Pilot study of nelarabine in combination with intensive chemotherapy in high-risk T-cell acute lymphoblastic leukemia

A report from the Children's Oncology Group

Kimberly P. Dunsmore, Meenakshi Devidas, Stephen B. Linda, Michael J. Borowitz, Naomi Winick, Stephen P. Hunger, William L. Carroll, Bruce M. Camitta

Research output: Contribution to journalArticle

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Abstract

Purpose: Children's Oncology Group study AALL00P2 was designed to assess the feasibility and safety of adding nelarabine to a BFM 86-based chemotherapy regimen in children with newly diagnosed T-cell acute lymphoblastic leukemia (T-ALL). Patients and Methods: In stage one of the study, eight patients with a slow early response (SER) by prednisone poor response (PPR; ≥ 1,000 peripheral blood blasts on day 8 of prednisone prephase) received chemotherapy plus six courses of nelarabine 400 mg/m2 once per day; four patients with SER by high minimal residual disease (MRD; ≥ 1% at day 36 of induction) received chemotherapy plus five courses of nelarabine; 16 patients with a rapid early response (RER) received chemotherapy without nelarabine. In stage two, all patients received six 5-day courses of nelarabine at 650 mg/m 2 once per day (10 SER patients [one by MRD, nine by PPR]) or 400 mg/m 2 once per day (38 RER patients; 12 SER patients [three by MRD, nine by PPR]). Results: The only significant difference in toxicities was decreased neutropenic infections in patients treated with nelarabine (42% with v 81% without nelarabine). Five-year event-free survival (EFS) rates were 73% for 11 stage one SER patients and 67% for 22 stage two SER patients treated with nelarabine versus 69% for 16 stage one RER patients treated without nelarabine and 74% for 38 stage two RER patients treated with nelarabine. Five-year EFS for all patients receiving nelarabine (n = 70) was 73% versus 69% for those treated without nelarabine (n = 16). Conclusion: Addition of nelarabine to a BFM 86-based chemotherapy regimen was well tolerated and produced encouraging results in pediatric patients with T-ALL, particularly those with a SER, who have historically fared poorly.

Original languageEnglish (US)
Pages (from-to)2753-2759
Number of pages7
JournalJournal of Clinical Oncology
Volume30
Issue number22
DOIs
StatePublished - Aug 1 2012

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Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Drug Therapy
nelarabine
Prednisone
Disease-Free Survival
Induction Chemotherapy
Residual Neoplasm

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Pilot study of nelarabine in combination with intensive chemotherapy in high-risk T-cell acute lymphoblastic leukemia : A report from the Children's Oncology Group. / Dunsmore, Kimberly P.; Devidas, Meenakshi; Linda, Stephen B.; Borowitz, Michael J.; Winick, Naomi; Hunger, Stephen P.; Carroll, William L.; Camitta, Bruce M.

In: Journal of Clinical Oncology, Vol. 30, No. 22, 01.08.2012, p. 2753-2759.

Research output: Contribution to journalArticle

Dunsmore, Kimberly P. ; Devidas, Meenakshi ; Linda, Stephen B. ; Borowitz, Michael J. ; Winick, Naomi ; Hunger, Stephen P. ; Carroll, William L. ; Camitta, Bruce M. / Pilot study of nelarabine in combination with intensive chemotherapy in high-risk T-cell acute lymphoblastic leukemia : A report from the Children's Oncology Group. In: Journal of Clinical Oncology. 2012 ; Vol. 30, No. 22. pp. 2753-2759.
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title = "Pilot study of nelarabine in combination with intensive chemotherapy in high-risk T-cell acute lymphoblastic leukemia: A report from the Children's Oncology Group",
abstract = "Purpose: Children's Oncology Group study AALL00P2 was designed to assess the feasibility and safety of adding nelarabine to a BFM 86-based chemotherapy regimen in children with newly diagnosed T-cell acute lymphoblastic leukemia (T-ALL). Patients and Methods: In stage one of the study, eight patients with a slow early response (SER) by prednisone poor response (PPR; ≥ 1,000 peripheral blood blasts on day 8 of prednisone prephase) received chemotherapy plus six courses of nelarabine 400 mg/m2 once per day; four patients with SER by high minimal residual disease (MRD; ≥ 1{\%} at day 36 of induction) received chemotherapy plus five courses of nelarabine; 16 patients with a rapid early response (RER) received chemotherapy without nelarabine. In stage two, all patients received six 5-day courses of nelarabine at 650 mg/m 2 once per day (10 SER patients [one by MRD, nine by PPR]) or 400 mg/m 2 once per day (38 RER patients; 12 SER patients [three by MRD, nine by PPR]). Results: The only significant difference in toxicities was decreased neutropenic infections in patients treated with nelarabine (42{\%} with v 81{\%} without nelarabine). Five-year event-free survival (EFS) rates were 73{\%} for 11 stage one SER patients and 67{\%} for 22 stage two SER patients treated with nelarabine versus 69{\%} for 16 stage one RER patients treated without nelarabine and 74{\%} for 38 stage two RER patients treated with nelarabine. Five-year EFS for all patients receiving nelarabine (n = 70) was 73{\%} versus 69{\%} for those treated without nelarabine (n = 16). Conclusion: Addition of nelarabine to a BFM 86-based chemotherapy regimen was well tolerated and produced encouraging results in pediatric patients with T-ALL, particularly those with a SER, who have historically fared poorly.",
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T2 - A report from the Children's Oncology Group

AU - Dunsmore, Kimberly P.

AU - Devidas, Meenakshi

AU - Linda, Stephen B.

AU - Borowitz, Michael J.

AU - Winick, Naomi

AU - Hunger, Stephen P.

AU - Carroll, William L.

AU - Camitta, Bruce M.

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N2 - Purpose: Children's Oncology Group study AALL00P2 was designed to assess the feasibility and safety of adding nelarabine to a BFM 86-based chemotherapy regimen in children with newly diagnosed T-cell acute lymphoblastic leukemia (T-ALL). Patients and Methods: In stage one of the study, eight patients with a slow early response (SER) by prednisone poor response (PPR; ≥ 1,000 peripheral blood blasts on day 8 of prednisone prephase) received chemotherapy plus six courses of nelarabine 400 mg/m2 once per day; four patients with SER by high minimal residual disease (MRD; ≥ 1% at day 36 of induction) received chemotherapy plus five courses of nelarabine; 16 patients with a rapid early response (RER) received chemotherapy without nelarabine. In stage two, all patients received six 5-day courses of nelarabine at 650 mg/m 2 once per day (10 SER patients [one by MRD, nine by PPR]) or 400 mg/m 2 once per day (38 RER patients; 12 SER patients [three by MRD, nine by PPR]). Results: The only significant difference in toxicities was decreased neutropenic infections in patients treated with nelarabine (42% with v 81% without nelarabine). Five-year event-free survival (EFS) rates were 73% for 11 stage one SER patients and 67% for 22 stage two SER patients treated with nelarabine versus 69% for 16 stage one RER patients treated without nelarabine and 74% for 38 stage two RER patients treated with nelarabine. Five-year EFS for all patients receiving nelarabine (n = 70) was 73% versus 69% for those treated without nelarabine (n = 16). Conclusion: Addition of nelarabine to a BFM 86-based chemotherapy regimen was well tolerated and produced encouraging results in pediatric patients with T-ALL, particularly those with a SER, who have historically fared poorly.

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