Intensive oral methotrexate protects against lymphoid marrow relapse in childhood B-precursor acute lymphoblastic leukemia

N. Winick, J. J. Shuster, W. P. Bowman, M. Borowitz, A. Farrow, D. Jacaruso, G. R. Buchanan, B. A. Kamen

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Abstract

Purpose: To describe the use of combination chemotherapy, including divided-dose oral methotrexate (dMTX), for children with B-precursor acute lymphoblastic leukemia (ALL). dMTX produced prolonged MTX exposure on an outpatient basis. Patients and Methods: Two hundred forty-three patients were treated from January 1986 to May 1992. dMTX was given weekly during consolidation and biweekly for the first 16 months of continuation therapy with mercaptopurine (6-MP) and asparaginase (L-ASP). Initially, etaposide (VP-16) and cytarabine (Aro-C) pulses were included. Treatment continued for 30 months with single-dose weekly MTX replacing dMTX during continuation, part 2. Unexpected acute neurotoxicity was eliminated by the addition of leucovorin. VP-16 and Ara-C were omitted in the face of acute myelogenous leukemia (AML). Results: Two hundred thirty-nine patients entered remission: 16 had a lymphoid marrow relapse, two each with testicular or CNS relapse; 19 a CNS relapse; 16 secondary AML; three other second malignancies; two withdrew for transplant; three died in remission; 16 withdrew because of noncompliance, and nine withdrew with toxicity. Event-free survival (EFS) at 4 years was 73 ± 4%; 81 ± 4% for 150 patients with better risk features and 60 ± 7% for 93 with high-risk features. Lymphoid marrow relapse-free survival in the standard- and highrisk patients was 94 ± 3% and 86% ± 6%, respectively. The most common adverse event was secondary AML in the standard-risk group and isolated CNS relapse in the high-risk group. Conclusion: This therapy produced an overall EFS similar to other published regimens, but the pattern of failures is very different, with few patients having a lymphoid marrow relapse. These data suggest that highly effective therapy for children with ALL can be delivered on an outpatient basis using a regimen featuring repetitive dMTX.

Original languageEnglish (US)
Pages (from-to)2803-2811
Number of pages9
JournalJournal of Clinical Oncology
Volume14
Issue number10
StatePublished - 1996

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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Methotrexate
Bone Marrow
Recurrence
Acute Myeloid Leukemia
Cytarabine
Etoposide
Disease-Free Survival
Outpatients
Asparaginase
6-Mercaptopurine
Second Primary Neoplasms
Leucovorin
Therapeutics
Combination Drug Therapy
Transplants
Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Winick, N., Shuster, J. J., Bowman, W. P., Borowitz, M., Farrow, A., Jacaruso, D., ... Kamen, B. A. (1996). Intensive oral methotrexate protects against lymphoid marrow relapse in childhood B-precursor acute lymphoblastic leukemia. Journal of Clinical Oncology, 14(10), 2803-2811.

Intensive oral methotrexate protects against lymphoid marrow relapse in childhood B-precursor acute lymphoblastic leukemia. / Winick, N.; Shuster, J. J.; Bowman, W. P.; Borowitz, M.; Farrow, A.; Jacaruso, D.; Buchanan, G. R.; Kamen, B. A.

In: Journal of Clinical Oncology, Vol. 14, No. 10, 1996, p. 2803-2811.

Research output: Contribution to journalArticle

Winick, N, Shuster, JJ, Bowman, WP, Borowitz, M, Farrow, A, Jacaruso, D, Buchanan, GR & Kamen, BA 1996, 'Intensive oral methotrexate protects against lymphoid marrow relapse in childhood B-precursor acute lymphoblastic leukemia', Journal of Clinical Oncology, vol. 14, no. 10, pp. 2803-2811.
Winick, N. ; Shuster, J. J. ; Bowman, W. P. ; Borowitz, M. ; Farrow, A. ; Jacaruso, D. ; Buchanan, G. R. ; Kamen, B. A. / Intensive oral methotrexate protects against lymphoid marrow relapse in childhood B-precursor acute lymphoblastic leukemia. In: Journal of Clinical Oncology. 1996 ; Vol. 14, No. 10. pp. 2803-2811.
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abstract = "Purpose: To describe the use of combination chemotherapy, including divided-dose oral methotrexate (dMTX), for children with B-precursor acute lymphoblastic leukemia (ALL). dMTX produced prolonged MTX exposure on an outpatient basis. Patients and Methods: Two hundred forty-three patients were treated from January 1986 to May 1992. dMTX was given weekly during consolidation and biweekly for the first 16 months of continuation therapy with mercaptopurine (6-MP) and asparaginase (L-ASP). Initially, etaposide (VP-16) and cytarabine (Aro-C) pulses were included. Treatment continued for 30 months with single-dose weekly MTX replacing dMTX during continuation, part 2. Unexpected acute neurotoxicity was eliminated by the addition of leucovorin. VP-16 and Ara-C were omitted in the face of acute myelogenous leukemia (AML). Results: Two hundred thirty-nine patients entered remission: 16 had a lymphoid marrow relapse, two each with testicular or CNS relapse; 19 a CNS relapse; 16 secondary AML; three other second malignancies; two withdrew for transplant; three died in remission; 16 withdrew because of noncompliance, and nine withdrew with toxicity. Event-free survival (EFS) at 4 years was 73 ± 4{\%}; 81 ± 4{\%} for 150 patients with better risk features and 60 ± 7{\%} for 93 with high-risk features. Lymphoid marrow relapse-free survival in the standard- and highrisk patients was 94 ± 3{\%} and 86{\%} ± 6{\%}, respectively. The most common adverse event was secondary AML in the standard-risk group and isolated CNS relapse in the high-risk group. Conclusion: This therapy produced an overall EFS similar to other published regimens, but the pattern of failures is very different, with few patients having a lymphoid marrow relapse. These data suggest that highly effective therapy for children with ALL can be delivered on an outpatient basis using a regimen featuring repetitive dMTX.",
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T1 - Intensive oral methotrexate protects against lymphoid marrow relapse in childhood B-precursor acute lymphoblastic leukemia

