Prevention of CNS disease in intermediate-risk acute lymphoblastic leukemia: comparison of cranial radiation and intrathecal methotrexate and the importance of systemic therapy: a Childrens Cancer Group report.

Tubergen, David G.; Gilchrist, Gerald S.; O’Brien, Richard T.; Coccia, Peter F.; Sather, Harland N.; Waskerwitz, Mary J.; Hammond, G. Denman

doi:10.1200/jco.1993.11.3.520

Cited by 140 publications

(63 citation statements)

References 17 publications

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“…However, BFM-based intensive chemotherapy using extended intrathecal chemotherapy has reported lower than 5% incidence of CNS relapse. 15,[19][20][21] Similar results are seen in the I911 protocol, where an extended triple inrathecal MTX regimen with intensive systemic therapy achieved a 2% cumulative incidence of CNS relapse in the IR patients. Thus, it is likely that systemic intravenous infusions of HDMTX could not be substituted for intrathecal injections of MTX in the maintenance therapy for CNS protection.…”

Section: Discussionsupporting

confidence: 63%

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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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Section: Discussionsupporting

confidence: 63%

“…[15][16][17][18][19] In our study, the LR patients of L874B and L911 who received HDMTX therapy as CNS prophylaxis showed 7-9% cumulative incidence of isolated CNS relapse. However, BFM-based intensive chemotherapy using extended intrathecal chemotherapy has reported lower than 5% incidence of 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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“…'Intermediate risk' patients were randomly allocated to receive standard or intensive induction/consolidation, delayed intensification (DI) or no intensification, and 18 Gy cranial irradiation or 12-weekly doses of maintenance intrathecal methotrexate on CCG-105. 14,22 'Higher risk' patients with lymphomatous features 20 were randomly allocated to LSA 2 L 2 with or without cranial irradiation, the New York (NY) I regimen, or the CCG modified BFM regimen 9 on CCG-123. 20,21 'Higher risk' patients without lymphomatous features were randomly allocated to the standard CCG regimen, NYI, or the CCG-modified BFM regimen 9 on CCG-106.…”

Section: Methodsmentioning

confidence: 99%

Children's Cancer Group trials in childhood acute lymphoblastic leukemia: 1983–1995

et al. 2000

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Since 1968, the Children's Cancer Group (CCG) has treated more than 16 000 children with acute lymphoblastic leukemia (ALL). Herein, we report improvements obtained in CCG trials during two successive series of studies (1983-1988 and 1989-1995). Overall, 10-year EFS was 62% ± 10% for the 1983-1988 series and 72% ± 1% for the 1988-1995 series (P Ͻ 0.0001). Five-year cumulative rates of isolated CNS relapses were 5.9% and 4.4%. Therapy based on the Berlin-Frankfurt-Mü nster 76/79 study improved outcomes for intermediate and higher risk patients in the first series. For intermediate risk patients, delayed intensification (DI) was most crucial for improved outcome and cranial irradiation was safely replaced with maintenance intrathecal methotrexate, providing patients received intensified systemic therapy. In the second series, randomized trials showed better outcome with one vs no DI phase for lower risk patients, with two vs one DI phase for intermediate risk patients, and with the CCG 'augmented regimen' for higher risk patients with a slow day 7 marrow response. Cranial irradiation was safely replaced with additional intrathecal methotrexate for higher risk patients with a rapid day 7 marrow response. In a subsequent study, substitution of dexamethasone in place of prednisone in induction and maintenance improved outcome for standard risk patients. All patients received dexamethasone in DI. These successful treatment strategies form the basis for our current ALL trials. Leukemia (2000) 14, 2223-2233.

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“…CNS-directed treatment is a standard component of therapy for ALL. Evidence of a detrimental effect of prophylactic cranial irradiation on neurocognitive function in children with ALL (Cousens et al, 1988;Jankovic et al, 1994;Meadows et al, 1981) has resulted in reduction of the use of cranial irradiation and the development of chemotherapy-only protocols with the same or better rate of treatment success (Kamps et al, 2002;Tubergen et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

Visuomotor control in survivors of childhood acute lymphoblastic leukemia treated with chemotherapy only

Buizer

Sonneville

Heuvel‐Eibrink

et al. 2005

J. Inter. Neuropsych. Soc.

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Treatment for childhood acute lymphoblastic leukemia (ALL), which includes CNS prophylaxis, is associated with central and peripheral neurotoxicity. The purpose of the present study was to analyze the effects of chemotherapy on various levels of visuomotor control in survivors of childhood ALL treated without cranial irradiation, and to identify risk factors for possible deficits. Visuomotor function was compared between children after treatment for ALL (n 5 34), children after treatment for Wilms tumor, which consists of non-CNS directed chemotherapy (n 5 38), and healthy controls (n 5 151). Three tasks were administered: a simple visual reaction time task and two tasks measuring visuomotor control with one requiring a higher level of cognitive control than the other. Visuomotor deficits were detected only in the ALL group, with poorer performance restricted to the condition requiring the highest level of control. Significant risk factors for poorer performance were female gender and a short time since end of treatment, and a trend was found for a young age at diagnosis. A high cumulative methotrexate dose was an adverse predictive factor in girls. The results indicate that chemotherapy-induced central neurotoxicity in childhood ALL treatment is associated with higher order visuomotor control deficits. Girls appear to be particularly vulnerable. (JINS, 2005, 11, 554-565.)

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Prevention of CNS disease in intermediate-risk acute lymphoblastic leukemia: comparison of cranial radiation and intrathecal methotrexate and the importance of systemic therapy: a Childrens Cancer Group report.

Cited by 140 publications

References 17 publications

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

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

Children's Cancer Group trials in childhood acute lymphoblastic leukemia: 1983–1995

Visuomotor control in survivors of childhood acute lymphoblastic leukemia treated with chemotherapy only

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