Treatment-related myelodysplasia and acute leukemia in non-Hodgkin's lymphoma patients

James Olen Armitage, Paul P. Carbone, Joseph M. Connors, Alexandra Levine, John M. Bennett, Stewart Kroll

Research output: Contribution to journalArticle

188 Citations (Scopus)

Abstract

Purpose: Standard therapies for non-Hodgkin's lymphoma (NHL) are associated with an increased risk of developing treatment-related myelodysplastic syndrome or acute myelogenous leukemia (tMDS/AML). However, there is considerable debate over the incidence or risk of tMDS/ AML in NHL patients treated with any particular modality and the factors that contribute to malignant transformation. Design: Conclusions were based on thorough analysis of data reported in the peer-reviewed literature and careful examination of the statistical methodology and methods for identifying cases of tMDS/AML. Unless noted, data are reported only for NHL patients, excluding Hodgkin's disease patients. Results: Despite differences in methods used to identify cases and to estimate the cumulative incidence over time (actuarial v cumulative calculations), up to 10% of NHL patients treated with either conventional-dose chemotherapy or high-dose therapy and autologous stem-cell transplantation may develop tMDS/AML within 10 years of primary therapy. Kaplan-Meier estimates of the actuarial incidence, which are based on censoring of patients who died without developing tMDS/AML, can lead to artificially high estimates with large confidence intervals at later time points. Although there is much debate about the cause(s) of tMDS/AML, there is compelling evidence that alkylating agents, certain other leukemogenic agents, and total-body irradiation (TBI) cause chromosomal damage that can lead to tMDS/AML. Conclusion: Limiting exposure to alkylating agents and eliminating TBI from transplantation conditioning regimens may reduce the relative risk of tMDS/AML.

Original languageEnglish (US)
Pages (from-to)897-906
Number of pages10
JournalJournal of Clinical Oncology
Volume21
Issue number5
DOIs
StatePublished - Mar 1 2003

Fingerprint

Non-Hodgkin's Lymphoma
Leukemia
Myelodysplastic Syndromes
Acute Myeloid Leukemia
Therapeutics
Whole-Body Irradiation
Alkylating Agents
Incidence
Transplantation Conditioning
Kaplan-Meier Estimate
Stem Cell Transplantation
Hodgkin Disease
Confidence Intervals
Drug Therapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Treatment-related myelodysplasia and acute leukemia in non-Hodgkin's lymphoma patients. / Armitage, James Olen; Carbone, Paul P.; Connors, Joseph M.; Levine, Alexandra; Bennett, John M.; Kroll, Stewart.

In: Journal of Clinical Oncology, Vol. 21, No. 5, 01.03.2003, p. 897-906.

Research output: Contribution to journalArticle

Armitage, James Olen ; Carbone, Paul P. ; Connors, Joseph M. ; Levine, Alexandra ; Bennett, John M. ; Kroll, Stewart. / Treatment-related myelodysplasia and acute leukemia in non-Hodgkin's lymphoma patients. In: Journal of Clinical Oncology. 2003 ; Vol. 21, No. 5. pp. 897-906.
@article{f7b175e167f544b1b3e3ab46c57ded67,
title = "Treatment-related myelodysplasia and acute leukemia in non-Hodgkin's lymphoma patients",
abstract = "Purpose: Standard therapies for non-Hodgkin's lymphoma (NHL) are associated with an increased risk of developing treatment-related myelodysplastic syndrome or acute myelogenous leukemia (tMDS/AML). However, there is considerable debate over the incidence or risk of tMDS/ AML in NHL patients treated with any particular modality and the factors that contribute to malignant transformation. Design: Conclusions were based on thorough analysis of data reported in the peer-reviewed literature and careful examination of the statistical methodology and methods for identifying cases of tMDS/AML. Unless noted, data are reported only for NHL patients, excluding Hodgkin's disease patients. Results: Despite differences in methods used to identify cases and to estimate the cumulative incidence over time (actuarial v cumulative calculations), up to 10{\%} of NHL patients treated with either conventional-dose chemotherapy or high-dose therapy and autologous stem-cell transplantation may develop tMDS/AML within 10 years of primary therapy. Kaplan-Meier estimates of the actuarial incidence, which are based on censoring of patients who died without developing tMDS/AML, can lead to artificially high estimates with large confidence intervals at later time points. Although there is much debate about the cause(s) of tMDS/AML, there is compelling evidence that alkylating agents, certain other leukemogenic agents, and total-body irradiation (TBI) cause chromosomal damage that can lead to tMDS/AML. Conclusion: Limiting exposure to alkylating agents and eliminating TBI from transplantation conditioning regimens may reduce the relative risk of tMDS/AML.",
author = "Armitage, {James Olen} and Carbone, {Paul P.} and Connors, {Joseph M.} and Alexandra Levine and Bennett, {John M.} and Stewart Kroll",
year = "2003",
month = "3",
day = "1",
doi = "10.1200/JCO.2003.07.113",
language = "English (US)",
volume = "21",
pages = "897--906",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "5",

