Factors influencing lymphocyte reconstitution after allogeneic hematopoietic stem cell transplantation in children / 대한혈액학회지

BACKGROUND: Immune reconstitution (IR) after hematopoietic stem cell transplantation (HSCT) reduces transplantation-related complications such as infection and improves HSCT outcomes. METHODS: We retrospectively analyzed IR of lymphocyte subpopulations in 38 pediatric patients for hematologic malignant diseases after allogeneic HSCT from April 2006 to July 2008. T-cell-, B-cell-, and natural killer (NK) cell-associated antigens were assayed in peripheral blood by flow cytometry analysis of 5 lymphocyte subsets, CD3+, CD3+/CD4+, CD4+/CD8+, CD16+/CD56+, and CD19+, before and 3 and 12 months after transplantation. RESULTS: Reconstitutions of CD16+/CD56+ and CD3+/CD8+ lymphocytes were achieved rapidly, whereas that of CD3+/CD19+ lymphocytes occurred later. Age was not related to reconstitution of any lymphocyte subset. Total body irradiation (TBI) and anti-thymocyte globulin (ATG) administration were related to delayed reconstitution of total lymphocytes and CD3+ lymphocytes, respectively. Reconstitutions of CD3+/CD4+ lymphocytes and CD3+/CD8+ lymphocytes were significantly delayed in patients who received umbilical cord blood stem cells. In patients with chronic graft-versus-host disease (cGVHD), recovery of the total lymphocyte count and CD19+ lymphocytes at 3 months post-transplant were significantly delayed. However, acute GVHD (aGVHD) and cytomegalovirus (CMV) reactivation did not influence the IR of any lymphocyte subset. Further, delayed reconstitution of lymphocyte subsets did not correspond to inferior survival outcomes in this study. CONCLUSION: We observed that some lymphocyte reconstitutions after HSCT were influenced by the stem cell source and preparative regimens. However, delayed CD19+ lymphocyte reconstitution may be associated with cGVHD.

Improved outcome in childhood ALL with intensive consolidation and hematopoietic stem cell transplant / 대한혈액학회지

BACKGROUND: Despite advances in chemotherapy, the prognosis of relapsed acute lymphoblastic leukemia (ALL) remains poor. Few studies on relapsed ALL have reported the importance of intensive consolidation followed with or without allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: We evaluated the post-relapse outcomes in 47 Korean children with a first marrow relapse, and analyzed the prognostic factors. RESULTS: A second complete remission (CR) was achieved in 40 patients (85.1%), and at the time of this study, second CR was maintained in 12 of these patients. The estimated 3-yr event-free survival (EFS) rate after the first marrow relapse was 29.8+/-6.7%, and the overall survival (OS) rate was 45.3+/-7.5%. We found that second remission, consolidation of pediatric oncology group chemotherapy regimen (POG 9411), and HSCT significantly affected the outcome of the disease after relapse (P<0.001; P=0.004; P=0.05). CONCLUSION: The results of our study revealed that an intensified POG 9411 consolidation chemotherapy regimen followed by HSCT can improve the outcome of patients with relapsed ALL.

A case of anemia caused by combined vitamin B12 and iron deficiency manifesting as short stature and delayed puberty / 소아과

Anemia caused by vitamin B12 deficiency resulting from inadequate dietary intake is rare in children in the modern era because of improvements in nutritional status. However, such anemia can be caused by decreased ingestion or impaired absorption and/or utilization of vitamin B12. We report the case of an 18-year-old man with short stature, prepubertal sexual maturation, exertional dyspnea, and severe anemia with a hemoglobin level of 3.3 g/dL. He had a history of small bowel resection from 50 cm below the Treitz ligament to 5 cm above the ileocecal valve necessitated by midgut volvulus in the neonatal period. Laboratory tests showed deficiencies of both vitamin B12 and iron. A bone marrow examination revealed dyserythropoiesis and low levels of hemosiderin particles, and a cytogenetic study disclosed a normal karyotype. After treatment with parenteral vitamin B12 and elemental iron, both anemia and growth showed gradual improvement. This is a rare case that presented with short stature and delayed puberty caused by nutritional deficiency anemia in Korea.

