title: Postinduction minimal residual disease monitoring by polymerase chain reaction in children with acute lymphoblastic leukemia.
abstract: OBJECTIVE
  Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. Monitoring minimal residual disease (MRD) by using real-time quantitative polymerase chain reaction (RQ-PCR) provides information for patient stratification and individual risk-directed treatment. Cooperative studies have documented that measurement of blast clearance from the bone marrow during and after induction therapy identifies patient populations with different risk of relapse. We explored the possible contribution of measurements of MRD during the course of treatment.
  
  
  METHODS
  We used RQ-PCR to detect MRD in 110 unselected patients treated in Italy in the International Collaborative Treatment Protocol for Children and Adolescents With Acute Lymphoblastic Leukemia (AIEOP-BFM ALL 2000). The trial took place in AIEOP centers during postinduction chemotherapy. Results were categorized as negative, low positive (below the quantitative range [< 5 × 10(-4)]), or high positive (≥ 5 × 10(-4)). Patients with at least one low-positive or high-positive result were assigned to the corresponding subgroup.
  
  
  RESULTS
  Patients who tested high positive, low positive, or negative had significantly different cumulative incidences of leukemia relapse: 83.3%, 34.8%, and 8.6%, respectively (P < .001). Two thirds of positive cases were identified within 4 months after induction-consolidation therapy, suggesting that this time frame may be most suitable for cost-effective MRD monitoring, particularly in patients who did not clear their disease at the end of consolidation.
  
