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

Research output: Contribution to journalArticle


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<5×10−4 and 70 with MRD≥5×10−4 had a comparable 5-year cumulative incidence of relapse of 36.4 (15.4) and 35.2 (5.9), respectively. Patients who achieved MRD negativity at TP2 had a low relapse risk (5-yr cumulative incidence of relapse (CIR)=14.3[9.8]), whereas those who attained MRD negativity at a later date showed higher CIR, comparable to patients with positive MRD at any level. BCR/ABL1 MRD negative patients at TP1 had a relapse risk similar to those who were IG/TR MRD negative (1/8 relapses). The overall concordance between the two methods is 69%, with significantly higher positivity by BCR/ABL1. In conclusion, MRD monitoring by both methods may be functional not only for measuring response but also for guiding biological studies aimed at investigating causes for discrepancies, although from our data IG/TR MRD monitoring appears to be more reliable. Early MRD negativity is highly predictive of favorable outcome. The earlier MRD negativity is achieved, the better the prognosis.


  • Giovanni Cazzaniga
  • Paola de Lorenzo
  • Julia Alten
  • Silja Röttgers
  • Jeremy Hancock
  • Vaskar Saha
  • 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
External organisations
  • Berlin-Frankfurt-Munster Group Germany (BFMG)
  • Children’s Cancer and Leukaemia Group (CCLG)
  • Nordic Society of Paediatric Haematology and Oncology (NOPHO)
  • Dutch Childhood Oncology Group (DCOG)
  • Czech Pediatric Hematology Working Group (CPH)
  • Cooperative study group for treatment of ALL (COALL)
  • Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP)
  • European Organisation for Research and Treatment of Cancer
  • European Institute of Oncology
  • University of Milano-Bicocca
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology
  • Pediatrics
Original languageEnglish
Pages (from-to)107-115
Number of pages9
Issue number1
Publication statusPublished - 2018 Jan 1
Publication categoryResearch
Externally publishedYes