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

doi:10.1038/sj.leu.2402132

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 journal › Article › peer-review

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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 language	English (US)
Pages (from-to)	1038-1045
Number of pages	8
Journal	Leukemia
Volume	15
Issue number	7
DOIs	https://doi.org/10.1038/sj.leu.2402132
State	Published - 2001

Keywords

B-precursor ALL
Early intensive chemotherapy
High risk childhood ALL

ASJC Scopus subject areas

Hematology
Oncology
Cancer Research

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10.1038/sj.leu.2402132

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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. (2001). 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. Leukemia, 15(7), 1038-1045. https://doi.org/10.1038/sj.leu.2402132

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

Research output: Contribution to journal › Article › peer-review

Lauer, SJ, Shuster, JJ, Mahoney, DH, Winick, N, Toledano, S, Munoz, L, Kiefer, G, Pullen, JD, Steuber, CP & Camitta, BM 2001, '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', Leukemia, vol. 15, no. 7, pp. 1038-1045. https://doi.org/10.1038/sj.leu.2402132

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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.}",

note = "Funding Information: This work was supported in part by the following grants from the National Cancer Institute, Bethesda, MD: CA 20549, CA 29139, CA 03161, CA 33625, CA 32053, CA 15989, CA 30969.",

year = "2001",

doi = "10.1038/sj.leu.2402132",

language = "English (US)",

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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.

N1 - Funding Information: This work was supported in part by the following grants from the National Cancer Institute, Bethesda, MD: CA 20549, CA 29139, CA 03161, CA 33625, CA 32053, CA 15989, CA 30969.

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.

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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

Keywords

ASJC Scopus subject areas

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