AU - Winick, N.

AU - Shuster, J. J.

AU - Bowman, W. P.

AU - Borowitz, M.

AU - Farrow, A.

AU - Jacaruso, D.

AU - Buchanan, G. R.

AU - Kamen, B. A.

PY - 1996

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N2 - Purpose: To describe the use of combination chemotherapy, including divided-dose oral methotrexate (dMTX), for children with B-precursor acute lymphoblastic leukemia (ALL). dMTX produced prolonged MTX exposure on an outpatient basis. Patients and Methods: Two hundred forty-three patients were treated from January 1986 to May 1992. dMTX was given weekly during consolidation and biweekly for the first 16 months of continuation therapy with mercaptopurine (6-MP) and asparaginase (L-ASP). Initially, etaposide (VP-16) and cytarabine (Aro-C) pulses were included. Treatment continued for 30 months with single-dose weekly MTX replacing dMTX during continuation, part 2. Unexpected acute neurotoxicity was eliminated by the addition of leucovorin. VP-16 and Ara-C were omitted in the face of acute myelogenous leukemia (AML). Results: Two hundred thirty-nine patients entered remission: 16 had a lymphoid marrow relapse, two each with testicular or CNS relapse; 19 a CNS relapse; 16 secondary AML; three other second malignancies; two withdrew for transplant; three died in remission; 16 withdrew because of noncompliance, and nine withdrew with toxicity. Event-free survival (EFS) at 4 years was 73 ± 4%; 81 ± 4% for 150 patients with better risk features and 60 ± 7% for 93 with high-risk features. Lymphoid marrow relapse-free survival in the standard- and highrisk patients was 94 ± 3% and 86% ± 6%, respectively. The most common adverse event was secondary AML in the standard-risk group and isolated CNS relapse in the high-risk group. Conclusion: This therapy produced an overall EFS similar to other published regimens, but the pattern of failures is very different, with few patients having a lymphoid marrow relapse. These data suggest that highly effective therapy for children with ALL can be delivered on an outpatient basis using a regimen featuring repetitive dMTX.

AB - Purpose: To describe the use of combination chemotherapy, including divided-dose oral methotrexate (dMTX), for children with B-precursor acute lymphoblastic leukemia (ALL). dMTX produced prolonged MTX exposure on an outpatient basis. Patients and Methods: Two hundred forty-three patients were treated from January 1986 to May 1992. dMTX was given weekly during consolidation and biweekly for the first 16 months of continuation therapy with mercaptopurine (6-MP) and asparaginase (L-ASP). Initially, etaposide (VP-16) and cytarabine (Aro-C) pulses were included. Treatment continued for 30 months with single-dose weekly MTX replacing dMTX during continuation, part 2. Unexpected acute neurotoxicity was eliminated by the addition of leucovorin. VP-16 and Ara-C were omitted in the face of acute myelogenous leukemia (AML). Results: Two hundred thirty-nine patients entered remission: 16 had a lymphoid marrow relapse, two each with testicular or CNS relapse; 19 a CNS relapse; 16 secondary AML; three other second malignancies; two withdrew for transplant; three died in remission; 16 withdrew because of noncompliance, and nine withdrew with toxicity. Event-free survival (EFS) at 4 years was 73 ± 4%; 81 ± 4% for 150 patients with better risk features and 60 ± 7% for 93 with high-risk features. Lymphoid marrow relapse-free survival in the standard- and highrisk patients was 94 ± 3% and 86% ± 6%, respectively. The most common adverse event was secondary AML in the standard-risk group and isolated CNS relapse in the high-risk group. Conclusion: This therapy produced an overall EFS similar to other published regimens, but the pattern of failures is very different, with few patients having a lymphoid marrow relapse. These data suggest that highly effective therapy for children with ALL can be delivered on an outpatient basis using a regimen featuring repetitive dMTX.

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