Incidence of Therapy-related Myeloid Neoplasia after Initial Therapy for CLL with Fludarabine-Cyclophosphamide versus Fludarabine: Long-Term Follow-up of US Intergroup Study E2997.

Publication Type:

Journal Article


Blood, Volume 118, Issue 3, p.3525-3527 (2011)


2011, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Bone Marrow Neoplasms, Center-Authored Paper, Clinical Research Division, Cohort Studies, Cyclophosphamide, Female, Follow-Up Studies, Humans, Incidence, Leukemia, Lymphocytic, Chronic, B-Cell, Male, Middle Aged, Neoplasms, Second Primary, September 2011, Time Factors, United States, Vidarabine


Chemotherapy related myeloid neoplasia (t-MN) is a significant late toxicity concern after cancer therapy. In the randomized intergroup Phase III E2997 trial, initial therapy of CLL with fludarabine and cyclophosphamide (FC) compared with fludarabine (F) 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 median 6.4 year follow-up. Thirteen (4.7%) cases of t-MN occurred at a median of 5 years from initial CLL therapy, 9 after FC and 4 after F. By cumulative incidence methodology, rates of t-MN at 7 years are 8.2% after FC and 4.6% after F (p=0.09). Seven of the 9 t-MN after FC occurred without additional therapy. Abnormalities involving chromosomes 5 and/or 7 were found in 10 cases, suggesting alkylator involvement. These data suggest that FC may induce more t-MN than F alone.