ABSTRACT
BACKGROUND: Tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) and incorporation of 131I-metaiodobenzylguanidine (131I-MIBG) treatment have shown positive outcomes in high-risk neuroblastoma. However, more optimized treatment strategies are still needed. PROCEDURE: The NB-2014 study was a nonrandomized, prospective trial that examined survival outcomes in metastatic high-risk neuroblastoma patients using response-adapted consolidation therapy. We used post-induction residual 123I-MIBG status at metastatic sites as a treatment response marker. Patients achieving complete resolution of MIBG uptake at metastatic sites underwent a reduced first HDCT/auto-SCT with a 20% dose reduction in HDCT. After the first HDCT/auto-SCT, patients with remaining MIBG uptake received dose-escalated (18 mCi/kg) 131I-MIBG treatment. In contrast, those with complete resolution of MIBG at metastatic sites received a standard dose (12 mCi/kg) of 131I-MIBG. We compared survival and toxicity outcomes with a historical control group from the NB-2009. RESULTS: Of 65 patients treated, 63% achieved complete resolution of MIBG uptake at metastatic sites following induction chemotherapy, while 29% of patients still had MIBG uptake at metastatic sites after the first HDCT/auto-SCT. The 3-year event-free survival (EFS) and overall survival (OS) rates were 68.2% ± 6.0% and 86.5% ± 4.5%, respectively. Compared to NB-2009, EFS was similar (p = .855); however, NB-2014 had a higher OS (p = .031), a lower cumulative incidence of treatment-related mortality (p = .036), and fewer acute and late toxicities. CONCLUSIONS: Our results suggest that response-adaptive consolidation therapy based on chemotherapy response at metastatic sites facilitates better treatment tailoring, and appears promising for patients with metastatic high-risk neuroblastoma.
Subject(s)
3-Iodobenzylguanidine , Consolidation Chemotherapy , Neuroblastoma , Humans , Neuroblastoma/therapy , Neuroblastoma/mortality , Neuroblastoma/pathology , Neuroblastoma/drug therapy , Female , Male , Child, Preschool , Infant , Child , 3-Iodobenzylguanidine/therapeutic use , Prospective Studies , Survival Rate , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Adolescent , Follow-Up Studies , Transplantation, Autologous , Prognosis , Hematopoietic Stem Cell Transplantation , RadiopharmaceuticalsABSTRACT
We reviewed the medical records of five patients with T-B+NK- severe combined immunodeficiency (SCID) who received minimal dose allogeneic hematopoietic cell transplantation (HCT) (total nucleated cell count (TNC) lower than 1.0 × 108/kg). Patients were administered a median of 5.0 mL of bone marrow or peripheral blood without conditioning (in four) or with anti-thymocyte globulin alone (in one). Three patients received HCT from a matched sibling donor, one from unrelated donor, and one from familial mismatched donor. The median TNC and CD34+ cells were 0.54 (0.29-0.84) × 108/kg and 0.61 (0.35-0.84) × 106/kg, respectively. Engraftment was achieved in all. Total T cell, CD4+ cell, and CD8+ cell recovery was obtained within a year in four, and immunoglobulin replacement was discontinued in all. All patients survived, exhibiting stable donor chimerism. We obtained sufficient therapeutic effects with minimal dose transplantation without intensive conditioning in patients with T-B+NK- SCID.
Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Severe Combined Immunodeficiency , Humans , Severe Combined Immunodeficiency/therapy , Transplantation Conditioning , CD4-Positive T-Lymphocytes , Killer Cells, NaturalABSTRACT
BACKGROUND: Patients with relapsed osteosarcoma have poor treatment outcomes. High-dose chemotherapy with autologous stem cell transplantation (HDCT/ASCT) has been used in several high-risk malignant solid tumors; however, few studies have evaluated their role in treating osteosarcoma. We evaluated the effectiveness of HDCT/ASCT in relapsed pediatric osteosarcoma cases. PROCEDURE: We retrospectively reviewed the medical records of 40 patients diagnosed with and treated for relapsed osteosarcoma at Asan Medical Center and Samsung Medical Center from January 1996 to July 2019. RESULTS: The median age of this cohort was 13.4 years (range: 6.1-18.2). The cohort's 5-year overall survival (OS) was 51.0% ± 0.1% during a median follow-up period of 67.5 months. Twenty-five patients (62.5%) achieved complete remission (CR) with salvage treatment, and the 5-year OS was 82.4% ± 0.1%, whereas none of the remaining 15 patients who did not achieve CR survived (p < .0001). Of the 25 CR cases, 15 underwent subsequent HDCT/ASCT. We compared the effect of HDCT/ASCT among patients who achieved CR. There were no significant differences in the 5-year OS outcomes between patients who did and did not receive HDCT/ASCT (83.9% ± 0.1%, 13/15 vs. 80.0% ± 0.1%, 8/10, respectively; p = .923). CONCLUSION: To our knowledge, we report the first comparative cohort study that proved HDCT/ASCT does not significantly improve survival outcomes in relapsed osteosarcoma. Achievement of CR remains the most crucial factor for good survival outcomes.
