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The aim of this study is to validate the clinical utility of the flow cytometric scoring system (FCSS), quantifying phenotypic aberrancies in the myelomonocytic lineages, in the diagnosis and prognosis for conventionally treated myelodysplastic syndromes (MDS) patients. The bone marrow samples from 56 consecutive newly diagnosed MDS patients were characterized by the FCSS and compared with findings in 27 non-MDS cytopenic patients. The FCSS scores were significantly higher in patients with MDS than those in the non-MDS control. A flow score of 2 or more allowed for a specificity of 100% with 75% sensitivity in distinguishing these two groups. The FCSS scores correlated directly with validated prognostic systems including WHO classification, International Prognostic Scoring System (IPSS), WHO-adjusted prognostic scoring system (WPSS) and transfusion dependency. The median survival of conventionally treated MDS patients was directly related to FCSS group; severe: 6 months; moderate: 19 months and normal/mild: not reached. The multivariate analyses suggested the FCSS risk categories were an independent prognostic factor after adjustment for sex, age (above or below 70 years), IPSS or WPSS risk categories. These results confirm that quantifying aberrancies in the myelomonocytic lineage by FCSS is useful in MDS diagnosis and extends the prognostic utility for conventionally treated/untreated patients, especially among patients classified within the refractory cytopenia with multilineage dysplasia (RCMD) subgroup., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Granulocyte colony-stimulating factor (G-CSF)-mediated mobilization of hematopoietic stem cells (HSCs) is a well-established method to prepare HSCs for transplantation nowadays. A sufficient number of HSCs is critical for successful HSC transplantation. However, approximately 2–6% of healthy stem cell donors are G-CSF-poor mobilizers for unknown reasons; thus increasing the uncertainties of HSC transplantation. The mechanism underlining G-CSF-mediated HSC mobilization remains elusive, so detailed mechanisms and an enhanced HSC mobilization strategy are urgently needed. Evidence suggests that P-selectin and P-selectin glycoprotein ligand-1 (PSGL-1) are one of the cell–cell adhesion ligand–receptor pairs for HSCs to keep contacting bone marrow (BM) stromal cells before being mobilized into circulation. This study hypothesized that blockage of PSGL-1 and P-selectin may disrupt HSC-stromal cell interaction and facilitate HSC mobilization. Methods: The plasma levels of soluble P-selectin (sP-sel) before and after G-CSF administration in humans and male C57BL/6J mice were analyzed using enzyme-linked immunosorbent assay. Male mice with P-selectin deficiency (Selp−/−) were further employed to investigate whether P-selectin is essential for G-CSF-induced HSC mobilization and determine which cell lineage is sP-sel derived from. Finally, wild-type mice were injected with either G-CSF or recombinant sP-sel to investigate whether sP-sel alone is sufficient for inducing HSC mobilization and whether it accomplishes this by binding to HSCs and disrupting their interaction with stromal cells in the BM. Results: A significant increase in plasma sP-sel levels was observed in humans and mice following G-CSF administration. Treatments of G-CSF induced a decrease in the level of HSC mobilization in Selp−/− mice compared with the wild-type (Selp+/+) controls. Additionally, the transfer of platelets derived from wild-type mice can ameliorate the defected HSC mobilization in the Selp−/− recipients. G-CSF induces the release of sP-sel from platelets, which is sufficient to mobilize BM HSCs into the circulation of mice by disrupting the PSGL-1 and P-selectin interaction between HSCs and stromal cells. These results collectively suggested that P-selectin is a critical factor for G-CSF-induced HSC mobilization. Conclusions: sP-sel was identified as a novel endogenous HSC-mobilizing agent. sP-sel injections achieved a relatively faster and more convenient regimen to mobilize HSCs in mice than G-CSF. These findings may serve as a reference for developing and optimizing human HSC mobilization in the future. [ABSTRACT FROM AUTHOR]

