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.

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.

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.

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.

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.

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.

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.

Preharvest hematopoietic progenitor cell counts predict CD34+ cell yields in granulocyte-colony-stimulating factor-mobilized peripheral blood stem cell harvest in healthy donors.

BACKGROUND: The hematopoietic progenitor cell (HPC) count measured by the Sysmex hematology analyzer can determine the timing for leukapheresis in autologous peripheral blood stem cell (PBSC) harvest. We evaluated whether a HPC count could predict CD34+ cell yield in healthy, unrelated donors after granulocyte-colony-stimulating factor mobilization. STUDY DESIGN AND METHODS: A total of 117 healthy donors underwent 161 PBSC leukapheresis procedures in our institution. The HPCs and CD34+ cells were identified by an automated hematology analyzer and flow cytometry, respectively. Using Spearman's rank test, we evaluated the relationships between preharvest HPCs, CD34+ cell counts, and CD34+ cell yields in the apheresis product. A receiver operating characteristic (ROC) curve analysis was used to identify the cutoff value of HPC for adequate mobilization and harvest yield. RESULTS: The HPC count had a moderate correlation with the preharvest CD34+ cell count (r = 0.502, p < 0.001), and an HPC count of more than 21.3 x 10(6)/L could exclude poor mobilization (<20 x 10(6) CD34+ cells/L) with sensitivity and specificity of 89.2 and 83.3%. However, the relationship between HPC count and CD34+ cell yield was not marked (r = 0.321, p < 0.001). The area under the curve for HPCs was significantly smaller than the preharvest CD34+ cell count on the ROC curve for predicting adequate harvest yield (>10 x 10(6) CD34+ cells/L of processed blood volume, 0.678 vs. 0.850, p = 0.001). CONCLUSION: Although the preapheresis HPC count could predict mobilization in healthy donors before leukapheresis, it may not be a superior index for predicting CD34+ cell yield compared with the preharvest CD34+ cell count.

Is a boosting dose of granulocyte-colony-stimulating factor necessary for healthy PBSC donors undergoing secondary apheresis? An institute's experience.

Successful allogeneic PBSC transplantation depends upon the infusion of an adequate number of CD34+ cells to patients. Granulocyte-colony-stimulating factors (G-CSF) mobilized PBSC were harvested on 5th day after stimulation from donors. When the CD34+ cell target yield was not achieved; secondary apheresis was performed the following day. Before September 2006, 67 donors (Group A) received five doses of G-CSF. After September 2006, a sixth dose of G-CSF was administered to 35 donors (Group B) to improve CD34+ yield. The mean CD34+-cell concentration of the second PBSC harvest was significantly higher in Group B (1,087 x 10(6)/l vs. 767 x 10(6)/l; P = 0.031).

Factors associated with peripheral blood stem cell yield in volunteer donors mobilized with granulocyte colony-stimulating factors: the impact of donor characteristics and procedural settings.

Peripheral blood stem cells (PBSCs) are increasingly used as the source of hematopoietic stem cells, but there are large variations in harvest outcome between individuals mobilized by granulocyte colony-stimulating factor (G-CSF). We examined the effects of donor characteristics and procedure factors on the day 1 CD34+ cell yield in 373 unrelated healthy donors. G-CSF was administered subcutaneously at a planned dose of 8.3 to 11 microg/kg daily for 5 days, followed by harvest started on day 5 of G-CSF treatment. Of the 373 donors, 159 (42.6%) had the radial artery as the inlet access for harvest. Poor day 1 cell yield was defined as <10x10(6) CD34+ cells/L of processed blood for the first apheresis; 62 donors (16.6%) did not attain this threshold. The male donors had significantly higher yields at harvest compared with the female donors. The female donors had higher CD34+ cell yields if the circulation access was through an artery than if is was through a vein. In a multiple regression analysis, donor age, sex, body mass index (BMI), preharvest white blood cell and circulating immature cell counts, access type, and flow rate correlated with day 1 yield. Female sex, older age, venous access, and a higher flow rate were significantly associated with greater risk for a day 1 poor yield of CD34+ cells (odds ratio=3.0074, 1.045, 4.3362, and 1.1131, respectively). A higher BMI may decrease the risk (odds ratio=0.8472). In donors at higher risk for poor CD34+ cell yield, strategies for increasing CD34+ cells must be considered.

Microbial contamination of the Tzu-Chi Cord Blood Bank from 2005 to 2006.

BACKGROUND: In total, 4502 units of cord blood (CB) were collected during a 2-year period from 2005 to 2006 by the Buddhist Tzu-Chi Stem Cells Center. The aim of this study was to analyze the incidence of microbial contamination and type of organism present in the cord blood. The clinical impact of microbial contamination on hematopoietic progenitor cell (HPC) grafts used for HPC transplantation is also discussed. METHODS: First and second specimens were obtained for microbial assessment. These were collected in laboratory after cord blood collection and after cord blood unit manipulation, respectively. The samples were cultured and the results reviewed. RESULTS: The overall incidence of microbiological contamination was 1.8% (82/4502). Three CB units were contaminated with two different organisms. Infectious organisms comprised 9.4% (8/85) of total isolated microbes. These infectious microorganisms were beta-Streptococci group B, Candida tropicalis and Staphylococcus aureus which were isolated in 6, 1 and 1 of CB units respectively. Escherichia coli, Bacteroides fragilis, Lactobacillus spp., Enterococcus, beta-Streptococcus Group B, Bacteroides valgatus, Corynebacterium spp., Klebsiella pneumonia and Peptococcus spp. were the most frequently encountered microorganisms. A higher contamination rate of the CB units was noted after vaginal delivery (2.16%) compared to caesarian section (0.85%) (p < 0.01). CONCLUSIONS: Extensive training in CB collection, good procedures and good protocols can decrease the rate of microbial contamination. The use of a closed collecting system and an ex utero method have the advantage of a lower contamination rate. In our cord blood bank, we use a closed system but an in utero method. Similar to other studies, most of microorganisms reported here as contaminants are non-pathogenic.

Childhood scrub typhus in eastern Taiwan: ten-year experience from a medical center.

BACKGROUND: Scrub typhus, a potentially fatal rickettsial infection, is endemic in western Pacific Rims including Taiwan. Most reports have been concerned about mainly adult patients, whereas serologic surveys suggested that as many as one-half of cases of scrub typhus might be in children. METHODS: We conducted a retrospective study of childhood scrub typhus in our hospital from January 1997 to December 2006. Scrub typhus was diagnosed on the basis of serology tests or polymerase chain reaction (PCR) examination in fifteen children. RESULTS: Fever and chigger bite history were presented in all 15 cases, and eschar lesion was identified in 12 patients (80%). Nine (60%) patients had headache and six (40%) complained of abdominal pain. Three patients (20%) had meningoencephalitis, and two (13%) hemophagocytic syndrome were confirmed by bone marrow biopsy. One patient died of progressive acute respiratory distress syndrome (ARDS) and pulmonary hemorrhage. Myocarditis was revealed in autopsy. All surviving patient responded well to antibiotic therapy, and the average duration to defervescence after treatment was 1.8 days. CONCLUSIONS: We conclude that scrub typhus should be taken into consideration among patients of acute systemic febrile illness, especially those with suspected exposure history and typical skin lesion. Although most patients responded well to treatment, severe complications such as meningoencephalitis, interstitial pneumonia, acute respiratory distress syndrome, hemophagocytic syndrome, and myocarditis might lead to morbidity and mortality.