Efficacy of imatinib mesylate-based front-line therapy in pediatric chronic myelogenous leukemia / 소아과

PURPOSE: Despite the established role of imatinib (IM) in chronic myelogenous leukemia (CML) in adults, there are few reports on its efficacy in children. In this study, we compared the outcomes of children with CML before and after the advent of IM-based treatment. METHODS: The study cohort consisted of 52 patients treated for CML at the Department of Pediatrics, The Catholic University of Korea from January 1995 to October 2010. Patients were divided and analyzed according to the preImatinib group (pre-IMG) and imatinib group (IMG). RESULTS: Median age at diagnosis for the overall cohort (pre-IMG, n=27; IMG, n=25) was 9 years, with a median follow-up duration of survivors of 84 months. Except for 5 patients in the IMG, all were diagnosed in chronic phase (CP). The overall survival (OS) of patients diagnosed in CP was 45.7% and 89.7% for pre-IMG and IMG, respectively (P=0.025). The OS of hematopoietic stem cell transplantation (HSCT) recipients in the 2 groups was similar, but the OS of patients diagnosed in CP who did not receive HSCT was superior in IMG (91.7% vs. 16.7%, P=0.014). Of the 12 patients in IMG who remained on IM without HSCT, 2 showed disease progression, compared to 11 of 12 in pre-IMG. No difference was observed in the progression free survival (PFS) of matched donor HSCT recipients and IM-based treatment recipients. CONCLUSION: Similar PFS of patients treated with IM and those who received matched donor HSCT underscore the potential of IM as effective first-line treatment in childhood CML.

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.

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.