Shorter donor leukocyte telomere length is associated with poor peripheral blood stem cell mobilization induced by granulocyte colony-stimulating factor.

BACKGROUND/PURPOSE: Insufficient numbers of peripheral blood stem cells (PBSC) after granulocyte colony-stimulating factor (G-CSF) mobilization occurs in a significant proportion of PBSC collections, often from older age donors. Telomere length (TL) is often used as an indicator of an individual's biological age. This study aimed to investigate the relationship between donors' leukocyte TL and the outcome of G-CSF-induced PBSC mobilization in healthy unrelated donors. METHODS: Donors' leukocyte TLs and the outcome of G-CSF-induced PBSC mobilization, as assessed by pre-harvest CD34+ cell counts, were analyzed in 39 healthy PBSC donors. TL in a non-mobilized general population (n = 90) was included as a control group. G-CSF mobilization effect was categorized into three groups according to pre-harvest CD34+ cell count: poor (≤25/µL, PMD), intermediate (between 25 and 180/µL), and good (≥180/µl, GMD). RESULTS: Leukocyte TL of PBSC donors correlated well with pre-harvest CD34+ cell counts (r = 0.645, p < 0.001). Leukocyte TLs of PMDs (n = 8) were significantly shorter than those of GMDs (n = 9) and non-mobilization controls (p < 0.05). Moreover, all PMD TLs were below the 50th percentile, and 62.5% of PMDs had TLs below the 10th percentile of age-matched control participants. In contrast, no GMD TLs were below the 10th percentile; in fact, 33.3% (3/9) of them were above the 90th percentile. CONCLUSION: Our results indicate that shorter donor leukocyte TL is associated with poor G-CSF-induced PBSC mobilization. TL, which represents a donor's biological age, could be a potential predictor for mobilization outcome.

Long-term follow-up of cancer and catastrophic diseases in hematopoietic stem cell donors: a comprehensive matched cohort study.

Hematopoietic stem cell (HSC) transplantation, using either bone marrow (BM) or peripheral blood stem cells (PBSC), is a well-established therapy for various hematologic and non-hematologic diseases. However, the long-term health outcomes after HSC donation remain a major concern for several potential donors. Thus, we aimed to conduct a matched cohort study of 5003 unrelated donors (1099 BM and 3904 PBSC) and randomly selected 50,030 matched controls based on age, sex, and resident area from the donor registry between 1998 and 2018. The medical insurance claims of all the participants were retrieved from the Taiwan National Health and Welfare Data Science Center after de-identification. Our findings revealed no differences in the incidence of cancer, death, and catastrophic diseases between HSC donors and matched healthy participants during long-term follow-up. Kaplan-Meier curves depicting the cumulative incidence of cancer and overall mortality throughout the follow-up period also demonstrated similar outcomes between donors and non-donors. In conclusion, our results indicate that HSC donation, whether through BM or PBSC, is safe and not associated with an increased risk of cancer, death, or catastrophic diseases. These findings provide valuable information for counseling potential HSC donors and for long-term management of HSC donor health.

Platelet-derived circulating soluble P-selectin is sufficient to induce hematopoietic stem cell mobilization.

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.

Is pinworm infection still a public health concern among children in resource-rich regions? Trends in pinworm infection prevalence and associated factors among children in Hualien County, Taiwan: a retrospective cross-sectional study.