We retrospectively analyzed the impact of donor characteristics and HLA matching on outcomes in Chinese patients undergoing unrelated hematopoietic stem cell transplantation (HSCT). A total of 693 patients with hematologic malignancies who underwent HSCT between 2005 and 2010 had available survival data at 100 days or 1 year posttransplantation in the Buddhist Tzu-Chi Stem Cell Center database. The overall survival rates at 100 days and 1 year were 83.3% and 65.2%, respectively. Mismatches of HLA-A, -B, and -DRB1 at the antigen or allele level, along with inadequate cell dose, were associated with a significant risk of mortality (hazard ratio [HR] = 2.36, P < .001; HR = 1.44, P = .005; and HR = 2.20, P = .009, respectively). In 107 donors with matched HLA-A, -B and -DRB1 and known HLA-C match status, 22.4% had an HLA-C antigen mismatch, resulting in an HR of 2.87 for mortality relative to complete 8/8 matches (P = .005). Recipients with unknown HLA-C match status also had a significantly worse outcome (HR = 1.73; P = .039). Multivariate analysis revealed that cell dose and HLA-A, -B, -C, and -DRB1 antigen match status significantly affected the final outcome of survival (P = .012 and <.001, respectively). Our data indicate that HLA-C match status should be confirmed before HSCT from an unrelated donor. Inadequate cell dose remains an important determinant of poor transplantation survival. Further studies to elucidate the importance of matching of specific HLA loci are needed to better understand the risk of HSCT and improve patient outcomes. [Copyright &y& Elsevier]

To improve bone marrow (BM) harvest of the volunteer donors in our institute, we changed from the single-hole needle to the multi–side-hole needle after March 2002, and examined the midway total nucleated cell (TNC) counts during collection after September 2004. The aims of this retrospective study were to evaluate BM harvest yields obtained through different strategies and to examine the correlation between final and midway BM harvests. The distribution of BM harvesting by different strategies was 235 donors with single-hole needles (group A), 389 donors with 5–side-hole needles (group B), and 365 donors with 5–side-hole needles and midway TNC counts (group C). The nucleated cell density of the collected BM was significantly improved by modifying the harvest strategy (0.202 × 108/mL in group A, 0.219 × 108/mL in group B, and 0.250 × 108/mL in group C; P < .001). The percentage of unacceptable TNC dose (<2 × 108/kg) was also decreased in all 3 groups (to 5.9%, 3.6%, and 0%, respectively; P < .001). Multiple regression analysis revealed that donor weight, white blood cell count, and harvest strategy were positively correlated with BM TNC density (P < .001), whereas harvested BM volume was negatively correlated with TNC density (P < .001). On linear regression analysis, highly significant correlations were noted between midway and final TNC densities (r = 0.8774; P < .001) as well as between harvested BM volume and TNC count (r = 0.7937; P < .001). Changing the harvesting needle and checking the midway TNC count improved the harvest outcome. [Copyright &y& Elsevier]

Abstract: Objectives: Unrelated hematopoietic stem cell donors may donate twice. We studied donors’ preference for peripheral blood stem cell (PBSC) collection or bone marrow (BM) harvest and compared the yields of and side effects associated with two BM harvests. Materials and Methods: The psychosocial and physical experience of 13 donors who underwent two different stem cell collection procedures and their preferences were collected via a self-reported questionnaire. Among four donors who underwent two BM harvests, we compared the yields of and the side effects associated with the first and second harvest via chart review and self-reported questionnaire, respectively. Results: The median recovery time associated with PBSC (1 day) was significantly shorter than that associated with BM harvest (7 days) (p <0.01). Although most of the donors who underwent both procedures felt that BM harvest was more physically demanding, caused more preprocedural anxiety, was more time consuming, and was more inconvenient than PBSC collection, 63.6% of them preferred BM donation. This preference for BM harvest over PBSC collection is different from previous studies. There was no significant difference in the yields of marrow nucleated cells (p =0.25) and no significant differences in the incidence of side effects and recovery time between the first and second BM donations. Conclusion: Further understanding of donors’ preferences and reducing side effects associated with stem cell harvesting procedures will help the registry improve its work. [Copyright &y& Elsevier]