TY - JOUR
T1 - Improved risk classification for risk-specific therapy based on the molecular study of minimal residual disease (MRD) in adult acute lymphoblastic leukemia (ALL)
AU - Bassan, Renato
AU - Spinelli, Orietta
AU - Oldani, Elena
AU - Intermesoli, Tamara
AU - Tosi, Manuela
AU - Peruta, Barbara
AU - Rossi, Giuseppe
AU - Borlenghi, Erika
AU - Pogliani, Enrico M.
AU - Terruzzi, Elisabetta
AU - Fabris, Pietro
AU - Cassibba, Vincenzo
AU - Lambertenghi-Deliliers, Giorgio
AU - Cortelezzi, Agostino
AU - Bosi, Alberto
AU - Gianfaldoni, Giacomo
AU - Ciceri, Fabio
AU - Bernardi, Massimo
AU - Gallamini, Andrea
AU - Mattei, Daniele
AU - Di Bona, Eros
AU - Romani, Claudio
AU - Scattolin, Anna Maria
AU - Barbui, Tiziano
AU - Rambaldi, Alessandro
PY - 2009
Y1 - 2009
N2 - Clinical risk classification is inaccurate in predicting relapse in adult patients with acute lymphoblastic leukemia, sometimes resulting in patients receiving inappropriate chemotherapy or stem cell transplantation (SCT). We studied minimal residual disease (MRD) as a predictive factor for recurrence and as a decisional tool for postconsolidation maintenance (in MRDneg) or SCT (in MRDpos). MRD was tested at weeks 10, 16, and 22 using real-time quantitative polymerase chain reaction with 1 or more sensitive probes. Only patients with t(9; 22) or t(4;11) were immediately eligible for allogeneic SCT. Of 280 registered patients (236 in remission), 34 underwent an early SCT, 60 suffered from relapse or severe toxicity, and 142 were evaluable for MRD at the end of consolidation. Of these, 58 were MRDneg, 54 MRDpos, and 30 were not assessable. Five-year overall survival/ disease-free survival rates were 0.75/0.72 in the MRDneg group compared with 0.33/ 0.14 in MRDpos (P = .001), regardless of the clinical risk class. MRD was the most significant risk factor for relapse (hazard ratio, 5.22). MRD results at weeks 16 to 22 correlated strongly with the earlier time point (P = .001) using a level of 10-4 or higher to define persistent disease. MRD analysis during early postremission therapy improves risk definitions and bolsters risk-oriented strategies. ClinicalTrials. gov identifier: NCT00358072.
AB - Clinical risk classification is inaccurate in predicting relapse in adult patients with acute lymphoblastic leukemia, sometimes resulting in patients receiving inappropriate chemotherapy or stem cell transplantation (SCT). We studied minimal residual disease (MRD) as a predictive factor for recurrence and as a decisional tool for postconsolidation maintenance (in MRDneg) or SCT (in MRDpos). MRD was tested at weeks 10, 16, and 22 using real-time quantitative polymerase chain reaction with 1 or more sensitive probes. Only patients with t(9; 22) or t(4;11) were immediately eligible for allogeneic SCT. Of 280 registered patients (236 in remission), 34 underwent an early SCT, 60 suffered from relapse or severe toxicity, and 142 were evaluable for MRD at the end of consolidation. Of these, 58 were MRDneg, 54 MRDpos, and 30 were not assessable. Five-year overall survival/ disease-free survival rates were 0.75/0.72 in the MRDneg group compared with 0.33/ 0.14 in MRDpos (P = .001), regardless of the clinical risk class. MRD was the most significant risk factor for relapse (hazard ratio, 5.22). MRD results at weeks 16 to 22 correlated strongly with the earlier time point (P = .001) using a level of 10-4 or higher to define persistent disease. MRD analysis during early postremission therapy improves risk definitions and bolsters risk-oriented strategies. ClinicalTrials. gov identifier: NCT00358072.
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U2 - 10.1182/blood-2008-11-185132
DO - 10.1182/blood-2008-11-185132
M3 - Article
C2 - 19141862
AN - SCOPUS:66149141393
VL - 113
SP - 4153
EP - 4162
JO - Blood
JF - Blood
SN - 0006-4971
IS - 18
ER -