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.

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.

OBJECTIVE To investigate anti-müllerian hormone (AMH) as a best test of ovarian reserve in women with transfusion-dependent β-thalassaemia, and the relationship between AMH and iron overload. DESIGN AND SETTING A case-control study in a tertiary medical centre. POPULATION Twenty-nine women with transfusion-dependent β-thalassaemia and 29 healthy controls of a similar age were recruited. METHODS Blood sampling, questionnaires and medical record reviews were used. MAIN OUTCOME MEASURES The history of iron overload-related morbidities, haematological phenotypes, serum levels of AMH and ferritin, and hormonal profiles were analysed. RESULTS The serum levels of AMH, luteinising hormone, and estradiol were lower in women with transfusion-dependent β-thalassaemia than in age-matched normal controls. In women with transfusion-dependent β-thalassaemia, the serum AMH level was significantly inversely related to the ferritin level, but not related to the presence of hypogonadotrophic hypogonadism, diabetes and haematological phenotypes. The serum ferritin level was positively associated with advanced age and the presence of hypogonadotrophic hypogonadism in the study participants. However, the inverse relationship between AMH and ferritin still exists after further adjustment for advanced age in women with transfusion-dependent β-thalassaemia. CONCLUSIONS The present study indicates that the serum AMH levels in women with transfusion-dependent β-thalassaemia are lower when compared with normal healthy women of a similar age, and are significantly negatively correlated with their serum ferritin levels. This implies that ovarian function might be impaired by the chronic iron overload status in women with transfusion-dependent β-thalassaemia.

BACKGROUND:: Anterior mediastinal tumors in pediatric patients may cause severe cardiorespiratory compromise and sudden collapse, especially when anesthesia or analgesic is required. METHOD:: We report a 15-year-old boy with a huge anterior mediastinal tumor that caused complete obliteration of right pulmonary artery and left bronchus, that is, complete ventilation-perfusion mismatch. Cardiopulmonary collapse happened after meperidine injection, and extracorporeal membrane oxygenation (ECMO) was instituted. RESULTS:: We then put bronchial stents to restore airway patency and proceeded chemotherapy under ECMO support. Extracorporeal membrane oxygenation was removed 40 hours later. However, the patient died of neutropenic sepsis 9 days after admission. CONCLUSIONS:: We emphasized the devastating consequences of anterior mediastinal tumor compression on the pulmonary artery and the contralateral-side bronchus and the use of ECMO as a rescue.

Improved treatment of childhood acute lymphoblastic leukemia (ALL) depends on the identification of new molecular markers that are able to predict treatment response and clinical outcome. The development of impaired apoptosis in leukemic cells is one factor that may influence their response to treatment. We investigated the expression of three apoptosis related genes, BCL2L13, CASP8AP2, and Livin, as well as their prognostic significance, in a retrospective study of 90 pediatric ALL patients diagnosed between 1996 and 2007 in Taiwan. Univariant analysis revealed that high expression of BCL2L13 was associated with inferior event-free survival and overall survival (p<0.001 and 0.005, respectively). Multivariate analysis for EFS and OS demonstrated that high expression of BCL2L13 was an independent prognostic factor for childhood ALL in this ethnic group.

Although pancreatoblastoma (PB) is an extremely rare tumor, it is the most common pancreatic tumor in children. We reported 2 cases of PB treated at a medical center in Taiwan. One was a 3.5-year-old boy who presented with abdominal pain. Physical examination demonstrated abdominal masses. Multiple pancreatic and hepatic masses were noted by magnetic resonance imaging. He underwent surgical resection but tumor could not be removed completely, which was confirmed by the pathology. He received chemotherapy consisting of cisplatin and doxorubicin after the surgery but the tumor progressed rapidly. He died of progressive disease and sepsis. The other case was a 4-year-old boy presented with abdominal pain. Computed tomography showed pancreatic tumor. He underwent surgical resection and pathology showed PB. He received chemotherapy after complete tumor resection. He is disease free till now. Complete tumor resection is the major difference of these 2 patients and is the most important factor affecting the outcome.

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.

OBJECTIVES: This retrospective study evaluates the role of pharmacogenomic determinants in the treatment of childhood acute lymphoblastic leukemia (ALL) in the Taiwanese population. METHODS: A total of 105 childhood ALL patients received combined chemotherapy of different intensities based on risk-directed Taiwan Pediatric Oncology Group (TPOG)-ALL-93 protocols. Seventeen genetic polymorphisms in 13 pharmacogenomic targets were analyzed by PCR-based restriction fragment length polymorphism (RFLP) and sequence-specific oligonucleotide (SSO) probe hybridization. Pharmacogenomic polymorphisms were correlated with event-free survival (EFS) of patients, with confounding effects adjusted by multivariate regression. RESULTS: Three polymorphic alleles in the multi-drug resistance 1 (MDR1) ABCB1 gene, and homozygotic MDR1 2677GG, 3435CC, and 2677G-3435C genotypes were highly associated with a significant reduction in EFS in those patients treated by the standard risk (SR) protocol (TPOG-ALL-93-SR). The hazard ratios were 6.8 (p = 0.01), 21.7 (p = 0.009), and 6.8 (p = 0.01), respectively. CONCLUSIONS: Independent pharmacogenomic determinants associated with treatment outcome were identified in subsets of Taiwanese ALL patients. Pediatr Blood Cancer.(c) 2009 Wiley-Liss, Inc.