Minimal Residual Disease Assessment and Risk-based Therapy in Acute Lymphoblastic Leukemia

• Published in: Clinical lymphoma, myeloma and leukemia myeloma and leukemia, 2017-07, Vol.17, p.S2-S9
• Main Authors: Bassan, Renato, Intermesoli, Tamara, Scattolin, Annamaria, Viero, Piera, Maino, Elena, Sancetta, Rosaria, Carobolante, Francesca, Gianni, Francesca, Stefanoni, Paola, Tosi, Manuela, Spinelli, Orietta, Rambaldi, Alessandro
• Format: Article
• Language: English
• Subjects: Adult; ALL; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Child; Disease-Free Survival; Hematopoietic Stem Cell Transplantation - methods; Humans; Management; MRD; Neoplasm, Residual - diagnosis; Outcome Assessment (Health Care) - methods; Outcome Assessment (Health Care) - statistics & numerical data; Precursor Cell Lymphoblastic Leukemia-Lymphoma - therapy; Prognosis; Risk classification; Risk Factors
• ISSN: 2152-2650; 2152-2669
• DOI: 10.1016/j.clml.2017.02.019

The study of minimal residual disease (MRD) in adult patients with acute lymphoblastic leukemia (ALL) allows a greater refinement of the individual risk classification and is the best support for risk-specific therapy with or without allogeneic hematopoietic cell transplantation (HCT). Using case-specific sensitive molecular probes or multiparametric flow cytometry on marrow samples obtained from the end of induction until midconsolidation, MRD assays can detect up to 1 leukemic cell of 10,000 total mononuclear cells (sensitivity, 0.01%; ie, ≥104). This cutoff, presently bound to technical limitations and subject to improvement, reflects the individual chemosensitivity and is strongly correlated with treatment outcome. The chance for cure is approximately 70% in the MRD-negative subset but only 20% to 30% in MRD-positive patients, in any diagnostic and risk subset. As shown by prospective trials from Germany, Italy, Spain, and France-Switzerland-Belgium, approximately 50% to 70% of unselected adult patients with Philadelphia-negative ALL achieve and maintain an early MRD response, whereas the remainder do not, including a substantial proportion of clinically standard-risk patients, and require an HCT to avert at least partially the risk of relapse. Along with the diffusion of more effective “pediatric-inspired” chemotherapy programs, the MRD analysis is an integral part of a modern management strategy, guiding the decision process to transplant or not, in which case nonrelapse mortality using HCT in first remission—still 10% to 20%—is totally abolished. The use of new agents such as monoclonal antibodies, small inhibitors, and chimeric antigen receptor T cells is opening a new era of MRD-directed therapies, that will further increase survival rates.