Hsiu-Ju Yen

A rare complication in a child undergoing chemotherapy for acute lymphoblastic leukemia: Superior sagittal sinus thrombosis

We report the case of a 4-year-old boy with acute lymphoblastic leukemia in high-risk group who suffered from generalized tonic-colonic seizure evolving into status epilepticus, and subsequent left hemiparesis during his first reinduction chemotherapy, consisting of dexamethasone, vincristine, l-asparaginase, and epirubicin. Superior sagittal sinus and cerebral venous thrombosis, predominantly in right side, were proved by brain magnetic resonance imaging. After aggressive treatment with low-molecular weight heparin (LMWH), left hemiparesis improved in 1 week. And he was fully ambulatory 3 weeks later. The second cycle of reinduction chemotherapy was conducted smoothly with the concomitant use of LMWH. This case illustrates the strong correlation of the rare thrombotic complication, superior sagittal sinus thrombosis, and hypercoagulable status secondary to combination use of l-asparaginase and corticosteroid. Early and vigilant recognition of superior sagittal sinus thrombosis and prompt anticoagulation with LMWH may prevent further neurological damage.

Acute Sciatica : An Unusual Presentation of Extramedullary Relapse of Acute Lymphoblastic Leukemia

A 10-year-old boy who had been treated for acute lymphoblastic leukemia presented with persistent numbness of the left big toe and progressive pain of the ipsilateral lower leg. He had received allogeneic bone marrow transplantation 3 months after a testicular relapse. He was in hematologic remission at admission but as progressive swelling of his left leg continued, bone marrow relapse developed. A muscle biopsy revealed leukemic infiltrates in the surrounding muscles of the left sciatic nerve, and swelling of the nerve was found on a magnetic resonance imaging scan. His symptoms/signs subsided soon after reinduction chemotherapy. Unfortunately, he didn’t survive because of a fungal sepsis that developed during the neutropenic state. This case represents a rare neurologic complication of what is currently an uncommon presentation for relapse of acute lymphoblastic leukemia, with acute sciatica and without coexisting epidural or leptomeningeal leukemia.

Long-term mixed full-donor chimerism with dominance reversion after a double-unit cord blood transplant.

To the Editor: Previous reports have documented that recipients of double-unit cord blood transplants (CBT) were eventually engrafted with only one of the two units after 4 months (1–6). We found long-term mixed full-donor chimerism (DC) and dominance reversion (DR) during regular follow-up for more than 16 months after doubleunit CBT in a 15-year-old boy with acute lymphoblastic leukemia (pre-B cell type with 47, XY, +13 diagnosed in 2003). Complete remission was achieved by induction, consolidation and maintenance chemotherapy. As no human leucocyte antigen (HLA)-matched sibling or unrelated donor was available, a double-unit CBT (with a HLA 2-loci mismatch between donors and patient) was performed 16 months after initial diagnosis. The conditioning regimen was busulfan (4 mg ⁄kg ⁄day, day -7 to day -4), cyclophosphamide (60 mg ⁄kg ⁄day, day -3, day -2) and anti-thymocyte globulin (Fresenius, Gräfelfing, Germany; 15 mg ⁄kg ⁄day, day -2 to day 0). The characteristics of the patient and the cord blood (CB) are presented in Table 1. No information about T-cells in these two infused CB units was available. Cyclosporine and methotrexate were administered for graft-versus-host disease (GVHD) prophylaxis. Granulocyte colony-stimulating-factor (300 lg ⁄day; Kirin, Tokyo, Japan) and Neumega (50 lg ⁄kg ⁄day; Wyeth, Madison, NJ, USA) were given from day 1 until neutrophil engraftment on day 35 and platelet engraftment on day 59 after CBT, respectively. Cord blood B (CB-B) cells were predominant in bone marrow since day 21 (Fig. 1). Full DC was achieved on day 35. The fraction of CB-B cells declined gradually from day 28 after CBT. Each of the two units contributed almost equally to the level of chimerism until day 170. Cord blood A (CB-A) cells began to predominate from day 253 and by day 479, cells were 70% of CB-A origin and 30% of CB-B origin. Barker et al. (2) assessed transplantation of two units of partially HLA-matched CBT in 23 patients with Figure 1 Engraftment kinetics analysed by the serial chimerism of recipient, cord blood A and cord blood B after double units of cord blood transplants (CBT). Mixed full-donor chimerism was detected until latest follow-up (479 days after CBT) and the dominance reversion was identified since day 133 after CBT with over-riding predominance since day 253 after CBT.

