Response to chemotherapy in juvenile myelomonocytic leukemia and its clinical implications for survival: A retrospective registry-based study of the Korean Pediatric Hematology-Oncology Group.

Juvenile myelomonocytic leukemia (JMML) is a life-threatening myeloproliferative neoplasm. The chemotherapeutic effect on survival remains unclear, and feasible standardized response criteria are yet to be established. We aimed to evaluate the chemotherapeutic response and its effect on survival in patients with JMML. A retrospective registry was reviewed for children diagnosed with JMML between 2000 and 2019. Response was assessed according to the criteria proposed by the International JMML Symposium in 2007 (criteria I) and the updated version in 2013 with its modifications (criteria II). A total of 73 patients were included in this study. Complete response (CR) rates were 46.6% and 28.8% using the criteria I and criteria II, respectively. A platelet count ≥ 40 × 109/L at diagnosis was associated with higher CR rates using the criteria II. Patients with criteria I-based CR had a better overall survival (OS) than those without CR (81.1% vs. 49.1% at 5 years). Patients with criteria II-based CR showed better OS (85.7% vs. 55.5% at 5 years) and event-free survival (EFS) (71.1% vs. 44.7% at 5 years) than those without CR. Additionally, a trend toward better EFS was observed in patients with criteria II-based CR than in those with criteria I-based CR but without criteria II-based CR (71.1% vs. 53.8% at 5 years). Chemotherapeutic response is associated with better survival outcomes. Along with splenomegaly, the addition of platelet count recovery, existence of extramedullary leukemic infiltration, and more stringent leukocyte counts to the response criteria allows for a more sensitive prediction of survival outcomes.

Epidemiologic and Clinical Outcomes of Pediatric Renal Tumors in Korea: A Retrospective Analysis of The Korean Pediatric Hematology and Oncology Group (KPHOG) Data.

PURPOSE: Renal tumors account for approximately 7% of all childhood cancers. These include Wilms tumor (WT), clear cell sarcoma of the kidney (CCSK), malignant rhabdoid tumor of the kidney (MRTK), renal cell carcinoma (RCC), congenital mesoblastic nephroma (CMN) and other rare tumors. We investigated the epidemiology of pediatric renal tumors in Korea. MATERIALS AND METHODS: From January 2001 to December 2015, data of pediatric patients (0-18 years) newly-diagnosed with renal tumors at 26 hospitals were retrospectively analyzed. RESULTS: Among 439 patients (male, 240), the most common tumor was WT (n=342, 77.9%), followed by RCC (n=36, 8.2%), CCSK (n=24, 5.5%), MRTK (n=16, 3.6%), CMN (n=12, 2.7%), and others (n=9, 2.1%). Median age at diagnosis was 27.1 months (range 0-225.5) and median follow-up duration was 88.5 months (range 0-211.6). Overall, 32 patients died, of whom 17, 11, 1, and 3 died of relapse, progressive disease, second malignant neoplasm, and treatment-related mortality. Five-year overall survival and event free survival were 97.2% and 84.8% in WT, 90.6% and 82.1% in RCC, 81.1% and 63.6% in CCSK, 60.3% and 56.2% in MRTK, and 100% and 91.7% in CMN, respectively (p < 0.001). CONCLUSION: The pediatric renal tumor types in Korea are similar to those previously reported in other countries. WT accounted for a large proportion and survival was excellent. Non-Wilms renal tumors included a variety of tumors and showed inferior outcome, especially MRTK. Further efforts are necessary to optimize the treatment and analyze the genetic characteristics of pediatric renal tumors in Korea.

Allogeneic hematopoietic cell transplantation in patients with juvenile myelomonocytic leukemia in Korea: a report of the Korean Pediatric Hematology-Oncology Group.