BACKGROUND: Enterobius vermicularis (pinworm) is a common intestinal parasitic infection in children. A gradual decrease in the prevalence of pinworm infection has been noted in resource-rich settings, such as Taiwan. However, the influence of sociodemographic factors on the temporal trend in pinworm infection rates in children under the current pinworm infection prevention policy in Taiwan is not well characterized. This study aimed to evaluate the trend of pinworm infection prevalence and the associated factors among children in Hualien County, Taiwan. METHODOLOGY: In this retrospective cross-sectional study, we included a total of 56,197 students (aged 6-10 years) in grades 1 and 4 in Hualien in 2009-2018. Children were screened for pinworm infection using adhesive cellophane perianal swabs in the routine student health examination. Logistic regression was conducted to evaluate the factors associated with pinworm infection. Associations between dependent and independent variables were measured by odds ratios. The Cochran-Armitage test was used to assess whether there were significant trends in different stratifications. Variables with P-values < 0.05 were considered statistically significant. RESULTS: A total of 56,197 school-age children from grades 1 and 4 during 2009-2018 were included. Young age and male sex were risk factors for pinworm infection (P < 0.001). A negative correlation between body mass index and enterobiasis was observed, and decreased pinworm infection was noted during the study reference period. Children living in suburban and rural areas had higher odds of having a pinworm infection than those living in urban areas (P < 0.001). A significant decrease in the overall prevalence rate of pinworm infection was observed among children in 2009-2018 (P < 0.001). However, there was no obvious change in the pinworm infection rate in rural areas during this period (P = 0.953), and it was higher than that in urban and suburban areas. CONCLUSIONS: The overall prevalence of pinworm infection gradually decreased from 2009 to 2018 among school-age children in Hualien. However, there was no declining trend in pinworm infection in rural areas. Young age, male sex, and rural residence were significantly associated with pinworm infection. Pinworm infection remains a major public health concern among children in rural areas of Hualien.

Correlation of Body Mass Index and Proinflammatory Cytokine Levels with Hematopoietic Stem Cell Mobilization.

This study investigated the correlation of body mass index (BMI) and proinflammatory cytokine levels with hematopoietic stem cell (HSC) mobilization triggered by granulocyte colony-stimulating factor (G-CSF). Stem cell donors (n = 309) were recruited between August 2015 and January 2018 and grouped into four groups according to their BMI: underweight (BMI < 18.5 kg/m2, n = 10), normal (18.5 kg/m2 ≦ BMI < 25 kg/m2, n = 156), overweight (25 kg/m2 ≦ BMI < 30 kg/m2, n = 102), and obese (BMI ≧ 30 kg/m2, n = 41). The participants were then administered with five doses of G-CSF and categorized as good mobilizers (CD34 ≧ 180/µL, n = 15, 4.85%) and poor mobilizers (CD34 ≦ 25/µL, n = 14, 4.53%) according to the number of CD34+ cells in their peripheral blood after G-CSF administration. The correlation between BMI and HSC mobilization was then analyzed, and the levels of proinflammatory cytokines in the plasma from good and poor mobilizers were examined by ProcartaPlex Immunoassay. Results showed that BMI was highly correlated with G-CSF-triggered HSC mobilization (R2 = 0.056, p < 0.0001). Compared with poor mobilizers, good mobilizers exhibited higher BMI (p < 0.001) and proinflammatory cytokine [interferon gamma (IFN-γ) (p < 0.05), interleukin-22 (IL-22) (p < 0.05), and tumor necrosis factor alpha (TNF-α) levels (p < 0.05)]. This study indicated that BMI and proinflammatory cytokine levels are positively correlated with G-CSF-triggered HSC mobilization.

COVID-19 pandemic decreased the ophthalmic outpatient numbers and altered the diagnosis distribution in a community hospital in Taiwan: An observational study.

The aim of this study was to determine the effect of Coronavirus disease 2019 (COVID-19) pandemic on ophthalmic outpatient numbers and ophthalmic diagnosis distribution in a community hospital (Taipei City Hospital Zhongxiao Branch) in Taiwan. The COVID-19 pandemic period in Taiwan was defined as May 1 to July 31, 2021. Demographic data, including age, gender, and top 10 diagnoses from ophthalmic outpatients during this period, were collected. A corresponding control group from the same time in 2020 was also collected. The distribution of different diagnoses was analyzed, and the data of 10 most prominent diagnoses with decreased percentage of case numbers during the COVID-19 pandemic period were obtained. The number of cases during the COVID-19 pandemic decreased by 46.9% compared to the control group. The top three most common diagnoses were dry eye syndrome, glaucoma, and macular diseases. The 10 most prominent diagnoses with decreased number of cases during the COVID-19 pandemic were cataract, refraction & accommodation, macular degeneration, conjunctivitis, retinal detachment, vitreous body disorders, ophthalmic complications of diabetes mellitus, glaucoma, dry eye, and retinal vein occlusion. Identifying and treating these patients as scheduled may yield the highest cost-benefit effect in preventing visual loss during the COVID-19 pandemic.