Subject(s)
Hematopoietic Stem Cell Transplantation , Osteosarcoma , Humans , Child , Adolescent , Retrospective Studies , Cohort Studies , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Transplantation, Autologous , Disease-Free Survival , Stem Cell TransplantationABSTRACT
BACKGROUND: Data on the status of long-term follow-up (LTFU) care for childhood cancer survivors (CCSs) in Korea is lacking. This study was conducted to evaluate the current status of LTFU care for CCSs and relevant physicians' perspectives. METHODS: A nationwide online survey of pediatric hematologists/oncologists in the Republic of Korea was undertaken. RESULTS: Overall, 47 of the 74 board-certified Korean pediatric hematologists/oncologists currently providing pediatric hematology/oncology care participated in the survey (response rate = 63.5%). Forty-five of the 47 respondents provided LTFU care for CCSs five years after the completion of primary cancer treatment. However, some of the 45 respondents provided LTFU care only for CCS with late complications or CCSs who requested LTFU care. Twenty of the 45 respondents oversaw LTFU care for adult CCSs, although pediatric hematologists/oncologists experienced more difficulties managing adult CCSs. Many pediatric hematologists/oncologists did not perform the necessary screening test, although CCSs had risk factors for late complications, mostly because of insurance coverage issues and the lack of Korean LTFU guidelines. Regarding a desirable LTFU care system for CCSs in Korea, 27 of the 46 respondents (58.7%) answered that it is desirable to establish a multidisciplinary CCSs care system in which pediatric hematologists/oncologists and adult physicians cooperate. CONCLUSION: The LTFU care system for CCS is underdeveloped in the Republic of Korea. It is urgent to establish an LTFU care system to meet the growing needs of Korean CCSs, which should include Korean CCSs care guidelines, provider education plans, the establishment of multidisciplinary care systems, and a supportive national healthcare policy.
Subject(s)
Cancer Survivors , Neoplasms , Oncologists , Physicians , Child , Adult , Humans , Republic of KoreaABSTRACT
Cytomegalovirus (CMV) infection remains an important cause of morbidity and mortality post cord blood transplantation (CBT). It has been suggested that the graft-versus-host disease (GVHD) and immunosuppressants have an impact on CMV infection. This study evaluated the incidence, outcomes, and risk factors of CMV infection, while focusing on GVHD and the use of immunosuppressants, in 103 children who had received CBT. Among the patients, 92.2% were positive for CMV serology, while CMV antigenemia was observed in 68.9% and CMV disease developed in 26.2%. CMV enterocolitis was the most common, followed by retinitis and pneumonia. Patients with positive CMV serology and grade II to IV GVHD were independently associated with CMV antigenemia. Recurrent CMV antigenemia was observed significantly more frequently in patients with extensive chronic GVHD. Patients with CMV disease showed significantly worse overall survival, relapse-free survival, and non-relapse mortality than those without CMV disease. In conclusion, CMV infection is common post-CBT in countries with a high rate of CMV seropositivity in the general population and is related to worse outcomes. GVHD severity is associated with the development and recurrence of CMV infection. Thus, efforts need to be made to prevent CMV infection in children post-CBT.
Subject(s)
Cytomegalovirus Infections/etiology , Fetal Blood/transplantation , Graft vs Host Disease/complications , Immunosuppressive Agents/therapeutic use , Adolescent , Adult , Child , Child, Preschool , Cytomegalovirus/isolation & purification , Female , Graft vs Host Disease/etiology , Humans , Immunosuppressive Agents/adverse effects , Infant , Male , Retrospective Studies , Risk Factors , Survival Analysis , Young AdultABSTRACT
BACKGROUND: The implication of residual metaiodobenzylguanidine (MIBG)-positive disease in the era of tandem high-dose chemotherapy (HDCT) with autologous stem cell transplantation (auto-SCT) has not yet been established in neuroblastoma. Moreover, most published studies have not evaluated the long-term prognosis of patients with residual MIBG-positive disease following treatment completion. Therefore, we investigated the prognostic significance of residual MIBG-positive disease at each treatment phase and after treatment completion. METHODS: We assessed MIBG scans labeled with either iodine-123 (123 I) or 131 I from 150 patients with MIBG-avid and high-risk neuroblastoma enrolled in the NB-2004, -2009, and -2014 trials at postinduction, posttandem HDCT/auto-SCT, and completion of treatment. RESULTS: The residual MIBG-positive disease at postinduction and posttandem HDCT/auto-SCT evaluation was highly correlated with the risk of progression. However, at treatment completion, there was no significant difference in survival and risk of progression between patients with residual MIBG-positive disease and MIBG-negative patients. Patients with persistent MIBG-positive disease at the end of treatment were more likely to have indolent tumor characteristics, such as favorable histology at diagnosis, lower incidence of MYCN amplification, and slow response to chemotherapy. CONCLUSION: Residual MIBG-positive disease during treatment predicted unfavorable outcomes for patients with high-risk neuroblastoma, even under tandem HDCT/auto-SCT. However, persistent MIBG uptake at the completion of all treatments may not always indicate an active disease.