  
  CONCLUSIONS
  These findings provide further insights into the dynamic of MRD and the ongoing effort to define molecular relapse in childhood ALL.
authors.affiliation: Maddalena Paganin, Giulia Fabbri, Katia Polato, and Giuseppe Basso, Università di Padova, Padova; Valentino Conter, Ospedale San Gerardo; Maria Grazia Valsecchi, Università di Milano Bicocca, Monza; Elena Barisone and Franca Fagioli, Ospedale Infantile Regina Margherita, Torino; Giovanni Cazzaniga, Università di Milano Bicocca, Milan; Eugenia Giraldi and Maurizio Aricò, Ospedale Papa Giovanni XXIII di Bergamo, Italy.
authors.forename: Maddalena
authors.initials: M
authors.lastname: Paganin
authors.affiliation: Maddalena Paganin, Giulia Fabbri, Katia Polato, and Giuseppe Basso, Università di Padova, Padova; Valentino Conter, Ospedale San Gerardo; Maria Grazia Valsecchi, Università di Milano Bicocca, Monza; Elena Barisone and Franca Fagioli, Ospedale Infantile Regina Margherita, Torino; Giovanni Cazzaniga, Università di Milano Bicocca, Milan; Eugenia Giraldi and Maurizio Aricò, Ospedale Papa Giovanni XXIII di Bergamo, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Fabbri
authors.affiliation: Maddalena Paganin, Giulia Fabbri, Katia Polato, and Giuseppe Basso, Università di Padova, Padova; Valentino Conter, Ospedale San Gerardo; Maria Grazia Valsecchi, Università di Milano Bicocca, Monza; Elena Barisone and Franca Fagioli, Ospedale Infantile Regina Margherita, Torino; Giovanni Cazzaniga, Università di Milano Bicocca, Milan; Eugenia Giraldi and Maurizio Aricò, Ospedale Papa Giovanni XXIII di Bergamo, Italy.
authors.forename: Valentino
authors.initials: V
authors.lastname: Conter
authors.affiliation: Maddalena Paganin, Giulia Fabbri, Katia Polato, and Giuseppe Basso, Università di Padova, Padova; Valentino Conter, Ospedale San Gerardo; Maria Grazia Valsecchi, Università di Milano Bicocca, Monza; Elena Barisone and Franca Fagioli, Ospedale Infantile Regina Margherita, Torino; Giovanni Cazzaniga, Università di Milano Bicocca, Milan; Eugenia Giraldi and Maurizio Aricò, Ospedale Papa Giovanni XXIII di Bergamo, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Barisone
authors.affiliation: Maddalena Paganin, Giulia Fabbri, Katia Polato, and Giuseppe Basso, Università di Padova, Padova; Valentino Conter, Ospedale San Gerardo; Maria Grazia Valsecchi, Università di Milano Bicocca, Monza; Elena Barisone and Franca Fagioli, Ospedale Infantile Regina Margherita, Torino; Giovanni Cazzaniga, Università di Milano Bicocca, Milan; Eugenia Giraldi and Maurizio Aricò, Ospedale Papa Giovanni XXIII di Bergamo, Italy.
authors.forename: Katia
authors.initials: K
authors.lastname: Polato
authors.affiliation: Maddalena Paganin, Giulia Fabbri, Katia Polato, and Giuseppe Basso, Università di Padova, Padova; Valentino Conter, Ospedale San Gerardo; Maria Grazia Valsecchi, Università di Milano Bicocca, Monza; Elena Barisone and Franca Fagioli, Ospedale Infantile Regina Margherita, Torino; Giovanni Cazzaniga, Università di Milano Bicocca, Milan; Eugenia Giraldi and Maurizio Aricò, Ospedale Papa Giovanni XXIII di Bergamo, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cazzaniga
authors.affiliation: Maddalena Paganin, Giulia Fabbri, Katia Polato, and Giuseppe Basso, Università di Padova, Padova; Valentino Conter, Ospedale San Gerardo; Maria Grazia Valsecchi, Università di Milano Bicocca, Monza; Elena Barisone and Franca Fagioli, Ospedale Infantile Regina Margherita, Torino; Giovanni Cazzaniga, Università di Milano Bicocca, Milan; Eugenia Giraldi and Maurizio Aricò, Ospedale Papa Giovanni XXIII di Bergamo, Italy.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Giraldi
authors.affiliation: Maddalena Paganin, Giulia Fabbri, Katia Polato, and Giuseppe Basso, Università di Padova, Padova; Valentino Conter, Ospedale San Gerardo; Maria Grazia Valsecchi, Università di Milano Bicocca, Monza; Elena Barisone and Franca Fagioli, Ospedale Infantile Regina Margherita, Torino; Giovanni Cazzaniga, Università di Milano Bicocca, Milan; Eugenia Giraldi and Maurizio Aricò, Ospedale Papa Giovanni XXIII di Bergamo, Italy.
authors.forename: Franca
authors.initials: F
authors.lastname: Fagioli
authors.affiliation: Maddalena Paganin, Giulia Fabbri, Katia Polato, and Giuseppe Basso, Università di Padova, Padova; Valentino Conter, Ospedale San Gerardo; Maria Grazia Valsecchi, Università di Milano Bicocca, Monza; Elena Barisone and Franca Fagioli, Ospedale Infantile Regina Margherita, Torino; Giovanni Cazzaniga, Università di Milano Bicocca, Milan; Eugenia Giraldi and Maurizio Aricò, Ospedale Papa Giovanni XXIII di Bergamo, Italy. maurizio.arico@ittumori.it.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Aricò
authors.affiliation: Maddalena Paganin, Giulia Fabbri, Katia Polato, and Giuseppe Basso, Università di Padova, Padova; Valentino Conter, Ospedale San Gerardo; Maria Grazia Valsecchi, Università di Milano Bicocca, Monza; Elena Barisone and Franca Fagioli, Ospedale Infantile Regina Margherita, Torino; Giovanni Cazzaniga, Università di Milano Bicocca, Milan; Eugenia Giraldi and Maurizio Aricò, Ospedale Papa Giovanni XXIII di Bergamo, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Valsecchi
authors.affiliation: Maddalena Paganin, Giulia Fabbri, Katia Polato, and Giuseppe Basso, Università di Padova, Padova; Valentino Conter, Ospedale San Gerardo; Maria Grazia Valsecchi, Università di Milano Bicocca, Monza; Elena Barisone and Franca Fagioli, Ospedale Infantile Regina Margherita, Torino; Giovanni Cazzaniga, Università di Milano Bicocca, Milan; Eugenia Giraldi and Maurizio Aricò, Ospedale Papa Giovanni XXIII di Bergamo, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Basso
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007558:Italy; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D009364:Neoplasm Recurrence, Local; D018365:Neoplasm, Residual; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction; D012074:Remission Induction; D013256:Steroids / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D013256:Steroids; D008727:Methotrexate