Comparison of Growth Velocity Among School Age Children With Different Body Mass Index From Childhood Into Early Adolescence in Hualien County, Taiwan: A Retrospective Cohort Study.

Objective: This study aimed to investigate the contribution of high body mass index (BMI) to growth velocity among school-aged children who remained in the same BMI categories for a 6-year period. Methods: This retrospective cohort study included children who enrolled in the school year 2009 and remained in the same BMI categories during their 1st, 4th, and 7th grades (6-7, 9-10, 12-13 years of age). Annual linear growth velocity and weight gain were calculated and compared between sexes, BMI groups, and different times. Risk analysis and repeated measures analysis of variance were performed to identify the impact of BMI on growth velocity. Results: Of the 1,637 subjects, 53.0% were male, and 2.5% and 10.9% belonged to BMI groups of overweight and obese, respectively. In students between 6 and 13 years of age, obesity was associated with higher annual weight gain and height gain. Risk analysis showed that obese subjects had higher linear growth velocity than normal BMI groups of both sexes between 6 and 9 years of age. Unexpectedly, overweight and obese girls between 9 and 13 years of age had less linear growth velocity than underweight girls at the same interval. Repeated measures analysis of variance in both sexes showed a significant statistical association between BMI and different times of growth. However, the effect was less in girls between 9 and 13 years of age. Conclusion: Puberty may dominate over BMI as the main contributor to high growth velocity in girls with underweight BMI emerging into pubertal age.

Treatment outcomes of pediatric acute myeloid leukemia: a retrospective analysis from 1996 to 2019 in Taiwan.

Improvement in outcomes of children with acute myeloid leukemia (AML) is attributed to several refinements in clinical management. We evaluated treatment outcomes of Taiwanese pediatric AML patients in the past 20 years. Overall, 860 de novo AML patients aged 0-18 years and registered in the Childhood Cancer Foundation of R.O.C during January 1996-December 2019 were included. Survival analysis was performed to identify factors that improved treatment outcomes. Regardless of treatment modalities used, patients during 2008-2019 had better 5-year event-free survival (EFS) and overall survival (OS) rates than patients during 1996-2007. For patients received the TPOG-AML-97A treatment, only 5-year OS rates were significantly different between patients diagnosed before and after 2008. Patients with RUNX1-RUNX1T1 had similar relapse-free survival rates, but 5-year OS rates were better during 2008-2019. However, the survival of patients who received hematopoietic stem-cell transplantations (HSCT) did not differ significantly before and after 2008. For patients without relapse, the 5-year OS improved during 2008-2019. Non-relapse mortality decreased annually, and cumulative relapse rates were similar. In conclusion, 5-year EFS and OS rates improved during 2008-2019, though intensities of chemotherapy treatments were similar before and after 2008. Non-relapse mortality decreased gradually. Further treatment strategies including more intensive chemotherapy, novel agents' use, identification of high-risk patients using genotyping and minimal residual disease, early intervention of HSCT, and antibiotic prophylaxis can be considered for future clinical protocol designs in Taiwan.

Socio-Demographic Factors Affect the Prevalence of Hematuria and Proteinuria Among School Children in Hualien, Taiwan: A Longitudinal Localization-Based Cohort Study.

