Dose intensification of methotrexate and cytarabine during intensified continuation chemotherapy for high-risk B-precursor acute lymphoblastic leukemia

POG 9406: A report from the children's oncology group

Richard L. Tower, Tamekia Jones, Bruce M. Camitta, Barbara L. Asselin, Beverly A. Bell, Allen Chauvenet, Meenakshi Devidas, Edward C. Halperin, Jeanette Pullen, Jonathan J. Shuster, Naomi Winick, Joanne Kurtzberg

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

PURPOSE: To determine the efficacy and toxicity of higher dose versus standard dose intravenous methotrexate (MTX) and pulses of high-dose cytosine arabinoside with asparaginase versus standard dose cytosine arabinoside and teniposide during intensified continuation therapy for higher risk pediatric B-precursor acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: From 1994 to 1999, the Pediatric Oncology Group conducted a randomized phase III clinical trial in higher risk pediatric B-precursor ALL. A total of 784 patients were randomized in a 2×2 factorial design to receive MTX 1 g/m versus 2.5 g/m and to cytosine arabinoside/teniposide versus high-dose cytosine arabinoside/asparaginase during intensified continuation therapy. RESULTS: Patients receiving standard dose MTX had a 5-year disease-free survival (DFS) of 71.8±2.4%; patients receiving higher dose MTX had a 5-year DFS of 71.7±2.4% (P=0.55). Outcomes on cytosine arabinoside/teniposide (DFS of 70.4±2.4) were similar to higher dose cytosine arabinoside/asparaginase (DFS of 73.1±2.3%) (P=0.41). Overall survival rates were not different between MTX doses or cytosine arabinoside/teniposide versus cytosine arabinoside/asparaginase. CONCLUSIONS: Increasing MTX dosing to 2.5 g/m did not improve outcomes in higher risk pediatric B-precursor ALL. Giving high-dose cytarabine and asparaginase pulses instead of standard dose cytarabine and teniposide produced nonsignificant differences in outcomes, allowing for teniposide to be removed from ALL therapy.

Original languageEnglish (US)
Pages (from-to)353-361
Number of pages9
JournalJournal of pediatric hematology/oncology
Volume36
Issue number5
DOIs
StatePublished - Jan 1 2014

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Cytarabine
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Methotrexate
Teniposide
Asparaginase
Drug Therapy
Disease-Free Survival
Pediatrics
Phase III Clinical Trials
Therapeutics
Survival Rate
Randomized Controlled Trials

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

Cite this

Dose intensification of methotrexate and cytarabine during intensified continuation chemotherapy for high-risk B-precursor acute lymphoblastic leukemia : POG 9406: A report from the children's oncology group. / Tower, Richard L.; Jones, Tamekia; Camitta, Bruce M.; Asselin, Barbara L.; Bell, Beverly A.; Chauvenet, Allen; Devidas, Meenakshi; Halperin, Edward C.; Pullen, Jeanette; Shuster, Jonathan J.; Winick, Naomi; Kurtzberg, Joanne.

In: Journal of pediatric hematology/oncology, Vol. 36, No. 5, 01.01.2014, p. 353-361.

Research output: Contribution to journalArticle

Tower, Richard L. ; Jones, Tamekia ; Camitta, Bruce M. ; Asselin, Barbara L. ; Bell, Beverly A. ; Chauvenet, Allen ; Devidas, Meenakshi ; Halperin, Edward C. ; Pullen, Jeanette ; Shuster, Jonathan J. ; Winick, Naomi ; Kurtzberg, Joanne. / Dose intensification of methotrexate and cytarabine during intensified continuation chemotherapy for high-risk B-precursor acute lymphoblastic leukemia : POG 9406: A report from the children's oncology group. In: Journal of pediatric hematology/oncology. 2014 ; Vol. 36, No. 5. pp. 353-361.
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abstract = "PURPOSE: To determine the efficacy and toxicity of higher dose versus standard dose intravenous methotrexate (MTX) and pulses of high-dose cytosine arabinoside with asparaginase versus standard dose cytosine arabinoside and teniposide during intensified continuation therapy for higher risk pediatric B-precursor acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: From 1994 to 1999, the Pediatric Oncology Group conducted a randomized phase III clinical trial in higher risk pediatric B-precursor ALL. A total of 784 patients were randomized in a 2×2 factorial design to receive MTX 1 g/m versus 2.5 g/m and to cytosine arabinoside/teniposide versus high-dose cytosine arabinoside/asparaginase during intensified continuation therapy. RESULTS: Patients receiving standard dose MTX had a 5-year disease-free survival (DFS) of 71.8±2.4{\%}; patients receiving higher dose MTX had a 5-year DFS of 71.7±2.4{\%} (P=0.55). Outcomes on cytosine arabinoside/teniposide (DFS of 70.4±2.4) were similar to higher dose cytosine arabinoside/asparaginase (DFS of 73.1±2.3{\%}) (P=0.41). Overall survival rates were not different between MTX doses or cytosine arabinoside/teniposide versus cytosine arabinoside/asparaginase. CONCLUSIONS: Increasing MTX dosing to 2.5 g/m did not improve outcomes in higher risk pediatric B-precursor ALL. Giving high-dose cytarabine and asparaginase pulses instead of standard dose cytarabine and teniposide produced nonsignificant differences in outcomes, allowing for teniposide to be removed from ALL therapy.",
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T1 - Dose intensification of methotrexate and cytarabine during intensified continuation chemotherapy for high-risk B-precursor acute lymphoblastic leukemia

