Ye Jee Shim

Novel influenza A (H1N1) 2009 infection in the pediatric patients with hematologic and oncologic diseases in the Yeungnam region

Purpose Natural history and consequences of the novel 2009 influenza A H1N1 (2009 H1N1) infection in immunocompromised pediatric patients are not yet fully understood. In this study, we investigated the clinical features and outcomes of the 2009 H1N1 infection in pediatric patients with hematological and oncological diseases. Methods We retrospectively reviewed the medical records of 528 patients who had hematological and oncological diseases and who were treated at 7 referral centers located in the Yeungnam region. Among the 528 patients, 27 with definite diagnosis of 2009 H1N1 infection were the subjects of this study. All patients were divided into the following 3 groups: patients who were receiving chemotherapy (group 1), patients who were immunosuppressed due to a non-malignant hematological disease (group 2), and patients who were off chemotherapy and had undergone their last chemotherapy course within 2 years from the influenza A pandemic (group 3). Results All 28 episodes of 2009 H1N1 infection were treated with the antiviral agent oseltamivir (Tamiflu®), and 20 episodes were treated after hospitalization. Group 1 patients had higher frequencies of lower respiratory tract infection and longer durations of fever and hospitalization as compared to those in group 2. Ultimately, all episodes resolved completely with no complications. Conclusion These results suggest that early antiviral therapy did not influence the morbidity or mortality of pediatric patients with hematological and oncological diseases in the Yeungnam region of Korea after the 2009 H1N1 infection. However, no definite conclusions can be drawn because of the small sample size.

School performance of childhood cancer survivors in Korea: A multi-institutional study on behalf of the Korean Society of Pediatric Hematology and Oncology

To investigate school performance of childhood cancer survivors focusing on the childs functioning, including peer relationships, school attendance, and academic achievement.

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-onco

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).

A case of inherited type 1 and type 2A von Willebrand disease confirmed by diagnostic exome sequencing

A 10‐year‐old male and his family members visited a pediatric hematology clinic due to coagulopathy. Laboratory tests indicated von Willebrand disease (vWD) in all the family members. We conducted diagnostic exome sequencing for confirmation. The patient was confirmed to be a compound heterozygote for vWD: c.2574C > G (p.Cys858Trp) from his father (known variant of vWD type 1) and c.3390C > T (p.Pro1127_Gly1180delinsArg) from his mother (variant known to result in exon 26 skipping in vWD type 2A). He was managed with factor VIII and von Willebrand factor complex concentrate during palatoplasty due to bleeding despite pre‐operative desmopressin injection. The operation was completed successfully.

A cross-sectional retrospective study to analyze the underlying causes and clinical characteristics of children with reactive thrombocytosis at a Korean tertiary medical center

Background Reactive thrombocytosis (RT) is a common condition among children, although no studies have examined the etiology or clinical characteristics of RT among Korean children. Methods This retrospective study evaluated children with RT at a single Korean tertiary center during a 10-year period. Results RT accounted for 13.5% of children who were admitted to the pediatric ward (4,113/30,355): mild RT, 82.7%; moderate RT, 14.1%; severe RT, 1.1%; and extreme RT, 2.1%. There was a negative correlation between platelet count and Hb level (P=0.008). There were positive correlations between platelet count and WBC (P=0.001), erythrocyte sedimentation rate (ESR) (P=0.007), and admission duration (P=0.006). The most common cause of RT was infection and the second most common was Kawasaki disease (KD). The highest proportion of lower respiratory tract infection was observed in extreme RT (P<0.001). The proportion of KD was highest in extreme RT (P<0.001) and in children aged 1–7.9 years (P<0.001). The proportion of refractory KD was highest in extreme RT (P=0.005). In cases of KD, there was a positive correlation between platelet count and fever duration (P=0.006). Non-KD autoimmune inflammation was only observed in mild/moderate RT, and its proportion was highest in children aged 8–18 years (P<0.001). Conclusion In children, more severe RT was associated with lower Hb, increased WBC, ESR, and prolonged admission. With respiratory infection or KD, extreme RT was associated with more severe disease course.

