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Minimal residual disease and outcome characteristics in infant KMT2A-germline acute lymphoblastic leukaemia treated on the Interfant-06 protocol

Publikation: Bidrag til tidsskriftTidsskriftartikelpeer review

DOI

  • J Stutterheim
  • P de Lorenzo
  • I M van der Sluis
  • J Alten
  • P Ancliffe
  • A Attarbaschi
  • L Aversa
  • J M Boer
  • A Biondi
  • B Brethon
  • P Diaz
  • G Cazzaniga
  • G Escherich
  • A Ferster
  • R S Kotecha
  • B Lausen
  • Alex Wk Leung
  • F Locatelli
  • L Silverman
  • J Stary
  • T Szczepanski
  • V H J van der Velden
  • A Vora
  • J Zuna
  • M Schrappe
  • M G Valsecchi
  • R Pieters
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BACKGROUND: The outcome of infants with KMT2A-germline acute lymphoblastic leukaemia (ALL) is superior to that of infants with KMT2A-rearranged ALL but has been inferior to non-infant ALL patients. Here, we describe the outcome and prognostic factors for 167 infants with KMT2A-germline ALL enrolled in the Interfant-06 study.

METHODS: Univariate analysis on prognostic factors (age, white blood cell count at diagnosis, prednisolone response and CD10 expression) was performed on KMT2A-germline infants in complete remission at the end of induction (EOI; n = 163). Bone marrow minimal residual disease (MRD) was measured in 73 patients by real-time quantitative polymerase chain reaction at various time points (EOI, n = 68; end of consolidation, n = 56; and before OCTADAD, n = 57). MRD results were classified as negative, intermediate (<5∗10-4), and high (≥5∗10-4).

RESULTS: The 6-year event-free and overall survival was 73.9% (standard error [SE] = 3.6) and 87.2% (SE = 2.7). Relapses occurred early, within 36 months from diagnosis in 28 of 31 (90%) infants. Treatment-related mortality was 3.6%. Age <6 months was a favourable prognostic factor with a 6-year disease-free survival (DFS) of 91% (SE = 9.0) compared with 71.7% (SE = 4.2) in infants >6 months of age (P = 0.04). Patients with high EOI MRD ≥5 × 10-4 had a worse outcome (6-year DFS 61.4% [SE = 12.4], n = 16), compared with patients with undetectable EOI MRD (6-year DFS 87.9% [SE = 6.6], n = 28) or intermediate EOI MRD <5 × 10-4 (6-year DFS 76.4% [SE = 11.3], n = 24; P = 0.02).

CONCLUSION: We conclude that young age at diagnosis and low EOI MRD seem favourable prognostic factors in infants with KMT2A-germline ALL and should be considered for risk stratification in future clinical trials.

OriginalsprogEngelsk
TidsskriftEuropean journal of cancer (Oxford, England : 1990)
Vol/bind160
Sider (fra-til)72-79
Antal sider8
ISSN0959-8049
DOI
StatusUdgivet - jan. 2022

Bibliografisk note

Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.

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