Isolated CNS relapse of acute lymphoblastic leukemia treated with intensive systemic chemotherapy and delayed CNS radiation: A pediatric oncology group study

Julio Barredo, Meenakshi Devidas, Stephen J. Lauer, Amy Billett, MaryAnne Marymont, Jeanette Pullen, Bruce Camitta, Naomi Winick, William Carroll, A. Kim Ritchey

Research output: Contribution to journalArticle

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Abstract

Purpose: Prognosis and outcome of children with isolated CNS relapse of acute lymphoblastic leukemia (ALL) has depended on duration of first complete remission (CR1). This study intensified systemic therapy by delaying CNS radiation for 12 months and tailored CNS radiation by CR1 duration. Patients and Methods: Seventy-six children with first isolated CNS relapse of ALL were treated with systemic chemotherapy that effectively penetrates into the CSF and intrathecal chemotherapy for 12 months. Patients with CR1 of less than 18 months received craniospinal radiation (24 Gy cranial/15 Gy spinal), whereas those with CR1 of 18 months or more received cranial radiation only (18 Gy), followed by maintenance chemotherapy. Additionally, asymptomatic patients were enrolled in a thiotepa up-front therapeutic window. Results: Seventy-four (97.4%) of 76 eligible patients achieved a second remission. Overall 4-year event-free survival (EFS) for the 71 precursor B-cell patients was 70.1% ± 5.8%. CR1 duration and National Cancer Institute (NCI; National Institutes of Health, Bethesda, MD) risk group at initial diagnosis predicted outcome. Patients with CR1 of less than 18 months and 18 months or more had a 4-year EFS of 51.6% ± 11.3% and 77.7% ± 6.4% (P = .027), respectively. NCI high-versus standard-risk 4-year EFS was 51.4% ± 10.8% and 80.2% ± 6.3% (P = .0018), respectively. A significant difference in EFS between standard risk/CR1 of at least 18 months and both high risk/CR1 of less than 18 months and high risk/CR1 of at least 18 months groups was detected (P = .0068 and .0314, respectively). Response rate to thiotepa was 78%. Most relapses involved the bone marrow, and three second malignancies were reported. Conclusion: Twelve months of intensive systemic chemotherapy with reduced dose cranial radiation (18 Gy) is highly effective for children with isolated CNS relapse and CR1 of 18 months or more. Novel strategies are needed for patients with CR1 of less than 18 months.

Original languageEnglish
Pages (from-to)3142-3149
Number of pages8
JournalJournal of Clinical Oncology
Volume24
Issue number19
DOIs
StatePublished - Jul 1 2006
Externally publishedYes

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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Radiation
Pediatrics
Recurrence
Drug Therapy
Disease-Free Survival
Thiotepa
Radiation Dosage
Maintenance Chemotherapy
B-Lymphoid Precursor Cells
Second Primary Neoplasms
National Cancer Institute (U.S.)
National Institutes of Health (U.S.)
Bone Marrow
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Isolated CNS relapse of acute lymphoblastic leukemia treated with intensive systemic chemotherapy and delayed CNS radiation : A pediatric oncology group study. / Barredo, Julio; Devidas, Meenakshi; Lauer, Stephen J.; Billett, Amy; Marymont, MaryAnne; Pullen, Jeanette; Camitta, Bruce; Winick, Naomi; Carroll, William; Ritchey, A. Kim.

In: Journal of Clinical Oncology, Vol. 24, No. 19, 01.07.2006, p. 3142-3149.