T2 - POG 9406: A report from the children's oncology group

AU - Tower, Richard L.

AU - Jones, Tamekia

AU - Camitta, Bruce M.

AU - Asselin, Barbara L.

AU - Bell, Beverly A.

AU - Chauvenet, Allen

AU - Devidas, Meenakshi

AU - Halperin, Edward C.

AU - Pullen, Jeanette

AU - Shuster, Jonathan J.

AU - Winick, Naomi

AU - Kurtzberg, Joanne

PY - 2014/1/1

Y1 - 2014/1/1

N2 - PURPOSE: To determine the efficacy and toxicity of higher dose versus standard dose intravenous methotrexate (MTX) and pulses of high-dose cytosine arabinoside with asparaginase versus standard dose cytosine arabinoside and teniposide during intensified continuation therapy for higher risk pediatric B-precursor acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: From 1994 to 1999, the Pediatric Oncology Group conducted a randomized phase III clinical trial in higher risk pediatric B-precursor ALL. A total of 784 patients were randomized in a 2×2 factorial design to receive MTX 1 g/m versus 2.5 g/m and to cytosine arabinoside/teniposide versus high-dose cytosine arabinoside/asparaginase during intensified continuation therapy. RESULTS: Patients receiving standard dose MTX had a 5-year disease-free survival (DFS) of 71.8±2.4%; patients receiving higher dose MTX had a 5-year DFS of 71.7±2.4% (P=0.55). Outcomes on cytosine arabinoside/teniposide (DFS of 70.4±2.4) were similar to higher dose cytosine arabinoside/asparaginase (DFS of 73.1±2.3%) (P=0.41). Overall survival rates were not different between MTX doses or cytosine arabinoside/teniposide versus cytosine arabinoside/asparaginase. CONCLUSIONS: Increasing MTX dosing to 2.5 g/m did not improve outcomes in higher risk pediatric B-precursor ALL. Giving high-dose cytarabine and asparaginase pulses instead of standard dose cytarabine and teniposide produced nonsignificant differences in outcomes, allowing for teniposide to be removed from ALL therapy.

AB - PURPOSE: To determine the efficacy and toxicity of higher dose versus standard dose intravenous methotrexate (MTX) and pulses of high-dose cytosine arabinoside with asparaginase versus standard dose cytosine arabinoside and teniposide during intensified continuation therapy for higher risk pediatric B-precursor acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: From 1994 to 1999, the Pediatric Oncology Group conducted a randomized phase III clinical trial in higher risk pediatric B-precursor ALL. A total of 784 patients were randomized in a 2×2 factorial design to receive MTX 1 g/m versus 2.5 g/m and to cytosine arabinoside/teniposide versus high-dose cytosine arabinoside/asparaginase during intensified continuation therapy. RESULTS: Patients receiving standard dose MTX had a 5-year disease-free survival (DFS) of 71.8±2.4%; patients receiving higher dose MTX had a 5-year DFS of 71.7±2.4% (P=0.55). Outcomes on cytosine arabinoside/teniposide (DFS of 70.4±2.4) were similar to higher dose cytosine arabinoside/asparaginase (DFS of 73.1±2.3%) (P=0.41). Overall survival rates were not different between MTX doses or cytosine arabinoside/teniposide versus cytosine arabinoside/asparaginase. CONCLUSIONS: Increasing MTX dosing to 2.5 g/m did not improve outcomes in higher risk pediatric B-precursor ALL. Giving high-dose cytarabine and asparaginase pulses instead of standard dose cytarabine and teniposide produced nonsignificant differences in outcomes, allowing for teniposide to be removed from ALL therapy.

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