Objective: Child hematuria/proteinuria is a risk factor for chronic kidney disease (CKD) in later life, and mass urinary screening could detect asymptomatic glomerulonephritis at an early stage. This study aimed to evaluate the longitudinal prevalence of hematuria/proteinuria and its association with socio-demographic factors among school children in Hualien, Taiwan. Methods: The study cohort consisted of first and fourth graders enrolled from 2008 to 2015 in Hualien. We combined the data from two consecutive health examinations to ensure the validity of the body mass index (BMI), urbanization, proteinuria, and hematuria grouping. Prevalence and health status differences between sex, age, BMI, and urbanization level were examined. Results: A total of 16,990 students within the same BMI and urbanization categories were included during the study interval. The prevalence of persistent hematuria was 1.0%. Fourth graders (odds ratio OR: 1.68, p = 0.002), girls (OR: 1.48, p = 0.014), and students from suburban/rural areas (OR: 1.99, and OR: 4.93, respectively; both p < 0.001) demonstrated higher hematuria risk. The prevalence of proteinuria was 0.2%. Fourth graders (OR: 4.44, p < 0.001) and students in suburban areas (OR: 0.27, p = 0.031) were associated with persistent proteinuria. After stratifying by age, the significant association remained. A higher risk of proteinuria was noted in underweight subjects (OR: 2.52, p = 0.023) among the fourth-grade students. Conclusion: The prevalence of hematuria/proteinuria in Hualien was higher than the average reported for Taiwan. Hematuria/proteinuria was significantly associated with sex, age, BMI, and urbanization. Our longitudinal results can provide information for future pediatric CKD prevention in Taiwan.

Lower platelet count with increased density of platelet antigens in granulocyte colony-stimulating factor mobilized peripheral blood stem cell donors.

BACKGROUND/PURPOSE: Granulocyte colony-stimulating factor (G-CSF) is widely used for prophylaxis and treatment of neutropenia in cancer patients and also for peripheral blood stem cells (PBSC) mobilization. The aim of this study is to evaluate the possible changes of platelet surface antigens after G-CSF injection in PBSC donors compared with healthy control. METHODS: Between January 1st and December 31st, 2014, 48 healthy voluntary PBSC donors were eligible for this study. Donors received G-CSF (Filgrastim) subcutaneously for five days, and then their whole blood was collected for complete blood count. Analysis of platelet antigens was performed by flow cytometry. Sixteen healthy controls were also included for comparison. RESULTS: Lower platelet counts were found in PBSC donors after G-CSF use and in comparison with health controls. The platelet size evaluated by forward scattering (FSC) showed smaller platelets in PBSC donors after G-CSF use compared with healthy controls (39.3 vs 46.7 mean fluorescence intensity, P = 0.015). CD31 were higher in PBSC donor (203.2 vs. 120.7, P < 0.001). Except CD31, other platelet surface antigens were not different between PBSC donors and healthy controls. After adjusting by FSC data, the mean antigen intensity/FSC of CD31, CD41a, CD42a, CD42b and CD61 showed 5.45 vs 2.78 (P < 0.001), 4.35 vs 3.47 (P = 0.007), 3.87 vs 3.17 (P = 0.015), 20.45 vs 16.94 (P = 0.045), and 5.98 vs 4.88 (P = 0.018) respectively. CONCLUSION: We noted higher density of platelet surface antigens, lower platelet count and smaller platelet size after G-CSF injection.

Janus kinase 2 V617F mutation in an unrelated peripheral blood stem cell donor.

Polycythemia vera (PV) is relatively uncommon in early adulthood, and evidence about the prevalence of the Janus kinase 2 (JAK2) V617F mutation in the general population is limited. Here, we report a previously healthy volunteer peripheral blood stem cell (PBSC) donor who developed symptomatic PV with the JAK2 V617F mutation 2 years after PBSC mobilization and harvest. The characteristic mutation was identified retrospectively in the blood sample of the donor at the confirmation typing stage, which was before granulocyte colony-stimulating factor injection. This report presents a safety issue for both donor and recipient of hematopoietic stem cell transplantation. Clinicians should be aware of this during health workup and postdonation follow-up of unrelated PBSC donors. Any abnormal and/or equivocal laboratory data, especially during the donor workup stage, should not be overlooked.

Treatment of childhood acute lymphoblastic leukemia with delayed first intrathecal therapy and omission of prophylactic cranial irradiation: Results of the TPOG-ALL-2002 study.

