Reinduction platform for children with first marrow relapse in acute lymphoblastic lymphoma

Elizabeth A. Raetz, Michael J Borowitz, Meenakshi Devidas, Stephen B. Linda, Stephen P. Hunger, Naomi J. Winick, Bruce M. Camitta, Paul S. Gaynon, William L. Carroll

Research output: Contribution to journalArticle

Abstract

Purpose: Treatment of childhood relapsed acute lymphoblastic leukemia (ALL) remains a significant challenge. The goal of the Children's Oncology Group (COG) AALL01P2 study was to develop a safe and active chemotherapy reinduction platform, which could be used to evaluate novel agents in future trials. Patients and Methods: One hundred twenty-four patients with ALL and first marrow relapse received three, 35-day blocks of reinduction chemotherapy: 69 with early relapse (ER; <36 months from initial diagnosis) and 55 with late relapse (LR). Minimal residual disease (MRD) was measured by flow cytometry after each treatment block. Results: Second complete remission (CR2) rates at the end of block 1 in 117 assessable patients were 68% ± 6% for ER (n = 63) and 96% ± 3% for LR (n = 54; P <.0001). Five of seven patients with T-cell ALL (T-ALL) failed to achieve CR2. Among patients in CR2, MRD greater than 0.01% was detected at the end of block 1 in 75% ± 7% of ER (n = 36) versus 51% ± 8% of LR (n = 43; P = .0375) and 12-month event-free survival was 80% ± 7% versus 58% ± 7% in MRD-negative versus positive patients (P <.0005). Blocks 2 and 3 of therapy resulted in reduction of MRD burden in 40 of 56 patients who were MRD positive after block 1. Toxicity was acceptable during all three blocks with five deaths (4%) from infections. Conclusion: The AALL01P2 regimen is a tolerable and active reinduction platform, suitable for testing in combination with novel agents in B-precursor ALL. Alternative strategies are needed for T-ALL. Serial MRD measurements were feasible and prognostic of outcome.

Original languageEnglish (US)
Pages (from-to)3971-3978
Number of pages8
JournalJournal of Clinical Oncology
Volume26
Issue number24
DOIs
StatePublished - 2008

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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Residual Neoplasm
Bone Marrow
Recurrence
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Drug Therapy
Disease-Free Survival
Flow Cytometry
Therapeutics
T-Lymphocytes
Infection

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Raetz, E. A., Borowitz, M. J., Devidas, M., Linda, S. B., Hunger, S. P., Winick, N. J., ... Carroll, W. L. (2008). Reinduction platform for children with first marrow relapse in acute lymphoblastic lymphoma. Journal of Clinical Oncology, 26(24), 3971-3978. https://doi.org/10.1200/JCO.2008.16.1414

Reinduction platform for children with first marrow relapse in acute lymphoblastic lymphoma. / Raetz, Elizabeth A.; Borowitz, Michael J; Devidas, Meenakshi; Linda, Stephen B.; Hunger, Stephen P.; Winick, Naomi J.; Camitta, Bruce M.; Gaynon, Paul S.; Carroll, William L.

In: Journal of Clinical Oncology, Vol. 26, No. 24, 2008, p. 3971-3978.

Research output: Contribution to journalArticle

Raetz, EA, Borowitz, MJ, Devidas, M, Linda, SB, Hunger, SP, Winick, NJ, Camitta, BM, Gaynon, PS & Carroll, WL 2008, 'Reinduction platform for children with first marrow relapse in acute lymphoblastic lymphoma', Journal of Clinical Oncology, vol. 26, no. 24, pp. 3971-3978. https://doi.org/10.1200/JCO.2008.16.1414
Raetz, Elizabeth A. ; Borowitz, Michael J ; Devidas, Meenakshi ; Linda, Stephen B. ; Hunger, Stephen P. ; Winick, Naomi J. ; Camitta, Bruce M. ; Gaynon, Paul S. ; Carroll, William L. / Reinduction platform for children with first marrow relapse in acute lymphoblastic lymphoma. In: Journal of Clinical Oncology. 2008 ; Vol. 26, No. 24. pp. 3971-3978.
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abstract = "Purpose: Treatment of childhood relapsed acute lymphoblastic leukemia (ALL) remains a significant challenge. The goal of the Children's Oncology Group (COG) AALL01P2 study was to develop a safe and active chemotherapy reinduction platform, which could be used to evaluate novel agents in future trials. Patients and Methods: One hundred twenty-four patients with ALL and first marrow relapse received three, 35-day blocks of reinduction chemotherapy: 69 with early relapse (ER; <36 months from initial diagnosis) and 55 with late relapse (LR). Minimal residual disease (MRD) was measured by flow cytometry after each treatment block. Results: Second complete remission (CR2) rates at the end of block 1 in 117 assessable patients were 68{\%} ± 6{\%} for ER (n = 63) and 96{\%} ± 3{\%} for LR (n = 54; P <.0001). Five of seven patients with T-cell ALL (T-ALL) failed to achieve CR2. Among patients in CR2, MRD greater than 0.01{\%} was detected at the end of block 1 in 75{\%} ± 7{\%} of ER (n = 36) versus 51{\%} ± 8{\%} of LR (n = 43; P = .0375) and 12-month event-free survival was 80{\%} ± 7{\%} versus 58{\%} ± 7{\%} in MRD-negative versus positive patients (P <.0005). Blocks 2 and 3 of therapy resulted in reduction of MRD burden in 40 of 56 patients who were MRD positive after block 1. Toxicity was acceptable during all three blocks with five deaths (4{\%}) from infections. Conclusion: The AALL01P2 regimen is a tolerable and active reinduction platform, suitable for testing in combination with novel agents in B-precursor ALL. Alternative strategies are needed for T-ALL. Serial MRD measurements were feasible and prognostic of outcome.",
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AU - Borowitz, Michael J

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AU - Winick, Naomi J.

AU - Camitta, Bruce M.

AU - Gaynon, Paul S.

AU - Carroll, William L.

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