Sung Chul Won

Posterior reversible encephalopathy syndrome in childhood with hematologic/oncologic diseases.

Posterior reversible encephalopathy syndrome (PRES) is a clinico-neuroradiologic disease entity represented by characteristic magnetic resonance image (MRI) findings of subcortical/cortical hyperintensity in T2-weighted sequences, more often observed in parieto-occipital lobes, accompanied by clinical neurologic alterations. PRES is a rare central nervous system complication in childhood hematologic-oncologic patients and shows very different neurologic symptoms between patients, from numbness on extremities to generalized seizure. The etiology of PRES was not well known until these days. In this study, 8 patients with PRES were reviewed, retrospectively. There were 4 patients with acute lymphocytic leukemia, 1 with aplastic anemia, and 3 with solid tumors (1 patient each for neuroblastoma, Ewing sarcoma, and osteosarcoma). Allogeneic stem cell transplantation was performed in 2 patients. Immunosuppressive agents such as tacrolimus and cyclosporine A were used in 3 patients. One neuroblastoma patient was in immediate postoperative status. All patients experienced seizure attacks of different types and showed typical MRI findings. Follow-up MRIs revealed significant improvements. From this review, we might consider chemotherapy and surgery as additive causes for PRES other than immunosuppressive agents. Therefore, careful examination of the patients receiving chemotherapy and surgery was needed to find out this uncommon but good prognostic complication.

Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation in Young Children with Atypical Teratoid/Rhabdoid Tumor of the Central Nervous System

The feasibility and effectiveness of tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT) were evaluated in children younger than 3 yr of age with atypical teratoid/rhabdoid tumors (ATRT). Tandem HDCT/autoSCT was administered following six cycles of induction chemotherapy. Radiotherapy (RT) was administered if the tumor relapsed or progressed, otherwise, it was administered after 3 yr of age. Tumors relapsed or progressed during induction chemotherapy in 5 of 9 patients enrolled; 3 of these 5 received tandem HDCT/autoSCT as a salvage treatment. One patient died from sepsis during induction chemotherapy. The remaining 3 patients proceeded to tandem HDCT/autoSCT; however, 2 of these patients showed tumor relapse/progression after tandem HDCT/autoSCT. All 7 relapses/progressions occurred at primary sites even in patients with leptomeningeal seeding. Toxicities during tandem HDCT/autoSCT were manageable. A total of 5 patients were alive with a median follow-up of 20 (range 16-70) months from diagnosis. Four of 5 patients who received RT after relapse/progression are alive. The probability of overall survival at 3 yr from diagnosis was 53.3% ± 17.3%. Our tandem HDCT/autoSCT is feasible; however, early administration of RT prior to tandem HDCT/autoSCT should be considered to improve the outcome after tandem HDCT/autoSCT.

Autologous peripheral blood stem cell transplantation in children with non-Hodgkin’s lymphoma: a report from the Korean society of pediatric hematology-oncology

Recent development of stratified chemotherapeutic regimens has rapidly improved the survival rate of non-Hodgkin’s lymphoma (NHL) of childhood. Despite these improvements, the outcome for children with recurrent or refractory NHL remains dismal. We explored the use of high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (HDC/PBSCT) for children with either refractory or recurrent NHL, and we evaluated various factors influencing outcome of HDC/PBSCT. Thirty-three patients underwent HDC/PBSCT in 11 institutes were enrolled. All patients had refractory or recurrent NHL. Sex, stage at diagnosis, histologic subtype (lymphoblastic, Burkitt’s, and large-cell lymphoma), LDH level at diagnosis, disease status at transplantation, and preparative regimens for HDC/PBSCT were explored. In regard to the patients, six had Burkitt’s lymphoma, 13 had lymphoblastic lymphoma, and 14 had large-cell lymphoma. The 2-year event-free survival (EFS) was 59.1±9.3%. The EFS for Burkitt’s, lymphoblastic, and large-cell lymphoma was 66.7±27.2, 50.5±14.8, and 82.1±11.7%, respectively. In comparison with lymphoblastic and non-lymphoblastic lymphoma, the relative risk for lymphoblastic lymphoma was higher than the others (P=0.037). EFS between anaplastic large-cell and diffuse large-cell lymphoma was 100 and 55.6±24.9%, respectively (P=0.106). Status at transplantation was the most predictive factor for the survival after HDC/PBSCT (EFS for CR 70.8±9.5% vs non-CR 20.0±17.9%, P=0.008). Transplantation-related complications were minimal, and infection was the most prevalent complication. HDC/PBSCT is considered applicable to recurrent or refractory pediatric NHL patients safely and it could replace conventional chemotherapy. In this study, children with CR status at the time of HDC/PBSCT showed higher survival rate. However, refractory or recurrent lymphoblastic lymphoma patients showed dismal results. Therefore, new therapeutic modalities may be needed for this group of NHL patients.

Efficacy and safety of deferiprone (Ferriprox), an oral iron-chelating agent, in pediatric patients

Background Iron overload is a predictable and life-threatening complication in patients dependent on the regular transfusion of RBCs. The aims of this study were to investigate the efficacy and safety of deferiprone in a variety of pediatric hematologic and/or oncologic patients with a high iron overload. Methods Seventeen patients (age: 1.1-20.4 years; median: 10.6 years) from 7 hospitals who were treated with deferiprone from 2006 to 2009 were enrolled in this study. Medical records of enrolled patients were reviewed retrospectively. Results Serum ferritin levels were 4,677.8±1,130.9 µg/L at baseline compared to 3,363.9±1,149.7 µg/L at the end of deferiprone treatment (P=0.033). Only 1 patient developed neutropenia as a complication. Conclusion Deferiprone treatment is relatively safe for pediatric patients suffering from various hematologic and oncologic diseases that require RBC transfusions as part of treatment. However, the potential development of critical complications such as agranulocytosis and/or neutropenia remains a concern.

FEASIBILITY OF SEQUENTIAL HIGH-DOSE CHEMOTHERAPY IN ADVANCED PEDIATRIC SOLID TUMORS

The purpose of this study was to evaluate the feasibility and tumor response of 3 cycles of sequential high-dose chemotherapy (HDCT) in advanced pediatric solid tumor patients. Medical records of 11 children who underwent 2 consequent courses of reduced conditioning HDCT followed by final HDCT with autologous HSC infusion were reviewed in a retrospective manner. Each median time to an absolute neutrophil count > 0.5 × 109/L was 12, 13, and 12 days. Major toxic reactions were fever, infection, and vomiting. One patient experienced transplantation-related mortality. Nine patients showed complete and partial responses to the therapy at 6 months follow-up after final HDCT. Finally, 6 patients are alive without evidence of disease at median follow-up of 24 months. Even though it is a preliminary result, the authors think that this treatment could be a feasible treatment option for advanced pediatric solid tumor patients.