A comparison of early intensive methotrexate/mercaptopurine with early intensive alternating combination chemotherapy for high-risk B-precursor acute lymphoblastic leukemia: A Pediatric Oncology Group phase III randomized trial

S. J. Lauer, J. J. Shuster, D. H. Mahoney, N. Winick, S. Toledano, L. Munoz, G. Kiefer, J. D. Pullen, C. P. Steuber, B. M. Camitta

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

A prospective, randomized multicenter study was performed to evaluate the relative efficacy of two different concepts for early intensive therapy in a randomized trial of children with B-precursor acute lymphoblastic leukemia (ALL) at high risk (HR) for relapse. Four hundred and ninety eligible children with HR-ALL were randomized on the Pediatric Oncology Group (POG) 9006 phase III trial between 7 January 1991 and 12 January 1994. After prednisone (PDN), vincristine (VCR), asparaginase (ASP) and daunorubicin (DNR) induction, 470 patients received either 12 intensive parenteral treatments of intermediate dose (1 g/m2 each) methotrexate (MTX) and mercaptopurine (MP) over 24 weeks (regimen A) or 12 intensive course of alternating myelosuppressive drug combinations given over 30 weeks (regimen B). These drug combinations included MTX/MP, teniposide (VM-26)/cytosine arabinoside (AC) and VCR/PDN/DNR/AC/ASP. Central nervous system (CNS) prophylaxis was age-adjusted triple intrathecal chemotherapy. Patients with CNS disease at diagnosis were treated with craniospinal irradiation after the intensive phase. Continuation was standard doses of MTX and MP for 2 years. This trial was closed early because of an apparent early difference favoring regimen B. Results show that 470 patients achieved remission (97%). Two hundred and thirty two were randomized to regimen A and 238 to regimen B. The estimated 4-year event-free survival (EFS) for patients treated with regimen A is 61.6% (s.e. = 3.3%) and with regimen B is 69.4% (s.e. = 3.1%), P = 0.091. Toxicities were more frequent on regimen B. In conclusion, for children with B-precursor ALL at high risk to relapse, early intensification with myelosuppressive combination chemotherapy was more toxic but produced no significant difference in EFS when compared to those treated with parenteral methotrexate and mercaptopurine.

Original languageEnglish (US)
Pages (from-to)1038-1045
Number of pages8
JournalLeukemia
Volume15
Issue number7
DOIs
StatePublished - 2001

Fingerprint

6-Mercaptopurine
Combination Drug Therapy
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Methotrexate
Pediatrics
Teniposide
Asparaginase
Daunorubicin
Vincristine
Drug Combinations
Prednisone
Disease-Free Survival
Craniospinal Irradiation
Recurrence
Poisons
Central Nervous System Diseases
Cytarabine
Secondary Prevention
Multicenter Studies
Central Nervous System

Keywords

  • B-precursor ALL
  • Early intensive chemotherapy
  • High risk childhood ALL

ASJC Scopus subject areas

  • Hematology
  • Cancer Research

Cite this

A comparison of early intensive methotrexate/mercaptopurine with early intensive alternating combination chemotherapy for high-risk B-precursor acute lymphoblastic leukemia : A Pediatric Oncology Group phase III randomized trial. / Lauer, S. J.; Shuster, J. J.; Mahoney, D. H.; Winick, N.; Toledano, S.; Munoz, L.; Kiefer, G.; Pullen, J. D.; Steuber, C. P.; Camitta, B. M.

In: Leukemia, Vol. 15, No. 7, 2001, p. 1038-1045.