Subject(s)
Hematopoietic Stem Cell Transplantation , Neuroblastoma , 3-Iodobenzylguanidine , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Follow-Up Studies , Humans , Infant , Neoplasm, Residual/drug therapy , Neuroblastoma/drug therapy , Neuroblastoma/therapy , Stem Cell Transplantation , Transplantation, AutologousABSTRACT
BACKGROUND: Although survival rate among patients with non-high-risk neuroblastoma is excellent, a gross residual tumor (GRT) is often present at the end of treatment. However, reliable data do not exist on the relevance of a GRT for the risk of progression and the role of adjuvant therapy for patients with GRT. METHODS: A retrospective review of 131 patients with non-high-risk neuroblastoma who underwent chemotherapy was performed. GRT was defined as >1 cm3 residual soft tissue density on end-of-chemotherapy scans. Progression-free survival (PFS) and overall survival (OS) rates were compared between patients with GRT and those without GRT. A proportional hazards model was also used to assess the effects of GRT and adjuvant therapies, including radiation and isotretinoin therapy on outcomes. RESULTS: GRT was found in 52 (40%) patients in the study cohort. Correlation was not found between GRT and outcomes (PFS; p = .954, OS; p = .222). In multivariable analysis, GRT remained a nonsignificant predictor of outcome after adjusting for confounders. Local radiation and isotretinoin therapy did not affect outcome for patients with GRT. However, within GRT subgroups, the degree of volume reduction, as well as absolute residual volume in the primary tumor after induction treatment, were significantly associated with outcomes. CONCLUSION: GRT in non-high-risk neuroblastoma may not indicate active disease that requires additional treatment. However, risk of progression is increased in patients with GRT whose response to treatment was less prominent, thus adjuvant therapy should be reserved only for those patients.
Subject(s)
Neuroblastoma , Disease Progression , Disease-Free Survival , Humans , Isotretinoin , Neoplasm Staging , Neoplasm, Residual/pathology , Neuroblastoma/drug therapy , Neuroblastoma/pathology , Prognosis , Retrospective Studies , Treatment OutcomeABSTRACT
PURPOSE: Pegteograstim (Neulapeg) is a recombinant human granulocyte colony-stimulating factor conjugated with methoxy-maleimide-polyethylene glycol. We conducted a single-arm study investigating its safety and noninferiority to conventional filgrastim in children and adolescents. MATERIALS AND METHODS: Patients younger than 21 years with solid tumors were eligible for the study. Pegteograstim was administered on day 7 of the fourth chemotherapy cycle. Toxicities were monitored, and the change in absolute neutrophil count was compared with that of the historic control (conventional filgrastim). This trial was registered at ClinicalTrials.gov as NCT02787876. RESULTS: Thirty-two patients were enrolled. Adverse events possibly related to pegteograstim were musculoskeletal pain (n=3), skin nodule (n=1), paroxysmal cough (n=1), urticaria (n=2), rash (n=1), and itching (n=1). These adverse events were all grade 1 or 2. Duration of neutropenia (ANC<500/µL) was shorter in the pegteograstim group compared with the historic control (median 6.5 vs. 10 d, P=0.004). The time from day 0 to neutrophil recovery (ANC>500/µL) was shorter in the pegteograstim group (median 15 vs. 18 d, P=0.003). CONCLUSIONS: Pegteograstim is safe and shows comparable efficacy to conventional filgrastim in children and adolescents. Randomized controlled trials are needed to confirm its safety and efficacy.
