Predictive value of minimal residual disease in Philadelphia-chromosome-positive acute lymphoblastic leukemia treated with imatinib in the European intergroup study of post-induction treatment of Philadelphia-chromosome-positive acute lymphoblastic leukemia, based on immunoglobulin/T-cell receptor and BCR/ABL1 methodologies
Giovanni Cazzaniga,
Paola De Lorenzo,
Julia Alten,
Silja Röttgers,
Jeremy Hancock,
Vaskar Saha,
Anders Castor,
Hans O. Madsen,
Virginie Gandemer,
Hélène Cavé,
Veronica Leoni,
Rolf Köhler,
Giulia M. Ferrari,
Kirsten Bleckmann,
Rob Pieters,
Vincent van der Velden,
Jan Stary,
Jan Zuna,
Gabriele Escherich,
Udo zur Stadt,
Maurizio Aricò,
Valentino Conter,
Martin Schrappe,
Maria Grazia Valsecchi,
Andrea Biondi
Affiliations
Giovanni Cazzaniga
Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP), Centro Ricerca Tettamanti, Pediatric Department, University of Milano-Bicocca, Monza, Italy
Paola De Lorenzo
Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP), Centro Ricerca Tettamanti, Pediatric Department, University of Milano-Bicocca, Monza, Italy;European intergroup study of post-induction treatment of Philadelphia-chromosome-positive acute lymphoblastic leukemia (EsPhALL) Trial Data Center, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
Julia Alten
Berlin-Frankfurt-Münster Group Germany (BFM-G), Germany and Switzerland
Silja Röttgers
Berlin-Frankfurt-Münster Group Germany (BFM-G), Germany and Switzerland
Jeremy Hancock
Children’s Cancer and Leukaemia Group (CCLG), UK
Vaskar Saha
Children’s Cancer and Leukaemia Group (CCLG), UK
Anders Castor
Nordic Society of Paediatric Haematology and Oncology (NOPHO), Sweden, Denmark, Norway, Finland and Iceland
Hans O. Madsen
Nordic Society of Paediatric Haematology and Oncology (NOPHO), Sweden, Denmark, Norway, Finland and Iceland
Virginie Gandemer
French Acute Lymphoblastic Leukemia Study Groups (French Acute Lymphoblastic Leukemia Study Group, FRALLE and European Organisation for Research and Treatment of Cancer, EORTC), Italy
Hélène Cavé
French Acute Lymphoblastic Leukemia Study Groups (French Acute Lymphoblastic Leukemia Study Group, FRALLE and European Organisation for Research and Treatment of Cancer, EORTC), Italy
Veronica Leoni
Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP), Pediatric Department, University of Milano-Bicocca, Fondazione MBBM, Monza, Italy
Rolf Köhler
Berlin-Frankfurt-Münster Group Germany (BFM-G), Germany and Switzerland
Giulia M. Ferrari
Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP), Pediatric Department, University of Milano-Bicocca, Fondazione MBBM, Monza, Italy
Kirsten Bleckmann
Berlin-Frankfurt-Münster Group Germany (BFM-G), Germany and Switzerland
Rob Pieters
Dutch Childhood Oncology Group (DCOG), the Netherlands
Vincent van der Velden
Dutch Childhood Oncology Group (DCOG), the Netherlands
Jan Stary
Czech Pediatric Hematology Working Group (CPH), Czech Republic
Jan Zuna
Czech Pediatric Hematology Working Group (CPH), Czech Republic
Gabriele Escherich
Cooperative study group for treatment of ALL (COALL), Germany
Udo zur Stadt
Cooperative study group for treatment of ALL (COALL), Germany
Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP), Pediatric Department, University of Milano-Bicocca, Fondazione MBBM, Monza, Italy
Martin Schrappe
Berlin-Frankfurt-Münster Group Germany (BFM-G), Germany and Switzerland
Maria Grazia Valsecchi
European intergroup study of post-induction treatment of Philadelphia-chromosome-positive acute lymphoblastic leukemia (EsPhALL) Trial Data Center, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
Andrea Biondi
Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP), Centro Ricerca Tettamanti, Pediatric Department, University of Milano-Bicocca, Monza, Italy;Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP), Pediatric Department, University of Milano-Bicocca, Fondazione MBBM, Monza, Italy
The prognostic value of minimal residual disease (MRD) in Philadelphia-chromosome-positive (Ph+) childhood acute lymphoblastic leukemia (ALL) treated with tyrosine kinase inhibitors is not fully established. We detected MRD by real-time quantitative polymerase chain reaction (RQ-PCR) of rearranged immunoglobulin/T-cell receptor genes (IG/TR) and/or BCR/ABL1 fusion transcript to investigate its predictive value in patients receiving Berlin-Frankfurt-Münster (BFM) high-risk (HR) therapy and post-induction intermittent imatinib (the European intergroup study of post-induction treatment of Philadelphia-chromosome-positive acute lymphoblastic leukemia (EsPhALL) study). MRD was monitored after induction (time point (TP)1), consolidation Phase IB (TP2), HR Blocks, reinductions, and at the end of therapy. MRD negativity progressively increased over time, both by IG/TR and BCR/ABL1. Of 90 patients with IG/TR MRD at TP1, nine were negative and none relapsed, while 11 with MRD
