Therapy-Related Myeloid Neoplasms (t-MN) in Chronic Lymphocytic Leukemia Patients Treated with the FCR Chemotherapy Regimen.
Yi Zhou, Guilin Tang, Chi Y OK, L Jeffrey Medeiros, William Wierda, Sa A Wang. UT, MD Anderson Cancer Center, Houston, TX
Background: Therapy-related myeloid neoplasms (t-MN) in relation to causative agents are difficult to characterize, since many patients developed t-MN after receiving multiple cytotoxic agents. The FCR regimen, consisting of nucleoside analog Fludarabine, alkylating agent Cyclophosphamide and monoclonal antibody Rituximab, has emerged as a promising frontline therapy for patients with chronic lymphocytic leukemia (CLL). Here, we report the clinicopathologic features of t-MN that arose in patients treated with FCR regimen.
Design: We searched the pathology files for patients diagnosed with CLL who subsequently developed t-MN. Laboratory and cytogenetic data and bone marrow (BM) biopsy were reviewed. Cases with a confirmed diagnosis of t-MN were included. Patients who received cytotoxic therapies other than the FCR regimen were excluded.
Results: From 3506 documented CLL patients, 74 had confirmed t-MN. Among them, 37 received various cytotoxic agents other than FCR. The remaining 37 patients received FCR only, and the incidence was approximately 2%. These cases included 12 therapy-related acute myeloid leukemia (t-AML) and 25 myelodysplastic syndromes (t-MDS). There were 25 men and 12 women with a median age of 66 years (range, 40-80 years). At the time of t-MN diagnosis, 17 patients had persistent CLL in the BM and 20 patients had no evidence of CLL. Cytogenetic abnormalities were observed in 36 (97%) cases. Clinically, 15(40%) patients developed t-MN following a “prolonged myelosuppression” post FCR treatment, whereas 22 patients recovered blood counts after FCR but later developed cytopenias. The median duration from FCR treatment to t-MN was 32 months (range, 3-118 months), significantly shorter than t-MN secondary to other alkylating agents (5-7 years, as reported in the literature). Patients received various treatments for t-MN, including stem cell transplant for 8 patients. With a median follow-up of 8 months (alive and dead), 25 (73%) patients died of t-MN with a median disease specific survival of 7.5 months.
Conclusions: FCR treatment poses a low but real risk for t-MN. Fludarabine, a nucleoside analog, by itself associates with a very low risk for t-MN, may synergize with cyclophosphamide, resulting a short duration between therapy and of t-MN. t-MN developing in CLL patients treated with FCR regimen harbors cytogenetic alterations that are similar to cases of t-MN that arise secondary to other alkylating agents, and is associated with very poor outcome.
Monday, February 28, 2011 1:15 PM
Platform Session: Section B, Monday Afternoon