Subject(s)
Antineoplastic Agents , Neoplasms , Neutropenia , Recombinant Proteins , Adolescent , Antineoplastic Agents/adverse effects , Child , Filgrastim/therapeutic use , Granulocyte Colony-Stimulating Factor , Humans , Neoplasms/drug therapy , Neutropenia/chemically induced , Neutropenia/drug therapy , Polyethylene Glycols/adverse effects , Recombinant Proteins/adverse effectsABSTRACT
BACKGROUND: Recent genomic studies identified four discrete molecular subgroups of medulloblastoma (MB), and the risk stratification of childhood MB in the context of subgroups was refined in 2015. In this study, we investigated the effect of molecular subgroups on the risk stratification of childhood MB. METHODS: The nCounter® system and a customized cancer panel were used for molecular subgrouping and risk stratification in archived tissues. RESULTS: A total of 44 patients were included in this study. In clinical risk stratification, based on the presence of residual tumor/metastasis and histological findings, 24 and 20 patients were classified into the average-risk and high-risk groups, respectively. Molecular subgroups were successfully defined in 37 patients using limited gene expression analysis, and DNA panel sequencing additionally classified the molecular subgroups in three patients. Collectively, 40 patients were classified into molecular subgroups as follows: WNT (n = 7), SHH (n = 4), Group 3 (n = 8), and Group 4 (n = 21). Excluding the four patients whose molecular subgroups could not be determined, among the 17 average-risk group patients in clinical risk stratification, one patient in the SHH group with the TP53 variant was reclassified as very-high-risk using the new risk classification system. In addition, 5 out of 23 patients who were initially classified as high-risk group in clinical risk stratification were reclassified into the low- or standard-risk groups in the new risk classification system. CONCLUSION: The new risk stratification incorporating integrated diagnosis showed some discrepancies with clinical risk stratification. Risk stratification based on precise molecular subgrouping is needed for the tailored treatment of MB patients.
Subject(s)
Cerebellar Neoplasms , Medulloblastoma , Cerebellar Neoplasms/diagnosis , Cerebellar Neoplasms/genetics , Humans , Medulloblastoma/diagnosis , Medulloblastoma/genetics , Risk Assessment , Risk FactorsABSTRACT
Chronic myeloid leukemia (CML) is rare in children and accounts for ≤15% of all myeloid leukemia cases. When we initiated this study with nilotinib, imatinib was the only tyrosine kinase inhibitor indicated for pediatric patients with Philadelphia chromosome-positive (Ph+) CML in chronic phase (CP); alternative treatment options were needed, particularly for patients who developed resistance or intolerance (R/I) to imatinib. This phase 2 study enrolled pediatric patients with either Ph+ CML-CP R/I to imatinib or dasatinib or newly diagnosed Ph+ CML-CP. Data presented are from analyses with minimum follow-up of up to 24 cycles (1 cycle is 28 days). Fifty-nine patients with Ph+ CML-CP were enrolled, and 58 were treated (R/I, n = 33; newly diagnosed, n = 25). Major molecular response (MMR) rate at cycle 6 in the R/I cohort was 39.4% (primary end point); 57.6% of patients achieved or maintained MMR and 81.8% achieved or maintained complete cytogenetic response (CCyR) by 24 cycles. In patients with newly diagnosed disease, rates of MMR by cycle 12 and CCyR at cycle 12 were 64.0% each (primary end points); by cycle 24, cumulative MMR and CCyR rates were 68.0% and 84.0%, respectively. The safety profile of nilotinib in pediatric patients was generally comparable with the known safety profile in adults, although cardiovascular events were not observed in this study, and hepatic laboratory abnormalities were more frequent; no new safety signals were identified. In summary, nilotinib demonstrated efficacy and a manageable safety profile in pediatric patients with Ph+ CML-CP. This trial was registered at www.clinicaltrials.gov as #NCT01844765.
Subject(s)
Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Philadelphia Chromosome , Pyrimidines/administration & dosage , Adolescent , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/blood , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis , Male , Pyrimidines/adverse effectsABSTRACT
BACKGROUND: The optimal conditioning regimen in cord blood transplantation (CBT) needs to be determined. This study aimed to identify the impact of conditioning regimen on the outcome of CBT in children with acute leukemia. METHODS: Medical records of patients with acute leukemia who received CBT were retrospectively reviewed. RESULTS: A total of 71 patients were allocated into 2 groups; patients who received total body irradiation 10 Gy, cyclophosphamide 120 mg/kg, and fludarabine 75 mg/m² were named as TCF group (n = 18), while the non-TCF group (n = 53) included patients conditioned with regimens other than the TCF regimen. All patients in the TCF group were successfully engrafted, while 22.6% in the non-TCF group (n = 12) failed to achieve donor-origin hematopoiesis (P = 0.028). The incidence of cytomegalovirus diseases was 5.6% in the TCF group and 30.2% in the non-TCF group (P = 0.029). The 5-year overall survival rates of the TCF and non-TCF groups were 77.8% and 44.2%, respectively (P = 0.017). CONCLUSION: Patients conditioned with the TCF regimen achieved better engraftment and survival rates, less suffering from cytomegalovirus disease. Our data suggest that the TCF regimen is a preferred option for CBT in children with acute leukemia.
