Nervous System Relapse In Children Research Articles

Obesity as a Prognostic Factor of Central Nervous System Relapse in Children with Acute Lymphoblastic Leukemia: A Single-Centre Study and Literature Review.

Relapse as the commonest treatment failure through chemotherapy of child presented with acute lymphoblastic leukemia (ALL) is usually within 3 years of remission. Central nervous system (CNS) is expected as a site of extramedullary relapse in 3–8% of child leukemia, often leading to a poor prognosis. A few patients may have headache and vomiting and can be diagnosed without difficulty. However, most patients present with asymptomatic conditions. Obesity has become one of the greatest reported complications of children ALL survivors. Rarely, obesity presentation can be the first manifestation of CNS leukemia. Here, we present three unusual cases with B-ALL presentation of obesity as the first symptom at the time of CNS relapse after achieving remission. This highly localized presentation is unusual and would hopefully inform clinicians to have a high index of suspicion for relapse in children with ALL.

No evidence for routine cerebrospinal fluid cytology in detecting asymptomatic central nervous system relapse in children with acute lymphoblastic leukaemia: 20 years’ experience of a UK primary treatment centre

No evidence for routine cerebrospinal fluid cytology in detecting asymptomatic central nervous system relapse in children with acute lymphoblastic leukaemia: 20 years’ experience of a <scp>UK</scp> primary treatment centre

The role of routine surveillance for silent central nervous system relapse in children with acute lymphoblastic leukaemia

The role of routine surveillance for silent central nervous system relapse in children with acute lymphoblastic leukaemia

Incidence and risk factors for central nervous system relapse in children and adolescents with acute lymphoblastic leukemia.

BackgroundDespite all the advances in the treatment of childhood acute lymphoblastic leukemia, central nervous system relapse remains an important obstacle to curing these patients. This study analyzed the incidence of central nervous system relapse and the risk factors for its occurrence in children and adolescents with acute lymphoblastic leukemia. Methods This study has a retrospective cohort design. The studied population comprised 199 children and adolescents with a diagnosis of acute lymphoblastic leukemia followed up at Hospital das Clinicas, Universidade Federal de Minas Gerais (HC-UFMG) between March 2001 and August 2009 and submitted to the Grupo Brasileiro de Tratamento de Leucemia da Infância - acute lymphoblastic leukemia (GBTLI-LLA-99) treatment protocol. Results The estimated probabilities of overall survival and event free survival at 5 years were 69.5% (± 3.6%) and 58.8% (± 4.0%), respectively. The cumulative incidence of central nervous system (isolated or combined) relapse was 11.0% at 8 years. The estimated rate of isolated central nervous system relapse at 8 years was 6.8%. In patients with a blood leukocyte count at diagnosis ≥ 50 x 109/L, the estimated rate of isolated or combined central nervous system relapse was higher than in the group with a count < 50 x 109/L (p-value = 0.0008). There was no difference in cumulative central nervous system relapse (isolated or combined) for the other analyzed variables: immunophenotype, traumatic lumbar puncture, interval between diagnosis and first lumbar puncture and place where the procedure was performed. Conclusions These results suggest that a leukocyte count > 50 x 109/L at diagnosis seems to be a significant prognostic factor for a higher incidence of central nervous system relapse in childhood acute lymphoblastic leukemia.

Incidence and risk factors for central nervous system relapse in children and adolescents with acute lymphoblastic leukemia

Incidence and risk factors for central nervous system relapse in children and adolescents with acute lymphoblastic leukemia

Methotrexate concentrations in cerebrospinal fluid and serum, and the risk of central nervous system relapse in children with acute lymphoblastic leukaemia

The aim of the study was to characterize the relationship between the pharmacokinetics of methotrexate in serum and concentrations in the cerebrospinal fluid, and to analyse the association to risk of a central nervous system relapse in children with acute lymphoblastic leukaemia. In this retrospective study, 353 children with acute lymphoblastic leukaemia treated with high-dose methotrexate according to the Nordic Society of Pediatric Haematology and Oncology-92 acute lymphoblastic leukaemia protocol were studied. Data from 18 patients with a subsequent central nervous system relapse and 335 event-free patients were available. In 34 patients the methotrexate concentrations were monitored repeatedly during each 24-h methotrexate intravenous infusion and a cerebrospinal fluid sample was taken at the end of the infusion. Using statistics separating interindividual and intraindividual variability, methotrexate concentration in cerebrospinal fluid was found to be significantly dependent upon both serum concentrations at the end of infusion and the area under the concentration curve in serum (P<0.0017 and <0.002, respectively). The logistic regression analysis revealed that high patient median serum methotrexate concentrations at the end of infusion were significantly associated with decreased risk for a central nervous system relapse in the standard risk group (P=0.02) and the number of courses with a calculated cerebrospinal fluid concentration of more than 1 mumol/l (P=0.048) with a decreased risk of a central nervous system relapse in the combined (standard risk and intermediate) risk group. In conclusion, methotrexate concentrations in cerebrospinal fluid are dependent on methotrexate concentrations in serum and serum area under the concentration curve. Multivariate analysis indicates that an increased exposure to methotrexate is related to decreased risk for central nervous system relapse.

