Cytarabine Monotherapy as Bridging Treatment for Hematopoietic Stem Cell Transplantation in Children with Juvenile Myelomonocytic Leukemia / 임상소아혈액종양

BACKGROUND: Mutations leading to hyperactivation of the RAS pathway play a critical role in the pathogenesis of juvenile myelomonocytic leukemia (JMML). Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative therapy, and the role of anti-leukemic treatment prior to HSCT is still controversial. In this study, we analyzed the response of cytarabine monotherapy as a bridging therapy for HSCT in children recently diagnosed with JMML. METHODS: We retrospectively reviewed the medical records of patients with JMML at Seoul St. Mary's Hospital from December 2009 to April 2012. RESULTS: A total 7 patients with JMML were diagnosed and treated with chemotherapy and HSCT. At presentation, all patients showed hepatosplenomegaly and the median leukocyte count was 41.9x109/L (range, 34.3-85.0), median monocyte count was 5.6x109/L (range, 2.7-26.3) and median fetal hemoglobin (HbF) was 13.5% (range, 2.8-42.7). Karyotypic abnormalities in bone marrow cells were noted in 2 cases. Three patients had mutation of NRAS and 2 patients had mutation of NF1. One of the patients with NF1 mutations had characteristic clinical features and familial history of neurofibromatosis. All patients were treated with non-intensive sequential cytarabine chemotherapy (70 mg/m2/day, I.V., 4-12 days) before HSCT and achieved complete hematologic response. All patients underwent unrelated (N=2) or familial mismatched (N=5) HSCT, and all patients successfully engrafted. All patients, except one who relapsed, are alive with leukemia free, although the duration of follow-up is short. CONCLUSION: In our cohort of NRAS prevalent patients, non-intensive cytarabine monotherapy was effective as pre-transplant bridging treatment for JMML.

Clinical Predictors of Cerebrospinal Fluid Pleocytosis in Neonates: Clinical Predictors of CSF Pleocytosis in Neonates

PURPOSE: Young infants with suspected sepsis routinely undergo laboratory evaluation. In particular, when an infant is a newborn baby, evaluation of the cerebrospinal fluid (CSF) has been frequently included, because the prognosis is poor, irrespectively of the etiology of meningitis. We aimed to examine the clinical predictors of CSF pleocytosis among the newborns. METHODS: We retrospectively reviewed the records of all infants, aged 30 days or younger, requiring lumbar puncture. Electronic data sources provided the demographic data of the newborns, the clinical manifestations, and all laboratory values. After a univariate analysis, logistic regression analysis was performed to predict newborns at increased risk for CSF pleocytosis. RESULTS: One hundred thirteen newborns were studied; 20 of whom (17.7%) had CSF pleocytosis. Fever was significantly associated with CSF pleocytosis (P=0.008, OR=5.08, 95% CI, 1.39-18.54). The infants with lethargic appearance also had an increased risk for CSF pleocytosis. Blood urea nitrogen level was higher in patients with pleocytosis. Logistic regression analysis revealed that other clinical features and laboratory data were not significant, except for fever and lethargy. A total of 45% of the infants with CSF pleocytosis were diagnosed with serious bacterial infection, as opposed to 19.4% of those without CSF pleocytosis. CONCLUSION: In case of neonates, it would be better to perform lumbar puncture, when the infant has fever or lethargic appearance, although, the results of routine laboratory tests were nonspecific.

Factors Affecting Growth Velocity during Gonadotropin-Releasing Hormone Agonist Treatment in Girls with Idiopathic Central Precocious Puberty

PURPOSE: In some girls with central precocious puberty (CPP), growth velocity (GV) decreases below the age-appropriate normal range during gonadotropin-releasing hormone agonist (GnRHa) treatment. The purpose of this study was to investigate clinical and laboratory factors related to changes in GV during GnRHa treatment in girls with CPP. METHODS: We analyzed clinical and laboratory data of 49 girls (aged 7.8+/-0.5 years) with idiopathic CPP who were treated with GnRHa. GV, height standard deviation score (SDS), hormonal parameters, pubertal stage, chronological age and bone age (BA) were evaluated. RESULTS: GV during the first year of GnRHa treatment was 5.9+/-1.0 cm/yr and decreased significantly to 5.4+/-1.1 cm/yr during the second year of treatment (P = 0.005). GV during the third year (5.0+/-1.0 cm/yr) was not different from GV during the second year. During the second year of treatment, 8.2% and 36.7% of the girls had a GV or = 11 yr) at 1 year (55.6% vs. 19.4%; odds ratio [OR], 5.2; P = 0.022). In multivariate logistic regression analysis, more advanced BA at 1 year (OR, 6.1; 95% confidence interval [CI], 1.57-23.87) and lower height SDS for BA at 1 year (OR, 0.24; 95% CI, 0.06-0.94) were associated with relatively decreased GV (< 5 cm/yr) during the second year of GnRHa treatment. CONCLUSION: GV during and after the second year of GnRHa treatment in girls with idiopathic CPP remains within the normal prepubertal range, and relatively low GV during GnRHa treatment is associated with more advanced BA and lower height SDS for BA.