Clinical characteristics and treatment courses for cytomegalovirus-associated thrombocytopenia in immunocompetent children after neonatal period

Background Cytomegalovirus (CMV) causes severe diseases in premature infants and immunocompromised hosts, and antiviral therapy is often required for disease control. However, the clinical manifestations and treatment courses for CMV-associated thrombocytopenia in immunocompetent children are unclear. Methods Medical records of the children who suffered from thrombocytopenia, and showed positive CMV polymerase chain reaction and CMV-like symptoms were retrospectively analyzed at three university hospitals in Daegu from January 2000 to March 2017. Patients suffering from leukemia, immunodeficiency, and other infections were excluded. Results Among 1,065 children with thrombocytopenia, 29 (2.7%) displayed CMV-associated thrombocytopenia. The median age at diagnosis was 15 months and the median platelet count was 26,000/µL. They were classified into the CMV-induced thrombocytopenia (23/29) and CMV-related secondary immune thrombocytopenia (ITP, 6/29) groups. Fourteen subjects had hepatic dysfunction, four had Evans syndrome, two had pneumonitis, and one had gastritis. IVIG was used for 21 patients, and six patients among them showed recurrence, for whom IVIG or antiviral therapy was used. All, except one, recurrent or chronic cases belonged to the CMV-induced thrombocytopenia group. Antiviral therapy was used more frequently for the CMV-induced thrombocytopenia group (8/23, 34.8%) than for the CMV-related secondary ITP group (0/6); however, the results were not statistically significant (P=0.148). Conclusion CMV is a rare but unique etiology of thrombocytopenia, and observed even in healthy children after the neonatal period. About one-third patients need antiviral therapy for disease control. Further, CMV-induced thrombocytopenia is more complex than CMV-related secondary ITP.

Sequential strategy for umbilical cord blood transplantation in a Korean Fanconi anemia girl with refractory acute myelomonocytic leukemia and complex karyotype

A 5yearold girl with Fanconi anemia (FA) was admitted because of prolonged fever and dizziness for several days. She had been diagnosed with aplastic anemia at 7 months of age, and FA was confirmed by genetic testing at 2 years of age (FANCG, c.307+1G>C, homozygote). Because there was no suitable donor, she had been conservatively managed with several transfusions for 3 years. At admission, bone marrow (BM) analysis showed that FA transformed into acute myelomonocytic leukemia. The BM karyotype was complex—46, XX, der(1)t(1;13)(p36;q21), del(8)(q?24), der(12)t(12:?)(q21:?), der(17) t(17;?)(p11.2;?), der(20)t(20:?)(p11.2:?). The result of multiplex RTPCR (HemaVision®, Risskov, Denmark) was negative. The first cycle of chemotherapy consisted of fludarabine 30 mg/m2 on day 24, AraC 300 mg/m2 on day 24, and GCSF 5 μg/kg on day 15.1 The second cycle of chemotherapy included idarubicin 5 mg/m2 on day 13 and AraC 50 mg/m2 on day 17. However, there was no response and BM cellularity was severely decreased to fewer than 5%. The complex karyotype of BM persisted. We planned a sequential strategy for hematopoietic stem cell transplantation (HSCT).2 The third chemotherapy was intensified with AraC 1000 mg/m2 q 12 hours on days 14 and mitoxantrone 10 mg/m2 on days 46. Two days after completion of the third chemotherapy, peripheral leukocyte count decreased to 8090/mm3 and her BM became acellular. It was not clear whether remission occurred because the BM karyotype could not be done, due to the absence of mitosis. The conditioning regimen included 4.5 gray (Gy) total body irradiation (TBI) on day −7 (single), fludarabine 30 mg/m2 on day −6 to −2, cyclophosphamide 10 mg/kg on day −5 to −2, and rabbit antithymocyte globulin 2.5 mg/kg on day −4 to −2.3,4 The conditioning started 3 weeks after the third cycle of chemotherapy, in a state of pancytopenia and acellular marrow. Only one cord blood with a 6/8 match was available for HSCT (TNC: 5.9×107/kg and CD34: 1.3×105/kg). Cyclosporine and mycophenolate mofetil were used for graftversushost disease (GVHD) prophylaxis. The patient suffered from mucositis (CTCAE Grade 3) and also had two episodes of febrile bacteremia until engraftment (Enterococcus faecium and Staphylococcus epidermidis). Because of positive cytomegalovirus PCR in blood and urine, the patient received preemptive therapy with intravenous ganciclovir. There was no evidence of acute GVHD or venoocclusive disease. Neutrophils and platelets were engrafted on day +29 and +54, respectively. Examination of variable number tandem repeat analysis at 1, 3, and 6 months postHSCT showed complete donor chimerism. The BM chromosome showed normal karyotype. Now, 10 months after transplantation, she is healthy without leukemia recurrence. Generally, very poor outcome of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) transformed from FA is known because chemotherapy is associated with significant toxicity and prolonged pancytopenia in FA patients.5 Allogeneic HSCT from a human leukocyte antigenmatched sibling generally provides the best outcome if performed before development of MDS/AML.5 However, such a donor is not available in every FA child. The patient reported here had no suitable donor at the time of diagnosis of FA and ultimately developed AML. In Mehta et al.,1 the reduced intensity FLAG regimen prior to HSCT is well tolerated in four of the FAMDS/AML children, but one of them had persistent leukemia and further chemotherapy was needed. The patient reported here also had refractory leukemia despite the aforementioned regimen and needed more intensified chemotherapy. Recently, the outcome of a French treatment following the sequential strategy for HSCT in six FAMDS/AML patients was described.2 Although the number of cases studied was small (six patients), the survival outcome was satisfactory (median 28 months followup, survival 100%). Because the FAAML patient reported here had refractory leukemia with complex karyotype, we decided to intensify induction chemotherapy including mitoxantrone and then apply sequential HSCT during a state of persistent aplasia. The TBI dose was also increased to 4.5 Gy.3,4 Despite mucositis and febrile bacteremia, this intensified sequential regimen was feasible for the patient. It is the first Korean case of FAAML patient who showed successful transplantation outcome.

