The Utility of Performing the Initial Lumbar Puncture on Day 8 in Remission Induction Therapy for Childhood Acute Lymphoblastic Leukemia: TCCSG L99-15 Study
Department of Pediatrics, St. Luke's International Hospital, Tokyo, Japan. Pediatric Blood & Cancer
(Impact Factor: 2.39).
01/2012; 58(1):23-30. DOI: 10.1002/pbc.22965
Traumatic lumbar puncture with leukemic blasts (TLP+), which has been reported to occur 5-10%, in the previous studies, adversely affects the outcome of children with acute lymphoblastic leukemia (ALL). Based on the results from our previous study, we deferred the initial lumbar puncture until day 8 in remission induction therapy in order to reduce the frequency of cases with TLP+.
The study was conducted as a prospective cohort study within the Tokyo Children's Cancer Study Group (TCCSG) L99-15 study. Between April 1999 and June 2003, 754 children with newly diagnosed ALL enrolled. The patients received the initial intrathecal chemotherapy after 7 days of prednisolone treatment. The incidence of central nervous system (CNS)-positive (the presence of leukemic blasts in cerebrospinal fluid or cranial nerve palsy) including TLP+ cases and cumulative incidence of CNS relapse were examined.
The incidence of CNS-positive and TLP+ was 2.9% (n = 22) and 0.8% (n = 6), respectively. These incidences were much lower than those in the representative study groups employing the initial IT on day 1. Of 22 patients with CNS-positive, only one patient relapsed in CNS, whereas 22 of the remaining CNS-negative 723 patients suffered from CNS relapse. Overall, event-free survival at 4 year was 78.2 ± 1.6%. Four-year cumulative incidence of any CNS relapse was 3.3 ± 0.7%, which improved from our previous study in spite of limiting the use of cranial irradiation.
Our strategy reduced the frequency of CNS-positive patients who required reinforcement of CNS-directed therapy without compromising overall outcome.
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- "Another possible contributing
factor maybe the delay in performing LP in 40% of the patients. In a Japanese study in
which the first LP was set to be performed on the eighth day of the chemotherapy
induction phase, only 0.5% of patients were classified as CNS3(18). The results of both of these studies
differ from most of the literature in childhood ALL, as demonstrated by Table 2. "
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ABSTRACT: Despite 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.
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.
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 10(9)/L, the estimated rate of isolated or combined central nervous system relapse was higher than in the group with a count < 50 x 10(9)/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.
These results suggest that a leukocyte count > 50 x 10(9)/L at diagnosis seems to be a significant prognostic factor for a higher incidence of central nervous system relapse in childhood acute lymphoblastic leukemia.
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ABSTRACT: With improvement in survival, it is important to evaluate the impact of treatment on secondary cancers in acute lymphoblastic leukaemia (ALL) survivors. A retrospective cohort study comprising 2918 children diagnosed with ALL and enrolled on Tokyo Children's Cancer Study Group (TCCSG) protocols between 1984 and 2005 was conducted to evaluate the incidence of secondary cancers and associated factors including treatment protocol, cranial irradiation and other characteristics of the primary ALL. Thirty-seven patients developed secondary cancers, including acute myeloid leukaemia (n = 11), myelodysplastic syndrome (n = 5), non-Hodgkin lymphoma (n = 2), brain tumours (n = 13) and other solid carcinomas (n = 6) within a median follow-up duration of 9·5 years. The cumulative incidence of any secondary cancers was 1·0% (95% confidence interval (CI), 0·7-1·4%) at 10 years and 2·4% (95% CI, 1·5-3·7%) at 20 years, respectively. Standardized incidence rate ratio of secondary cancers was 9·3 (95% CI, 6·5-12·8). Multivariate analyses showed an increased risk of secondary cancers associated with the recent treatment protocol and cranial irradiation. There was no evidence of a reduction in secondary cancer incidence despite marked decreases in cranial irradiation use in the recent protocols.
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ABSTRACT: The Tokyo Children's Cancer Study Group conducted a randomized controlled study to evaluate the effect of experimental early intensification using high-dose cytarabine and L-asparaginase in paediatric intermediate-risk (IR) acute lymphoblastic leukaemia (ALL). A total of 310 IR ALL patients were randomized to receive either experimental early intensification (n = 156) or standard early intensification including standard-dose cytarabine arm (n = 154) after induction therapy. The experimental arm consisted of high-dose cytarabine and L-asparaginase, while the standard arm consisted of standard-dose cytarabine, oral 6-mercaptopurine and cyclophosphamide. The probabilities of event-free survival at 8 years in the experimental and standard arms were 72·3 ± 3·7% and 77·5 ± 3·5%, respectively (P = 0·32). The 8-year overall survival rates for these two arms were 85·0 ± 3·0% and 86·9 ± 2·8%, respectively (P = 0·72). The frequency of infectious events was significantly higher in the experimental arm (66·4%) than in the standard arm (24·6%) (P < 0·001). In conclusion, experimental early intensification including high-dose cytarabine followed by L-asparaginase had no advantage over standard early intensification in paediatric IR ALL patients.
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