BACKGROUND/PURPOSE Neutropenia is a decrease in the number of circulating neutrophils. When neutropenia persists for more than 3 months, it becomes chronic. A heterogeneous group of diseases in children can cause chronic neutropenia. The aim of the present study was to categorize the diseases and present their clinical manifestations, treatment, and outcomes. METHODS Medical charts of patients with pediatric chronic neutropenia from the last 21 years (1988-2008) were reviewed in a tertiary referral center. RESULTS Twenty-nine patients were documented during the study period: seven with congenital neutropenia syndromes (CNSs), seven with autoimmune neutropenia (AIN), and 15 with chronic idiopathic neutropenia (CIN). Three CNS patients had severe chronic neutropenia, one had the Chediak-Higashi syndrome, one had the hyper-IgM syndrome, one had the glycogen storage disease type Ib, and one had the Barth syndrome. CNS patients had severe neutropenia early with frequent infections causing high morbidity and mortality. CNS patients usually required prophylactic antibiotics, granulocyte colony-stimulating factor therapies, or umbilical cord blood transplantations to improve or correct clinical conditions. However, most AIN and CIN patients later recovered spontaneously and did not require granulocyte colony-stimulating factor therapy. The mean absolute neutrophil count at onset, the mean onset age of neutropenia, and the mean duration of neutropenia of the two groups of patients did not significantly differ. Some AIN patients had anemia, and some CIN patients had anemia and/or thrombocytopenia. CONCLUSION It is difficult and risky to draw any conclusion from such a small-scale study; however, we believe that promptly diagnosing underlying diseases and administering appropriate disease-oriented therapy would be crucial for the treatment of patients with chronic neutropenia, particularly with regard to CNSs.

Semiconductor nanostructures exhibit unique properties distinct from their bulk counterparts by virtue of nanoscale dimensions; in particular, exceptionally large surface area-to-volume ratios relative to that of the bulk produce variations in surface state populations that have numerous consequences on materials properties. Of the low-dimensional semiconductor nanostructures, nanowires offer a unique prospect in nanoscale optoelectronics due to their one-dimensional architecture. Already, many devices based upon individual nanowires have been demonstrated, but questions about how nano-size and structural variations affect the underlying materials properties still remain unanswered. Here, we focus on understanding the growth mechanism and kinetics of ZnO nanowires and related nanowalls, and their effects on nanoscale structural and optical properties.

We investigated and evaluated the demographics, clinical and laboratory features, treatment responses, and disease duration of 25 children with immune thrombocytopenia (ITP) eligible for detection of antiplatelet antibodies. We found that patients without antecedent of preceding infection (API) were more likely to have anti-GPIa/IIa than those with API (42.9% vs. 5.5%, P=0.048). Age groups of <2 years and 2 to 10 years were more likely to show response (R) or complete response (CR) to given treatments, whereas none of the patients whose onset age >10 years showed R or CR to given treatments (88.9% and 100% vs 0%, P=0.001). The percentage of newly diagnosed ITP was higher in age groups of <2 years (100%) and in 2 to 10 years (90%) than the age group of >10 years (16.7%, P=0.001). Patients without API (71.4%) were more likely to develop chronic ITP than those with API (5.6%, P=0.002). In conclusion, younger age was a favorable prognostic factor, especially in patients <2 years of age with respect to treatment responses and disease duration. In addition, API was associated with a short disease course as well as absence of anti-GPIa/IIa.

BACKGROUND: The absence of biallelic TCRγ deletion (ABD) is a characteristic of early thymocyte precursors before V(D)J recombination. The ABD was reported to predict early treatment failure in T-cell acute lymphoblastic leukemia (ALL). This study aimed to investigate its prognostic value in Taiwanese patients with T-cell ALL. PROCEDURE: Forty-five children with T-cell ALL were enrolled from six medical centers in Taiwan. Quantitative DNA polymerase chain reaction (Q-PCR) was performed to check the status of TCRγ deletion. The threshold for homozygous deletions by Q-PCR was defined as a fold-change <0.35. RESULTS: ABD was found in 20 patients [20:45] who had higher incidences of induction failure than those without ABD (P = 0.03; hazard ratio [HR] = 8.13; 95% confidence interval [95% CI] = 1.23-53.77) after multivariate regression analysis. Patents with ABD also had inferior EFS and OS (P = 0.071 and 0.0196, respectively). Multivariate Cox analysis indicated that the association between ABD and overall survival was independent of age and leukocyte count on presentation (P = 0.036; HR = 4.25; 95% CI = 1.10-16.42). CONCLUSIONS: The absence of TCRγ deletion is a predictor of a poor response to induction chemotherapy for pediatric patients with T-cell ALL in Taiwan. Providing patients with T-cell ALL and ABD with alternative regimens may be worthwhile to test in future clinical trials. Pediatr Blood Cancer © 2011 Wiley Periodicals, Inc.

