Augmented therapy improves outcome for pediatric high risk acute lymphocytic leukemia

Results of Children's Oncology Group trial P9906

W. Paul Bowman, Eric L. Larsen, Meenakshi Devidas, Stephen B. Linda, Laurie Blach, Andrew J. Carroll, William L. Carroll, D. Jeanette Pullen, Jonathan Shuster, Cheryl L. Willman, Naomi Winick, Bruce M. Camitta, Stephen P. Hunger, Michael J Borowitz

Research output: Contribution to journalArticle

Abstract

Background: The augmented BFM regimen improves outcome for children with NCI high acute lymphoblastic leukemia (ALL). Patient age, sex, and presenting white blood cell count (WBC) can be used to identify a subset of approximately 12% of children with B-precursor ALL that had a 5-year continuous complete remission (CCR) rate of only about 50% on earlier Pediatric Oncology Group (POG) trials. Procedures: Children's Oncology Group trial P9906 evaluated a modified augmented BFM regimen in 267 patients with particularly high risk B-precursor ALL. Minimal residual disease (MRD) was assessed in blood at day 8 and in marrow at day 29 of induction and correlated with outcome. Results: The 5-year CCR probability for patients in P9906 was significantly better than that observed for similar patients on POG trials 8602/9006 (62.2±3.7% vs. 50.6±2.4%; P=0.0007) but similar to POG 9406 (63.5±2.4%; P=0.81). Interim analysis showed poor central nervous system (CNS) control, especially in patients with initial WBC ≥100,000/microliter. Day 29 marrow MRD positive (≥0.01%) vs. negative patients had 5 year CCR rates of 37.1±7.4% vs. 72.6±4.3%; day 8 blood MRD positive vs. negative patients had 5 year CCR rates of 57.1±4.6% vs.83.6±6.3%. End induction marrow MRD predicted marrow but not CNS relapse. In multivariate analysis, day 29 MRD>0.01%, initial WBC≥100,000/μl, male gender, and day 8 blood MRD>0.01% were significant prognostic factors. Conclusions: Augmented BFM therapy improved outcome for children with higher risk ALL. Day 8 blood and day 29 marrow MRD were strong prognostic factors in these patients.

Original languageEnglish (US)
Pages (from-to)569-577
Number of pages9
JournalPediatric Blood and Cancer
Volume57
Issue number4
DOIs
StatePublished - Oct 2011

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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Residual Neoplasm
Pediatrics
Bone Marrow
Therapeutics
Leukocyte Count
Central Nervous System
Multivariate Analysis
Recurrence

Keywords

  • Acute lymphocytic leukemia
  • Minimal residual disease
  • Phase III clinical trial
  • Prognostic factors

ASJC Scopus subject areas

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

Cite this

Augmented therapy improves outcome for pediatric high risk acute lymphocytic leukemia : Results of Children's Oncology Group trial P9906. / Bowman, W. Paul; Larsen, Eric L.; Devidas, Meenakshi; Linda, Stephen B.; Blach, Laurie; Carroll, Andrew J.; Carroll, William L.; Pullen, D. Jeanette; Shuster, Jonathan; Willman, Cheryl L.; Winick, Naomi; Camitta, Bruce M.; Hunger, Stephen P.; Borowitz, Michael J.

In: Pediatric Blood and Cancer, Vol. 57, No. 4, 10.2011, p. 569-577.