}

TY - JOUR

T1 - Treatment-related myelodysplasia and acute leukemia in non-Hodgkin's lymphoma patients

AU - Armitage, James Olen

AU - Carbone, Paul P.

AU - Connors, Joseph M.

AU - Levine, Alexandra

AU - Bennett, John M.

AU - Kroll, Stewart

PY - 2003/3/1

Y1 - 2003/3/1

N2 - Purpose: Standard therapies for non-Hodgkin's lymphoma (NHL) are associated with an increased risk of developing treatment-related myelodysplastic syndrome or acute myelogenous leukemia (tMDS/AML). However, there is considerable debate over the incidence or risk of tMDS/ AML in NHL patients treated with any particular modality and the factors that contribute to malignant transformation. Design: Conclusions were based on thorough analysis of data reported in the peer-reviewed literature and careful examination of the statistical methodology and methods for identifying cases of tMDS/AML. Unless noted, data are reported only for NHL patients, excluding Hodgkin's disease patients. Results: Despite differences in methods used to identify cases and to estimate the cumulative incidence over time (actuarial v cumulative calculations), up to 10% of NHL patients treated with either conventional-dose chemotherapy or high-dose therapy and autologous stem-cell transplantation may develop tMDS/AML within 10 years of primary therapy. Kaplan-Meier estimates of the actuarial incidence, which are based on censoring of patients who died without developing tMDS/AML, can lead to artificially high estimates with large confidence intervals at later time points. Although there is much debate about the cause(s) of tMDS/AML, there is compelling evidence that alkylating agents, certain other leukemogenic agents, and total-body irradiation (TBI) cause chromosomal damage that can lead to tMDS/AML. Conclusion: Limiting exposure to alkylating agents and eliminating TBI from transplantation conditioning regimens may reduce the relative risk of tMDS/AML.

AB - Purpose: Standard therapies for non-Hodgkin's lymphoma (NHL) are associated with an increased risk of developing treatment-related myelodysplastic syndrome or acute myelogenous leukemia (tMDS/AML). However, there is considerable debate over the incidence or risk of tMDS/ AML in NHL patients treated with any particular modality and the factors that contribute to malignant transformation. Design: Conclusions were based on thorough analysis of data reported in the peer-reviewed literature and careful examination of the statistical methodology and methods for identifying cases of tMDS/AML. Unless noted, data are reported only for NHL patients, excluding Hodgkin's disease patients. Results: Despite differences in methods used to identify cases and to estimate the cumulative incidence over time (actuarial v cumulative calculations), up to 10% of NHL patients treated with either conventional-dose chemotherapy or high-dose therapy and autologous stem-cell transplantation may develop tMDS/AML within 10 years of primary therapy. Kaplan-Meier estimates of the actuarial incidence, which are based on censoring of patients who died without developing tMDS/AML, can lead to artificially high estimates with large confidence intervals at later time points. Although there is much debate about the cause(s) of tMDS/AML, there is compelling evidence that alkylating agents, certain other leukemogenic agents, and total-body irradiation (TBI) cause chromosomal damage that can lead to tMDS/AML. Conclusion: Limiting exposure to alkylating agents and eliminating TBI from transplantation conditioning regimens may reduce the relative risk of tMDS/AML.

UR - http://www.scopus.com/inward/record.url?scp=0037364352&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037364352&partnerID=8YFLogxK

U2 - 10.1200/JCO.2003.07.113

DO - 10.1200/JCO.2003.07.113

M3 - Article

VL - 21

SP - 897

EP - 906

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 5

ER -