BACKGROUND: To eliminate cranial irradiation (CrRT)-related sequelae and to minimize the adverse impact of traumatic lumbar puncture (TLP) with blasts, the Taiwan Pediatric Oncology Group (TPOG) introduced a modified central nervous system (CNS)-directed regimen characterized by delayed triple intrathecal therapy (TIT) and the omission of CrRT for all children with newly diagnosed acute lymphoblastic leukemia (ALL). METHODS: This study compared the treatment outcomes of patients overall and patients with a non-CNS-1 status (CNS-2, CNS-3, or TLP with blasts) in 2 treatment eras, one before and another after the revision of the TPOG-ALL-2002 protocol by the introduction of the modification (era 1 [2002-2008] with CrRT and era 2 [2009-2012] with delayed first TIT and no CrRT). RESULTS: There were no statistically significant differences in major outcomes between the 903 patients treated in era 1 and the 444 patients treated in era 2: the 5-year event-free survival (EFS) rates were 75.7% ± 1.4% and 72.1% ± 2.4%, respectively (P = .260), and the cumulative risks of isolated CNS relapse were 4.0% ± 0.7% and 4.1% ± 1.0%, respectively (P = .960). There were also no differences between non-CNS-1 patients treated in era 1 (n = 76) and era 2 (n =28): the 5-year EFS rates were 52.3% ± 5.8% and 62.9% ± 9.4%, respectively (P = .199), and the cumulative risks of isolated CNS relapse were 6.3% ± 3.1% and 3.6% ± 3.5%, respectively (P = .639). Notably, TLP with blasts was completely eliminated after the first TIT was delayed in era 2. CONCLUSIONS: The delay of the first TIT until the clearance of circulating blasts and the total omission of CrRT did not compromise survival or CNS control in patients with childhood ALL, including those with a non-CNS-1 status.

Treatment for childhood acute lymphoblastic leukemia in Taiwan: Taiwan Pediatric Oncology Group ALL-2002 study emphasizing optimal reinduction therapy and central nervous system preventive therapy without cranial radiation.

BACKGROUND: Reinduction therapy has improved the outcomes in children with acute lymphoblastic leukemia (ALL). We sought to determine the optimal course(s) of reinduction therapy for standard-risk (SR, or "low-risk" in other groups) patients. Also, we evaluated outcomes using triple intrathecal therapy without cranial radiation (CrRT) for central nervous system (CNS) preventive therapy. PROCEDURE: From 2002 to 2012, all newly diagnosed children with ALL in Taiwan were enrolled in Taiwan Pediatric Oncology Group ALL-2002 protocol. SR patients were randomized to receive single or double reinduction courses. The patients enrolled before 2009 received CrRT, while those enrolled later did not. The Kaplan-Meier method was used to estimate survival rates and the difference between two groups was compared by the two-sided log-rank test. RESULTS: In 1,366 eligible patients, the 5-year overall survival (OS) was 81.6 ± 1.1% (standard error) and 5-year event-free survival (EFS) was 74.3 ± 1.2%. In SR patients, the 5-year OS for one and two reinduction courses was 91.6 ± 2.1% and 93.7 ± 1.8%, respectively, and the 5-year EFS was 85.2 ± 2.7% and 89.8 ± 2.3%, respectively. There were no significant differences in survival between these two groups. Patients with MLL or BCR-ABL1 had the worst outcomes: 5-year EFS was 23.4 and 31.8% and 5-year OS was 28.6 and 44.7%, respectively. There was no significant difference in CNS relapse or survival between the era with or without CrRT. CONCLUSIONS: For SR patients, one-course reinduction was adequate. Triple intrathecal therapy alone successfully prevented CNS relapse.

Reasons for exclusion of 6820 umbilical cord blood donations in a public cord blood bank.