Subject(s)
Antineoplastic Agents/therapeutic use , Cord Blood Stem Cell Transplantation/methods , Cyclophosphamide/therapeutic use , Immunosuppressive Agents/therapeutic use , Leukemia, Myeloid, Acute/surgery , Vidarabine/analogs & derivatives , Whole-Body Irradiation , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Retrospective Studies , Survival Rate , Transplantation Conditioning , Treatment Outcome , Vidarabine/therapeutic useABSTRACT
This corrects the article on p. e393 in vol. 35, PMID: 33258329.
ABSTRACT
Although long-term antiviral prophylaxis is recommended to prevent varicella zoster virus (VZV) infection in seropositive recipients of allogeneic and autologous (auto-) hematopoietic cell transplantation (HCT), studies of VZV infections in pediatric auto-HCT recipients are rare. This study aimed to investigate the incidence and characteristics of VZV infection in pediatric auto-HCT recipients and explore the risk factors of VZV infection and its effect on survival outcomes. This study included all pediatric patients who underwent auto-HCT at Samsung Medical Center, Seoul, Korea, between January 1998 and December 2013. Before 2006, short-term acyclovir prophylaxis was provided until neutrophil engraftment; thereafter, routine prophylaxis was not provided. Patients who developed either herpes zoster or chickenpox within 2 years from transplantation were identified, and a chart review was performed. A total of 413 recipients and 698 auto-HCTs were included. Sixty-one episodes of VZV infections were identified in 54 patients. Fourteen cases of VZV infection (23%; 14 of 61) occurred within 30 days after auto-HCT. The cumulative incidence of the first episode of VZV infection at 2 years after transplantation was 14% (95% confidence interval [CI], 7.9% to 22.8%) in all recipients and 9% (95% CI, 1.0 to 26.6) in VZV-seronegative patients. Notably, the VZV infection rate increased with age and the VZV infection rate in patients age 15 to 19 years was almost three times higher than in patients age 0 to 4 years (28% versus 10%; P = .003). However, there was no difference in the VZV infection rate between recipients of single auto-HCT and recipients of tandem auto-HCT. Two patients died of disseminated VZV infection. VZV infection is a considerable risk in auto-HCT recipients with or without short-term prophylaxis. Universal antiviral prophylaxis might be considered, particularly in older children, regardless of VZV serologic results. To our knowledge, this is the largest study of VZV infection in pediatric auto-HCT recipients reported to date.
Subject(s)
Chickenpox , Hematopoietic Stem Cell Transplantation , Herpes Zoster , Varicella Zoster Virus Infection , Adolescent , Adult , Antiviral Agents/therapeutic use , Chickenpox/drug therapy , Child , Child, Preschool , Hematopoietic Stem Cell Transplantation/adverse effects , Herpes Zoster/drug therapy , Herpes Zoster/epidemiology , Herpes Zoster/etiology , Herpesvirus 3, Human , Humans , Infant , Infant, Newborn , Republic of Korea , Retrospective Studies , Varicella Zoster Virus Infection/drug therapy , Young AdultABSTRACT
BACKGROUND: NUDT15 and TPMT variants are strong genetic determinants of thiopurine-induced hematological toxicity that results in therapeutic failure in pediatric acute lymphoblastic leukemia (ALL). However, many patients with both wild-type (WT) NUDT15 and TPMT still suffer from thiopurine toxicity and therapeutic failure. METHODS: Whole-exome sequencing was done for discovery (N = 244) and replication (N = 76) cohorts. Age- and sex-adjusted multiple regression analyses of both WT patients were performed to identify (p < 0.01, N = 188 for discovery) and validate (p < 0.05, N = 52 for replication) candidate variants for the tolerated last-cycle 6-mercaptopurine (6-MP) dose intensity percentage (DIP). Both independent and additive effects of the candidate variants on well-known NUDT15 and TPMT were evaluated by multigene prediction models. RESULTS: Among the 12 candidate variants from the discovery phase, the rs3821169 variant of the gene encoding Cysteine-Rich Transmembrane BMP Regulator 1 (CRIM1) was successfully replicated (p < 0.05). It showed high interethnic variability with an impressively high allele frequency in East Asians (T = 0.255) compared to Africans (0.001), Americans (0.02), Europeans (0.009), and South Asians (0.05). Homozygote carriers of the CRIM1 rs3821169 variant (N = 12, 5%) showed significantly lower last-cycle 6-MP DIPs in the discovery, replication, and combined cohorts (p = 0.025, 0.013, and 0.001, respectively). The traditional two-gene model (NUDT15 and TPMT) for predicting 6-MP DIP < 25% was outperformed by the three-gene model that included CRIM1, in terms of the area under the receiver operating characteristic curve (0.734 vs. 0.665), prediction accuracy (0.759 vs. 0.756), sensitivity (0.636 vs. 0.523), positive predictive value (0.315 vs. 0.288), and negative predictive value (0.931 vs. 0.913). CONCLUSIONS: The CRIM1 rs3821169 variant is suggested to be an independent and/or additive genetic determinant of thiopurine toxicity beyond NUDT15 and TPMT in pediatric ALL.