Juvenile myelomonocytic leukemia (JMML) is a life-threatening myeloproliferative neoplasm. This multicenter study evaluated the characteristics, outcomes, and prognostic factors of allogeneic hematopoietic cell transplantation (HCT) in recipients with JMML who were diagnosed between 2000 and 2019 in Korea. Sixty-eight patients were retrospectively enrolled-28 patients (41.2%) received HCT during 2000-2010 and 40 patients (58.8%) during 2011-2020. The proportion of familial mismatched donors increased from 3.6 to 37.5%. The most common conditioning therapy was changed from Busulfan/Cyclophosphamide-based to Busulfan/Fludarabine-based therapy. The 5-year probabilities of event-free survival (EFS) and overall survival (OS) were 52.6% and 62.3%, respectively. The 5-year incidence of transplant-related mortality was 30.1%. Multivariate analysis revealed that the proportion of hemoglobin F ≥ 40%, abnormal cytogenetics, and matched sibling donors were independent risk factors for a higher relapse rate. Patients whose donor chimerism was below 99% had a significantly higher relapse rate. Better OS and lower treatment-related mortality were observed in patients with chronic graft-versus-host disease (GVHD), whereas grade III or IV acute GVHD was associated with worse EFS. In conclusion, the number of transplant increased along with the increase in alternative donor transplants, nevertheless, similar results were maintained. Alternative donor transplantation should be encouraged.

Radiologic placement of Hickman catheters using intravenous sedation in pediatric patients under 20 kg.

ABSTRACT: Surgeons generally perform Hickman catheter insertion in children under general anesthesia. At times, it is difficult to perform procedures with an anesthesiologist for an interventional radiologist. Several diagnostic and therapeutic procedures are efficiently and safely conducted using intravenous (IV) sedation in children with a pediatrician. This study aims to evaluate the efficacy and safety of radiologically placed Hickman catheters using IV sedation in children under 20 kg.Fifty-nine catheters were inserted in 45 children under IV sedation. With continuous monitoring of vital signs, IV midazolam and ketamine were slowly infused by a pediatrician. Mean age and body weights were 3.2 years and 15.2 kg, respectively. Acute leukemia was the most common disease for the procedure (72.9%). The location of the catheter tip was evaluated by measuring the height of the thoracic vertebra.Technical success rate was 100%, and IV sedation-related complications did not occur. The right internal jugular vein was accessed for 51 catheters (86.4%), and the mean procedure time was 21.5 minutes. The 2 vertebral body units below the carina were the cavoatrial junction on a fluoroscopy image. Mean catheter life was 285 days, and catheters were removed post-treatment (35.6%). During follow-up, complications occurred in 29 cases (1.72 per 1000 catheter-days). Catheter-related infections were suspected in 4 patients (6.8%), with 1 positive result.Radiological Hickman catheter placement in children under 20 kg using IV sedation by pediatricians is effective and safe, with minimal complications. The carina is a landmark to estimate the cavoatrial junction in pediatric patients.

Clinical Characteristics and Treatment Outcomes of Childhood Acute Promyelocytic Leukemia in Korea: A Nationwide Multicenter Retrospective Study by Korean Pediatric Oncology Study Group.

PURPOSE: Acute promyelocytic leukemia (APL) is a rare disease in children and there are some different characteristics between children and adult. We aimed to evaluate incidence, clinical characteristics and treatment outcomes of pediatric APL in Korea. MATERIALS AND METHODS: Seventy-nine pediatric APL patients diagnosed from January 2009 to December 2016 in 16 tertiary medical centers in Korea were reviewed retrospectively. RESULTS: Of 801 acute myeloid leukemia children, 79 (9.9%) were diagnosed with APL. The median age at diagnosis was 10.6 years (range, 1.3 to 18.0). Male and female ratio was 1:0.93. Thirty patients (38.0%) had white blood cell (WBC) count greater than 10×109/L at diagnosis. All patients received induction therapy consisting of all-trans retinoic acid and chemotherapy. Five patients (6.6%) died during induction chemotherapy and 66 patients (86.8%) achieved complete remission (CR) after induction chemotherapy. The causes of death were three intracranial hemorrhage, one cerebral infarction, and one sepsis. Five patients (7.1%) suffered a relapse during or after maintenance chemotherapy. The estimated 4-year event-free survival and overall survival (OS) rates were 82.1%±4.4%, 89.7%±5.1%, respectively. The 4-year OS was significantly higher in patients with initial WBC < 10×109/L than in those with initial WBC ≥ 10×109/L (p=0.020). CONCLUSION: This study showed that the CR rates and survival outcomes in Korean pediatric APL patients were relatively good. The initial WBC count was the most important prognostic factor and most causes of death were related to serious bleeding in the early stage of treatment.

