Despite the established role of imatinib (IM) in chronic myelogenous leukemia (CML) in adults, there are few reports on its efficacy in children. In this study, we compared the outcomes of children with CML before and after the advent of IM-based treatment.
The study cohort consisted of 52 patients treated for CML at the Department of Pediatrics, The Catholic University of Korea from January 1995 to October 2010. Patients were divided and analyzed according to the preImatinib group (pre-IMG) and imatinib group (IMG).
Median age at diagnosis for the overall cohort (pre-IMG, n=27; IMG, n=25) was 9 years, with a median follow-up duration of survivors of 84 months. Except for 5 patients in the IMG, all were diagnosed in chronic phase (CP). The overall survival (OS) of patients diagnosed in CP was 45.7% and 89.7% for pre-IMG and IMG, respectively (P=0.025). The OS of hematopoietic stem cell transplantation (HSCT) recipients in the 2 groups was similar, but the OS of patients diagnosed in CP who did not receive HSCT was superior in IMG (91.7% vs. 16.7%, P=0.014). Of the 12 patients in IMG who remained on IM without HSCT, 2 showed disease progression, compared to 11 of 12 in pre-IMG. No difference was observed in the progression free survival (PFS) of matched donor HSCT recipients and IM-based treatment recipients.
Similar PFS of patients treated with IM and those who received matched donor HSCT underscore the potential of IM as effective first-line treatment in childhood CML.
Chronic myelogenous leukemia; Imatinib mesylate; Allogeneic transplantation; Children
In this study, we analyzed a cohort of children with chronic graft-versus-host disease (GvHD) according to the NIH consensus classification (NCC) in order to observe whether global assessment at diagnosis correlates with GvHD-specific endpoints. We then studied the clinical course of these patients, specifically with regards to episodes of GvHD exacerbation requiring treatment escalation.
Materials and Methods
Recipients of either allogeneic bone marrow transplantation (BMT) or peripheral blood stem cell transplantation (PBSCT) from January 2006 to August 2008 at the Department of Pediatrics, The Catholic University of Korea were evaluated for chronic GvHD, which was diagnosed according to the NCC. The course of chronic GvHD in these patients was then followed.
Of 59 evaluable patients, 23 developed chronic GvHD for a cumulative incidence of 39.3%. Upon multivariate analysis, previous acute GvHD (≥grade II) had a significant impact on chronic GvHD incidence. With a median duration of systemic treatment for chronic GvHD of 501 days, no significant relationship was found between initial global severity of chronic GvHD and either duration of immunosuppressive treatment or final clinical response to treatment. Fifteen patients (65%) experienced at least one episode of chronic GvHD exacerbation during the period of follow-up, with a median of four exacerbations in the subgroup of patients who experienced such events. Lung GvHD resulted in the highest number of exacerbations per diagnosed patient, followed by oral GvHD.
Analysis of this small cohort indicates that global assessment as proposed by the NCC may have limited correlations with GvHD-specific endpoints, possibly due to the favorable response of children to treatment.
Chronic GvHD; NIH consensus criteria; children
Childhood chronic myelogenous leukemia (CML) is a rare hematologic disease, with limited literature on the methods of treatment. Previously, allogeneic hematopoietic stem cell transplantation (HSCT) was considered the only curative treatment for this disease. Treatment with imatinib, a selective inhibitor of the BCR-ABL tyrosine kinase (TKI), has resulted in prolonged molecular response with limited drug toxicity. Imatinib is now implemented in the primary treatment regimen for children, but the paucity of evidence on its ability to result in permanent cure and the potential complications that may arise from long-term treatment with TKIs have prevented imatinib from superseding HSCT as the primary means of curative treatment in children. The results of allogeneic HSCT in children with CML are similar to those observed in adults; HSCT-related complications such as transplant-related mortality and graft-versus-host disease remain significant challenges. An overall consensus has been formed with regards to the need for HSCT in patients with imatinib resistance or those with advanced-phase disease. However, issues such as when to undertake HSCT in chronic-phase CML patients or how best to treat patients who have relapsed after HSCT are still controversial. The imatinib era calls for a reevaluation of the role of HSCT in the treatment of CML. Specific guidelines for the treatment of pediatric CML have not yet been formulated, underscoring the importance of prospective studies on issues such as duration of imatinib treatment, optimal timing of HSCT and the type of conditioning utilized, possible treatment pre- and post-HSCT, and the role of second-generation TKIs.
