Granulocyte colony-stimulating factor and the risk of secondary myeloid malignancy after etoposide treatment

Mary V. Relling, James M. Boyett, Javier G. Blanco, Susana Raimondi, Frederick G. Behm, John T. Sandlund, Gaston K. Rivera, Larry E. Kun, William E. Evans, Ching Hon Pui

Research output: Contribution to journalArticle

122 Citations (Scopus)

Abstract

Event-free survival for children with acute lymphoblastic leukemia (ALL) now exceeds 80% in the most effective trials. Failures are due to relapse, toxicity, and second cancers such as therapy-related myeloid leukemia or myelodysplasia (t-ML). Topoisomerase II inhibitors and alkylators can induce t-ML; additional risk factors for t-ML remain poorly defined. The occurrence of t-ML among children who had received granulocyte colony-stimulating factor (G-CSF) following ALL remission induction therapy prompted us to examine this and other putative risk factors for t-ML in 412 children treated on 2 consecutive ALL protocols from 1991 to 1998. All children received etoposide and anthracyclines, 99 of whom received G-CSF; 284 also received cyclophosphamide, 58 of whom also received cranial irradiation. There were 20 children who developed t-ML at a median of 2.3 years (range, 1.0-6.0 years), including 16 cases of acute myeloid leukemia, 3 myelodysplasia, and 1 chronic myeloid leukemia. Stratifying by protocol, the cumulative incidence functions differed (P = .017) according to the use of G-CSF and irradiation: 6-year cumulative incidence (standard error) of t-ML of 12.3% (5.3%) among the 44 children who received irradiation without G-CSF, 11.0% (3.5%) among the 85 children who received G-CSF but no irradiation, 7.1% (7.2%) among the 14 children who received irradiation plus G-CSF, and 2.7% (1.3%) among the 269 children who received neither irradiation nor G-CSF. Even when children receiving irradiation were excluded, the incidence was still higher in those receiving G-CSF (P = .019). In the setting of intensive antileukemic therapy, short-term use of G-CSF may increase the risk of t-ML.

Original languageEnglish (US)
Pages (from-to)3862-3867
Number of pages6
JournalBlood
Volume101
Issue number10
DOIs
StatePublished - May 15 2003

Fingerprint

Granulocyte Colony-Stimulating Factor
Etoposide
Irradiation
Neoplasms
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Therapeutics
Incidence
Topoisomerase II Inhibitors
Cranial Irradiation
Remission Induction
Alkylating Agents
Anthracyclines
Myeloid Leukemia
Second Primary Neoplasms
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Cyclophosphamide
Toxicity
Acute Myeloid Leukemia
Disease-Free Survival
Recurrence

ASJC Scopus subject areas

  • Immunology
  • Biochemistry
  • Hematology
  • Cell Biology

Cite this

Relling, M. V., Boyett, J. M., Blanco, J. G., Raimondi, S., Behm, F. G., Sandlund, J. T., ... Pui, C. H. (2003). Granulocyte colony-stimulating factor and the risk of secondary myeloid malignancy after etoposide treatment. Blood, 101(10), 3862-3867. https://doi.org/10.1182/blood-2002-08-2405

Granulocyte colony-stimulating factor and the risk of secondary myeloid malignancy after etoposide treatment. / Relling, Mary V.; Boyett, James M.; Blanco, Javier G.; Raimondi, Susana; Behm, Frederick G.; Sandlund, John T.; Rivera, Gaston K.; Kun, Larry E.; Evans, William E.; Pui, Ching Hon.

In: Blood, Vol. 101, No. 10, 15.05.2003, p. 3862-3867.

Research output: Contribution to journalArticle

Relling, MV, Boyett, JM, Blanco, JG, Raimondi, S, Behm, FG, Sandlund, JT, Rivera, GK, Kun, LE, Evans, WE & Pui, CH 2003, 'Granulocyte colony-stimulating factor and the risk of secondary myeloid malignancy after etoposide treatment', Blood, vol. 101, no. 10, pp. 3862-3867. https://doi.org/10.1182/blood-2002-08-2405
Relling MV, Boyett JM, Blanco JG, Raimondi S, Behm FG, Sandlund JT et al. Granulocyte colony-stimulating factor and the risk of secondary myeloid malignancy after etoposide treatment. Blood. 2003 May 15;101(10):3862-3867. https://doi.org/10.1182/blood-2002-08-2405
Relling, Mary V. ; Boyett, James M. ; Blanco, Javier G. ; Raimondi, Susana ; Behm, Frederick G. ; Sandlund, John T. ; Rivera, Gaston K. ; Kun, Larry E. ; Evans, William E. ; Pui, Ching Hon. / Granulocyte colony-stimulating factor and the risk of secondary myeloid malignancy after etoposide treatment. In: Blood. 2003 ; Vol. 101, No. 10. pp. 3862-3867.
@article{6ca47439af2a489caf0e3a5d3eb182db,
title = "Granulocyte colony-stimulating factor and the risk of secondary myeloid malignancy after etoposide treatment",
abstract = "Event-free survival for children with acute lymphoblastic leukemia (ALL) now exceeds 80{\%} in the most effective trials. Failures are due to relapse, toxicity, and second cancers such as therapy-related myeloid leukemia or myelodysplasia (t-ML). Topoisomerase II inhibitors and alkylators can induce t-ML; additional risk factors for t-ML remain poorly defined. The occurrence of t-ML among children who had received granulocyte colony-stimulating factor (G-CSF) following ALL remission induction therapy prompted us to examine this and other putative risk factors for t-ML in 412 children treated on 2 consecutive ALL protocols from 1991 to 1998. All children received etoposide and anthracyclines, 99 of whom received G-CSF; 284 also received cyclophosphamide, 58 of whom also received cranial irradiation. There were 20 children who developed t-ML at a median of 2.3 years (range, 1.0-6.0 years), including 16 cases of acute myeloid leukemia, 3 myelodysplasia, and 1 chronic myeloid leukemia. Stratifying by protocol, the cumulative incidence functions differed (P = .017) according to the use of G-CSF and irradiation: 6-year cumulative incidence (standard error) of t-ML of 12.3{\%} (5.3{\%}) among the 44 children who received irradiation without G-CSF, 11.0{\%} (3.5{\%}) among the 85 children who received G-CSF but no irradiation, 7.1{\%} (7.2{\%}) among the 14 children who received irradiation plus G-CSF, and 2.7{\%} (1.3{\%}) among the 269 children who received neither irradiation nor G-CSF. Even when children receiving irradiation were excluded, the incidence was still higher in those receiving G-CSF (P = .019). In the setting of intensive antileukemic therapy, short-term use of G-CSF may increase the risk of t-ML.",
author = "Relling, {Mary V.} and Boyett, {James M.} and Blanco, {Javier G.} and Susana Raimondi and Behm, {Frederick G.} and Sandlund, {John T.} and Rivera, {Gaston K.} and Kun, {Larry E.} and Evans, {William E.} and Pui, {Ching Hon}",
year = "2003",
month = "5",
day = "15",
doi = "10.1182/blood-2002-08-2405",
language = "English (US)",
volume = "101",
pages = "3862--3867",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "10",

