title: Minimal residual disease is an independent predictor for 10-year survival in CLL.
abstract: Minimal residual disease (MRD) negativity, defined as <1 chronic lymphocytic leukemia (CLL) cell detectable per 10 000 leukocytes, has been shown to independently predict for clinical outcome in patients receiving combination chemoimmunotherapy in the frontline setting. However, the long-term prognostic value of MRD status in other therapeutic settings remains unclear. Here, we retrospectively analyzed, with up to 18 years follow-up, all patients at our institution who achieved at least a partial response (PR) with various therapies between 1996 and 2007, and received a bone marrow MRD assessment at the end of treatment according to the international harmonized approach. MRD negativity correlated with both progression-free survival (PFS) and overall survival (OS) independent of the type and line of treatment, as well as known prognostic factors including adverse cytogenetics. The greatest impact of achieving MRD negativity was seen in patients receiving frontline treatment, with 10-year PFS of 65% vs 10% and 10-year OS of 70% vs 30% for MRD-negative vs MRD-positive patients, respectively. Our results demonstrate the long-term benefit of achieving MRD negativity, regardless of the therapeutic setting and treatment modality, and support its use as a prognostic marker for long-term PFS and as a potential therapeutic goal in CLL.
authors.affiliation: Haematological Malignancy Diagnostic Service, Department of Haematology, St. James's University Hospital, Leeds, United Kingdom.|Centre for Clinical Haematology, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom; and.
authors.forename: Marwan
authors.initials: M
authors.lastname: Kwok
authors.affiliation: Haematological Malignancy Diagnostic Service, Department of Haematology, St. James's University Hospital, Leeds, United Kingdom.
authors.forename: Andy C
authors.initials: AC
authors.lastname: Rawstron
authors.affiliation: Haematological Malignancy Diagnostic Service, Department of Haematology, St. James's University Hospital, Leeds, United Kingdom.
authors.forename: Abraham
authors.initials: A
authors.lastname: Varghese
authors.affiliation: Haematological Malignancy Diagnostic Service, Department of Haematology, St. James's University Hospital, Leeds, United Kingdom.
authors.forename: Paul A S
authors.initials: PA
authors.lastname: Evans
authors.affiliation: Haematological Malignancy Diagnostic Service, Department of Haematology, St. James's University Hospital, Leeds, United Kingdom.
authors.forename: Sheila J M
authors.initials: SJ
authors.lastname: O'Connor
authors.affiliation: Haematological Malignancy Diagnostic Service, Department of Haematology, St. James's University Hospital, Leeds, United Kingdom.
authors.forename: Chi
authors.initials: C
authors.lastname: Doughty
authors.affiliation: Section of Experimental Haematology, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, United Kingdom.
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Newton
authors.affiliation: Haematological Malignancy Diagnostic Service, Department of Haematology, St. James's University Hospital, Leeds, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Moreton
authors.affiliation: Section of Experimental Haematology, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Hillmen
mesh_terms: D020732:Cytogenetic Analysis; D018572:Disease-Free Survival; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000473:pathology*; D015999:Multivariate Analysis; D018365:Neoplasm, Residual / Q000473:pathology*; D016896:Treatment Outcome