Subject(s)
Neutropenia , Pyrophosphatases , Bone Morphogenetic Protein Receptors , Child , Homozygote , Humans , Mercaptopurine/adverse effects , Methyltransferases/genetics , Pyrophosphatases/geneticsABSTRACT
OBJECTIVE: This study aims to explore prognostic factors for high-risk neuroblastoma patients with response failure to tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT). METHODS: Survival outcomes were compared according to characteristics at initial diagnosis, at relapse/progression, and after relapse/progression in patients who experienced relapse/progression after tandem HDCT/auto-SCT from 2006 to 2018. RESULTS: Forty-nine patients experienced relapse/progression after tandem HDCT/auto-SCT during the study period: 43 received salvage treatment and 30 underwent allogeneic SCT (allo-SCT) after reinduction treatment. Although all six patients who did not undergo salvage treatment died, 13 of the 43 patients who did remain alive. The 3-year probabilities of event-free survival (EFS) and overall survival (OS) from initial relapse/progression among the 49 patients were 14.4% ± 5.2% and 21.2% ± 6.4%, respectively. A higher neuron-specific enolase (NSE) level (>24 ng/mL) at relapse/progression was an independent prognostic factor for worse OS. Nine of 30 patients who underwent allo-SCT remain alive, and the 3-year probabilities of EFS and OS from allo-SCT were 16.5% ± 7.2% and 21.6% ± 8.3%, respectively. A higher NSE level and no incorporation of high-dose 131 I-metaiodobenzylguanidine (HD-MIBG) treatment into allo-SCT were independent prognostic factors for worse EFS and OS after allo-SCT. CONCLUSION: The results suggest that a higher serum NSE level at relapse/progression is a predictor of worse prognosis in patients with response failure to tandem HDCT/auto-SCT, and that incorporation of HD-MIBG treatment into allo-SCT may improve outcomes.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/blood , Hematopoietic Stem Cell Transplantation/mortality , Induction Chemotherapy/mortality , Neoplasm Recurrence, Local/mortality , Neuroblastoma/mortality , Phosphopyruvate Hydratase/blood , Child, Preschool , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Male , Neoplasm Recurrence, Local/blood , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/therapy , Neuroblastoma/blood , Neuroblastoma/pathology , Neuroblastoma/therapy , Prognosis , Prospective Studies , Survival Rate , Transplantation, AutologousABSTRACT
BACKGROUND: Infants and very young children with malignant brain tumors have a poorer survival and a higher risk for neurologic deficits. The present study evaluated the feasibility and effectiveness of multimodal treatment including tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) in minimizing use of radiotherapy (RT) in very young children with non-metastatic malignant brain tumors. METHODS: Twenty consecutive patients younger than 3 years were enrolled between 2004 and 2017. Tandem HDCT/auto-SCT was performed after six cycles of induction chemotherapy. Local RT was administered only to patients with post-operative gross residual tumor at older than 3 years. Since September 2015, early post-operative local RT for patients with atypical teratoid/rhabdoid tumor or primitive neuroectodermal tumor was administered. RESULTS: All 20 enrolled patients underwent the first HDCT/auto-SCT, and 18 proceeded to the second. Two patients died from toxicity during the second HDCT/auto-SCT, and four patients experienced relapse/progression (one localized and three metastatic), three of whom remained alive after salvage treatment including RT. A total of 17 patients remained alive at a median 7.8 (range, 2.5-5.7) years from diagnosis. Nine survivors received no RT, six survivors received local RT alone, and two survivors who experienced metastatic relapse after tandem HDCT/auto-SCT received both local and craniospinal RT. The 5-year overall, event-free, and craniospinal RT-free survival rates were 85.0% ± 8.0%, 70.0% ± 10.2%, and 75.0% ± 9.7%, respectively. Neuroendocrine and neurocognitive functions evaluated 5 years after tandem HDCT/auto-SCT were acceptable. CONCLUSION: Our results suggest that non-metastatic malignant brain tumors in very young children could be treated with multimodal therapy including tandem HDCT/auto-SCT while minimizing RT, particularly craniospinal RT.