Human cytomegalovirus (HCMV) is a common human pathogen that causes significant morbidity and mortality. The efficacy of anti-HCMV drugs such as ganciclovir, foscarnet and cidofovir is limited because of drug toxicities and frequent development of resistance. Here, we report an alternative anti-HCMV method using RNA silencing. Combinatorial use of second-generation short hairpin RNAs (shRNA-miRs) targeting various transcripts of HCMV and an RNA-silencing endonuclease Argonaute-2 (Ago2) expression vector were applied to inhibit replication of HCMV AD169. Normal human fetal lung MRC-5 fibroblasts were transfected with pSM30-shRNA-miRs harbouring single or multiple shRNA-miR cassettes with or without Ago2 and then infected with HCMV AD169. Production of small interfering RNA (siRNA) was quantified by reverse transcription PCR. Virus secretion was evaluated by plaque reduction assays. The use of shRNA-miRs targeting a single HCMV gene suppressed HCMV AD169 viral titres by 50-70%. Polycistronic shRNA-miRs targeting UL46+UL122 and UL70+UL46+UL122 reached nearly 80% of inhibition. Coexpression of Ago2 with shRNA-miRs targeting UL46+UL122 and UL70+UL46+UL122 achieved a 95% reduction in viral maturation. Coexpression of Ago2 with shRNA-miRs enhanced the production of mature siRNAs and increased the efficiency of RNA silencing in the suppression of HCMV replication. This strategy may be universally applied to RNA interference-based therapies.

To date, patients with bony metastases were only a small fraction of the samples studied, or they were entirely excluded. Patients with metastatic cancers, such as bone metastases, are more likely to report pain, compared to patients without metastatic cancer (50-74% and 15%, respectively). Their cancer pain results in substantial morbidity and disrupted quality of life in 34-45% of cancer patients. Massage therapy (MT) appears to have positive effects in patients with cancer; however, the benefits of MT, specifically in patients with metastatic bone pain, remains unknown. The purpose of this randomized clinical trial was to compare the efficacy of MT to a social attention control condition on pain intensity, mood status, muscle relaxation, and sleep quality in a sample (n=72) of Taiwanese cancer patients with bone metastases. In this investigation, MT was shown to have beneficial within- or between-subjects effects on pain, mood, muscle relaxation, and sleep quality. Results from repeated-measures analysis of covariance demonstrated that massage resulted in a linear trend of improvements in mood and relaxation over time. More importantly, the reduction in pain with massage was both statistically and clinically significant, and the massage-related effects on relaxation were sustained for at least 16-18 hours postintervention. Furthermore, massage-related effects on sleep were associated with within-subjects effects. Future studies are suggested with increased sample sizes, a longer interventional period duration, and an objective and sensitive measure of sleep. Overall, results from this study support employing MT as an adjuvant to other therapies in improving bone pain management.

Despite current risk-directed therapy, approximately 15-20% of pediatric patients with acute lymphoblastic leukemia (ALL) have relapses. Recent genome-wide analyses have identified that an alteration of IKZF1 is associated with very poor outcomes in B-cell progenitor ALL. In this study, we determined the prognostic significance of IKZF1 deletions in patients with childhood ALL. This study analyzed 242 pediatric B-cell progenitor ALL patients in Taiwan. We developed a simple yet sensitive multiplex quantitative PCR coupled with capillary electrophoresis to accurately determine the allele dose of IKZF1, and high resolution melting was used for mutation screening for all coding exons of IKZF1. Twenty-six (10.7%) pediatric B-cell progenitor ALL patients were found to harbor these deletions. Most of the deletions were broader deletions that encompassed exon 3 to exon 6, consistent with previous reports. Genomic sequencing of IKZF1 was carried out in all cases and no point mutations were identified. Patients with IKZF1 deletions had inferior event-free survival (P < 0.001), and overall survival (P = 0.0016). The association between IKZF1 deletions and event-free survival was independent of age, leukocyte count at presentation, and cytogenetic subtype by multivariate Cox analysis (P = 0.003, hazard ratio = 2.45). This study indicates that detection of IKZF1 deletions upon diagnosis of B-cell progenitor ALL may help to identify patients at risk of treatment failure. IKZF1 deletions could be incorporated as a new high-risk prognostic factor in future treatment protocols. To the best of our knowledge, this is the first study to examine the poor prognosis of IKZF1 deletions in an Asian population.

PURPOSE: This study investigated the immune response to 2009 pandemic H1N1 influenza monovalent vaccine in children with cancer receiving chemotherapy. METHODS: We enrolled 25 pediatric patients. Ten patients younger than 10 years old received two vaccinations and the remaining 15 patients older than 10 years old received one. We checked hemagglutination-inhibition (HAI) antibody titers in sera of patients before and 3-4 weeks after vaccination. Seroprotective titer was defined as HAI antibody titer ≥40 and seroresponse as ≥4-fold increase in HAI antibody titers after vaccination. RESULTS: The pre- and post-vaccination seroprotective rates were 52% and 72%(P = 0.24). Sixteen (64%) patients were possibly exposed to 2009 pandemic H1N1 influenza previously, and there was significant association between possible exposure and pre-vaccination seroprotective rate (P = 0.03). Post-vaccination seroresponse rate was 32%, and seroresponse was greater in patients without pre-vaccination seroprotective titer than those with pre-vaccination seroprotective titer (50% vs. 15%, P = 0.07). Children with lymphocyte counts above 1,500/µl during vaccination period had better seroresponse than those with lymphocyte counts below 1,500/µl (P = 0.008). Post-vaccination geometric mean titer (GMT) significantly increased in patients younger than 10 years receiving two vaccinations (pre- and post-vaccination GMT were 21.4 and 60.6, respectively; P = 0.025). CONCLUSIONS: Monovalent vaccine for the 2009 pandemic H1N1 influenza A was found to be partially immunogenic in children with cancer, as evidenced by 32% of seroresponse rate. Immune response can be improved with vaccinations administered to patients whose absolute lymphocyte counts returned to a level of 1,500/µl or higher. Pediatr Blood Cancer © 2011 Wiley-Liss, Inc.