OBJECTIVETo investigate the clinical features and outcomes of neuroblastoma (NB) children aged above 5 years, and to provide a theoretical basis for improving prognosis.

METHODSA retrospective analysis was performed for the clinical data of 54 previously untreated NB children, and their clinical features and outcome were analyzed. The Kaplan-Meier method was used for survival analysis.

RESULTSAmong the 54 children, there were 36 boys and 18 girls, and all of them had stage 3 or 4 NB. Of all the children, 41 (41/54, 76%) had retroperitoneal space-occupying lesions, 10 (10/54, 18%) had mediastinal space-occupying lesions, 2 (2/54, 4%) had intraspinal space-occupying lesions, and 1 (1/54, 2%) had pelvic space-occupying lesions. At the end of the follow-up, 30 children (30/54, 56%) survived, among whom 23 (77%) achieved disease-free survival (9 achieved complete remission after chemotherapy for recurrence), 6 (20%) achieved partial remission of tumor (all of them received chemotherapy again due to recurrence), and 1 (3%) experienced progression (with progression after chemotherapy again due to recurrence); 24 children (44%) died, among whom 22 died after chemotherapy again due to recurrence and 2 died of multiple organ failure during the first treatment. According to the Kaplan-Meier survival analysis, the mean survival time was 53.8 months, and the children with stage 3 NB had a significantly higher overall survival rate than those with stage 4 NB (80% vs 53%; p<0.01). The children with recurrence had a significantly lower mean survival time than those without recurrence (51.68 months vs 62.57 months; p<0.01).

CONCLUSIONSOlder children often have late-stage NB, but standard treatment can improve their outcomes.

Adolescent ; Child ; Child, Preschool ; Combined Modality Therapy ; Female ; Humans ; Male ; Neuroblastoma ; mortality ; therapy ; Retrospective Studies

OBJECTIVETo investigate the clinical features, treatment modalities and the prognosis of advanced neuroblastoma in children.

METHODSThe medical records of 63 children with stage III or IV neuroblastoma from January 1996 to December 2005 were retrospectively reviewed. Sixty patients were treated by tumor resection and (or) chemotherapy and (or) radiation. Fourteen out of the 60 patients received another autologous peripheral blood stem cell transplantation.

RESULTSOf the 63 patients with advanced neuroblastoma, the male/female ratio was 2.7:1 and the median age at diagnosis was 4 years old. Most of the initial symptoms included pyrexia, abdominal pain, abdominal mass, and leg or articular pain. Primary tumor sites were adrenal (38%), retroperitoneal (35%), mediastinal (17%), pelvic (6%) and cervical (2%). The sites of metastasis at diagnosis included local (41%) and (or) distant (37%) lymph nodes, bone marrow (60%), bone (46%) and liver (16%). The median survival time of the 63 patients was 32.7 months. The 2-year survival rate was 44.3%. Statistical analysis demonstrated that unfavorable survival prognostic factors were the following: age > 1 year at diagnosis (P < 0.05); serum neuro-specific enolase > 100 mg/L (P < 0.05); serum lactic dehydrogenase > 1500 U/L (P < 0.01); serum ferritin >150 mg/L (P < 0.05). The overall survival period of the patients was prolonged through total resection of the primary tumor (P < 0.05). Intensive chemotherapy in combination with autologous peripheral blood stem cell transplantation could also result in a prolonged overall survival period (P < 0.01).

CONCLUSIONSNeuroblastoma with advanced stages often presents with various clinical manifestations and has a poor prognosis. It is beneficial to improve the prognosis of neuroblastoma through an early diagnosis and a comprehensive therapy including total resection of the primary tumor, autologous peripheral blood stem cell transplantation and intensive chemotherapy.

Adolescent ; Child ; Child, Preschool ; Combined Modality Therapy ; Female ; Humans ; Infant ; Male ; Neuroblastoma ; mortality ; therapy ; Prognosis