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Brain Neoplasms/drug therapy , Brain Neoplasms/mortality , Brain Neoplasms/pathology , Brain Neoplasms/radiotherapy , Carboplatin/administration & dosage , Child, Preschool , Craniospinal Irradiation , Etoposide/administration & dosage , Female , Hearing Loss/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Induction Chemotherapy , Infant , Male , Neoplasm Recurrence, Local , Progression-Free Survival , Risk Factors , Salvage Therapy , Survival Rate , Thiotepa/administration & dosage , Transplantation, Autologous/adverse effectsABSTRACT
BACKGROUND: This study aimed to investigate the incidence and clinical significance of segmental chromosomal aberrations (SCAs) in Korean patients with neuroblastoma. METHODS: Patients diagnosed with neuroblastoma from 2012 to 2018 were included for retrospective review. Fluorescence in situ hybridization (FISH) was used to analyze four SCAs (MYCN amplification, 1p deletion, 11q deletion, and 17q gain). Clinical characteristics at diagnosis, early tumor response (reduction in primary tumor volume and neuron-specific enolase level after the first three cycles of chemotherapy), and survival rates were compared according to SCAs. RESULTS: Among 173 patients with FISH results, 92 (53.2%) had at least one of the four SCAs, while 25 (14.5%) had two co-aberrations, and eight (4.6%) had three co-aberrations. SCAs detected in our study were MYCN amplification (n = 17, 9.8%), 1p deletion (n = 26, 15.2%), 11q deletion (n = 44, 25.6%), and 17q gain (n = 46, 27.1%). Patients with MYCN amplification showed a better early response but a worse survival than those without (5-year overall survival: 46.2% ± 13.1% vs. 88.6% ± 3.4%). Furthermore, 1p deletion was associated with a better early response but a worse survival; however, it was not an independent factor for survival. We could not find any prognostic significance associated with 11q deletion or 17q gain. CONCLUSION: This is the first study investigating SCAs in Korean neuroblastoma patients. Prognostic significance of SCAs other than MYCN amplification was different from those reported in western countries. Further study with a larger cohort and longer follow-up is needed to confirm our findings.
Subject(s)
Chromosome Aberrations , Neuroblastoma/genetics , Adolescent , Child , Child, Preschool , Chromosomes, Human , Female , Gene Amplification , Humans , In Situ Hybridization, Fluorescence , Infant , Infant, Newborn , Male , Republic of Korea , Retrospective Studies , Young AdultABSTRACT
BACKGROUND: Hereditary hemolytic anemia (HHA) is a rare disease characterized by premature red blood cell (RBC) destruction due to intrinsic RBC defects. The RBC Disorder Working Party of the Korean Society of Hematology established and updated the standard operating procedure for making an accurate diagnosis of HHA since 2007. The aim of this study was to investigate a nationwide epidemiology of Korean HHA. METHODS: We collected the data of a newly diagnosed pediatric HHA cohort (2007-2016) and compared this cohort's characteristics with those of a previously surveyed pediatric HHA cohort (1997-2006) in Korea. Each participant's information was retrospectively collected by a questionnaire survey. RESULTS: A total of 369 children with HHA from 38 hospitals distributed in 16 of 17 districts of Korea were investigated. RBC membranopathies, hemoglobinopathies, RBC enzymopathies, and unknown etiologies accounted for 263 (71.3%), 59 (16.0%), 23 (6.2%), and 24 (6.5%) of the cases, respectively. Compared to the cohort from the previous decade, the proportions of hemoglobinopathies and RBC enzymopathies significantly increased (P < 0.001 and P = 0.008, respectively). Twenty-three of the 59 hemoglobinopathy patients had immigrant mothers, mostly from South-East Asia. CONCLUSION: In Korea, thalassemia traits have increased over the past 10 years, reflecting both increased awareness of this disease and increased international marriages. The enhanced recognition of RBC enzymopathies is due to advances in diagnostic technique; however, 6.5% of HHA patients still do not have a clear diagnosis. It is necessary to improve accessibility of diagnosing HHA.
