title: Improved risk classification for risk-specific therapy based on the molecular study of minimal residual disease (MRD) in adult acute lymphoblastic leukemia (ALL).
abstract: 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 MRD(neg)) or SCT (in MRD(pos)). 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 MRD(neg), 54 MRD(pos), and 30 were not assessable. Five-year overall survival/disease-free survival rates were 0.75/0.72 in the MRD(neg) group compared with 0.33/0.14 in MRD(pos) (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.
authors.affiliation: Unità Strutturale Complessa di Ematologia, Ospedali Riuniti, Bergamo, Italy. rbassan@ospedaliriuniti.bergamo.it
authors.forename: Renato
authors.initials: R
authors.lastname: Bassan
authors.forename: Orietta
authors.initials: O
authors.lastname: Spinelli
authors.forename: Elena
authors.initials: E
authors.lastname: Oldani
authors.forename: Tamara
authors.initials: T
authors.lastname: Intermesoli
authors.forename: Manuela
authors.initials: M
authors.lastname: Tosi
authors.forename: Barbara
authors.initials: B
authors.lastname: Peruta
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Rossi
authors.forename: Erika
authors.initials: E
authors.lastname: Borlenghi
authors.forename: Enrico M
authors.initials: EM
authors.lastname: Pogliani
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Terruzzi
authors.forename: Pietro
authors.initials: P
authors.lastname: Fabris
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cassibba
authors.forename: Giorgio
authors.initials: G
authors.lastname: Lambertenghi-Deliliers
authors.forename: Agostino
authors.initials: A
authors.lastname: Cortelezzi
authors.forename: Alberto
authors.initials: A
authors.lastname: Bosi
authors.forename: Giacomo
authors.initials: G
authors.lastname: Gianfaldoni
authors.forename: Fabio
authors.initials: F
authors.lastname: Ciceri
authors.forename: Massimo
authors.initials: M
authors.lastname: Bernardi
authors.forename: Andrea
authors.initials: A
authors.lastname: Gallamini
authors.forename: Daniele
authors.initials: D
authors.lastname: Mattei
authors.forename: Eros
authors.initials: E
authors.lastname: Di Bona
authors.forename: Claudio
authors.initials: C
authors.lastname: Romani
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Scattolin
authors.forename: Tiziano
authors.initials: T
authors.lastname: Barbui
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rambaldi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000145:classification* / Q000401:mortality / Q000628:therapy*; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D033581:Stem Cell Transplantation; D015996:Survival Rate; D014178:Translocation, Genetic; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015514:Oncogene Proteins, Fusion