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

Abstract

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.

• Authors: 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
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 160 Pg. 72-79 (01 2022) ISSN: 1879-0852 [Electronic] England
• PMID: 34785111 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.

Topics

• Female
• Germ Cells
• Humans
• Infant
• Male
• Neoplasm, Residual (etiology, pathology)
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (complications, mortality, pathology)
• Prognosis
• Survival Analysis
• Treatment Outcome