Influence of Serum Ferritin on Transplant-related Outcomes and Complications in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation / 대한혈액학회지

BACKGROUND: Iron overload, primarily related to RBC transfusions, is a relatively common complication in hematopoietic stem cell transplant (HSCT) recipients. There are emerging data from retrospective studies that iron overload can significantly increase the risk of nonrelapse mortality after allogeneic HSCT. METHODS: One hundred and five children who received allogeneic HSCT between Jan 2004 and Feb 2009 at Asan Medical Center were analyzed. For indirect estimation of body iron stores, we measured serum ferritin serially in HSCT recipients at pre-transplant, 3 months and 1 year post-transplant. We also analyzed prevalence of hyperferritinemia, correlation of iron overload and transplant-related outcomes and complications. RESULTS: The prevalence of hyperferritinemia (> or =1,000 microgram/L) at pre-HSCT, 3 months and 1 year post-HSCT were 66.7% (70/105), 78% (71/91) and 40.9% (27/66), respectively. Children with hyperferritinemia (> or =1,000 microgram/L) at 3 months post-HSCT had worse 2-year OS (79% vs 95%; P=0.023) than those in the low ferritin group ( or =3,000 microgram/L) at 3 months post-HSCT were associated with increased incidence of treatment related mortality (23% vs 2%, P=0.001) and acute graft-versus-host disease (54% vs 26%, P=0.007) in univariate analysis. VHL of ferritin remained significant in multivariate analysis. CONCLUSION: Hyperferritinemia at 3 months post-HSCT had adverse impact for transplantation outcome in patients undergoing allogeneic stem cell transplantation. These results suggest that the screening and adequate treatment of iron overload in HSCT recipients might be helpful to improve the HSCT outcomes.

Outcome and risk factors of pediatric hemato-oncology patients admitted in pediatric intensive care unit / 소아과

PURPOSE: To evaluate the risk factors for mortality and prognostic factors in pediatric hemato-oncology patients admitted to the pediatric intensive care unit (PICU). METHODS: We retrospectively reviewed the medical records of pediatric hemato-oncology patients admitted at the PICU of the Asan Medical Center between September 2005 and July 2008. Patients admitted at the PICU for perioperative or terminal care were excluded. RESULTS: Total 88 patients were analyzed. Overall ICU mortality rate was 34.1%. Mean age at PICU admission was 7.0+/-5.7 years and mean duration of PICU stay was 18.1+/-22.2 days. Hematologic diseases contributed to 77.3% of all the primary diagnoses, and the primary cause of admission was respiratory failure (39.8%). The factors related to increased mortality were C-reactive protein level (P<0.01), ventilation or dialysis requirement (P<0.01), and hematopoietic stem cell transplantation (P<0.05). In all, 3 scoring systems were investigated [Number of Organ System Failures (OSF number), the Pediatric Risk of Mortality III (PRISM III) score, and the Sequential Organ Failure Assessment (SOFA) score]; higher score correlated with worse outcome (P<0.01). The Oncological Pediatric Risk of Mortality (O-PRISM) scores of the 21 patients who had received hematopoietic stem cell transplantation were higher among the non-survivors, but not statistically significant (P=0.203). CONCLUSION: The PRISM III and SOFA scores obtained within 24 hours of PICU admission were found to be useful as early mortality predictors. The highest OSF number during the PICU stay was closely related to poor outcome.

Phenotype-genotype correlations and the efficacy of growth hormone treatment in Korean children with Prader-Willi syndrome / 소아과

PURPOSE: Prader-Willi syndrome (PWS) is a complex genetic disorder, caused by the deletion of the paternally derived 15q11-13 region or the maternal uniparental disomy of chromosome 15 (mUPD(15)). In this study, we compared phenotypic differences between those patients whose disease was caused by microdeletion and those caused by mUPD(15). In addition, a comparison of the efficacy of growth hormone (GH) therapy between these two PWS genotypes was analyzed. METHODS: Fifty-three patients were diagnosed as having PWS based on molecular and cytogenetic analyses and clinical features. Data that included maternal age, birth weight, a feeding problem in the neonatal period, cryptorchidism, developmental delay or mental retardation, short stature, hypopigmentation, changes in height, weight, and body mass indexes (BMI) before and after GH treatment were obtained by a retrospective review of medical records. The data from the patients with microdeletion were compared with those from the patients with mUPD(15). RESULTS: Of the 53 patients with genetically confirmed PWS, 39 cases had microdeletion and 14 mUPD(15). Maternal ages were significantly higher in the mUPD(15) group, and hypopigmentation and a feeding problem in the neonatal period were more frequent in the microdeletion group. Growth hormone was administered to 20 patients [14 with microdeletion, 6 with mUPD(15)]. There were no differences between the two groups in height velocity, weight and height SDS, and BMI after GH therapy. CONCLUSION: Phenotype and genotype correlations were observed in Korean PWS patients, such as more advanced maternal ages in the mUPD(15) group and more feeding problems and hypopigmentations in the microdeletion group. Further long-term prospective studies are needed to correlate other aspects of the phenotypes.