Subject(s)
Anemia, Hemolytic, Congenital/epidemiology , Adolescent , Anemia, Hemolytic, Congenital/diagnosis , Anemia, Hemolytic, Congenital Nonspherocytic/diagnosis , Anemia, Hemolytic, Congenital Nonspherocytic/epidemiology , Child , Child, Preschool , Female , Glucosephosphate Dehydrogenase Deficiency/diagnosis , Glucosephosphate Dehydrogenase Deficiency/epidemiology , Hemoglobinopathies/diagnosis , Hemoglobinopathies/epidemiology , Hemoglobins/genetics , Hospitals , Humans , Infant , Infant, Newborn , Male , Polymorphism, Genetic , Pyruvate Kinase/deficiency , Pyruvate Metabolism, Inborn Errors/diagnosis , Pyruvate Metabolism, Inborn Errors/epidemiology , Republic of Korea/epidemiology , Retrospective Studies , Surveys and QuestionnairesABSTRACT
BACKGROUND: Hodgkin's lymphoma (HL) constitutes 10%-20% of all malignant lymphomas and has a high cure rate (5-year survival, around 90%). Recently, interest has increased concerning preventing secondary complications (secondary cancer, endocrine disorders) in long-term survivors. We aimed to study the epidemiologic features and therapeutic outcomes of HL in children, adolescents, and young adults in Korea. METHODS: We performed a multicenter, retrospective study of 224 patients aged < 25 years diagnosed with HL at 22 participating institutes in Korea from January 2007 to August 2016. RESULTS: A higher percentage of males was diagnosed at a younger age. Nodular sclerosis histopathological HL subtype was most common, followed by mixed cellularity subtype. Eighty-one (36.2%), 101 (45.1%), and 42 (18.8%) patients were classified into low, intermediate, and high-risk groups, respectively. Doxorubicin, bleomycin, vinblastine, dacarbazine was the most common protocol (n = 102, 45.5%). Event-free survival rate was 86.0% ± 2.4%, while five-year overall survival (OS) rate was 96.1% ± 1.4%: 98.7% ± 1.3%, 97.7% ± 1.6%, and 86.5% ± 5.6% in the low, intermediate, and high-risk groups, respectively (P = 0.021). Five-year OS was worse in patients with B-symptoms, stage IV disease, high-risk, splenic involvement, extra-nodal lymphoma, and elevated lactate dehydrogenase level. In multivariate analysis, B-symptoms and extra-nodal involvement were prognostic factors for poor OS. Late complications of endocrine disorders and secondary malignancy were observed in 17 and 6 patients, respectively. CONCLUSION: This is the first study on the epidemiology and treatment outcomes of HL in children, adolescents, and young adults in Korea. Future prospective studies are indicated to develop therapies that minimize treatment toxicity while maximizing cure rates in children, adolescents, and young adults with HL.
Subject(s)
Antineoplastic Agents/therapeutic use , Hodgkin Disease/drug therapy , Adolescent , Antineoplastic Agents/adverse effects , Bleomycin/adverse effects , Bleomycin/therapeutic use , Child , Child, Preschool , Doxorubicin/adverse effects , Doxorubicin/therapeutic use , Endocrine System Diseases/etiology , Female , Hematopoietic Stem Cell Transplantation , Hodgkin Disease/mortality , Hodgkin Disease/pathology , Humans , Infant , Infant, Newborn , Male , Republic of Korea , Retrospective Studies , Survival Rate , Treatment Outcome , Vinblastine/adverse effects , Vinblastine/therapeutic use , Young AdultABSTRACT
There is great interest in using natural supplements to treat various medical conditions. In this study, we evaluated the anti-oxidative and stem cell differentiation effects of a mixture of vitamin D, Lactobacillus rhamnosus, ginger, curcumin, and Boswellia extract. The calcein acetoxymethyl assay after H2O2 treatment showed that combined natural supplement had an anti-oxidative effect. NS-J also increased calcium deposition, as shown by Alizarin Red S staining, indicating bone formation activity. The contents of type II collagen and glycosaminoglycans, which are biomarkers of cartilage, were higher in mesenchymal stem cells treated with combined natural supplement than in cells treated with individual ingredients of the formula. In mesenchymal stem cells treated with human osteoarthritis synovial fluids, combined natural supplement enhanced the expression of type II collagen and PPAR-δ, overcoming the anti-chondrogenic effect of inflammatory conditions. Combined natural supplement also inhibited Oil Red O staining in cells, which indicates inhibited adipogenesis. Thus, combined natural supplement, a formula comprising vitamin D, Lactobacillus rhamnosus, ginger, curcumin and Boswellia extract, reduced oxidative stress, enhanced osteogenesis and chondrogenesis, and inhibited adipogenesis in mesenchymal stem cells to a greater extent than the individual ingredients, indicating synergistic interaction. In addition, combined natural supplement increased the expression PPAR-δ, suggesting that these effects correlate with the PPAR-δ pathway.