Autologous stem cell transplantation (ASCT) for the treatment of high-risk neuroblastoma (NBL) is an accepted method for restoring bone marrow depression after high dose chemotherapy. We retrospectively analyzed eighty eight cases of NBL that underwent ASCT following marrow ablative therapy at 12 transplant centers of the Korean Society of Pediatric Hematology-Oncology between January 1996 and September 2000. Seventy nine children were of stage IV NBL and 9 were of stage III with N-myc amplification. Various cytoreductive regimens were used. However, the main regimen was 'CEM' consisting of carboplatin, etoposide and melphalan, and this was used in 66 patients. Total body irradiation was also added in 36 patients for myeloablation. To reduce tumor cell contamination, stem cell infusions after CD34+ cell selection were performed in 16 patients. Post-transplantation therapies included the second transplantation in 18 patients, interleukin2 therapy in 45, 13-cis retinoic acid in 40, 131-meta-iodobenzylguanidine in 4, conventional chemotherapy in 11, and local radiotherapy in 8. Twenty two patients died, sixty six patients are surviving 1 to 46 months after ASCT (median followup duration, 14.5 months). Although the follow-up period was short and the number of patients small, we believe that ASCT might improve the survival rate in high-risk NBL.
Adolescent ; Child ; Child, Preschool ; Combined Modality Therapy ; Female ; Human ; Korea ; Male ; Myeloablative Agonists/therapeutic use ; Neuroblastoma/mortality ; Neuroblastoma/pathology ; Neuroblastoma/therapy* ; Retrospective Studies ; Stem Cell Transplantation* ; Survival Rate ; Transplantation Conditioning ; Transplantation, Autologous ; Treatment Outcome

The efficacy of tandem high-dose chemotherapy and autologous stem cell rescue (HDCT/ASCR) was investigated in patients with high-risk neuroblastoma. Patients over 1 yr of age who were newly diagnosed with stage 4 neuroblastoma from January 2000 to December 2005 were enrolled in The Korean Society of Pediatric Hematology-Oncology registry. All patients who were assigned to receive HDCT/ASCR at diagnosis were retrospectively analyzed to investigate the efficacy of single or tandem HDCT/ASCR. Seventy and 71 patients were assigned to receive single or tandem HDCT/ASCR at diagnosis. Fifty-seven and 59 patients in the single or tandem HDCT group underwent single or tandem HDCT/ASCR as scheduled. Twenty-four and 38 patients in the single or tandem HDCT group remained event free with a median follow-up of 56 (24-88) months. When the survival rate was analyzed according to intent-to-treat at diagnosis, the probability of the 5-yr event-free survival+/-95% confidence intervals was higher in the tandem HDCT group than in the single HDCT group (51.2+/-12.4% vs. 31.3+/-11.5%, P=0.030). The results of the present study demonstrate that the tandem HDCT/ASCR strategy is significantly better than the single HDCT/ASCR strategy for improved survival in the treatment of high-risk neuroblastoma patients.
Adolescent ; Child ; Child, Preschool ; Combined Modality Therapy/mortality ; Drug Therapy/*mortality ; Female ; Humans ; Infant ; Korea/epidemiology ; Longitudinal Studies ; Male ; Neuroblastoma/*mortality/*therapy ; Prevalence ; Risk Assessment/methods ; Risk Factors ; Stem Cell Transplantation/*mortality ; Survival Analysis ; Survival Rate ; Treatment Outcome

Disease relapse after autologous peripheral blood stem cell transplantation (APBSCT) is the main cause of treatment failure in high-risk neuroblastoma (NBL). To reduce relapse, various efforts have been made such as CD34+ selection and double APBSCT. Here the authors reviewed the clinical features and outcomes of highrisk NBL patients and analyzed their survival. The medical records of 36 patients with stage III or IV NBL who underwent APBSCT at Seoul National University Children's Hospital between May 1996 and May 2004 were reviewed. Total 46 APBSCTs were performed in 36 patients. Disease free survival (DFS) and overall survival of all patients were 47.7% and 68.8%, respectively. The patients were allocated to three groups according to the APBSCT type. The DFS of CD34+ non-selected single APBSCT patients (N=13), CD34+ selected single APBSCT patients (N=14), and CD34+ selected double APBSCT patients (N=9) were 55.6%, 40.6%, and 50.0%, respectively, which were not significantly different. Thus the survival was not found to be affected by CD34+ selection or transplantation number. To improve long-term survival, various efforts should be made such as chemotherapy dose intensification, more effective tumor purging, and control of minimal residual disease via the use of differentiating and immune-modulating agents.
Antigens, CD34/metabolism ; Child ; Child, Preschool ; Disease-Free Survival ; Female ; Hematopoietic Stem Cell Mobilization ; Humans ; Infant ; Korea/epidemiology ; Male ; Neuroblastoma/mortality/*therapy ; Peripheral Blood Stem Cell Transplantation/adverse effects/mortality ; Prognosis ; Retrospective Studies ; Survival Rate ; Transplantation Conditioning ; Transplantation, Autologous

