CNS-Directed Therapy for Childhood Acute Lymphoblastic Leukemia: Childhood ALL Collaborative Group Overview of 43 Randomized Trials

Clarke, Michael; Gaynon, P. S.; Hann, IM; Harrison, Gill; Masera, Giuseppe; Pető, Richárd; Richards, Sue

doi:10.1200/jco.2003.08.047

Cited by 128 publications

(91 citation statements)

References 70 publications

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“…In a metaanalysis of 43 randomized trials, high-dose methotrexate reduced the hematologic relapse rate and improved eventfree survival, but had only a marginal effect on the control of CNS leukemia. 35 This outcome may reflect the generally lower dose of methotrexate (0.5 to 1 g/m 2 ) used in the past, suggesting that higher doses (e.g., 5 g/m 2 as in many current trials) would be more effective in securing CNS control.…”

Section: Systemic Chemotherapymentioning

confidence: 98%

Central Nervous System Disease in Acute Lymphoblastic Leukemia: Prophylaxis and Treatment

Pui

2006

Hematology

105

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Improved treatment for acute lymphoblastic leukemia (ALL) has virtually eliminated testicular relapse. However, the control of central nervous system (CNS) leukemia remains a therapeutic challenge in childhood ALL, partly because of the late complications arising from cranial irradiation. In most current pediatric protocols, cranial irradiation (12 to 18 Gy) is given to 5% to 25% of patients—those with T-cell ALL, overt CNS disease (CNS3 status) or high-risk cytogenetics. CNS control is a less urgent concern in adults with ALL, in whom systemic relapse remains the major problem. With current approaches, approximately 2% to 10% of patients can be expected to develop CNS relapse. Children with B-cell precursor ALL who have a late CNS relapse (after an initial remission of 18 months or more) and did not receive cranial irradiation have an excellent outcome after retrieval therapy, with a 5-year event-free survival (EFS) rate approaching that in newly diagnosed patients. Innovative treatment options are needed for children who develop CNS relapses after a short initial remission or after receiving cranial irradiation, and in any adults with CNS leukemia at diagnosis or relapse.

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Section: Systemic Chemotherapymentioning

confidence: 98%

Central Nervous System Disease in Acute Lymphoblastic Leukemia: Prophylaxis and Treatment

Pui

2006

Hematology

105

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“…This is also supported by the results of meta-analysis of CNS-directed therapy, which show that radiotherapy can be replaced by long-term intrathecal therapy but not by intravenous MTX. 22 Whether CRT can be excluded from preventive therapy for HR patients is still subject to controversy. In ALL851, we employed CNS chemoprophylaxis without CRT for the HR patients, but failed to prevent CNS relapse.…”

Section: Discussionmentioning

confidence: 99%

Long-term results of the Japanese Childhood Cancer and Leukemia Study Group studies 811, 841, 874 and 911 on childhood acute lymphoblastic leukemia

et al. 2009

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We analyzed the long-term outcomes of 1021 patients with acute lymphoblastic leukemia (ALL), enrolled in four successive clinical trials (ALL811, ALL841, ALL874 and ALL911) between 1981 and 1993. All patients received risk-adopted therapy according to leukocyte count and age at the time of diagnosis. The median follow-up durations of the four studies were 17.8 years in ALL811, 15.5 years in ALL841, 11.9 years in ALL874 and 15.8 years in ALL911. Patients' event-free survival (EFS) and overall survival (OS) rates at 12 years were 41.0 and 54.3% in ALL811, 50.2 and 60.2% in ALL841, 57.3 and 64.7% in ALL874, and 63.4 and 71.7% in ALL911, respectively. Thus, cure can become a reality for about 70% of children with ALL. There is, however, still a significant difference in survival outcomes according to risk group. Late effects were observed in 70 patients out of 834 (8.4%); hepatitis and short stature were most commonly reported. Reduction of late adverse effects for all patients and development of new treatment strategies for very-high-risk patients are major issues for upcoming trials to address.

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“…Most current regimens do not administer cranial irradiation to infants or very young children, even if they are high risk (Pieters et al, 2007). Further, a review of 43 randomized trials reported that cranial irradiation is also not a necessary component of therapy for standard risk ALL (Clarke et al, 2003). For the high risk patients receiving CNS-directed therapy, cranial irradiation is initiated after patients have achieved bone marrow remission.…”

Section: Cranial Irradiation For Cns Prophylaxismentioning

confidence: 99%

Acute Lymphoblastic Leukemia: What Have We Learned About the Effects of This Disease and Its Treatment on the Nervous System?

Huynh¹,

Sender²,

Bota³

2011

Novel Aspects in Acute Lymphoblastic Leukemia

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CNS-Directed Therapy for Childhood Acute Lymphoblastic Leukemia: Childhood ALL Collaborative Group Overview of 43 Randomized Trials

Abstract: Radiotherapy can be replaced by long-term intrathecal therapy. Intravenous methotrexate gives some additional benefit by reducing non-CNS relapses.

Cited by 128 publications

References 70 publications

Central Nervous System Disease in Acute Lymphoblastic Leukemia: Prophylaxis and Treatment

Central Nervous System Disease in Acute Lymphoblastic Leukemia: Prophylaxis and Treatment

Long-term results of the Japanese Childhood Cancer and Leukemia Study Group studies 811, 841, 874 and 911 on childhood acute lymphoblastic leukemia

Acute Lymphoblastic Leukemia: What Have We Learned About the Effects of This Disease and Its Treatment on the Nervous System?

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