Chronic myelogenous leukemia; Children; Treatment; Imatinib; Transplantation; Tyrosine kinase inhibitors
Background and Objectives
Cardiovascular complications are the leading cause of morbidity and mortality in childhood cancer survivors. Hematopoietic stem cell transplantation (HSCT) is a curable therapy for pediatric cancer. However, changes in cardiac function in children after HSCT are not well known. We assessed left ventricular (LV) function in children after HSCT using speckle tracking echocardiography (STE).
Subjects and Methods
Forty consecutive patients with median age of 11.9 years (range, 1.5-16 years) who received HSCT for acute leukemia and had comprehensive echocardiography before and after (median 9.2 month) HSCT were included in this study. The LV function parameters including conventional tissue Doppler imaging (TDI) and STE data were collected from pre- and post-HSCT echocardiography. These data were compared to those of 39 age-matched normal controls.
Compared to normal controls, post HSCT patients had similar (p=0.06) LV ejection fraction. However, the following three LV function parameters were significantly decreased in post HSCT patients: rate-corrected velocity of circumferential fiber shortening (p=0.04), mitral inflow E velocity (p<0.001), and mitral septal annular E' velocity (p=0.03). The following four STE parameters were also significantly decreased in post HSCT patients: LV global circumferential systolic strain (p<0.01), strain rate (SR, p=0.01), circumferential diastolic SR (p<0.01), and longitudinal diastolic SR (p<0.001). There was no significant change in TDI or STE parameters after HSCT compared to pre-HSCT. Patients with anthracycline cumulative dose >400 mg/m2 showed significantly (p<0.05) lower circumferential systolic strain and circumferential diastolic SR.
Subclinical cardiac dysfunction is evident in children after HSCT. It might be associated with pre-HSCT anthracycline exposure with little effect of conditioning regimens. Serial monitoring of cardiac function is mandatory for all children following HSCT.
Childhood leukemia; Stem cell transplantation; Heart function; Speckle tracking; Echocardiography; Strain rate
Inherited bone marrow failure syndrome (IBMFS) encompasses a heterogeneous and complex group of genetic disorders characterized by physical malformations, insufficient blood cell production, and increased risk of malignancies. They often have substantial phenotype overlap, and therefore, genotyping is often a critical means of establishing a diagnosis. Current advances in the field of IBMFSs have identified multiple genes associated with IBMFSs and their pathways: genes involved in ribosome biogenesis, such as those associated with Diamond-Blackfan anemia and Shwachman-Diamond syndrome; genes involved in telomere maintenance, such as dyskeratosis congenita genes; genes encoding neutrophil elastase or neutrophil adhesion and mobility associated with severe congenital neutropenia; and genes involved in DNA recombination repair, such as those associated with Fanconi anemia. Early and adequate genetic diagnosis is required for proper management and follow-up in clinical practice. Recent advances using new molecular technologies, including next generation sequencing (NGS), have helped identify new candidate genes associated with the development of bone marrow failure. Targeted NGS using panels of large numbers of genes is rapidly gaining potential for use as a cost-effective diagnostic tool for the identification of mutations in newly diagnosed patients. In this review, we have described recent insights into IBMFS and how they are advancing our understanding of the disease's pathophysiology; we have also discussed the possible implications they will have in clinical practice for Korean patients.
Bone marrow failure syndromes; Fanconi anemia; Diamond-Blackfan anemia; Shwachman-Diamond syndrome; Severe congenital neutropenia
Varicella-zoster virus infection can lead to severe illness in immunocompromised patients. Further the mortality rate of disseminated varicella infection is extremely high particularly in immunocompromised children. We report a case of disseminated varicella infection in a child with acute lymphoblastic leukemia who was receiving chemotherapy, but was initially admitted with only for acute abdominal pain. The patient rapidly developed severe complications, including acute respiratory distress syndrome, acute hepatitis, disseminated intravascular coagulation, and encephalopathy. Acyclovir is a highly potent inhibitor of varicella-zoster virus infection. However, owing to rapid disease progression, it might not be sufficient to control a disseminated varicella infection, especially in immunocompromised patients. Immunoglobulin neutralize virus invasion and suppress viremia, acting synergistically with acyclovir. In this case, early administration of acyclovir and a high-dose of immunoglobulin, combined with mechanical respiratory support, proved adequate for treatment of this severe illness.