Research output: Contribution to journalArticle

Lauer, S. J. ; Shuster, J. J. ; Mahoney, D. H. ; Winick, N. ; Toledano, S. ; Munoz, L. ; Kiefer, G. ; Pullen, J. D. ; Steuber, C. P. ; Camitta, B. M. / A comparison of early intensive methotrexate/mercaptopurine with early intensive alternating combination chemotherapy for high-risk B-precursor acute lymphoblastic leukemia : A Pediatric Oncology Group phase III randomized trial. In: Leukemia. 2001 ; Vol. 15, No. 7. pp. 1038-1045.
@article{6c4052afa19146f2b693e197a58b2547,
title = "A comparison of early intensive methotrexate/mercaptopurine with early intensive alternating combination chemotherapy for high-risk B-precursor acute lymphoblastic leukemia: A Pediatric Oncology Group phase III randomized trial",
abstract = "A prospective, randomized multicenter study was performed to evaluate the relative efficacy of two different concepts for early intensive therapy in a randomized trial of children with B-precursor acute lymphoblastic leukemia (ALL) at high risk (HR) for relapse. Four hundred and ninety eligible children with HR-ALL were randomized on the Pediatric Oncology Group (POG) 9006 phase III trial between 7 January 1991 and 12 January 1994. After prednisone (PDN), vincristine (VCR), asparaginase (ASP) and daunorubicin (DNR) induction, 470 patients received either 12 intensive parenteral treatments of intermediate dose (1 g/m2 each) methotrexate (MTX) and mercaptopurine (MP) over 24 weeks (regimen A) or 12 intensive course of alternating myelosuppressive drug combinations given over 30 weeks (regimen B). These drug combinations included MTX/MP, teniposide (VM-26)/cytosine arabinoside (AC) and VCR/PDN/DNR/AC/ASP. Central nervous system (CNS) prophylaxis was age-adjusted triple intrathecal chemotherapy. Patients with CNS disease at diagnosis were treated with craniospinal irradiation after the intensive phase. Continuation was standard doses of MTX and MP for 2 years. This trial was closed early because of an apparent early difference favoring regimen B. Results show that 470 patients achieved remission (97{\%}). Two hundred and thirty two were randomized to regimen A and 238 to regimen B. The estimated 4-year event-free survival (EFS) for patients treated with regimen A is 61.6{\%} (s.e. = 3.3{\%}) and with regimen B is 69.4{\%} (s.e. = 3.1{\%}), P = 0.091. Toxicities were more frequent on regimen B. In conclusion, for children with B-precursor ALL at high risk to relapse, early intensification with myelosuppressive combination chemotherapy was more toxic but produced no significant difference in EFS when compared to those treated with parenteral methotrexate and mercaptopurine.",
keywords = "B-precursor ALL, Early intensive chemotherapy, High risk childhood ALL",
author = "Lauer, {S. J.} and Shuster, {J. J.} and Mahoney, {D. H.} and N. Winick and S. Toledano and L. Munoz and G. Kiefer and Pullen, {J. D.} and Steuber, {C. P.} and Camitta, {B. M.}",
year = "2001",
doi = "10.1038/sj.leu.2402132",
language = "English (US)",
volume = "15",
pages = "1038--1045",
journal = "Leukemia",
issn = "0887-6924",
publisher = "Nature Publishing Group",
number = "7",

}

TY - JOUR

T1 - A comparison of early intensive methotrexate/mercaptopurine with early intensive alternating combination chemotherapy for high-risk B-precursor acute lymphoblastic leukemia

T2 - A Pediatric Oncology Group phase III randomized trial

AU - Lauer, S. J.

AU - Shuster, J. J.

AU - Mahoney, D. H.

AU - Winick, N.

AU - Toledano, S.

AU - Munoz, L.

AU - Kiefer, G.

AU - Pullen, J. D.

AU - Steuber, C. P.

AU - Camitta, B. M.

