An intensive re-treatment protocol for children with an isolated CNS relapse of acute lymphoblastic leukemia

Raul C. Ribeiro, Gaston K. Rivera, Melissa Hudson, Raymond K. Mulhern, Michael L. Hancock, Larry Kun, Hazem Mahmoud, John T. Sandlund, William M. Crist, Ching Hon Pui

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Abstract

Purpose: To assess the salvage rate and long-term complications among children treated with an intensive regimen for isolated CNS relapse during first remission of acute lymphoblastic leukemia (ALL). Patients and Methods: Twelve boys and eight girls, diagnosed at a median age of 4 years, had CNS relapse at a median age of 7 years. Five had CNS leukemia at presentation, while five completed treatment before relapse. First complete remission lasted a median of 22.5 months. Ten patients had received cranial irradiation plus intrathecal (IT) therapy, and the remainder had received high-dose intravenous and/or IT methotrexate (MTX) as CNS-directed treatment. Retrieval therapy consisted of a five-agent intensive reinduction regimen followed by continuation therapy with four rotating drug pairs. Triple-IT therapy was administered weekly for 4 to 5 weeks, then every 6 weeks until craniospinal radiation (cranium, 24 Gy; spine, 15 Gy; both sites, 1.5 Gy per fraction) was administered. Results: All 20 children achieved a second complete remission. The 5-year estimate of disease-free survival (mean ± SE) was 70% ± 11%. Thirteen patients remain in remission at 71+ to 126+ months (median, 104+), and 10 of 13 patients tested have normal IQ scores. Four patients have had a second relapse (one CNS and three non-CNS), and three have developed other malignancies. Prior cranial irradiation was associated with subsequent failure; only three of 10 patients who previously received radiotherapy, compared with all of the other 10 patients, remained in second remission. Conclusion: This intensive retrieval therapy is effective and well tolerated by children with an isolated CNS relapse of ALL, especially those who have not received prior cranial irradiation. Most patients have no significant neuropsychologic impairment.

Original languageEnglish (US)
Pages (from-to)333-338
Number of pages6
JournalJournal of Clinical Oncology
Volume13
Issue number2
StatePublished - Feb 1 1995

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Clinical Protocols
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Recurrence
Cranial Irradiation
Therapeutics
Skull
Methotrexate
Disease-Free Survival
Leukemia
Spine
Radiotherapy
Radiation
Pharmaceutical Preparations
Neoplasms

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Ribeiro, R. C., Rivera, G. K., Hudson, M., Mulhern, R. K., Hancock, M. L., Kun, L., ... Pui, C. H. (1995). An intensive re-treatment protocol for children with an isolated CNS relapse of acute lymphoblastic leukemia. Journal of Clinical Oncology, 13(2), 333-338.

An intensive re-treatment protocol for children with an isolated CNS relapse of acute lymphoblastic leukemia. / Ribeiro, Raul C.; Rivera, Gaston K.; Hudson, Melissa; Mulhern, Raymond K.; Hancock, Michael L.; Kun, Larry; Mahmoud, Hazem; Sandlund, John T.; Crist, William M.; Pui, Ching Hon.

In: Journal of Clinical Oncology, Vol. 13, No. 2, 01.02.1995, p. 333-338.

Research output: Contribution to journalArticle

Ribeiro, RC, Rivera, GK, Hudson, M, Mulhern, RK, Hancock, ML, Kun, L, Mahmoud, H, Sandlund, JT, Crist, WM & Pui, CH 1995, 'An intensive re-treatment protocol for children with an isolated CNS relapse of acute lymphoblastic leukemia', Journal of Clinical Oncology, vol. 13, no. 2, pp. 333-338.
Ribeiro, Raul C. ; Rivera, Gaston K. ; Hudson, Melissa ; Mulhern, Raymond K. ; Hancock, Michael L. ; Kun, Larry ; Mahmoud, Hazem ; Sandlund, John T. ; Crist, William M. ; Pui, Ching Hon. / An intensive re-treatment protocol for children with an isolated CNS relapse of acute lymphoblastic leukemia. In: Journal of Clinical Oncology. 1995 ; Vol. 13, No. 2. pp. 333-338.
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abstract = "Purpose: To assess the salvage rate and long-term complications among children treated with an intensive regimen for isolated CNS relapse during first remission of acute lymphoblastic leukemia (ALL). Patients and Methods: Twelve boys and eight girls, diagnosed at a median age of 4 years, had CNS relapse at a median age of 7 years. Five had CNS leukemia at presentation, while five completed treatment before relapse. First complete remission lasted a median of 22.5 months. Ten patients had received cranial irradiation plus intrathecal (IT) therapy, and the remainder had received high-dose intravenous and/or IT methotrexate (MTX) as CNS-directed treatment. Retrieval therapy consisted of a five-agent intensive reinduction regimen followed by continuation therapy with four rotating drug pairs. Triple-IT therapy was administered weekly for 4 to 5 weeks, then every 6 weeks until craniospinal radiation (cranium, 24 Gy; spine, 15 Gy; both sites, 1.5 Gy per fraction) was administered. Results: All 20 children achieved a second complete remission. The 5-year estimate of disease-free survival (mean ± SE) was 70{\%} ± 11{\%}. Thirteen patients remain in remission at 71+ to 126+ months (median, 104+), and 10 of 13 patients tested have normal IQ scores. Four patients have had a second relapse (one CNS and three non-CNS), and three have developed other malignancies. Prior cranial irradiation was associated with subsequent failure; only three of 10 patients who previously received radiotherapy, compared with all of the other 10 patients, remained in second remission. Conclusion: This intensive retrieval therapy is effective and well tolerated by children with an isolated CNS relapse of ALL, especially those who have not received prior cranial irradiation. Most patients have no significant neuropsychologic impairment.",
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AU - Hancock, Michael L.

AU - Kun, Larry

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AU - Crist, William M.

AU - Pui, Ching Hon

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N2 - Purpose: To assess the salvage rate and long-term complications among children treated with an intensive regimen for isolated CNS relapse during first remission of acute lymphoblastic leukemia (ALL). Patients and Methods: Twelve boys and eight girls, diagnosed at a median age of 4 years, had CNS relapse at a median age of 7 years. Five had CNS leukemia at presentation, while five completed treatment before relapse. First complete remission lasted a median of 22.5 months. Ten patients had received cranial irradiation plus intrathecal (IT) therapy, and the remainder had received high-dose intravenous and/or IT methotrexate (MTX) as CNS-directed treatment. Retrieval therapy consisted of a five-agent intensive reinduction regimen followed by continuation therapy with four rotating drug pairs. Triple-IT therapy was administered weekly for 4 to 5 weeks, then every 6 weeks until craniospinal radiation (cranium, 24 Gy; spine, 15 Gy; both sites, 1.5 Gy per fraction) was administered. Results: All 20 children achieved a second complete remission. The 5-year estimate of disease-free survival (mean ± SE) was 70% ± 11%. Thirteen patients remain in remission at 71+ to 126+ months (median, 104+), and 10 of 13 patients tested have normal IQ scores. Four patients have had a second relapse (one CNS and three non-CNS), and three have developed other malignancies. Prior cranial irradiation was associated with subsequent failure; only three of 10 patients who previously received radiotherapy, compared with all of the other 10 patients, remained in second remission. Conclusion: This intensive retrieval therapy is effective and well tolerated by children with an isolated CNS relapse of ALL, especially those who have not received prior cranial irradiation. Most patients have no significant neuropsychologic impairment.

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