}

TY - JOUR

T1 - Granulocyte colony-stimulating factor and the risk of secondary myeloid malignancy after etoposide treatment

AU - Relling, Mary V.

AU - Boyett, James M.

AU - Blanco, Javier G.

AU - Raimondi, Susana

AU - Behm, Frederick G.

AU - Sandlund, John T.

AU - Rivera, Gaston K.

AU - Kun, Larry E.

AU - Evans, William E.

AU - Pui, Ching Hon

PY - 2003/5/15

Y1 - 2003/5/15

N2 - Event-free survival for children with acute lymphoblastic leukemia (ALL) now exceeds 80% in the most effective trials. Failures are due to relapse, toxicity, and second cancers such as therapy-related myeloid leukemia or myelodysplasia (t-ML). Topoisomerase II inhibitors and alkylators can induce t-ML; additional risk factors for t-ML remain poorly defined. The occurrence of t-ML among children who had received granulocyte colony-stimulating factor (G-CSF) following ALL remission induction therapy prompted us to examine this and other putative risk factors for t-ML in 412 children treated on 2 consecutive ALL protocols from 1991 to 1998. All children received etoposide and anthracyclines, 99 of whom received G-CSF; 284 also received cyclophosphamide, 58 of whom also received cranial irradiation. There were 20 children who developed t-ML at a median of 2.3 years (range, 1.0-6.0 years), including 16 cases of acute myeloid leukemia, 3 myelodysplasia, and 1 chronic myeloid leukemia. Stratifying by protocol, the cumulative incidence functions differed (P = .017) according to the use of G-CSF and irradiation: 6-year cumulative incidence (standard error) of t-ML of 12.3% (5.3%) among the 44 children who received irradiation without G-CSF, 11.0% (3.5%) among the 85 children who received G-CSF but no irradiation, 7.1% (7.2%) among the 14 children who received irradiation plus G-CSF, and 2.7% (1.3%) among the 269 children who received neither irradiation nor G-CSF. Even when children receiving irradiation were excluded, the incidence was still higher in those receiving G-CSF (P = .019). In the setting of intensive antileukemic therapy, short-term use of G-CSF may increase the risk of t-ML.

AB - Event-free survival for children with acute lymphoblastic leukemia (ALL) now exceeds 80% in the most effective trials. Failures are due to relapse, toxicity, and second cancers such as therapy-related myeloid leukemia or myelodysplasia (t-ML). Topoisomerase II inhibitors and alkylators can induce t-ML; additional risk factors for t-ML remain poorly defined. The occurrence of t-ML among children who had received granulocyte colony-stimulating factor (G-CSF) following ALL remission induction therapy prompted us to examine this and other putative risk factors for t-ML in 412 children treated on 2 consecutive ALL protocols from 1991 to 1998. All children received etoposide and anthracyclines, 99 of whom received G-CSF; 284 also received cyclophosphamide, 58 of whom also received cranial irradiation. There were 20 children who developed t-ML at a median of 2.3 years (range, 1.0-6.0 years), including 16 cases of acute myeloid leukemia, 3 myelodysplasia, and 1 chronic myeloid leukemia. Stratifying by protocol, the cumulative incidence functions differed (P = .017) according to the use of G-CSF and irradiation: 6-year cumulative incidence (standard error) of t-ML of 12.3% (5.3%) among the 44 children who received irradiation without G-CSF, 11.0% (3.5%) among the 85 children who received G-CSF but no irradiation, 7.1% (7.2%) among the 14 children who received irradiation plus G-CSF, and 2.7% (1.3%) among the 269 children who received neither irradiation nor G-CSF. Even when children receiving irradiation were excluded, the incidence was still higher in those receiving G-CSF (P = .019). In the setting of intensive antileukemic therapy, short-term use of G-CSF may increase the risk of t-ML.

UR - http://www.scopus.com/inward/record.url?scp=0037588995&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037588995&partnerID=8YFLogxK

U2 - 10.1182/blood-2002-08-2405

DO - 10.1182/blood-2002-08-2405

M3 - Article

C2 - 12531808

AN - SCOPUS:0037588995

VL - 101

SP - 3862

EP - 3867

JO - Blood

JF - Blood

SN - 0006-4971

IS - 10

ER -