Influence of creatinine levels on survival in patients with veno-occlusive disease treated with defibrotide.

BACKGROUND/AIMS: Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is one of the most fatal complications of hematopoietic cell transplantation (HCT), and defibrotide is the only curative drug. We conducted this study to confirm the survival rate of VOD/SOS patients diagnosed in Korea and assess the efficacy of defibrotide. METHODS: Patients diagnosed with VOD/SOS after allogenic HCT between 2003 and 2020 were enrolled. We investigated day +100 survival rates and associated risk factors in patients who satisfied the modified Seattle criteria within 50 days of HCT. RESULTS: A total of 110 patients satisfied the modified Seattle criteria, of which 65.5% satisfied the Baltimore criteria. Thirty-seven patients were treated with defibrotide. The day +100 survival rate of the 110 patients was 65.3%. The survival rates in patients who did not meet the Baltimore criteria and in those who did were 86.8% and 53.7%, respectively (p = 0.001). The day +100 survival rate of patients treated with defibrotide was 50.5%. Among the patients receiving defibrotide, those whose creatinine levels were more than 1.2 times the baseline had a significantly lower survival rate at 26.7% (p = 0.014). On multivariate regression analysis, the hazard ratio of satisfaction of the Baltimore criteria was 4.54 (95% confidence interval [CI], 1.69 to 12.21; p = 0.003). In patients treated with defibrotide, the hazard ratio was 8.70 (95% CI, 2.26 to 33.45; p = 0.002), when creatinine was more than 1.2 times the baseline on administration. CONCLUSION: The day +100 survival rate was significantly lower when the Baltimore criteria were satisfied, and when there was an increase in creatinine at the time of defibrotide administration.

Genetic Confirmation and Identification of Novel Variants for Glanzmann Thrombasthenia and Other Inherited Platelet Function Disorders: A Study by the Korean Pediatric Hematology Oncology Group (KPHOG).

The diagnosis of inherited platelet function disorders (IPFDs) is challenging owing to the unavailability of essential testing methods, including light transmission aggregometry and flow cytometry, in several medical centers in Korea. This study, conducted by the Korean Pediatric Hematology Oncology Group from March 2017 to December 2020, aimed to identify the causative genetic variants of IPFDs in Korean patients using next-generation sequencing (NGS). Targeted exome sequencing, followed by whole-genome sequencing, was performed for diagnosing IPFDs. Of the 11 unrelated patients with suspected IPFDs enrolled in this study, 10 patients and 2 of their family members were diagnosed with Glanzmann thrombasthenia (GT). The variant c.1913+5G>T of ITGB3 was the most common, followed by c.2333A>C (p.Gln778Pro) of ITGB2B. Known variants of GT, including c.917A>C (p.His306Pro) of ITGB3 and c.2975del (p.Glu992Glyfs*), c.257T>C (p.Leu86Pro), and c.1750C>T (p.Arg584*) of ITGA2B, were identified. Four novel variants of GT, c.1451G>T (p.Gly484Val) and c.1595G>T (p.Cys532Phe) of ITGB3 and c.1184G>T (p.Gly395Val) and c.2390del (p.Gly797Valfs*29) of ITGA2B, were revealed. The remaining patient was diagnosed with platelet type bleeding disorder 18 and harbored two novel RASGRP2 variants, c.1479dup (p.Arg494Alafs*54) and c.813+1G>A. We demonstrated the successful application of NGS for the accurate and differential diagnosis of heterogeneous IPFDs.

Treatment Outcomes of Pediatric Acute Myeloid Leukemia in the Yeungnam Region: A Multicenter Retrospective Study of the Study Alliance of Yeungnam Pediatric Hematology-Oncology (SAYPH).