Varicella-zoster virus; Acyclovir; Immunoglobulin
Diamond-Blackfan anemia (DBA) is a congenital bone marrow failure syndrome characterized by hypoproliferative anemia, associated physical malformations and a predisposition to cancer. DBA has been associated with mutations and deletions in the large and small ribosomal protein genes, and genetic aberrations have been detected in ∼50–60% of patients. In this study, nine Korean DBA patients were screened for mutations in eight known DBA genes (RPS19, RPS24, RPS17, RPS10, RPS26, RPL35A, RPL5 and RPL11) using the direct sequencing method. Mutations in RPS19, RPS26 and RPS17 were detected in four, two and one patient, respectively. Among the mutations detected in RPS19, two mutations were novel (c.26T>A, c.357-2A>G). For the mutation-negative cases, array-CGH analysis was performed to identify copy-number variations, and no deletions involving the known DBA gene regions were identified. The relative mRNA expression of RPS19 estimated using real-time quantitative PCR analysis revealed two- to fourfold reductions in RPS19 mRNA expression in three patients with RPS19 mutations, and p53 protein expression analysis by immunohistochemistry showed variable but significant nuclear staining in the DBA patients. In conclusion, heterozygous mutations in the known DBA genes RPS19, RPS26 and RPS17 were detected in seven out of nine Korean DBA patients. Among these patients, RPS19 was the most frequently mutated gene. In addition, decreased RPS19 mRNA expression and p53 overexpression were observed in the Korean DBA patients, which supports the hypothesis that haploinsufficiency and p53 hyperactivation represent a central pathway underlying the pathogenesis of DBA.
array-CGH; Diamond-Blackfan anemia; ribosomal protein; sequencing
Background and Objectives
Survivors of pediatric hematopoietic stem cell transplantation (HSCT) are at risk for developing hypertension. The objectives of this study are to evaluate the prevalence and risk factors of early onset hypertension during the engraftment period after HSCT.
Subjects and Methods
This is a retrospective study of 157 consecutive patients (mean age at HSCT: 9.1±5.1 years) who underwent HSCT for acute myeloid leukemia (n=47), acute lymphoblastic leukemia (n=43), severe aplastic anemia (n=41), and other reasons (n=26). Blood pressure data were collected at five time points: 0, 7, 14, 21, and 28 days after HSCT. Hypertension was defined as having systolic and/or diastolic blood pressure ≥95th percentile according to age, gender, and height. To analyze the risk factors related to hypertension, data, including patients' demographic and transplant characteristics, were reviewed.
Hypertension developed in 59 patients (38%), among whom 12 (7.6%) required long term therapy. Thirty-two (54%) patients had systolic and diastolic, 8 (14%) had only systolic, and 19 (32%) had only diastolic hypertension. Younger age, acute graft-versus-host disease, sinusoidal obstruction syndrome, treatment with antifungal agent, and greater increase in serum creatinine (Cr) levels were associated with hypertension. Multivariate analysis showed that younger age at HSCT and greater increase in serum Cr level were independent risk factors for hypertension.
Prevalence of hypertension during immediate post-HSCT period is high, especially in younger children. A greater increase in Cr after HSCT was significantly associated with hypertension. Further study is needed to elucidate long-term cardiovascular complications in pediatric HSCT survivors.
Hematopoletic stem cell transplantation; Child; Incidence; Blood pressure; Hypertension
The risk of osteoporosis or osteopenia is known to increase after childhood cancer treatment. The purpose of this study was to evaluate patterns of bone mineral density (BMD) and to identify factors related to the decreased BMD in childhood cancer survivors. We studied 78 patients (34 boys, 44 girls) treated for childhood cancer. Twenty (25.7%) patients had lumbar BMD (LBMD) standard deviation score (SDS) lower than -2. Nineteen (24.4%) patients had femur neck BMD (FNBMD) SDS lower than -2. The patients treated with hematopoietic stem cell transplantation had lower LBMD SDS (-1.17 ± 1.39 vs -0.43 ± 1.33, P = 0.025). The risk of having LBMD SDS < -2 was higher in the patients treated with glucocorticoid (GC) for graft-versus-host disease (GVHD) (36.6% vs 13.5%; odds ratio [OR], 3.7; P = 0.020). In multivariate logistic regression analysis, longer duration of GC treatment for GVHD (OR, 1.12; 95% confidence interval [CI], 1.05-1.20) and lower body mass index (BMI) SDS (OR, 0.59; 95% CI, 0.36-0.95) were associated with decreased LBMD SDS. These findings suggest that prolonged GC use and reduction in BMI are risk factors for decreased BMD in childhood cancer survivors. Anticipatory follow-up and appropriate treatment are necessary, especially for the patients with risk factors.