The Risk of Cancer in Patients with Congenital Heart Disease: A Nationwide Population-Based Cohort Study in Taiwan

Background The relationship between congenital heart disease (CHD) and malignancies has not been determined. This study aimed to explore the association of CHD with malignancies and examine the risk factors for the development of cancer after a diagnosis of CHD. Patients and Methods This nationwide, population-based cohort study on cancer risk evaluated 31,961 patients with newly diagnosed CHD using the Taiwan National Health Insurance Research Database (NHIRD) between 1998 and 2006. The standardized incidence ratios (SIRs) for all and specific cancer types were analyzed, while the Cox proportional hazard model was used to evaluate risk factors of cancer occurrence. Results Among patients with newly diagnosed CHD regardless of ages, 187 (0.6%) subsequently developed cancers after a diagnosis of CHD. Patients with CHD had increased risk of cancer (SIR, 1.45; 95% CI, 1.25–1.67), as well as significantly elevated risks of hematologic (SIR, 4.04; 95% CI, 2.76–5.70), central nervous system (CNS) (SIR, 3.51; 95% CI, 1.92–5.89), and head and neck (SIR, 1.81; 95% CI, 1.03–2.94) malignancies. Age (HR, 1.06; 95% CI, 1.05–1.06) and co-morbid chronic liver disease (HR, 1.91; 95% CI, 1.27–2.87) were independent risk factors for cancer occurrence among CHD patients. Conclusion Patients with CHD have significantly increased cancer risk, particularly hematologic, CNS, and head and neck malignancies. Physicians who care for patients with CHD should be aware of their predisposition to malignancy after the diagnosis of CHD. Further studies are warranted to clarify the association between CHD and malignancies.

Iron Deficiency Anemia in Predominantly Breastfed Young Children

BACKGROUND Due to the increase of breastfeeding in infants, iron deficiency anemia (IDA) related to prolonged, predominant breastfeeding should be of concern. Mostly, the manifestation of IDA is indistinguishable and the enthusiastic advocacy of breastfeeding without concomitant education of complementary food may lead to ignorance of breast milk-related IDA, which may result in impaired psychomotor development of the baby. This retrospective study was conducted to re-emphasize this easily ignored but still prevalent illness. METHODS This retrospective study involved 15 breastfeeding babies who were diagnosed with IDA between January 2007 and December 2010 at age 6-18 months. The clinical presentation, age at diagnosis, initial hemoglobin level and mean corpuscular volume, growth percentile, and duration of treatment were recorded and analyzed. RESULTS None of the babies was suspected to have anemia by caregivers. Pallor was noticed by physicians in nine patients; one patient had seizure, one patient had pica, and, for the remaining four patients, IDA was diagnosed incidentally due to other medical events. Oral iron supplementation for an average of 3.6 months improved both hemoglobin level (from 8.0 g/dL to 11.5 g/dL) and mean corpuscular volume (from 57.5 fL to 73.9 fL). Most babies had appropriate growth and normal neurological development; two babies had both IDA and thalassemia. CONCLUSION Although the association of IDA with prolonged, predominant breastfeeding is well known, its presentation is so subtle that its detection relies mainly on alert medical personnel.

Longitudinal association between early atopic dermatitis and subsequent attention-deficit or autistic disorder: A population-based case-control study.

AbstractAtopic dermatitis (AD) is one of the common allergic diseases in children. The presence of allergic diseases was found to have association with the risk of developing attention-deficit hyperactivity disorder (ADHD) or autistic spectrum disorder (ASD) in children, but it is still inconclusive. This study was to investigate the longitudinal relationship between AD developed during toddlerhood and subsequent development of ADHD or ASD in later childhood. Toddlers born between 1998 and 2008 and diagnosed with AD at the age younger than 3 years and older than 1 month were retrieved from Taiwans National Health Insurance Research Database. Age- and gender-matched toddlers with no lifetime AD were enrolled as the control group. All enrolled toddlers were followed until 2011 to identify the development of ADHD or ASD. Multivariate Cox regression analysis was performed to analyze the hazard ratios (HRs). The risks associated with allergic comorbidities were analyzed. A total of 18,473 toddlers were enrolled into the AD group. The presence of AD significantly increased the risk of developing ADHD (HR = 2.92, 95% confidence interval [CI] = 2.48–3.45) or ASD (HR = 8.90, 95% CI = 4.98–15.92) when aged 3 years or older. Children from the AD group with 3 comorbidities together, namely, allergic rhinitis, allergic conjunctivitis, and asthma, had the greatest risk of developing ADHD and ASD (ADHD: HR = 4.67, 95% CI = 3.81–5.43; ASD: HR = 16.65, 95% CI = 8.63–30.60). In conclusion, toddlers who suffer from AD at the age younger than 3 years are at a higher risk of developing ADHD and ASD during later childhood. Pediatricians taking care of toddlers with AD should have knowledge of this increased risk of developing ADHD and ASD later in life, especially when children have certain comorbidities such as allergic rhinitis, allergic conjunctivitis, and asthma.

Improvement in High-Grade Osteosarcoma Survival: Results from 202 Patients Treated at a Single Institution in Taiwan.

