Keun Wook Bae

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

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.

Early changes in SOFA score as a prognostic factor in pediatric oncology patients requiring mechanical ventilatory support.

Purpose To evaluate whether changes in outcome prediction scores during the first 72 hours after admission to a pediatric intensive care unit (PICU) are more predictive of outcome than single assessments at admission in pediatric oncology patients requiring mechanical ventilatory support for more than 3 days. Patients and Methods The medical records of 54 consecutive pediatric oncology patients requiring mechanical ventilation over 72 hours in the PICU of the Asan Medical Center, Seoul, Korea, between January 2006 and December 2008, were retrospectively reviewed. Results Although both initial Sequential Organ Failure Assessment (SOFA) score and change in SOFA score (Δ-SOFA) correlated well with mortality, Δ-SOFA score showed a significantly stronger correlation (P<0.001) and a larger area under the receiver operating characteristic curve than did initial SOFA score. Patients with positive and negative Δ-SOFA scores showed statistically significant differences in mortality (18.5% vs. 88.2%, P<0.001). In addition, early changes in respiratory parameters, such as PaO2/FiO2 (P/F) ratio, oxygenation index (OI), and ventilation index (VI), evaluated serially during the first 3 days, also correlated with mortality. Patients showing improvement in these respiratory parameters displayed significantly lower mortality than did patients with worsening of these parameters (P<0.01). Conclusions Serial evaluation of SOFA score during the first few days after PICU admission was a good predictor of prognosis in pediatric oncology patients mechanically ventilated over 3 days. Independent of initial SOFA score, Δ-SOFA score during the first 72 hours closely correlated with outcome. Early changes in respiratory parameters, such as P/F ratio, OI, and VI, may also provide valuable prognostic information in such patients.

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

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.

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

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.