Survival Outcome after the First Central Nervous System Relapse in Children with Acute Lymphoblastic Leukemia: A Retrospective Analysis of 79 Patients in a Joint Program Involving the Experience of Three Japanese Study Groups

In a retrospective review of the survival outcome of children with isolated central nervous system (CNS) relapse of acute lymphoblastic leukemia (ALL), we identified 79 patients with CNS relapse among the eligible patients enrolled in ALL trials of 3 Japanese pediatric oncology study groups (Japanese Children's Cancer and Leukemia Study Group [JCCLSG], Tokyo Children's Cancer Study Group [TCCSG], and Japan Association of Childhood Leukemia Study [JACLS]) between 1989 and 1999. CNS relapses were diagnosed as the first adverse event between 1991 and 1999. The median age at the time of CNS relapse was 5.0 years (range, 0.7-15.1 years). The duration of the first remission ranged from 1.4 to 54 months (median, 12.4 months), and the observation period after CNS relapse ranged from 1 to 131 months (median, 27 months). Overall, 75 of the 79 patients achieved a second complete remission, 44 of whom had second relapses in the following sites: CNS, 18 patients; bone marrow, 15 patients; combined sites, 8 patients; and testis, 2 patients. Rates of overall survival and event-free survival at 4 years were 43.7% +/- 5.8% (mean +/- SE) and 32.9% +/- 5.5%, respectively. The probability of remaining in second remission was significantly correlated with the leukocyte count (P= .005) and age (P= .02) at the initial diagnosis.

Early Intensification of Intrathecal Chemotherapy Virtually Eliminates Central Nervous System Relapse in Children With Acute Lymphoblastic Leukemia

Central nervous system (CNS) relapse has been an obstacle to uniformly successful treatment of childhood acute lymphoblastic leukemia (ALL) for many years. We therefore intensified intrathecal chemotherapy (simultaneously administered methotrexate, hydrocortisone, and cytarabine) for 165 consecutive children with newly diagnosed ALL enrolled in Total Therapy Study XIIIA from December 1991 to August 1994. The 64 patients (39%) who had 1 or more blast cells in cytocentrifuged preparations of cerebrospinal fluid at diagnosis, with or without associated higher-risk features, received additional doses of intrathecal chemotherapy during remission induction and the first year of continuation treatment. Patients with higher-risk leukemia, regardless of cerebrospinal fluid findings, also received additional doses of intrathecal chemotherapy during the first year of continuation treatment. Cranial irradiation was reserved for patients with higher-risk leukemia (22% of the total). The 5-year cumulative risk of an isolated CNS relapse among all 165 patients was 1.2% (95% confidence interval, 0% to 2.9%), whereas that of any CNS relapse was 3.2% (0.4% to 6.0%). The probability of surviving for 5 years without an adverse event of any type was 80.2% ± 9.2% (SE). Our results suggest that early intensification of intrathecal chemotherapy will reduce the risk of CNS relapse to a very low level in children with ALL, securing a higher event-free survival rate overall.

Early Intensification of Intrathecal Chemotherapy Virtually Eliminates Central Nervous System Relapse in Children With Acute Lymphoblastic Leukemia

AbstractCentral nervous system (CNS) relapse has been an obstacle to uniformly successful treatment of childhood acute lymphoblastic leukemia (ALL) for many years. We therefore intensified intrathecal chemotherapy (simultaneously administered methotrexate, hydrocortisone, and cytarabine) for 165 consecutive children with newly diagnosed ALL enrolled in Total Therapy Study XIIIA from December 1991 to August 1994. The 64 patients (39%) who had 1 or more blast cells in cytocentrifuged preparations of cerebrospinal fluid at diagnosis, with or without associated higher-risk features, received additional doses of intrathecal chemotherapy during remission induction and the first year of continuation treatment. Patients with higher-risk leukemia, regardless of cerebrospinal fluid findings, also received additional doses of intrathecal chemotherapy during the first year of continuation treatment. Cranial irradiation was reserved for patients with higher-risk leukemia (22% of the total). The 5-year cumulative risk of an isolated CNS relapse among all 165 patients was 1.2% (95% confidence interval, 0% to 2.9%), whereas that of any CNS relapse was 3.2% (0.4% to 6.0%). The probability of surviving for 5 years without an adverse event of any type was 80.2% ± 9.2% (SE). Our results suggest that early intensification of intrathecal chemotherapy will reduce the risk of CNS relapse to a very low level in children with ALL, securing a higher event-free survival rate overall.

The importance of an isolated central nervous system relapse in children with acute lymphoblastic leukemia.

We assessed the influence of an initial isolated meningeal relapse on treatment outcome in 839 children with acute lymphoblastic leukemia (ALL) who were admitted to St Jude Children's Research Hospital (Memphis) from mid-1967 through mid-1979. The patients were entered in a series of five clinical trials (Total Therapy Studies V through IX), each designed to test one or more modifications of treatment for ALL. Two groups were compared: 699 children who received CNS prophylaxis (2,400-rad craniospinal irradiation or 2,400-rad cranial irradiation plus intrathecal methotrexate) v 56 who did not. Our results, obtained with a time-dependent covariate model and a matching technique, indicate a 2 to 3.5-fold increase in the risk of hematologic relapse or death among patients who experienced an isolated CNS relapse compared with similar patients (matched for leukocyte count and length of complete remission) who remained free of CNS involvement. Of the 107 children with an initial isolated CNS relapse, 89 (83%) have died or have had a subsequent relapse. There was no detectable difference in the rate of hematologic relapse or death after a CNS relapse between patients who had received preventive therapy and those who had not. We conclude that CNS prophylaxis is important both for the prevention of initial CNS leukemia and for reducing the risk of hematologic relapse or death subsequent to a CNS relapse.