Incidence of therapy-related myeloid neoplasia after initial therapy for chronic lymphocytic leukemia with fludarabine-cyclophosphamide versus fludarabine

Long-term follow-up of US intergroup study E2997

Mitchell R. Smith, Donna Neuberg, Ian W. Flinn, Michael R. Grever, Hillard M. Lazarus, Jacob M. Rowe, Gordon Dewald, John M. Bennett, Elisabeth M. Paietta, John C. Byrd, Mohamad A. Hussein, Frederick R. Appelbaum, Richard A. Larson, Mark R. Litzow, Martin S. Tallman

Research output: Contribution to journalArticle

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Abstract

Chemotherapy-related myeloid neoplasia (t-MN) is a significant late toxicity concern after cancer therapy. In the randomized intergroup phase 3 E2997 trial, initial therapy of chronic lymphocytic leukemia with fludarabine plus cyclophosphamide (FC) compared with fludarabine alone yielded higher complete and overall response rates and longer progressionfree, but not overall, survival. Here, we report t-MN incidence in 278 patients enrolled in E2997 with a median 6.4-year follow-up. Thirteen cases (4.7%) of t-MN occurred at a median of 5 years from initial therapy for chronic lymphocytic leukemia, 9 after FC and 4 after fludarabine alone. By cumulative incidence methodology, rates of t-MN at 7 years were 8.2% after FC and 4.6% after fludarabine alone (P - .09). Seven of the 9 cases of t-MN after FC occurred without additional therapy. Abnormalities involving chromosomes 5 or 7 were found in 10 cases, which suggests alkylator involvement. These data suggest that FC may induce more t-MN than fludarabine alone.

Original languageEnglish (US)
Pages (from-to)3525-3527
Number of pages3
JournalBlood
Volume118
Issue number13
DOIs
StatePublished - Sep 29 2011

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B-Cell Chronic Lymphocytic Leukemia
Cyclophosphamide
Incidence
Neoplasms
Therapeutics
fludarabine
Chromosomes, Human, Pair 5
Chromosomes, Human, Pair 7
Chemotherapy
Alkylating Agents
Chromosomes
Toxicity
Drug Therapy
Survival

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Incidence of therapy-related myeloid neoplasia after initial therapy for chronic lymphocytic leukemia with fludarabine-cyclophosphamide versus fludarabine : Long-term follow-up of US intergroup study E2997. / Smith, Mitchell R.; Neuberg, Donna; Flinn, Ian W.; Grever, Michael R.; Lazarus, Hillard M.; Rowe, Jacob M.; Dewald, Gordon; Bennett, John M.; Paietta, Elisabeth M.; Byrd, John C.; Hussein, Mohamad A.; Appelbaum, Frederick R.; Larson, Richard A.; Litzow, Mark R.; Tallman, Martin S.

In: Blood, Vol. 118, No. 13, 29.09.2011, p. 3525-3527.

Research output: Contribution to journalArticle

Smith, MR, Neuberg, D, Flinn, IW, Grever, MR, Lazarus, HM, Rowe, JM, Dewald, G, Bennett, JM, Paietta, EM, Byrd, JC, Hussein, MA, Appelbaum, FR, Larson, RA, Litzow, MR & Tallman, MS 2011, 'Incidence of therapy-related myeloid neoplasia after initial therapy for chronic lymphocytic leukemia with fludarabine-cyclophosphamide versus fludarabine: Long-term follow-up of US intergroup study E2997', Blood, vol. 118, no. 13, pp. 3525-3527. https://doi.org/10.1182/blood-2011-03-342485
Smith, Mitchell R. ; Neuberg, Donna ; Flinn, Ian W. ; Grever, Michael R. ; Lazarus, Hillard M. ; Rowe, Jacob M. ; Dewald, Gordon ; Bennett, John M. ; Paietta, Elisabeth M. ; Byrd, John C. ; Hussein, Mohamad A. ; Appelbaum, Frederick R. ; Larson, Richard A. ; Litzow, Mark R. ; Tallman, Martin S. / Incidence of therapy-related myeloid neoplasia after initial therapy for chronic lymphocytic leukemia with fludarabine-cyclophosphamide versus fludarabine : Long-term follow-up of US intergroup study E2997. In: Blood. 2011 ; Vol. 118, No. 13. pp. 3525-3527.
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