte Immunotherapy in Treatment of Human Recurrent Pregnancy LossAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2009David A. Clark Problem, The allogeneic leukocytes in transfused blood can modulate the recipient's immune system so as to induce TGF-,-producing suppressor cells, and the cell-surface CD200 tolerance-signaling molecule on mononuclear dendritic cells is required for this effect. A subset of couples with unexplained recurrent pregnancy loss appears to benefit from transfusion of allogeneic paternal blood leukocytes (LIT), and considerable effort has been devoted to characterizing those who may benefit. Some data has been accumulated for LIT as sole therapy in patients with classical spontaneous abortions with respect to dose,response, duration of protection, need for boosting, excluding patients with autoimmunity, and inefficacy of paternal mononuclear cells stored at 4°C overnight before use which causes loss of cell-surface CD200. Recent data emphasize an important role of expression of the CD200 tolerance-signaling molecule on cells used to prevent abortions both in mice and humans. Method of study, An observational study of outcome as a function of the number of CD200+ paternal mononuclear cells was performed. Fourteen patients constituted the pilot group. Patients with autoimmunity who had failed inspite of treatment with IVIG + Heparin + Aspirin ± Prednisone were allowed to have paternal mononuclear cells added to their therapy. CD200 on purified paternal blood mononuclear cells was measured by flow cytometry. Results, The number of CD200+ cells administered was significantly greater in women achieving pregnancy (39.2 × 106 versus 20.8 × 106, P < 0.025) and in those who achieved a live birth (50.2 × 106 versus 20.8 × 106, P < 0.005) compared to those who did not achieve pregnancy, and % of paternal cells that were CD200+ was greater (11,12.5% versus 5.6%, P < 0.01). Amongst those achieving pregnancy which failed, the CD200+ cell dose was not significantly different from the non-pregnant group (30.5 × 106 versus 20.8 × 106). Conclusion, The number of CD200+ paternal mononuclear leukocytes may be an important determinant of subsequent reproductive outcome in a subset of patients. A lower % CD200+ cell number may also reflect hitherto unappreciated paternal factors bearing on reproductive success. It is feasible to recruit women to enter observational studies and to obtain useful data as a foundation for further studies. More complete patient characterization in a larger study is needed. [source] Improving outcomes of cord blood transplantation: HLA matching, cell dose and other graft- and transplantation-related factorsBRITISH JOURNAL OF HAEMATOLOGY, Issue 2 2009Vanderson Rocha Summary The use of unrelated umbilical cord blood (UCB) as an alternative source of haematopoietic stem cells transplantation (HSCT) has been widely used for patients lacking a human leucocyte antigen (HLA) matched donor. One of the disadvantages of using UCB is the limited number of haematopoietic stem cells and, consequently, delayed engraftment and increased risk of early mortality. Many approaches have been investigated in the attempt to improve engraftment and survival. Among those, studies analysing prognostic factors related to patients, disease, donor and transplantation have been performed. Variable factors have been identified, such as factors related to donor choice (HLA, cell dose and others) and transplantation (conditioning and graft- versus -host disease prophylaxis regimens). This review will focus on the interactions between HLA, cell dose and other modifiable factors related to the UCB unit selection and transplantation that may improve outcomes after UCB transplantation. [source] Influence of bone marrow nucleated red blood cell dose on outcome after allogeneic haematopoietic stem cell transplantationBRITISH JOURNAL OF HAEMATOLOGY, Issue 6 2008Marie Robin No abstract is available for this article. [source] High incidence of myelodysplasia and secondary leukaemia in the UK Medical Research Council Pilot of autografting in chronic lymphocytic leukaemiaBRITISH JOURNAL OF HAEMATOLOGY, Issue 2 2006Donald W. Milligan Summary We report a high incidence of myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML) in patients entered into the Medical Research Council Chronic Lymphocytic Leukaemia-5 trial. Of 115 newly diagnosed patients treated with fludarabine, 65 patients proceeded to autologous transplant. Conditioning was cyclophosphamide and total body irradiation in 49 (75%) patients and chemotherapy in 12 (18%). Ten patients have developed MDS/AML; eight had undergone an autograft. Five-year actuarial risk of developing MDS/AML postautograft was 12·4% (95% confidence interval, 2·5,24%). No analysed potential risk factor was predictive for MDS/AML development. We hypothesise that potential causative factors are fludarabine, low cell dose and transplant conditioning. [source] Analysis of CD34+ cell subsets in stem cell harvests can more reliably predict rapidity and durability of engraftment than total CD34+ cell dose, but steady state levels do not correlate with bone marrow reserveBRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2001G. Pratt In peripheral blood stem cell transplantation (PBSCT), the number of CD34+ cells transplanted has been shown to correlate well with both rapidity and durability of engraftment. However, it is clear that engraftment does not necessarily correlate with total CD34+ cell numbers in some patients. Consequently, there is increasing interest in evaluating the role of CD34+ subsets in haemopoietic recovery as a more accurate marker of harvest quality. We analysed the numbers of CD34+ cell subsets, namely Thy-1+, L-Selectin+ and CD38,, and correlated this with engraftment in 86 patients undergoing PBSCT. Adequate engraftment was defined as being a platelet count greater than 50 × 109/l and a neutrophil count greater than 1·0 × 109/l. CD34+L-Selectin+ provided the best prediction of engraftment rapidity, although the improvement over total CD34+ cell dose was minor. Only the dose of CD34+Thy-1+ cells transplanted correlated with durable engraftment. The probability of adequate 3-month engraftment increased with the dose of CD34+ cells transplanted, but 10% of patients receiving >,5 × 106/kg still showed poor engraftment at 3 months. However, all patients receiving >,2·5 × 105/kg CD34+Thy-1+ showed adequate engraftment at this time point. We also demonstrated that CD34+Thy-1+ progenitors were restricted to the bone marrow under normal conditions and, during stem cell mobilization, their kinetics generally paralleled total CD34+ numbers. [source] Redefining epithelial progenitor potential in the developing thymusEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 9 2007Simona Abstract Cortical and medullary epithelium represent specialised cell types that play key roles in thymocyte development, including positive and negative selection of the T cell repertoire. While recent evidence shows that these epithelial lineages share a common embryonic origin, the phenotype and possible persistence of such progenitor cells in the thymus at later stages of development remain controversial. Through use of a panel of reagents including the putative progenitor marker Mts24, we set out to redefine the stages in the development of thymic epithelium. In the early embryonic day (E)12 thymus anlagen we find that almost all epithelial cells are uniformly positive for Mts24 expression. In addition, while the thymus at later stages of development was found to contain distinct Mts24+ and Mts24, epithelial subsets, thymus grafting experiments show that both Mts24+ and Mts24, epithelial subsets share the ability to form organised cortical and medullary thymic microenvironments that support T cell development, a function shown previously to be lost in the Mts24, cells by E15 when lower cell doses were used. Our data help to clarify stages in thymic epithelial development and provide important information in relation to currently used markers of epithelial progenitors. See accompanying commentary: http://dx.doi.org/10.1002/eji.200737709 [source] | ||||||||||