Multiple daily injection of insulin regimen for a 10-month-old infant with type 1 diabetes mellitus and diabetic ketoacidosis

The incidence of type 1 diabetes is increasing worldwide, and the greatest increase has been observed in very young children under 4 years of age. A case of infantile diabetic ketoacidosis in a 10-month-old male infant was encountered by these authors. The infants fasting glucose level was 490 mg/dL, his PH was 7.13, his pCO2 was 15 mmHg, and his bicarbonate level was 5.0 mmol/L. The glycosylated hemoglobin level had increased to 9.4%. Ketonuria and glucosuria were detected in the urinalysis. The fasting C-peptide and insulin levels had decreased. The infant was positive for anti-insulin and antiglutamic acid decarboxylase antibodies. Immediately after the infants admission, fluid therapy and intravenous insulin infusion therapy were started. On the second day of the infants hospitalization and after fluid therapy, he recovered from his lethargic condition, and his general condition improved. Feeding was started on the third day, and he was fed a formula 5 to 7 times a day and ate rice, vegetables, and lean meat. Due to the frequent feeding, the frequency of rapid-acting insulin injection was increased from 3 times before feeding to 5 times, adjusted according to the feeding frequency. The total dose of insulin that was injected was 0.8–1.1 IU/kg/day, and the infant was discharged on the 12th day of his hospitalization. The case is presented herein with a brief review of the relevant literature.

Short stature and growth hormone deficiency in a girl with encephalocraniocutaneous lipomatosis and Jaffe-Campanacci syndrome: a case report

A 9-year-old Tajikistani girl presented to Keimyung University Dongsan Medical Center for evaluation of a skin lesion on her left eyelid, focal alopecia, unilateral ventricular dilatation, and aortic coarctation. She was diagnosed with encephalocraniocutaneous lipomatosis (ECCL) according to Moogs diagnostic criteria. Café-au-lait spots were found on the left side of her trunk. Multiple nonossifying fibromas were found on her left proximal humerus, left distal femur, both proximal tibias, and left proximal fibula, suggesting Jaffe-Campanacci syndrome (JCS), following imaging of the extremities. Many JCS cases with multiple Café-au-lait macules, multiple nonossifying fibromas may actually have Neurofibromatosis type-1 (NF1). Thus, comprehensive molecular analysis to exclude NF1 mutation was performed using her blood sample. The NF1 mutation was not found. Her height was under the 3rd percentile and her bone age was delayed as compared with her chronological age. Baseline growth hormone (GH) level was below the normal range. Using the insulin stimulation and levo-dihydroxyphenylalanine tests, GH deficiency was confirmed. We present a case of GH deficiency with typical features of ECCL and JCS.

Formula fed twin infants with recurrent hypocalcemic seizures with vitamin D deficient rickets and hyperphosphatemia

Vitamin D deficient rickets is generally known to occur in breast fed infants. And excessive phosphate ingestion is a main cause of late onset hypocalcemia in formula fed infants. Here we introduce 45-day-old formula fed hypocalcemic twins with recurrent seizure attacks. They were diagnosed as having both of vitamin D deficient rickets and hyperphosphatemia. Radiologic findings indicated mild rickets and the twins were treated with calcium and alfacalcidol. After 3-5 months of oral supplementation, medication was discontinued in both twins. They showed normal growth and calcium, phosphorus, and vitamin D levels during the 6-month follow-up period. Twins can be at risk for hypocalcemia because of their high risk of vitamin D deficiency, low birth weight, and premature birth. Therefore twin pregnant women need ingestion of sufficient vitamin D and calcium.