PURPOSE: Speed of blast clearance is an indicator of outcome in childhood acute lymphoblastic leukemia (ALL). Availability of measurement of minimal residual disease (MRD) at an early time point with a reduced-cost method is of clinical relevance. In the AIEOP-BFM-ALL (Associazione Italiana Ematologia Oncologia Pediatrica and Berlin-Frankfurt-Münster Study Group) 2000 trial, patients were stratified by levels of polymerase chain reaction (PCR) MRD at day +33 and +78. AIEOP studied the prognostic impact of MRD measured by flow cytometry (FCM) at day 15 of induction therapy. PATIENTS AND METHODS: Bone marrow samples from 830 Italian patients were collected on day 15, after 14 days of steroids, and one dose of intrathecal methotrexate, vincristine, daunorubicine, and asparaginase. Cells were analyzed by four-color FCM for detection of leukemia-associated immunophenotypes. RESULTS: Three patient risk groups were identified by FCM: standard (< 0.1% blast cells; 42% of the total), intermediate (0.1 to < 10%; 47%), and high (> or = 10%; 11%). Their 5-year cumulative incidences of relapse were 7.5% (SE, 1.5), 17.5% (SE, 2.1), and 47.2% (SE, 5.9), respectively. In multivariate analysis, FCM was the most important prognostic factor among those available by day 15, with two-fold and five-fold increase in the risk of relapse compared with patients with less than 0.1%. PCR MRD, when added to the model, had significant prognostic impact; yet high levels of FCM MRD retained an independent ability to detect a significantly higher risk of relapse. CONCLUSION: Measurement of FCM MRD in day 15 bone marrow was the most powerful early predictor of relapse, applicable to virtually all patients; it may complement PCR MRD-based stratification including later time points, thus allowing additional treatment tailoring.
RCT Entities:
PURPOSE: Speed of blast clearance is an indicator of outcome in childhood acute lymphoblastic leukemia (ALL). Availability of measurement of minimal residual disease (MRD) at an early time point with a reduced-cost method is of clinical relevance. In the AIEOP-BFM-ALL (Associazione Italiana Ematologia Oncologia Pediatrica and Berlin-Frankfurt-Münster Study Group) 2000 trial, patients were stratified by levels of polymerase chain reaction (PCR) MRD at day +33 and +78. AIEOP studied the prognostic impact of MRD measured by flow cytometry (FCM) at day 15 of induction therapy. PATIENTS AND METHODS: Bone marrow samples from 830 Italian patients were collected on day 15, after 14 days of steroids, and one dose of intrathecal methotrexate, vincristine, daunorubicine, and asparaginase. Cells were analyzed by four-color FCM for detection of leukemia-associated immunophenotypes. RESULTS: Three patient risk groups were identified by FCM: standard (< 0.1% blast cells; 42% of the total), intermediate (0.1 to < 10%; 47%), and high (> or = 10%; 11%). Their 5-year cumulative incidences of relapse were 7.5% (SE, 1.5), 17.5% (SE, 2.1), and 47.2% (SE, 5.9), respectively. In multivariate analysis, FCM was the most important prognostic factor among those available by day 15, with two-fold and five-fold increase in the risk of relapse compared with patients with less than 0.1%. PCR MRD, when added to the model, had significant prognostic impact; yet high levels of FCM MRD retained an independent ability to detect a significantly higher risk of relapse. CONCLUSION: Measurement of FCM MRD in day 15 bone marrow was the most powerful early predictor of relapse, applicable to virtually all patients; it may complement PCR MRD-based stratification including later time points, thus allowing additional treatment tailoring.
Authors: Maurizio Aricò; Martin Schrappe; Stephen P Hunger; William L Carroll; Valentino Conter; Stefania Galimberti; Atsushi Manabe; Vaskar Saha; André Baruchel; Kim Vettenranta; Keizo Horibe; Yves Benoit; Rob Pieters; Gabriele Escherich; Lewis B Silverman; Ching-Hon Pui; Maria Grazia Valsecchi Journal: J Clin Oncol Date: 2010-09-27 Impact factor: 44.544
Authors: Giuseppe Gaipa; Giovanni Cazzaniga; Maria Grazia Valsecchi; Renate Panzer-Grümayer; Barbara Buldini; Daniela Silvestri; Leonid Karawajew; Oscar Maglia; Richard Ratei; Alessandra Benetello; Simona Sala; Angela Schumich; Andre Schrauder; Tiziana Villa; Marinella Veltroni; Wolf-Dieter Ludwig; Valentino Conter; Martin Schrappe; Andrea Biondi; Michael N Dworzak; Giuseppe Basso Journal: Haematologica Date: 2012-05-11 Impact factor: 9.941
Authors: J J M van Dongen; L Lhermitte; S Böttcher; J Almeida; V H J van der Velden; J Flores-Montero; A Rawstron; V Asnafi; Q Lécrevisse; P Lucio; E Mejstrikova; T Szczepański; T Kalina; R de Tute; M Brüggemann; L Sedek; M Cullen; A W Langerak; A Mendonça; E Macintyre; M Martin-Ayuso; O Hrusak; M B Vidriales; A Orfao Journal: Leukemia Date: 2012-05-03 Impact factor: 11.528
Authors: Leonid Karawajew; Michael Dworzak; Richard Ratei; Peter Rhein; Giuseppe Gaipa; Barbara Buldini; Giuseppe Basso; Ondrej Hrusak; Wolf-Dieter Ludwig; Günter Henze; Karl Seeger; Arend von Stackelberg; Ester Mejstrikova; Cornelia Eckert Journal: Haematologica Date: 2015-05-22 Impact factor: 9.941