Bone Density; Neoplasms; Glucocorticoids
The use of cyclosporine and mini-dose methotrexate (MTX) is a common strategy for graft-versus-host disease (GVHD) prophylaxis in allogeneic transplants. We investigated whether patients who receive fewer than the planned MTX doses are at increased risk for GVHD.
The study cohort included 103 patients who received allogeneic transplants at the Department of Pediatrics of The Catholic University of Korea College of Medicine, from January 2010 to December 2011. MTX was administered on days 1, 3, 6, and 11 after transplant at a dose of 5 mg/m2 each. Within the cohort, 76 patients (74%) received all 4 doses of MTX [MTX(4) group], while 27 patients (26%) received 0-3 doses [MTX(0-3) group].
Although there was no difference in neutrophil engraftment between the 2 groups, platelet engraftment was significantly faster in the MTX(4) group (median, 15 days), compared to the MTX(0-3) group (median, 25 days; P=0.034). The incidence of grades II-IV acute GVHD was not different between the MTX(4) and MTX(0-3) groups (P=0.417). In the multivariate study, human leukocyte antigen mismatch was the most significant factor causing grades II-IV acute GVHD (P=0.002), followed by female donor to male recipient transplant (P=0.034). No difference was found between the MTX(4) and MTX (0-3) groups regarding grades III-IV acute GVHD, chronic GVHD, and disease-free survival.
Our results indicate that deviations from the full dose schedule of MTX for GVHD prophylaxis do not lead to increased incidence of either acute or chronic GVHD.
Methotrexate; Graft-versus-host disease; Prophylaxis
The purpose of this study was to evaluate short-term thyroid dysfunction and related risk factors in pediatric patients who underwent hematopoietic stem cell transplantation (HSCT) during childhood.
We studied 166 patients (100 boys and 66 girls) who underwent HSCT at the Catholic HSCT Center from January 2004 through December 2009. The mean age at HSCT was 10.0±4.8 years. Thyroid function of the patients was tested before and during 3 months of HSCT.
Out of 166 patients, 165 (99.4%) underwent allotransplantation. Acute graft-versus-host disease (GVHD, grades II to IV) developed in 76 patients. Conditioning regimens before HSCT include total body irradiation (n=57), busulfan (n=80), and reduced intensity (n=29). Forty-five (27.1%) had thyroid dysfunction during 3 months after HSCT (29 euthyroid sick syndrome [ESS], 6 subclinical hyperthyroidism, 4 subclinical hypothyroidism, 3 hypothyroxinemia, 2 overt hyperthyroidism, and 1 high T4 syndrome). In a univariate logistic regression analysis, age at HSCT (P=0.002) and acute GVHD (P=0.009) had statistically significant relationships with thyroid dysfunction during 3 months after HSCT. Also, in a univariate logistic regression analysis, ESS (P=0.014) showed a strong statistically significant association with mortality.
In our study 27.1% patients experienced thyroid dysfunction during 3 months after HSCT. Increase in age and acute GVHD may be risk factors for thyroid dysfunction during 3 months after HSCT. There was a significant association between ESS and mortality.
Hematopoietic stem cell transplantation; Thyroid dysfunction; Child; Graft-vs-host disease; Euthyroid sick syndrome
This study was performed to compare the clinical characteristics and antibiotic susceptibilities of viridans streptococcal bacteremia (VSB) between febrile neutropenic adults and children with hematologic malignancies.
The consecutive medical records of neutropenic patients with hematologic malignancies who were admitted to the Catholic Blood and Marrow Transplantation Center between April 2009 and July 2012, and who were subsequently diagnosed with VSB were reviewed retrospectively. A comparison was made between the clinical and laboratory characteristics of adults and pediatric patients and also between patients with cefepime susceptible or not susceptible VSB.