Acute myeloid leukemia (AML) is the second most common pediatric leukemia, with a survival rate of 70%. In this retrospective study, we evaluated the treatment outcomes of pediatric AML among 144 patients diagnosed between 2000 and 2013. After induction, 80.6% of patients achieved complete remission (CR). The 5-year overall survival (OS) and event-free survival (EFS) rates were 58.8 ± 4.2% and 49.8 ± 4.2%, respectively. Based on the response to induction therapy, the 5-year OS was 66.9 ± 5.7% in patients with CR (p < 0.001). Ninety-nine patients with CR after induction therapy were examined, and their 5-year OS and EFS were 66.4 ± 4.9% and 56.3 ± 5.1%, respectively. The 5-year OS rates according to treatment were 59.9 ± 7.4% in the chemotherapy group and 72.3 ± 6.3% in the hematopoietic stem cell transplantation (HSCT) group (p = 0.089). The EFS was 50.1 ± 7.4% in the chemotherapy group and 61.7 ± 6.9% in the HSCT group (p = 0.098). OS and EFS according to cytogenetics were insignificant. Our findings confirmed that the response to induction treatment was important for survival and HSCT had no significant survival benefits compared with those of chemotherapy. Moreover, many early induction deaths under the age of 2 years were observed.

Erratum: Correction of Affiliations in the Article "Clinical Characteristics and Treatment Outcomes in Children, Adolescents, and Young-adults with Hodgkin's Lymphoma: a KPHOG Lymphoma Working-party, Multicenter, Retrospective Study".

This corrects the article on p. e393 in vol. 35, PMID: 33258329.

Effectiveness and Safety of Clofarabine Monotherapy or Combination Treatment in Relapsed/Refractory Childhood Acute Lymphoblastic Leukemia: A Pragmatic, Non-interventional Study in Korea.

PURPOSE: Effectiveness and safety of clofarabine (one of the treatment mainstays in pediatric patients with relapsed/refractory acute lymphoblastic leukemia [ALL]) was assessed in Korean pediatric patients with ALL to facilitate conditional coverage with evidence development. MATERIALS AND METHODS: In this multicenter, prospective, observational study, patients receiving clofarabine as mono/combination therapy were followed up every 4-6 weeks for 6 months or until hematopoietic stem cell transplantation (HSCT). Response rates, survival outcomes, and adverse events were assessed. RESULTS: Sixty patients (2-26 years old; 65% B-cell ALL, received prior ≥ 2 regimen, 68.3% refractory to previous regimen) were enrolled and treated with at least one dose of clofarabine; of whom 26 (43.3%) completed 6 months of follow-up after the last dose of clofarabine. Fifty-eight patients (96.7%) received clofarabine combination therapy. Overall remission rate (complete remission [CR] or CR without platelet recovery [CRp]) was 45.0% (27/60; 95% confidence interval [CI], 32.4 to 57.6) and the overall response rate (CR, CRp, or partial remission [PR]) was 46.7% (28/60; 95% CI, 34.0 to 59.3), with 11 (18.3%), 16 (26.7%), and one (1.7%) patients achieving CR, CRp, and PR, respectively. The median time to remission was 5.1 weeks (95% CI, 4.7 to 6.1). Median duration of remission was 16.6 weeks (range, 2.0 to 167.6 weeks). Sixteen patients (26.7%) proceeded to HSCT. There were 24 deaths; 14 due to treatment-emergent adverse events. CONCLUSION: Remission with clofarabine was observed in approximately half of the study patients who had overall expected safety profile; however, there was no favorable long-term survival outcome in this study.

Clinical Characteristics and Treatment Outcomes in Children, Adolescents, and Young-adults with Hodgkin's Lymphoma: a KPHOG Lymphoma Working-party, Multicenter, Retrospective Study.

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.

Epidemiological Study of Hereditary Hemolytic Anemia in the Korean Pediatric Population during 1997-2016: a Nationwide Retrospective Cohort Study.

