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Minimal residual disease negative complete response (MRD-negative CR) provides an early marker for time to treatment failure (TTF) in CLL treated with fludarabine, cyclophosphamide, and rituximab (FCR). MRD was assessed after four FCR cycles (FCR4); MRD-negative CR patients discontinued treatment. Fifty-two patients (35M; 17F) were enrolled. Eighteen (18/52; 34.6%) patients reached MRD-negative CR after FCR4 and 29/52 (55.8%) were MRD-negative CR at end of treatment (EOT). Median TTF was 71.1 months (95% CI 61.3-84.1 months), with median overall survival not reached. Mutated immunoglobulin heavy chain gene rearrangements (IGHV) were associated with early MRD-negative remissions, translating into prolonged TTF. Unmutated-IGHV, mutated-SF3B1 and mutated-NOTCH1 were associated with shortened TTF. No TTF difference was observed between patients in MRD-negative CR after four versus six cycles (82.2 versus 85.3 months, p = .6306). Abbreviated FCR therapy is effective for patients achieving early MRD-negative remissions. Interim MRD assessment assists in personalizing therapy and reducing chemotherapy-associated toxicity.

Original publication




Journal article


Leuk Lymphoma

Publication Date





1338 - 1347


Chronic lymphocytic leukemia, abbreviated therapy, fludarabine cyclophosphamide rituximab, minimal residual disease, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols, Chromosome Aberrations, Chromosomes, Human, Pair 17, Cyclophosphamide, DNA Mutational Analysis, Female, Humans, Immunophenotyping, In Situ Hybridization, Fluorescence, Leukemia, Lymphocytic, Chronic, B-Cell, Male, Middle Aged, Neoplasm Staging, Neoplasm, Residual, Rituximab, Survival Analysis, Treatment Outcome, Vidarabine