PY - 2001

Y1 - 2001

N2 - A prospective, randomized multicenter study was performed to evaluate the relative efficacy of two different concepts for early intensive therapy in a randomized trial of children with B-precursor acute lymphoblastic leukemia (ALL) at high risk (HR) for relapse. Four hundred and ninety eligible children with HR-ALL were randomized on the Pediatric Oncology Group (POG) 9006 phase III trial between 7 January 1991 and 12 January 1994. After prednisone (PDN), vincristine (VCR), asparaginase (ASP) and daunorubicin (DNR) induction, 470 patients received either 12 intensive parenteral treatments of intermediate dose (1 g/m2 each) methotrexate (MTX) and mercaptopurine (MP) over 24 weeks (regimen A) or 12 intensive course of alternating myelosuppressive drug combinations given over 30 weeks (regimen B). These drug combinations included MTX/MP, teniposide (VM-26)/cytosine arabinoside (AC) and VCR/PDN/DNR/AC/ASP. Central nervous system (CNS) prophylaxis was age-adjusted triple intrathecal chemotherapy. Patients with CNS disease at diagnosis were treated with craniospinal irradiation after the intensive phase. Continuation was standard doses of MTX and MP for 2 years. This trial was closed early because of an apparent early difference favoring regimen B. Results show that 470 patients achieved remission (97%). Two hundred and thirty two were randomized to regimen A and 238 to regimen B. The estimated 4-year event-free survival (EFS) for patients treated with regimen A is 61.6% (s.e. = 3.3%) and with regimen B is 69.4% (s.e. = 3.1%), P = 0.091. Toxicities were more frequent on regimen B. In conclusion, for children with B-precursor ALL at high risk to relapse, early intensification with myelosuppressive combination chemotherapy was more toxic but produced no significant difference in EFS when compared to those treated with parenteral methotrexate and mercaptopurine.

AB - A prospective, randomized multicenter study was performed to evaluate the relative efficacy of two different concepts for early intensive therapy in a randomized trial of children with B-precursor acute lymphoblastic leukemia (ALL) at high risk (HR) for relapse. Four hundred and ninety eligible children with HR-ALL were randomized on the Pediatric Oncology Group (POG) 9006 phase III trial between 7 January 1991 and 12 January 1994. After prednisone (PDN), vincristine (VCR), asparaginase (ASP) and daunorubicin (DNR) induction, 470 patients received either 12 intensive parenteral treatments of intermediate dose (1 g/m2 each) methotrexate (MTX) and mercaptopurine (MP) over 24 weeks (regimen A) or 12 intensive course of alternating myelosuppressive drug combinations given over 30 weeks (regimen B). These drug combinations included MTX/MP, teniposide (VM-26)/cytosine arabinoside (AC) and VCR/PDN/DNR/AC/ASP. Central nervous system (CNS) prophylaxis was age-adjusted triple intrathecal chemotherapy. Patients with CNS disease at diagnosis were treated with craniospinal irradiation after the intensive phase. Continuation was standard doses of MTX and MP for 2 years. This trial was closed early because of an apparent early difference favoring regimen B. Results show that 470 patients achieved remission (97%). Two hundred and thirty two were randomized to regimen A and 238 to regimen B. The estimated 4-year event-free survival (EFS) for patients treated with regimen A is 61.6% (s.e. = 3.3%) and with regimen B is 69.4% (s.e. = 3.1%), P = 0.091. Toxicities were more frequent on regimen B. In conclusion, for children with B-precursor ALL at high risk to relapse, early intensification with myelosuppressive combination chemotherapy was more toxic but produced no significant difference in EFS when compared to those treated with parenteral methotrexate and mercaptopurine.

KW - B-precursor ALL

KW - Early intensive chemotherapy

KW - High risk childhood ALL

UR - http://www.scopus.com/inward/record.url?scp=0034900091&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034900091&partnerID=8YFLogxK

U2 - 10.1038/sj.leu.2402132

DO - 10.1038/sj.leu.2402132

M3 - Article

C2 - 11455971

AN - SCOPUS:0034900091

VL - 15

SP - 1038

EP - 1045

JO - Leukemia

JF - Leukemia

SN - 0887-6924

IS - 7

ER -