Allogeneic Hematopoietic Stem Cell Transplantation in Children with Acute Lymphoblastic Leukemia: Experiences in a Single Center / 대한소아혈액종양학회지

PURPOSE: To improve survival of children with acute lymphoblastic leukemia (ALL), allogeneic hematopoietc stem cell transplantation (HSCT) was applied. METHODS: From June 1999 to May 2002, 27 children with ALL received allogeneic HSCT at Samsung Medical Center. Patients in complete remission (CR) who received HLA-matched HSCT before relapse when HSCT was indicated were assigned to standard-risk, otherwise were assigned to high-risk. Cyclophosphamide and total body irradiation was basic conditioning regimen. For prophylaxis of GVHD, cyclosporine alone in related HSCT and cyclosporine methotrexate methylprednisolone in unrelated HSCT were used. RESULTS: Fifteen patients in first CR including 6 induction failures, 3 MLL rearrangements and 2 Philadelphia chromosomes, and 3 patients in second CR were assigned to standard-risk. Thirteen related HLA-matched, 11 unrelated HLA-matched, 2 related HLA-mismatched and 1 unrelated HLA-mismatched HSCT were applied. Sixteen of 18 standard-risk patients are still alive with median follow-up of 12.5 (range: 2~37) months and 13 of them are disease-free without relapse. Event-free survival rate (EFS) in 18 standard-risk and 9 high-risk patients were 68.2% and 14.8%, respectively. Confined to standard-risk patients, EFS in related and unrelated HSCT were 75.0%, 60.0%, respectively. CONCLUSION: When allogeneic HSCT is indicated in childhood ALL with available HLA-matched donor, early transplantation before clinical aggravation seems to be necessary.

Lactoferrin Sequestration and Its Contribution to Iron Deficiency Anemia in Helicobacter pylori Infected Gastric Mucosa / 대한소아소화기영양학회지

PURPOSE: It is known that lactoferrin serves as a source of iron for H. pylori in gastric mucosa. This study was undertaken to investigate the relationship between lactoferrin and H. pylori infection coexistent with iron-deficiency anemia by determining the lactoferrin levels in gastric biopsy specimens, and by locating the major sites of lactoferrin expression, according to the presence or absence of iron-deficiency anemia. METHODS: Fifty-five adolescents that underwent gastroduodenoscopy were divided into three groups: NL (n=19) for normal controls, HP (n=15) for patients with H. pylori, and IDA (n=21) for patients with H. pylori gastritis and coexisting iron-deficiency anemia. Histopathologic features were graded from null to marked on the basis of the Updated Sydney System. The gastric mucosal levels of lactoferrin were measured by immunoassay. Immunohistochemical technique was used to allow identification of the location and quantification of the lactoferrin expression. RESULTS: Lactoferrin levels in the antrum increased significantly, in proportion to, H. pylori density, polymorphonuclear cell infiltration, and chronic inflammation in the histologic specimens. Patients in the HP and IDA groups showed significantly increased mucosal levels of lactoferrin compared with that observed in the normal group (p=0.0001). The lactoferrin level in IDA group tended to be higher than that in the HP group (p=0.2614). The major sites of lactoferrin expression by immunohistochemistry were in glands and neutrophils within epithelium. Lactoferrin was stained weakly in NL, and strongly in HP and IDA. CONCLUSION: The lactoferrin sequestration in the gastric mucosa of IDA was remarkable, and this finding seems to give a clue that leads to the clarification of the mechanism by which H. pylori infection contributes to iron-deficiency anemia.

The Role of Neoadjuvant Chemotherapy for Advanced Stage Wilms Tumor

PURPOSE: This study was designed to exclude radiation in advanced(stage 3, 4) Wilms tumor (WT) by increasing the chance of complete surgical removal with preceding neoadjuvant chemotherapy, thereby reducing the incidence of late effects. METHODS: Between December 1998 and July 2002, we conducted neoadjuvant chemotherapy after needle aspiration biopsy on patients who had advanced WT. If needle biopsy was accessible, we conducted neoadjuvant chemotherapy(vincristine, adriamycin, dactinomycin) for 12 weeks and then performed surgical removal, excluded radiation therapy and conducted postoperative chemotherapy (vincristine, dactinomycin+/-adriamycin). In other cases, we firstly conducted the operation and then performed radiation and postoperative chemotherapy. RESULTS: Of the 17 patients diagnosed as WT, 12 patients had an advanced stage of disease. In two of the 12 patients, initial surgical removal was conducted. The median age of patients was 21 months(5-103 months). Of the 10 the patients who received neoadjuvant chemotherapy, eight patients were stage 1, one patient was stage 2, and the other was stage 3 at operation. In nine patients except one with stage 3 disease, we could perform complete surgical resection and there fore could omit radiation. In four cases we could also exclude adriamycin after operation. All but one patient was alive, disease-free, for a median follow-up of 21 months(9-43 months). CONCLUSIONS: After neoadjuvant chemotherapy, we could increase the chance of complete tumor resection, exclude radiation and decrease the intensity of postoperative chemotherapy in selected cases. Long term follow-up is needed to determine whether our method would significantly decrease late effects.

Clinical Characteristics and Genetic Analysis of Prader-Willi Syndrome

PURPOSE: Prader-Willi syndrome(PWS) is a complex disorder affecting multisystems with characteristic clinical features. Its genetic basis is an expression defect in the paternally derived chromosome 15q11-q13. We analyzed the clinical features and genetic basis of PWS patients for early detection and treatment. METHODS: We retrospectively studied 24 patients with PWS in Department of Pediatrics, Samsung Medical Center, from September 1997 to September 2001. We performed cytogenetic and molecular genetic techniques using high resolution GTG banding techniques, fluorescent in situ hybridization and methylation-specific PCR for CpG island of SNRPN gene region. RESULTS: The average birth weight of PWS patients was 2.67+/-0.47 kg and median age at diagnosis was 1.3 years. The average height and weight of PWS patients under one year at diagnostic time were located in a 3-10 percentile relatively, and a rapid weight gain was seen between two and six years. Feeding problems in infancy and neonatal hypotonia were the two most consistently positive major criteria in over 95% of the patients. In 18 of the 24 cases(75%), deletion of chromosome 15q11-q13 was demonstrated and one case among 18 had an unbalanced 14;15 translocation. In four cases without any cytogenetic abnormality, it may be considered as maternal uniparental disomy and the rest showed another findings. CONCLUSION: We suggest diagnostic testing for PWS in all infants/neonates with unexplained feeding problems and hypotonia. It is necessary for clinically suspicious patients to undergo an early genetic test. As the genetic basis of PWS was heterogenous and complex, further study is required.