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

J Clin Oncol. 2012 Aug 1;30(22):2753-9. doi: 10.1200/JCO.2011.40.8724. Epub 2012 Jun 25.

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/m(2) 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Arabinonucleosides / administration & dosage*
  • Arabinonucleosides / adverse effects
  • Child
  • Child, Preschool
  • Disease-Free Survival
  • Female
  • Humans
  • Infant
  • Male
  • Peripheral Nervous System Diseases / chemically induced
  • Pilot Projects
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / mortality

Substances

  • Arabinonucleosides
  • nelarabine