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.

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.

This study aimed to evaluate the frequency of the diverse causes of iron deficiency (ID) and iron deficiency anemia (IDA) and to investigate the treatment outcomes in children. ID was defined as a serum ferritin level<12mug/L and a transferrin saturation<10%. IDA was established as ID combined with a low hemoglobin level judged by age and gender-specific reference intervals. A total of 116 ID patients were categorized into 4 groups: group I:<2 years old (n=45), group II: 2 to 10 years old (n=13), group III:>10 years old, male (n=18), and group IV:>10 years old, female (n=40). One hundred of them (86.2%) were diagnosed with IDA. The most common causes of ID were inadequate intake in group I (55.6%) and blood loss in groups II (46.1%) and IV (37.5%). Helicobacter pylori-associated ID mainly occurred in children more than 10 years old. Forty-five of 57 (78.9%) IDA patients who had underlying diseases treatment and/or iron supplementation for 3 months recovered their hemoglobin levels (follow-up range: 6-27 mo). In conclusion, the peak incidences of childhood ID were ages under 2 years old and 10-18 years old. Different age groups and sexes showed characteristic etiologies. The outcomes of childhood ID were good.

Electrospray-assisted laser desorption ionization (ELDI) is a technique which combines laser desorption with subsequent electrospray ionization. It is useful for directly detecting small and large molecules in solid or liquid samples under ambient conditions. In this paper, the detection of the protein molecules desorbed on a dry protein spot by using pulse laser energies of up to 300 microJ was demonstrated. The influences of organic and inorganic matrices, the laser energy, the laser wavelength, and the sample plate material on desorption of protein molecules from sample plates were discussed. In addition, the effects of the composition of the electrospray solution on the ionization of the desorbed protein molecules were studied.

The long-term outcome of 1390 children with acute lymphoblastic leukemia (ALL), treated in two successive clinical trials (Taiwan Pediatric Oncology Group (TPOG)-ALL-97 and TPOG-ALL-2002) between 1997 and 2007, is reported. The event-free survival improved significantly (P=0.0004) over this period, 69.3+/-1.9% in 1997-2001 to 77.4+/-1.7% in 2002-2007. A randomized trial in TPOG-97 testing L-asparaginase versus epidoxorubicin in combination with vincristine and prednisolone for remission induction in standard-risk (SR; low-risk) patients yielded similar outcomes. Another randomized trial, in TPOG-2002, showed that for SR patients, two reinduction courses did not improve long-term outcome over one course. Decreasing use of prophylactic cranial irradiation in the period 1997-2008 was not associated with increased rates of CNS relapse, prompting complete omission of prophylactic cranial irradiation from TPOG protocols, beginning in 2009. Decreased use of etoposide and cranial irradiation likely contributed to the low incidence of second cancers. High-risk B-lineage ALL, T-cell, CD10 negativity, t(9;22), infant, and higher leukocyte count were consistently adverse factors, whereas hyperdiploidy >50 was a consistently favorable factor. Higher leukocyte count and t(9;22) retained prognostic significance in both TPOG-97 and TPOG-2002 by multivariate analysis. Although long-term outcome in TPOG clinical trials is comparable with results being reported worldwide, the persistent strength of certain prognostic variables and the lower frequencies of favorable outcome predictors, such as ETV6-RUNX1 and hyperdiploidy >50, in Taiwanese children warrant renewed effort to cure a higher proportion of patients while preserving their quality of life.Leukemia advance online publication, 17 December 2009; doi:10.1038/leu.2009.248.

BACKGROUND: The pathoetiology and outcomes of intussusception in older children are different from those in young children. This study aims to investigate the characteristics and outcomes of intussusception in children older than 5 years in a tertiary referring hospital. METHODS: A retrospective review of patients aged older than five years having received a postoperative or roentgenographic diagnosis of intussusception between 1988 and 2005 was conducted. The clinical presentations, diagnostic and treatment methods, and outcomes of all cases were reviewed. RESULTS: A total of 12 cases were recorded. They were eight males and four females, with a median age of 7.6 years (range 5.0-11.1 years). Four (33.3%) children had symptoms lasting more than one week before a prompt diagnosis was made. The most commonly encountered symptom was abdominal pain (100%), followed by nausea/vomiting (75.0%). Recurrent intussusception occurred in 33% of cases. Abdominal sonogram identified intussusceptum in all patients when this procedure was performed. Six patients were treated operatively. Lead lesions including two malignant lymphomas, one Meckel diverticulum, and one colon polyp were found in 4 cases. Three of the four lead points were diagnosed and treated by colonoscopy preoperatively. Complications after operations were adhesive ileus (33.3%) and recurrent intussusception (16.7%). All patients remained well, including those who had lead points identified after prompt treatments. CONCLUSIONS: Intussusception in older children presents a higher frequency of persistent symptoms, lead points, and recurrence. Pediatricians need to be aware of the etiology and treatment options for intussusception in older children.

Minimal residual disease (MRD) in 56 children with acute lymphoblastic leukemia (ALL) was quantified simultaneously by flow cytometry and by RQ-PCR of WT1 transcripts. Six patients failed remission induction, all had detectable MRD by flow cytometry, and two had undetectable MRD by WT1 assay. Among 41 patients, who achieved remission and had overexpression of WT1 transcripts at diagnosis, the two techniques gave concordant MRD results in 26 and discordant MRD results in 15. Nine patients did not show overexpression of WT1 at diagnosis. Our results indicate that RQ-PCR measurements of WT1 may be of limited value for monitoring MRD in childhood ALL.

The pathogenesis of hyaline vascular Castleman disease (HVCD) is poorly understood. Although generally considered reactive in nature, a subset of cases has been shown to harbor focal proliferations of stromal cells, such as follicular dendritic cell (FDC) and angiomyoid proliferations. We report two typical cases of HVCD with cytogenetic anomalies: one was t(1;22)(qter;q13) and the other was t(7;8)(q37.3;q12) in cultured stromal cells, as demonstrated by conventional cytogenetic analysis. The cultured cells were immunoreactive for smooth muscle actin but negative for CD21, CD31, and CD34, and ultrastructurally possessed thin filaments (5-7.5 nm) with dense bodies, and pinocytotic vesicles, characteristic of smooth muscle cells. The lack of monoclonality of lymphoid cells in lesional tissues by immunohistochemical and molecular analyses also supports the origin of these anomalies from the stromal cells, most likely myoid cells. Moreover, the absence of overt stromal proliferations suggests that cytogenetic changes in stromal cells of HVCD precede histologic evidence of stromal overgrowth, which may account for the occurrence of angiomyoid proliferations arising in some cases of HVCD. Further studies with more cases are needed to decipher whether part or even most of HVCD cases bear genetic changes in the beginning of the disease without morphologically stromal overgrowth.