BACKGROUND: To provide information for umbilical cord blood (UCB) banks to adopt optimal collection strategies and to make UCB banks operate efficiently, we investigated the reasons for exclusion of UCB units in a 3-year recruitment period. STUDY DESIGN AND METHODS: We analyzed records of the reasons for exclusion of the potential UCB donation from 2004 to 2006 in the Tzu-Chi Cord Blood Bank and compared the results over 3 years. We grouped these reasons for exclusion into five phases, before collection, during delivery, before processing, during processing, and after freezing according to the time sequence and analyzed the reasons at each phase. RESULTS: Between 2004 and 2006, there were 10,685 deliveries with the intention of UCB donation. In total, 41.2% of the UCB units were considered eligible for transplantation. The exclusion rates were 93.1, 48.4, and 54.1% in 2004, 2005, and 2006, respectively. We excluded 612 donations from women before their child birth, 133 UCB units during delivery, 80 units before processing, 5010 units during processing, and 421 units after freezing. There were 24 UCB units with unknown reasons of ineligibility. Low UCB weight and low cell count were the first two leading causes of exclusion (48.6 and 30.9%). The prevalence of artificial errors, holiday or transportation problem, low weight, and infant problems decreased year after year. CONCLUSION: The exclusion rate was high at the beginning of our study as in previous studies. Understanding the reasons for UCB exclusion may help to improve the efficiency of UCB banking programs in the future.

Poor harvest of peripheral blood stem cell in donors with microcytic red blood cells.

BACKGROUND: The outcome of peripheral blood stem cell (PBSC) harvest depends on mobilization and leukapheresis. Some poor harvests might not be directly related to poor mobilizations. STUDY DESIGN AND METHODS: We retrospectively analyzed the results of 793 consecutive healthy donors who underwent PBSC donation to evaluate the impact of low mean corpuscular volume (MCV) of red blood cells on the outcomes of hematopoietic stem cell mobilization and leukapheresis. RESULTS: The circulating CD34+ cells in peripheral blood after five doses of granulocyte-colony-stimulating factor injection were similar in donors with low MCV and those with normal MCV (68.0×10(6) /L vs. 69.2×10(6) /L, p=0.38). The procedural settings were not different between the two groups. However, the apheresis outcome of donors with low MCV was significantly lower in total CD34+ cells, cell dose, apheresis yield, and collection efficiency than those with normal MCV (277.6×10(6) vs. 455.0×10(6) ; 4.9×10(6) /kg vs. 8.2×10(6) /kg; 16.9×10(6) /L vs. 27.3×10(6) /L; 0.285 vs. 0.388; all p<0.0001). Similar results were noticed in subgroup analysis using the severity of microcytosis and Mentzer index for the donors with MCV of less than 80fL. The collection efficiency was significantly correlated with the MCV (r=0.30, p<0.0001). CONCLUSION: Low MCV was associated with poor apheresis outcomes in PBSC donors. This effect is not related to poor mobilization of CD34+ cells into the peripheral blood. Further studies to elucidate the detailed mechanism and develop strategy to avoid poor harvest are necessary.

Novel survivin inhibitor YM155 elicits cytotoxicity in glioblastoma cell lines with normal or deficiency DNA-dependent protein kinase activity.

BACKGROUND: Pediatric glioblastoma is a malignant disease with an extremely poor clinical outcome. Patients usually suffer from resistance to radiation therapy, so targeted drug treatment may be a new possibility for glioblastoma therapy. Survivin is also overexpressed in glioblastoma. YM155, a novel small-molecule survivin inhibitor, has not been examined for its use in glioblastoma therapy. METHODS: The human glioblastoma cell line M059K, which expresses normal DNA-dependent protein kinase (DNA-PK) activity and is radiation-resistant, and M059J, which is deficient in DNA-PK activity and radiation-sensitive, were used in the study. Cell viability, DNA fragmentation, and the expression of survivin and securin following YM155 treatment were examined using MTT (methylthiazolyldiphenyl-tetrazolium) assay, ELISA assay, and Western blot analysis, respectively. RESULTS: YM155 caused a concentration-dependent cytotoxic effect, inhibiting the cell viability of both M059K and M059J cells by 70% after 48 hours of treatment with 50 nM YM155. The half-maximal inhibitory concentration (IC50) was around 30-35 nM for both cell lines. Apoptosis was determined to have occurred in both cell lines because immunoreactive signals from the DNA fragments in the cytoplasm were increased 24 hours after treatment with 30 nM YM155. The expression of survivin and securin in the M059K cells was greater than that measured in the M059J cells. Treatment with 30 nM YM155, for both 24 and 48 hours, significantly suppressed the expression of survivin and securin in both cell lines. CONCLUSION: The novel survivin inhibitor YM155 elicits potent cytotoxicity in glioblastoma cells in vitro via DNA-PK-independent mechanisms. YM155 could be used as a new therapeutic agent for the treatment of human glioblastomas.