Research output: Contribution to journalArticle

Barredo, Julio ; Devidas, Meenakshi ; Lauer, Stephen J. ; Billett, Amy ; Marymont, MaryAnne ; Pullen, Jeanette ; Camitta, Bruce ; Winick, Naomi ; Carroll, William ; Ritchey, A. Kim. / Isolated CNS relapse of acute lymphoblastic leukemia treated with intensive systemic chemotherapy and delayed CNS radiation : A pediatric oncology group study. In: Journal of Clinical Oncology. 2006 ; Vol. 24, No. 19. pp. 3142-3149.
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abstract = "Purpose: Prognosis and outcome of children with isolated CNS relapse of acute lymphoblastic leukemia (ALL) has depended on duration of first complete remission (CR1). This study intensified systemic therapy by delaying CNS radiation for 12 months and tailored CNS radiation by CR1 duration. Patients and Methods: Seventy-six children with first isolated CNS relapse of ALL were treated with systemic chemotherapy that effectively penetrates into the CSF and intrathecal chemotherapy for 12 months. Patients with CR1 of less than 18 months received craniospinal radiation (24 Gy cranial/15 Gy spinal), whereas those with CR1 of 18 months or more received cranial radiation only (18 Gy), followed by maintenance chemotherapy. Additionally, asymptomatic patients were enrolled in a thiotepa up-front therapeutic window. Results: Seventy-four (97.4{\%}) of 76 eligible patients achieved a second remission. Overall 4-year event-free survival (EFS) for the 71 precursor B-cell patients was 70.1{\%} ± 5.8{\%}. CR1 duration and National Cancer Institute (NCI; National Institutes of Health, Bethesda, MD) risk group at initial diagnosis predicted outcome. Patients with CR1 of less than 18 months and 18 months or more had a 4-year EFS of 51.6{\%} ± 11.3{\%} and 77.7{\%} ± 6.4{\%} (P = .027), respectively. NCI high-versus standard-risk 4-year EFS was 51.4{\%} ± 10.8{\%} and 80.2{\%} ± 6.3{\%} (P = .0018), respectively. A significant difference in EFS between standard risk/CR1 of at least 18 months and both high risk/CR1 of less than 18 months and high risk/CR1 of at least 18 months groups was detected (P = .0068 and .0314, respectively). Response rate to thiotepa was 78{\%}. Most relapses involved the bone marrow, and three second malignancies were reported. Conclusion: Twelve months of intensive systemic chemotherapy with reduced dose cranial radiation (18 Gy) is highly effective for children with isolated CNS relapse and CR1 of 18 months or more. Novel strategies are needed for patients with CR1 of less than 18 months.",
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T2 - A pediatric oncology group study

AU - Barredo, Julio

AU - Devidas, Meenakshi

AU - Lauer, Stephen J.

AU - Billett, Amy

AU - Marymont, MaryAnne

AU - Pullen, Jeanette

AU - Camitta, Bruce

AU - Winick, Naomi

AU - Carroll, William

AU - Ritchey, A. Kim

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N2 - Purpose: Prognosis and outcome of children with isolated CNS relapse of acute lymphoblastic leukemia (ALL) has depended on duration of first complete remission (CR1). This study intensified systemic therapy by delaying CNS radiation for 12 months and tailored CNS radiation by CR1 duration. Patients and Methods: Seventy-six children with first isolated CNS relapse of ALL were treated with systemic chemotherapy that effectively penetrates into the CSF and intrathecal chemotherapy for 12 months. Patients with CR1 of less than 18 months received craniospinal radiation (24 Gy cranial/15 Gy spinal), whereas those with CR1 of 18 months or more received cranial radiation only (18 Gy), followed by maintenance chemotherapy. Additionally, asymptomatic patients were enrolled in a thiotepa up-front therapeutic window. Results: Seventy-four (97.4%) of 76 eligible patients achieved a second remission. Overall 4-year event-free survival (EFS) for the 71 precursor B-cell patients was 70.1% ± 5.8%. CR1 duration and National Cancer Institute (NCI; National Institutes of Health, Bethesda, MD) risk group at initial diagnosis predicted outcome. Patients with CR1 of less than 18 months and 18 months or more had a 4-year EFS of 51.6% ± 11.3% and 77.7% ± 6.4% (P = .027), respectively. NCI high-versus standard-risk 4-year EFS was 51.4% ± 10.8% and 80.2% ± 6.3% (P = .0018), respectively. A significant difference in EFS between standard risk/CR1 of at least 18 months and both high risk/CR1 of less than 18 months and high risk/CR1 of at least 18 months groups was detected (P = .0068 and .0314, respectively). Response rate to thiotepa was 78%. Most relapses involved the bone marrow, and three second malignancies were reported. Conclusion: Twelve months of intensive systemic chemotherapy with reduced dose cranial radiation (18 Gy) is highly effective for children with isolated CNS relapse and CR1 of 18 months or more. Novel strategies are needed for patients with CR1 of less than 18 months.

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