A total of 202 episodes (141 in adults, 61 in children) of VSB were identified. Among them, 26 (12.9%) cases had severe complications including four (2.0%) cases of death attributable to VSB. For antibacterial prophylaxis, most adults received ciprofloxacin (97.1%), but children more frequently received trimethoprim/sulfamethoxazole (86.9%). Oral mucositis (p = 0.005) and abdominal pain (p = 0.001) were found more frequently in adults, and cough was found more frequently in children (p = 0.004). The occurrence rates of severe complications and death attributable to VSB were not significantly different between adults and children. Susceptibility rate to cefepime was significantly higher in adults than children (85.7% vs. 66.1%, p = 0.002). However, in multivariate analysis, cefepime susceptibility had no impact on clinical outcome.
There was no significant difference in clinical outcome between adults and children with VSB despite a difference in cefepime susceptibility. Hence, different antibiotic treatment strategies may not be necessary.
Viridans streptococci; Bacteremia; Neutropenia; Fever
In children with acute leukemia, bone marrow genetic abnormalities (GA) have prognostic significance, and may be the basis for minimal residual disease monitoring. Since April 2007, we have used a multiplex reverse transcriptase-polymerase chain reaction tool (HemaVision) to detect of GA.
In this study, we reviewed the results of HemaVision screening in 270 children with acute leukemia, newly diagnosed at The Catholic University of Korea from April 2007 to December 2011, and compared the results with those of fluorescence in situ hybridization (FISH), and G-band karyotyping.
Among the 270 children (153 males, 117 females), 187 acute lymphoblastic leukemia and 74 acute myeloid leukemia patients were identified. Overall, GA was detected in 230 patients (85.2%). HemaVision, FISH, and G-band karyotyping identified GA in 125 (46.3%), 126 (46.7%), and 215 patients (79.6%), respectively. TEL-AML1 (20.9%, 39/187) and AML1-ETO (27%, 20/74) were the most common GA in ALL and AML, respectively. Overall sensitivity of HemaVision was 98.4%, with false-negative results in 2 instances: 1 each for TEL-AML1 and MLL-AF4. An aggregate of diseasesspecific FISH showed 100% sensitivity in detection of GA covered by HemaVision for actual probes utilized. G-band karyotype revealed GA other than those covered by HemaVison screening in 133 patients (49.3%). Except for hyperdiplody and hypodiploidy, recurrent GA as defined by the World Health Organizationthat were not screened by HemaVision, were absent in the karyotype.
HemaVision, supported by an aggregate of FISH tests for important translocations, may allow for accurate diagnosis of GA in Korean children with acute leukemia.
HemaVision; Acute leukemia; Child; Fluorescence in situ hybridization; Karyotype
Wiskott-Aldrich syndrome (WAS) is an inherited X-linked disorder. The WAS gene is located on the X chromosome and undergoes mutations, which affect various domains of the WAS protein, resulting in recurrent infection, eczema, and thrombocytopenia. However, the clinical features and severity of the disease vary according to the type of mutations in the WAS gene. Here, we describe the case of a 4-year-old boy with a history of marked thrombocytopenia since birth, who presented with recurrent herpes simplex infection and late onset of eczema. Examination of his family history revealed that older brother, who died from intracranial hemorrhage, had chronic idiopathic thrombocytopenia. Therefore, we proceeded with genetic analysis and found a new deletion mutation in the WAS gene: c.858delC (p.ser287Leufs*21) as a hemizygous form.
Wiskott-Aldrich syndrome; Mutation; Sequence deletion
Lymphocyte subset recovery is an important factor that determines the success of hematopoietic stem cell transplantation (HSCT). Temporal differences in the recovery of lymphocyte subsets and the factors influencing this recovery are important variables that affect a patient's post-transplant immune reconstitution, and therefore require investigation.
The time taken to achieve lymphocyte subset recovery and the factors influencing this recovery were investigated in 59 children who had undergone HSCT at the Department of Pediatrics, The Catholic University of Korea Seoul St. Mary's Hospital, and who had an uneventful follow-up period of at least 1 year. Analyses were carried out at 3 and 12 months post-transplant. An additional study was performed 1 month post-transplant to evaluate natural killer (NK) cell recovery. The impact of pre- and post-transplant variables, including diagnosis of Epstein-Barr virus (EBV) DNAemia posttransplant, on lymphocyte recovery was evaluated.