Association of ABO incompatibility with red blood cell indices of cord blood unit.

BACKGROUND: Maternal-fetal ABO incompatibility is one of the causes of neonatal hyperbilirubinemia. We postulate that hemoglobin (Hb), hematocrit (Hct), and red blood cell (RBC) values for cord blood units (CBUs) are lower and erythroblast values higher for maternal-fetal ABO incompatible dyads than for compatible dyads. OBJECTIVE: We investigated the relationship between Hb, Hct, RBC, and erythroblast CBU values and maternal-fetal ABO blood type compatibility. METHODS: Mothers having blood group O who gave birth to infants with blood group A, B, or AB were classified as Group I. According to baby's blood group, the members of Group I were further divided into AO (baby group A, mother group O), BO (baby group B, mother group O), and ABO (baby group AB, mother group O) subgroups. Mothers having blood group A who gave birth to infants with blood group B or AB and mothers having blood group B who gave birth to infants with blood group A or AB were classified as Group II. All other maternal-fetal blood type pairs were considered ABO compatible and were classified as Group III. We compared mean Hb, Hct, RBC, and erythroblast values for the infants' CBUs among these three groups including the subgroups of Group I. RESULTS: Group I had lower mean Hb, Hct, and RBC values than Group II and Group III (both p < 0.001). Although the mean Hb, Hct, and RBC values for Group II were lower than for Group III, the difference was not statistically significant. Mean Hb and RBC for the AO group were higher and nucleated RBC (nRBC) ratios were lower than for the BO group; however, these differences were also not statistically significant. Interestingly, the mean Hct value of the BO group was significantly lower than that of the AO group (p = 0.04). CONCLUSION: Group A or B neonates with a group O mother have lower mean Hb, Hct, and RBC values for CBUs than other neonates. The role of RBC indices in predicting neonatal hemolytic hyperbilirubinemia remains unclear and further studies are needed to identify the possible clinical association.

Bilateral hip pain caused by adductor pyomyositis as the initial presentation of chronic myeloid leukemia in a 17-year-old child.

Pyomyositis is a pyogenic muscular tissue infection mainly occurring in immunocompromised patients. Chronic myeloid leukemia (CML) accounts for only 2-3% of cases of childhood leukemia. Herein, we report on a 17-year-old male with bilateral hip pain caused by adductor pyomyositis before beginning the treatment course of CML. CML was diagnosed by bone marrow chromosome study and was treated initially with imatinib but switched to hydroxyurea 5 days later because of poor cytoreduction response. Subsequently, white blood cell counts decreased gradually; however, the hyperleukocytosis condition resolved very slowly again until we switched back to imatinib use on the 40(th) day of hospitalization. Pyomyositis was diagnosed by magnetic resonance imaging. Oxacillin was administered to cover Staphylococcus aureus, the most common pathogen of pyomyositis. Bilateral hip pain improved within 72 hours after antibiotic usage, but follow-up magnetic resonance imaging after 15 days of treatment revealed well-defined abscess and osteomyelitis of both femoral heads. Abscess incision and drainage were performed, and cultures of the drained pus grew no microorganisms. The patient completed 5 weeks of oxacillin treatment after the operation and recovered with a full range of motion of both hips. There was no residual disability. This is the first report of bilateral hip pain caused by pyomyositis as the initial presentation of CML. Pyomyositis needs to be considered in the differential diagnosis of hip pain in pediatric patients.