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.

Treatment Outcome in Pediatric Acute Lymphoblastic Leukemia With Hyperleukocytosis in the Yeungnam Region of Korea: A Multicenter Retrospective Study.

Acute lymphoblastic leukemia (ALL) with hyperleukocytosis at diagnosis is associated with early morbidity and mortality due to complications of leukostasis. Of 535 pediatric ALL patients (January 2004 to December 2016 from the Yeungnam region of Korea), 72 (13.5%) patients with an initial white blood cell (WBC) count of ≥100×10/L were included in this study, of whom 38 patients had extreme hyperleukocytosis (WBC>200×10/L) at diagnosis. Fourteen patients (19.4%) had ≥1 early respiratory and neurologic complications during induction therapy. Relapse occurred in 8 patients (24.2%) with extreme hyperleukocytosis and in 1 patient (3.0%) with an initial WBC count of 100 to 200×10/L (P=0.012). Estimated 10-year event-free survival rate (EFS) and overall survival rate were 78.3%±8.4% and 82.6%±7.7%, respectively. The 10-year EFS was significantly lower in patients with an initial WBC count of >200×10/L than in those with an initial WBC count of 100 to 200×10/L (65.7%±13.4% vs. 91.2%±7.9%; P=0.011). The 10-year EFS and overall survival rate did not differ significantly between patients with extreme hyperleukocytosis who received hematopoietic stem cell transplantation and those who received chemotherapy. In conclusion, pediatric ALL with hyperleukocytosis can lead to early complications and mortality. Patients with initial extreme hyperleukocytosis showed significantly poorer prognosis than those with WBC counts of 100 to 200×10/L.

Identification of a Novel MYH9 Mutation in a Young Adult With Inherited Thrombocytopenia and Recurrent Seizures by Targeted Exome Sequencing.

May-Hegglin anomaly (MHA) is a rare autosomal dominant disorder caused by a mutation in the myosin heavy chain 9 (MYH9) gene. MHA patients have variable clinical manifestations including thrombocytopenia, renal injury, hearing impairment, and cataracts. We describe a 25-year-old man with isolated thrombocytopenia initially. He experienced recurrent seizures with stable thrombocytopenia after the first seizures related to intracranial hemorrhage. He was identified a novel c.3452C>T mutation by targeted exome sequencing. If a patient with thrombocytopenia shows recurrent seizures as well as renal, hearing, visual symptoms, MHA should be suspected and the targeted exome sequencing is considered an effective diagnostic tool.

Mutation analysis in Korean patients with T-cell acute lymphoblastic leukemia.

Genomic studies have illuminated the alterations in pathways underlying T-cell acute lymphoblastic leukemia (T-ALL) pathogenesis, but detailed mutation data by next-generation sequencing have not been reported in Korean patients. We aimed to investigate mutation frequency, spectrum, and pattern in the Korean patients with T-ALL. We designed a multigene panel targeting 101 genes and validated it using 10 reference materials. The mutation analysis was done in a total of 10 patients with T-ALL. Clinical data and laboratory tests including immunophenotyping, cytogenetics, and molecular genetic tests were also investigated. All of the 10 patients harbored at least one mutation (range 1-6 per patient). A total of 34 clinically significant mutations including 15 novel mutations were identified in 23 genes. The median of variant allelic frequencies (VAFs) and blasts were counted upto 33% (range 5-91%) and 79% (range 38-90%), respectively. Recurrent mutations were involved in epigenetic regulators (60%), NOTCH1 signaling (40%), PI3K-AKT (40%), JAK-STAT (30%), and transcription factors (30%). We found that both NOTCH signaling and JAK-STAT signaling were positively associated with epigenetic regulators, while showed mutually exclusive patterns with PI3K-AKT pathway. This study showed that the frequency of mutations in epigenetic regulators in Korean patients was significantly higher than expected. Distribution of VAF as well as mutation spectrum is considerably heterogeneous in Korean patients with T-ALL. Although from a limited number of patients, this study provides the first detailed mutational portrait of T-ALL of Korean patients, and gives additional insight into molecular pathogenesis of the disease.