Research output: Contribution to journalArticle

Bowman, WP, Larsen, EL, Devidas, M, Linda, SB, Blach, L, Carroll, AJ, Carroll, WL, Pullen, DJ, Shuster, J, Willman, CL, Winick, N, Camitta, BM, Hunger, SP & Borowitz, MJ 2011, 'Augmented therapy improves outcome for pediatric high risk acute lymphocytic leukemia: Results of Children's Oncology Group trial P9906', Pediatric Blood and Cancer, vol. 57, no. 4, pp. 569-577. https://doi.org/10.1002/pbc.22944
Bowman, W. Paul ; Larsen, Eric L. ; Devidas, Meenakshi ; Linda, Stephen B. ; Blach, Laurie ; Carroll, Andrew J. ; Carroll, William L. ; Pullen, D. Jeanette ; Shuster, Jonathan ; Willman, Cheryl L. ; Winick, Naomi ; Camitta, Bruce M. ; Hunger, Stephen P. ; Borowitz, Michael J. / Augmented therapy improves outcome for pediatric high risk acute lymphocytic leukemia : Results of Children's Oncology Group trial P9906. In: Pediatric Blood and Cancer. 2011 ; Vol. 57, No. 4. pp. 569-577.
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abstract = "Background: The augmented BFM regimen improves outcome for children with NCI high acute lymphoblastic leukemia (ALL). Patient age, sex, and presenting white blood cell count (WBC) can be used to identify a subset of approximately 12{\%} of children with B-precursor ALL that had a 5-year continuous complete remission (CCR) rate of only about 50{\%} on earlier Pediatric Oncology Group (POG) trials. Procedures: Children's Oncology Group trial P9906 evaluated a modified augmented BFM regimen in 267 patients with particularly high risk B-precursor ALL. Minimal residual disease (MRD) was assessed in blood at day 8 and in marrow at day 29 of induction and correlated with outcome. Results: The 5-year CCR probability for patients in P9906 was significantly better than that observed for similar patients on POG trials 8602/9006 (62.2±3.7{\%} vs. 50.6±2.4{\%}; P=0.0007) but similar to POG 9406 (63.5±2.4{\%}; P=0.81). Interim analysis showed poor central nervous system (CNS) control, especially in patients with initial WBC ≥100,000/microliter. Day 29 marrow MRD positive (≥0.01{\%}) vs. negative patients had 5 year CCR rates of 37.1±7.4{\%} vs. 72.6±4.3{\%}; day 8 blood MRD positive vs. negative patients had 5 year CCR rates of 57.1±4.6{\%} vs.83.6±6.3{\%}. End induction marrow MRD predicted marrow but not CNS relapse. In multivariate analysis, day 29 MRD>0.01{\%}, initial WBC≥100,000/μl, male gender, and day 8 blood MRD>0.01{\%} were significant prognostic factors. Conclusions: Augmented BFM therapy improved outcome for children with higher risk ALL. Day 8 blood and day 29 marrow MRD were strong prognostic factors in these patients.",
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author = "Bowman, {W. Paul} and Larsen, {Eric L.} and Meenakshi Devidas and Linda, {Stephen B.} and Laurie Blach and Carroll, {Andrew J.} and Carroll, {William L.} and Pullen, {D. Jeanette} and Jonathan Shuster and Willman, {Cheryl L.} and Naomi Winick and Camitta, {Bruce M.} and Hunger, {Stephen P.} and Borowitz, {Michael J}",
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AU - Devidas, Meenakshi

AU - Linda, Stephen B.

AU - Blach, Laurie

AU - Carroll, Andrew J.

AU - Carroll, William L.

AU - Pullen, D. Jeanette

AU - Shuster, Jonathan

AU - Willman, Cheryl L.

AU - Winick, Naomi

AU - Camitta, Bruce M.

AU - Hunger, Stephen P.

AU - Borowitz, Michael J

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N2 - Background: The augmented BFM regimen improves outcome for children with NCI high acute lymphoblastic leukemia (ALL). Patient age, sex, and presenting white blood cell count (WBC) can be used to identify a subset of approximately 12% of children with B-precursor ALL that had a 5-year continuous complete remission (CCR) rate of only about 50% on earlier Pediatric Oncology Group (POG) trials. Procedures: Children's Oncology Group trial P9906 evaluated a modified augmented BFM regimen in 267 patients with particularly high risk B-precursor ALL. Minimal residual disease (MRD) was assessed in blood at day 8 and in marrow at day 29 of induction and correlated with outcome. Results: The 5-year CCR probability for patients in P9906 was significantly better than that observed for similar patients on POG trials 8602/9006 (62.2±3.7% vs. 50.6±2.4%; P=0.0007) but similar to POG 9406 (63.5±2.4%; P=0.81). Interim analysis showed poor central nervous system (CNS) control, especially in patients with initial WBC ≥100,000/microliter. Day 29 marrow MRD positive (≥0.01%) vs. negative patients had 5 year CCR rates of 37.1±7.4% vs. 72.6±4.3%; day 8 blood MRD positive vs. negative patients had 5 year CCR rates of 57.1±4.6% vs.83.6±6.3%. End induction marrow MRD predicted marrow but not CNS relapse. In multivariate analysis, day 29 MRD>0.01%, initial WBC≥100,000/μl, male gender, and day 8 blood MRD>0.01% were significant prognostic factors. Conclusions: Augmented BFM therapy improved outcome for children with higher risk ALL. Day 8 blood and day 29 marrow MRD were strong prognostic factors in these patients.

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