The lymphocyte subsets recovered in the following order: NK cells, cytotoxic T cells, B cells, and helper T cells. At 1 month post-transplant, acute graft-versus-host disease was found to contribute significantly to the delay of CD16+/56+ cell recovery. Younger patients showed delayed recovery of both CD3+/CD8+ and CD19+ cells. EBV DNAemia had a deleterious impact on the recovery of both CD3+ and CD3+/CD4+ lymphocytes at 1 year post-transplant.
In our pediatric allogeneic HSCT cohort, helper T cells were the last subset to recover. Younger age and EBV DNAemia had a negative impact on the post-transplant recovery of T cells and B cells.
Lymphocyte subset; Immune reconstitution inflammatory syndrome; Hematopoietic stem cell transplantation; Child
Improved survival of patients with childhood acute lymphoblastic leukemia (ALL) has drawn attention to the potential for late consequences of previous treatments among survivors, including metabolic syndrome. In this study, we evaluated changes in 3 parameters, namely, random blood glucose, body mass index (BMI), and Z score for BMI (Z-BMI), in children with ALL during chemotherapy and after completion of treatment.
Patients newly diagnosed with ALL from January, 2005 to December, 2008 at Saint Mary's Hospital, The Catholic University of Korea, who completed treatment with chemotherapy only were included (n=107). Random glucose, BMI, and Z-BMI were recorded at 5 intervals: at diagnosis, before maintenance treatment, at completion of maintenance treatment, and 6 and 12 months after completion of maintenance treatment. Similar analyses were conducted on 2 subcohorts based on ALL risk groups.
For random glucose, a paired comparison showed significantly lower levels at 12 months post-treatment compared to those at initial diagnosis (P<0.001) and before maintenance (P<0.001). The Z-BMI score was significantly higher before maintenance than at diagnosis (P<0.001), but decreased significantly at the end of treatment (P<0.001) and remained low at 6 months (P<0.001) and 12 months (P<0.001) post-treatment. Similar results were obtained upon analysis of risk group-based subcohorts.
For a cohort of ALL patients treated without allogeneic transplantation or cranial irradiation, decrease in random glucose and Z-BMI after completion of chemotherapy does not indicate future glucose intolerance or obesity.
Acute lymphoblastic leukemia; Random glucose; Body mass index; Child
The survival rate for childhood acute lymphoblastic leukemia (ALL) has improved significantly. However, overall prognosis for the 20 to 25% of patients who relapse is poor, and allogeneic hematopoietic stem cell transplantation (HSCT) offers the best chance for cure. In this study, we identified significant prognostic variables by analyzing the outcomes of allogeneic HSCT in ALL patients in second complete remission (CR).
Fifty-three ALL patients (42 men, 79%) who received HSCT in second CR from August 1991 to February 2009 were included (26 sibling donor HSCTs, 49%; 42 bone marrow transplantations, 79%). Study endpoints included cumulative incidence of acute and chronic graft-versus-host disease (GVHD), relapse, 1-year transplant-related mortality (TRM), disease-free survival (DFS), and overall survival (OS).
Cumulative incidences of acute GVHD (grade 2 or above) and chronic GVHD were 45.3% and 28.5%, respectively. The estimated 5-year DFS and OS for the cohort was 45.2±6.8% and 48.3±7%, respectively. Only donor type, i.e., sibling versus unrelated, showed significant correlation with DFS in multivariate analysis (P=0.010). The rates of relapse and 1 year TRM were 28.9±6.4% and 26.4±6.1%, respectively, and unrelated donor HSCT (P=0.002) and HLA mismatch (P=0.022) were significantly correlated with increased TRM in univariate analysis.
In this single institution study spanning more than 17 years, sibling donor HSCT was the only factor predicting a favorable result in multivariate analysis, possibly due to increased TRM resulting from unrelated donor HSCT.
Acute lymphoblastic leukemia; Child; Second complete remission; Transplantation
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.
Neuroblastoma; High-dose Chemotherapy; Transplantation, Autologous