AbstractThe aim of this study was to compare survival before and after 2004 and define the prognostic factors for high-grade osteosarcomas beyond those of typical young patients with localized extremity disease.Few studies have reported the long-term treatment outcomes of high-grade osteosarcoma in Taiwan.A total of 202 patients with primary high-grade osteosarcoma who received primary chemotherapy at Taipei Veterans General Hospital between January 1995 and December 2011 were retrospectively evaluated and compared by period (1995–2003 vs 2004–2011). Patients of all ages and tumor sites and those following or not following controlled protocols were included in analysis of demographic, tumor-related, and treatment-related variables and survival.Overall survival and progression-free survival at 5 years were, respectively, 67.7% and 48% for all patients (n = 202), 77.3% and 57.1% for patients without metastasis (n = 157), and 33.9% and 14.8% for patients with metastasis (n = 45). The survival rates of patients treated after 2004 were significantly higher (by 13%–16%) compared with those of patients treated before 2004, with an accompanying 30% increase in histological good response rate (P = .002). Factors significantly contributing to inferior survival in univariate and multivariate analyses were diagnosis before 2004, metastasis at diagnosis, and being a noncandidate for a controlled treatment protocol.By comparison with the regimens used at our institution before 2004, the current results support the effectiveness of the post-2004 regimens, which consisted of substantially reduced cycles of high-dose methotrexate and a higher dosage of ifosfamide per cycle, cisplatin, and doxorubicin, for treating high-grade osteosarcoma in Asian patients.

Osteosarcoma in preadolescent patients: experience in a single institute in Taiwan.

Background: The incidence of osteosarcoma peaks in adolescence and is much lower in preadolescence. However, reports on its clinical features in preadolescent patients are conflicting. In this study, we attempted to assess the differences in clinical appearance and prognosis of the malignancy between preadolescent and adolescent patients. Methods: Between January 1980 and January 2006, 13 preadolescent and 58 adolescent patients with high‐grade osteosarcoma were treated at our institute, and their medical records were reviewed and compared. Results: The sex distribution, primary metastasis rate, pathologic fracture, histologic type, primary tumor location, and percentage of high alkaline phosphatase level were not different between the 2 groups. Poor responders (tumor necrosis rate < 90%) were more common in the preadolescent group (80% vs. 43%, p = 0.035). Overall survival rates in the preadolescent and adolescent groups were 51.3% and 56.4%, respectively (p = 0.735). In patients without primary metastasis, the 5‐year overall survival rates were 60.6% and 66.7% for 11 preadolescents and 39 adolescents, respectively (p = 0.925). Conclusion: Considering the common findings in both groups, we suggest that preadolescent patients should be treated with the same regimen as that used for adolescent patients.

Sudden and unexpected and near death during the early neonatal period: A multicenter study

Background: To investigate the incidence, clinical presentation and possible etiologies or risk factors of early onset of sudden and unexpected death or near‐miss. Methods: From 2001 to 2005, a retrospective analysis of observational database of neonates who were younger than one week old without any risk factors at five tertiary medical centers. The demographic data, clinical manifestations, laboratory data and possible etiologies were retrospectively collected and analyzed. Results: Seventeen neonates presumed to be healthy at birth encountered early near death in five medical centers in Taipei city. The mean gestation age (GA) was 38.5 ± 1.2 weeks, mean birth body weight (BBW) was 2948.2 ± 327.8 gm. The median age at event was 26 hours old. Eleven patients were rooming‐in babies with exclusive breast feeding. Seven patients (41.2%) died; seven patients (41.2%) survived with neurological sequelas, and the remaining three patients (17.6%) survived without complication. Possible causative factors included infection in two cases, urea cycle disorder in one case, hypertrophic cardiomyopathy in one case, hypocalcemia only in one case, hypocalcemia plus airway obstruction in one case, dehydration‐related diseases in seven cases and unknown in 4 cases; there was no autopsy case. Conclusion: More effort on promotion of autopsy to discover the underlying disease is necessary and helpful. To build up an alarm system or protocol for education and early detection is the basis to prevent this tragedy.

Pre-pubertal and adolescent germ cell neoplasms in Taiwan: time trends and geographic variation

Evidence from our previous study suggested that the incidence of germ cell neoplasms in children and adolescents is increasing. The objectives of this analysis were to quantify this trend in patients aged 0–9 and 10–19 years (pre‐pubertal and adolescent groups, respectively) and compare rates in Taiwan according to geographic distribution. Germ cell neoplasm frequencies among 1267 patients aged 0–19 years spanning 1995–2009 were obtained from the population‐based Taiwan Cancer Registry. The incidence patterns according to sex, age, disease subgroup, and geographic distribution were analyzed. The incidence rates in the pre‐pubertal and adolescent groups were 10.58 and 16.06 per million person‐years, respectively. The overall rates increased significantly by 3.2% annually in the adolescent group during the 15‐year study period, and increased only among the males. In contrast, no change in trend was observed in the pre‐pubertal group. Subgroup analysis showed significant upward trends in the incidence rates of intracranial/intraspinal and testicular germ cell tumors (GCTs) in the adolescent males and extracranial/extragonadal GCTs in the pre‐pubertal boys. The most striking differences between the study population and white Americans were that the rates of testicular GCTs were 5‐fold higher and 4‐fold lower in the Taiwanese pre‐pubertal and adolescent groups, respectively. Significantly higher rates were found in Hualien and Chiayi Counties compared with the other areas of Taiwan. The upward trend of testicular GCTs in the adolescent males is consistent with findings from Western countries. The underlying causes that led to the high rate of testicular GCTs in the pre‐pubertal boys and significantly higher rates in specific counties warrant further investigation.