High-dose chemotherapy and autologous stem cell rescue (HDCT/ASCR) was applied to improve the prognosis of patients with high-risk stage 3 neuroblastoma. From January 1997 to December 2006, 28 patients were newly diagnosed as stage 3 neuroblastoma. Nine of 11 patients with N-myc amplification and 5 of 17 patients without N-myc amplification (poor response in 2 patients, persistent residual tumor in 2 and relapse in 1) underwent single or tandem HDCT/ASCR. Patients without high-risk features received conventional treatment modalities only. While 8 of 9 patients underwent single HDCT/ASCR and the remaining one patient underwent tandem HDCT/ASCR during the early study period, all 5 patients underwent tandem HDCT/ASCR during the late period. Toxicities associated with HDCT/ASCR were tolerable and there was no treatment-related mortality. While the tumor relapsed in two of eight patients in single HDCT/ASCR group, all six patients in tandem HDCT/ASCR group remained relapse free. The 5-yr event-free survival (EFS) from diagnosis, in patients with N-myc amplification, was 71.6+/-14.0%. In addition, 12 of 14 patients who underwent HDCT/ASCR remained event free resulting in an 85.1+/-9.7% 5-yr EFS after the first HDCT/ASCR. The present study demonstrates that HDCT/ASCR may improve the survival of patients with high-risk stage 3 neuroblastoma.
Adolescent ; Adult ; Child ; Combined Modality Therapy ; Female ; Granulocyte Colony Stimulating Factor, Recombinant/therapeutic use ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Neuroblastoma/drug therapy/mortality/*therapy ; *Peripheral Blood Stem Cell Transplantation ; Proto-Oncogene Proteins c-myc/analysis/genetics ; Survival Rate ; Tomography, X-Ray Computed ; Transplantation, Autologous

OBJECTIVEThe aim of the paper was to improve the prognosis of neuroblastoma (NB) stage III and IV in children through the comprehensive therapy including chemotherapy, delayed tumor resection, autologous stem cell transplantation (ASCT) and inducing differentiation and to analyze the factors affecting the prognosis.

METHODSNewly diagnosed neuroblastoma patients seen from Oct.1998 to Dec.2003 were divided into high, medium and low risk groups depending on clinical stage and age. Comprehensive protocol included accurate staging, delayed and/or second tumor resection for stage III and IV patients, chemotherapy of different intensity mainly composed of cell cycle nonspecific drugs and 13-cis-retinoid for inducing cell differentiation. ASCT was given at the end of therapy for high risk group.

RESULTForty-five patients, 6 months to 11 years of age, 32 males and 13 females, were analyzed. Of them, 15 were found to have the tumor in adrenal gland, 12 had the tumor extended to the retro-peritoneal space, while in 15 cases the tumor was beside the spinal column in chest and in 3 the tumor was located in other places. Nine cases had stage I, 1 case had stage II, 8 cases had III, 26 cases had stage IV and 1 case had stage IVs of the tumor. Depending on the age and stage of the tumor, 26 cases were aligned into high risk protocol, 10 into medium risk and 9 into low risk groups. Thirty nine cases were treated as planned. Eleven of them received ASCT including 2 cases who received second ASCT. Of the thirty-nine patients, 31 achieved complete remission (CR) and 8 partial remission (PR) after surgery and/or chemotherapy. During up to 21 months median following up period (range 14 to 64 months), 24 cases (62%) kept CR (median 22 months) and 4 survived with stable disease. The survival rate (SR) was 72%. Eleven cases died of relapse and disease progression. No death occurred from treatment complication. Statistical analysis showed that the age older than 18 months, and stage III and IV of the tumor were the factors predicting poor prognosis (P = 0.04 and 0.003, respectively). Patients who had the tumor originated from the retroperitoneal space, who had incomplete tumor resection, and those who did not receive ASCT had poorer prognosis, but the differences were not significant (P = 0.092, 0.55 and 0.60, respectively).

CONCLUSIONThe comprehensive protocol seemed to be reasonable. Age older than 18 months, and stage III and IV were the factors suggesting poor prognosis. The origin of the tumor, completeness of tumor resection, and use of ASCT had no significant impact on the prognosis.

Age Factors ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Chemotherapy, Adjuvant ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Infant ; Male ; Neoplasm Recurrence, Local ; prevention & control ; surgery ; therapy ; Neoplasm Staging ; Neuroblastoma ; diagnosis ; drug therapy ; mortality ; pathology ; surgery ; therapy ; Prognosis ; Remission Induction ; methods ; Retrospective Studies ; Severity of Illness Index ; Survival Rate ; Time Factors ; Transplantation, Autologous ; methods ; Treatment Outcome