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.
Author(s): 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.
Affiliation(s): Fox Chase Cancer Center, Philadelphia, PA, USA. m_smith@fccc.edu
Publication date & source: 2011, Blood. , 118(13):3525-7
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 progression-free, 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.
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