Minimal residual disease and outcome characteristics in infant KMT2A-germline acute lymphoblastic leukaemia treated
J Stutterheim1, P de Lorenzo2, I M van der Sluis1
1Pediatric Oncology, Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Insights
Young age at diagnosis and low end of induction minimal residual disease (MRD) are favorable prognostic factors for infants with KMT2A-germline acute lymphoblastic leukemia (ALL). These factors can improve risk stratification in future clinical trials for infant ALL.
Area of Science:
- Pediatric Oncology
- Hematology
- Genetics
Background:
- Infants with KMT2A-germline acute lymphoblastic leukemia (ALL) have a better outcome than those with KMT2A-rearranged ALL, but worse than older children.
- The Interfant-06 study investigated outcomes for 167 infants with KMT2A-germline ALL.
Purpose of the Study:
- To describe the outcomes of infants with KMT2A-germline ALL.
- To identify prognostic factors influencing survival in this patient group.
Main Methods:
- Univariate analysis of prognostic factors including age, white blood cell count, prednisolone response, and CD10 expression.
- Minimal residual disease (MRD) measurement using real-time quantitative polymerase chain reaction at various treatment points.
- Classification of MRD levels as negative, intermediate, or high.
Main Results:
- Six-year event-free survival was 73.9% and overall survival was 87.2%.
- Early relapses occurred in 90% of cases within 36 months.
- Younger age (<6 months) and low end of induction MRD (<5 × 10⁻⁴) were associated with significantly better disease-free survival.
Conclusions:
- Young age at diagnosis and low end of induction MRD are favorable prognostic indicators for infants with KMT2A-germline ALL.
- These factors should be incorporated into risk stratification for future clinical trials.
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.