Molecular diagnosis of hereditary spherocytosis by multi-gene target sequencing in Korea: matching with osmotic fragility test and presence of spherocyte.

BACKGROUND: Current diagnostic tests for hereditary spherocytosis (HS) focus on the detection of hemolysis or indirectly assessing defects of membrane protein, whereas direct methods to detect protein defects are complicated and difficult to implement. In the present study, we investigated the patterns of genetic variation associated with HS among patients clinically diagnosed with HS. METHODS: Multi-gene targeted sequencing of 43 genes (17 RBC membrane protein-encoding genes, 20 RBC enzyme-encoding genes, and six additional genes for the differential diagnosis) was performed using the Illumina HiSeq platform. RESULTS: Among 59 patients with HS, 50 (84.7%) had one or more significant variants in a RBC membrane protein-encoding genes. A total of 54 significant variants including 46 novel mutations were detected in six RBC membrane protein-encoding genes, with the highest number of variants found in SPTB (n = 28), and followed by ANK1 (n = 19), SLC4A1 (n = 3), SPTA1 (n = 2), EPB41 (n = 1), and EPB42 (n = 1). Concurrent mutations of genes encoding RBC enzymes (ALDOB, GAPDH, and GSR) were detected in three patients. UGT1A1 mutations were present in 24 patients (40.7%). Positive rate of osmotic fragility test was 86.8% among patients harboring HS-related gene mutations. CONCLUSIONS: This constitutes the first large-scaled genetic study of Korean patients with HS. We demonstrated that multi-gene target sequencing is sensitive and feasible that can be used as a powerful tool for diagnosing HS. Considering the discrepancies of clinical and molecular diagnoses of HS, our findings suggest that molecular genetic analysis is required for accurate diagnosis of HS.

T-Cell Receptor Rearrangements Determined Using Fragment Analysis in Patients With T-Acute Lymphoblastic Leukemia.

BACKGROUND: Chromosomal abnormalities and common genetic rearrangements related to T-acute lymphoblastic leukemia (T-ALL) are not clear. We investigated T-cell receptor (TCR) rearrangement in Korean T-ALL patients by fragment analysis, examining frequency, association between clinicopathologic characteristics and TCR clonality, and feasibility for detecting minimal residual disease (MRD). METHODS: In 51 Korean patients diagnosed as having T-ALL, TCR rearrangement was analyzed using the IdentiClone TCR gene clonality assay (InVivoScribe Technologies, San Diego, CA, USA) from archived bone marrow specimens. Limit of detection (LOD) and clonal stability at relapse were evaluated. The association between clinical prognosis and TCR clonality was examind by age and immunophenotypic classification. RESULTS: Thirty-eight patients (74.5%) had 62 clonal products of TCRß, TCRγ, and/or TCRδ rearrangements at diagnosis. Children with T-ALL (<12 years) showed a higher frequency of clonality (93.8%) than adolescents/adults (65.7%; ≥12 years). Patients with a mature immunophenotype (84.4%) showed a relatively higher frequency of clonality than those with the immature immunophenotype (57.9%). Survival and event-free survival were not influenced by immunophenotype or TCR clonality. The LOD was 1%. Clonal evolution at the relapse period was noted. CONCLUSIONS: The overall detection rate of TCR clonality was 74.5%. Survival did not differ by TCR clonality or immunophenotype and age group. Fragment analysis of TCR rearrangement cannot be used to assess MRD due to low sensitivity. Further research on the relationship between prognosis and frequency of TCR rearrangements is needed, using more sensitive methods to detect clonality and monitor MRD.

Comparison of survival outcome between donor types or stem cell sources for childhood acute myeloid leukemia after allogenic hematopoietic stem cell transplantation: A multicenter retrospective study of Study Alliance of Yeungnam Pediatric Hematology-oncology.