Factors Affecting Growth Velocity during Gonadotropin-Releasing Hormone Agonist Treatment in Girls with Idiopathic Central Precocious Puberty

PURPOSE: In some girls with central precocious puberty (CPP), growth velocity (GV) decreases below the age-appropriate normal range during gonadotropin-releasing hormone agonist (GnRHa) treatment. The purpose of this study was to investigate clinical and laboratory factors related to changes in GV during GnRHa treatment in girls with CPP. METHODS: We analyzed clinical and laboratory data of 49 girls (aged 7.8+/-0.5 years) with idiopathic CPP who were treated with GnRHa. GV, height standard deviation score (SDS), hormonal parameters, pubertal stage, chronological age and bone age (BA) were evaluated. RESULTS: GV during the first year of GnRHa treatment was 5.9+/-1.0 cm/yr and decreased significantly to 5.4+/-1.1 cm/yr during the second year of treatment (P = 0.005). GV during the third year (5.0+/-1.0 cm/yr) was not different from GV during the second year. During the second year of treatment, 8.2% and 36.7% of the girls had a GV or = 11 yr) at 1 year (55.6% vs. 19.4%; odds ratio [OR], 5.2; P = 0.022). In multivariate logistic regression analysis, more advanced BA at 1 year (OR, 6.1; 95% confidence interval [CI], 1.57-23.87) and lower height SDS for BA at 1 year (OR, 0.24; 95% CI, 0.06-0.94) were associated with relatively decreased GV (< 5 cm/yr) during the second year of GnRHa treatment. CONCLUSION: GV during and after the second year of GnRHa treatment in girls with idiopathic CPP remains within the normal prepubertal range, and relatively low GV during GnRHa treatment is associated with more advanced BA and lower height SDS for BA.

Cytarabine Monotherapy as Bridging Treatment for Hematopoietic Stem Cell Transplantation in Children with Juvenile Myelomonocytic Leukemia / 임상소아혈액종양

BACKGROUND: Mutations leading to hyperactivation of the RAS pathway play a critical role in the pathogenesis of juvenile myelomonocytic leukemia (JMML). Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative therapy, and the role of anti-leukemic treatment prior to HSCT is still controversial. In this study, we analyzed the response of cytarabine monotherapy as a bridging therapy for HSCT in children recently diagnosed with JMML.METHODS: We retrospectively reviewed the medical records of patients with JMML at Seoul St. Mary's Hospital from December 2009 to April 2012.RESULTS: A total 7 patients with JMML were diagnosed and treated with chemotherapy and HSCT. At presentation, all patients showed hepatosplenomegaly and the median leukocyte count was 41.9x109/L (range, 34.3-85.0), median monocyte count was 5.6x109/L (range, 2.7-26.3) and median fetal hemoglobin (HbF) was 13.5% (range, 2.8-42.7). Karyotypic abnormalities in bone marrow cells were noted in 2 cases. Three patients had mutation of NRAS and 2 patients had mutation of NF1. One of the patients with NF1 mutations had characteristic clinical features and familial history of neurofibromatosis. All patients were treated with non-intensive sequential cytarabine chemotherapy (70 mg/m2/day, I.V., 4-12 days) before HSCT and achieved complete hematologic response. All patients underwent unrelated (N=2) or familial mismatched (N=5) HSCT, and all patients successfully engrafted. All patients, except one who relapsed, are alive with leukemia free, although the duration of follow-up is short.CONCLUSION: In our cohort of NRAS prevalent patients, non-intensive cytarabine monotherapy was effective as pre-transplant bridging treatment for JMML.