Complete blood count reference values of cord blood in Taiwan and the influence of gender and delivery route on them.

BACKGROUND: Cord blood banking has become more popular in recent years. Checking cord blood complete blood count (CBC) and white blood cell (WBC) differential counts (DCs) is essential before cryopreserving the cord blood units. Therefore, establishing the normal reference values of cord blood CBC and WBC DC is important in clinical practice and research. OBJECTIVES: To obtain a large-scale population-based normal CBC and WBC DC reference values of healthy neonates' cord blood from a public cord blood bank and to investigate the influence of the gender and delivery route. METHODS: From September 2001 to November 2006, the cord blood of healthy Taiwanese neonates with gestational age 36 weeks and more were collected by Tzu Chi Cord Blood Bank with written informed consents. All cord blood samples were analyzed by Sysmex XE2100 automated hematology analyzer (Sysmex Corporation, Kobe, Japan) to obtain the CBC. The WBC DC was calculated by manual method. We used Student's t test and Mann-Whitney U test for investigating the influences of gender and delivery route on the CBC and WBC DC reference values. The results were presented by mean±standard deviation or 2.5-97.5th percentiles. RESULTS: In the study period, totally 5602 cord blood samples were collected eligibly for analysis. The cord blood CBC and WBC DC normal reference values were calculated. The female neonates had significantly higher mean corpuscular volume, platelet count, and WBC count, but lower red blood cell (RBC) count, hemoglobin (Hb), hematocrit, and mean corpuscular Hb concentration values (p<0.001). Newborns through vaginal delivery had significantly higher RBC count, Hb, hematocrit, platelet count, and WBC count (p<0.001). The percentages of some different types WBC were significantly influenced by gender and delivery routes. Male babies had higher lymphocyte, monocyte, eosinophil, basophil, and nucleated RBC ratios than the female neonates. Newborns through cesarean section had significantly lower neutrophil, monocyte, and nucleated RBC ratios, but higher lymphocyte and eosinophil ratios, than newborns through vaginal delivery. CONCLUSION: We successfully obtained the normal CBC and WBC DC reference values of the cord blood in Taiwan. Gender and delivery routes were important confounding factors that influenced the cord blood CBC and WBC DC values.

The role of donor characteristics and post-granulocyte colony-stimulating factor white blood cell counts in predicting the adverse events and yields of stem cell mobilization.

Granulocyte colony-stimulating factor (G-CSF) is now widely used for stem cell mobilization. We evaluated the role of post-G-CSF white blood cell (WBC) counts and donor factors in predicting adverse events and yields associated with mobilization. WBC counts were determined at baseline, after the third and the fifth dose of G-CSF in 476 healthy donors. Donors with WBC ≥ 50 × 10(3)/µL post the third dose of G-CSF experienced more fatigue, myalgia/arthralgia, and chills, but final post-G-CSF CD34(+) cell counts were similar. Although the final CD34(+) cell count was higher in donors with WBC ≥ 50 × 10(3)/µL post the fifth G-CSF, the incidence of side effects was similar. Females more frequently experienced headache, nausea/anorexia, vomiting, fever, and lower final CD34(+) cell count than did males. Donors with body mass index (BMI) ≥ 25 showed higher incidences of sweat and insomnia as well as higher final CD34(+) cell counts. Donor receiving G-CSF ≥ 10 µg/kg tended to experience bone pain, headache and chills more frequently. Multivariate analysis indicated that female gender is an independent factor predictive of the occurrence of most side effects, except for ECOG > 1 and chills. Higher BMI was also an independent predictor for fatigue, myalgia/arthralgia, and sweat. Higher G-CSF dose was associated with bone pain, while the WBC count post the third G-CSF was associated with fatigue only. In addition, one donor in the study period did not complete the mobilization due to suspected anaphylactoid reaction. Observation for 1 h after the first injection of G-CSF is required to prevent complications from unpredictable side effects.