We compared transplant outcomes between donor types and stem cell sources for childhood acute myeloid leukemia (AML). The medical records of children with AML in the Yeungnam region of Korea from January 2000 to June 2017 were reviewed. In all, 76 children with AML (male-to-female ratio = 46:30) received allogenic hematopoietic stem cell transplantation (allo-HSCT). In total, 29 patients received HSCT from either a matched-related donor or a mismatched-related donor, 32 patients received an unrelated donor, and 15 patients received umbilical cord blood. In term of stem cell sources, bone marrow was used in 15 patients and peripheral blood in 46 patients. For all HSCT cases, the 5-year overall survival (OS) was 73.1% (95% CI: 62.7-83.5) and the 5-year event-free survival (EFS) was 66.1% (95% CI: 54.5-77.7). There was no statistical difference in 5-year OS according to the donor types or stem cell sources (P = .869 and P = .911). There was no statistical difference in 5-year EFS between donor types or stem cell sources (P = .526 and P = .478). For all HSCT cases, the 5-year relapse rate was 16.1% (95% CI: 7.3-24.9) and the 5-year non-relapse mortality (NRM) was 13.3% (95% CI: 5.1-21.5). There was no statistical difference in the 5-year relapse rate according to the donor types or stem cell sources (P = .971 and P = .965). There was no statistical difference in the 5-year NRM between donor types or stem cell sources (P = .461 and P = .470).

Treatment outcome of pediatric acute lymphoblastic leukemia in Yeungnam region: Multicenter retrospective study of Study Alliance of Yeungnam Pediatric Hematology-Oncology (SAYPH).

OBJECTIVES: We aimed to evaluate treatment outcomes of pediatric acute lymphoblastic leukemia (ALL) subgroups by risk-stratification, in the Yeungnam region of Korea. METHODS: We reviewed the courses of 409 newly diagnosed ALL patients from January 2004 to December 2013 in the Yeungnam region. RESULTS: All patients were classified into three risk groups: standard risk (SR, n=212), high risk (HR, n=153) and very high risk (VHR, n=44). The mean follow-up time was 73.6 ± 39.4 months. The 7-year event-free survival (EFS) and overall survival (OS) rates were 78.7 ± 2.1% and 86.8 ± 1.8%, respectively. Significant 7-year EFS and OS rates for SR (84.0 ± 2.7%, 93.7 ± 1.8%), HR (76.5 ± 3.5%, 82.1 ± 3.3%), and VHR (60.6 ± 7.5%, 69.9 ± 7.5%) were observed (P<0.001), respectively. Relapse occurred in 52 patients, and the cumulative 7-year incidence of relapse differed according to risk groups (SR vs. HR vs. VHR=12.6% vs. 14.0% vs. 29.6%, P=0.003).For the 46 relapsed patients who were treated, the 3-year EFS and OS were 42.3 ± 8.3%and 46.4± 8.4%. Among the 44 VHR patients, EFS was not significantly different between the chemotherapy-treated patients and those received hematopoietic stem cell transplantation (P=0.533). The 7-year EFS of the hyperleukocytosis subgroup (24 cases, 14 under 10 years of age)showed a tendency for better prognosis than that of the other VHR subgroups (P=0.178). CONCLUSION: Our results revealed improved outcomes in pediatric ALL patients with risk-stratified therapy. The hyperleukocytosis subgroup without any combined chromosomal abnormalities may respond favorably to chemotherapy alone after first complete remission.

Dural Venous Sinus Thrombosis and Pulmonary Embolism Following Immunoglobulin Treatment in Pediatric Patient With Immune Thrombocytopenic Purpura.

Intravenous immunoglobulin (IVIG) is a widely used agent as the first choice of treatment of immune thrombocytopenic purpura (ITP). IVIG has several side effects, but it is a relatively safe treatment. Life-threatening thrombosis has been reported in adults and rarely in children. We report a case of a 14-year-old boy with dural venous sinus thrombosis and pulmonary embolism after treatment with IVIG for ITP. The patient was treated with low-molecular-weight heparin followed by warfarin and the symptoms were recovered. If a patient with ITP shows mental change or respiratory difficulty, we should consider thrombosis as well as hemorrhage.