Topiramate can reduce the number of episodic attacks in cyclic vomiting syndrome:a case report / 소아과

Cyclic vomiting syndrome (CVS) is a paroxysmal, recurrent vomiting disorder of unknown pathophysiology and target organ. It has been hypothesized that CVS shares the same mechanism as migraine. We describe here a 5-year-old boy with CVS characterized by episodic vomiting attacks. These recurrent vomiting episodes began at 3 years of age, occurred every month and lasted for 5 days at a time. At the time of admission, no abnormal physical or neurological findings were observed and laboratory findings, including brain MRI and endoscopic examination, revealed nothing specific. The vomiting episodes were self-limited but recurrent and severely interrupted his daily life. When this patient was treated with topiramate, he showed a marked increase of symptom-free periods.

Clinicopathologic features and prognosis of childhood IgA nephropathy / 소아과

PURPOSE: Clinicopathological features were investigated to clarify the outcome and prognostic indicators for patients with IgA nephropathy in Korean children. METHODS: We reviewed the outcomes of 61 patients in whom IgA nephropathy was diagnosed before the age of 15 years from 1991 to 2005 and followed-up at least for one year. All patients were confirmed by renal biopsy. RESULTS: After mean follow-up of 5.2 years from onset, 24 patients of 61 (39.3%) were in clinical remission at the last examination. Thirty patients (49.2%) had hematuria or mild proteinuria ( or =1 g/m2/d), and two (3.3%) had chronic renal failure. By univariate analysis, initial presentation at onset and Haas classification were less concordant with outcome. Hypertension during follow-up, rather than hypertension at presentation, was significantly correlated with outcomes (P<0.01). Sixty percent of patients who had more than 20% of glomerular sclerosis or crescent progressed to severe proteinuria or chronic renal failure, as compared with 7.1% of those who did not (P<0.01). CONCLUSION: Prognosis of childhood IgA nephropathy had a relatively benign course during a mean follow-up of 5.2 years. Persistent hypertension during follow-up and more than 20% of glomerular sclerosis or crescent were strong predictors of a progressive course of IgA nephropathy. A new histologic classification according to characteristics of childhood IgA nephropathy must be established to assess prognosis. Further efforts should be made to understand the prognosis of IgA nephropathy through long-term follow-up.

A cephalometric study on the vertical and anteroposterior dysplasia of the craniofacial skeleton / 대한치과교정학회지

The purposes of the present study were to describe the vertical and anteroposterior facial dysplasia, and to identify morphologic differences associated with various facial patterns. Anteroposterior dysplasia was classified by traditional Angle's malocclusion classification and according to vertical relationships based on the SN-MP angle, facial pattern was subclassified to 3 vertical groups in each malocclusion group. Each vertical group composed of 20 samples and total 180 samples aged from 9 to 14 years. The results were as follows; 1. The skeletal differences that lead to disportionate lower facial height in vertical and anteroposterior facial dysplasia were closely related to mandibular morphology. 2. Hyperdivergent group, compared with hypodivergent group, demonstrated decrease of SNA and SNB and linguoversion of maxillary and mandibular central incisors in all malocclusion groups. 3. Irrespective of rotation of the jaws, Wits appraisal was a useful measurement in evaluation of relative anteroposterior relationship of maxilla and mandible. 4. As SN-MP angle increased, anterior facial height, especially lower anterior facial height, demonstrated significant increase and intermaxillary space also tended to increase. 5. The correlation coefficients of SN-MP angle and PTFH/ATFH demonstrated the highest value in all malocclusion groups.