J Clin Oncol: Prognosis in non-infantile patients with acute lymphoblastic leukemia with 11q23/KMT2A rearrangement

Although 11q23/KMT2A rearrangement has adverse effects on the prognosis of infantile acute lymphoblastic leukaemia, its effect on the prognosis of non-infant patients is unclear
.
The purpose of this collaborative study was to evaluate the effects and prognostic factors
of allogeneic hematopoietic stem cell transplantation (allo-HSCT) at the first remission in non-infantile acute lymphoblastic leukemia patients treated with a chemotherapy regimen between 1995 and 2010.

The researchers retrospectively collected data from 629 11q23/KMT2A rearranged ALL patients from 17 members of the Ponte-di-Legno Childhood ALL Working Group and analyzed clinical and biological characteristics, early response to minimal residual lesion assessment at the end of induction therapy (EOI), and the impact
of allogeneic hematopoietic stem cell transplantation on prognosis.

A specific 11q23/KMT2A translocation companion gene was found in 84.
3% of patients, with the most common translocation being t (4; 11)(q21; q23) (n=273; 51.
5%)、t(11; 19)(q23; p13.
3) (n=106; 20.
0%)、t(9; 11)(p21_22; q23) (n=76; 14.
3%)、t(6; 11)(q27; q23) (n=20; 3.
8%) and t(10; 11)(p12; q23) (n=14; 2.
6%)； 41 (7.
7%) patients had a low frequency of
translocation partner gene recognition.
Different subgroups had different patient characteristics and early responses, suggesting greater biological heterogeneity and diversity
of treatment sensitivity in 11q23/KMT2A rearrangement ALL.

Survival after relapse in patients with ALL with 11q23/KMT2A rearrangement

The EOI response rate was 93.
2%, and the 5-year event-free survival (EFS) rate for the entire cohort was 69.
1% ± 1.
9%, t(9; 11) The 5-year EFS of patients with positive T-ALL(n=9) was 41.
7% ±17.
3%, t(4; 11) The 5-year EFS of positive B-ALL (n=266) patients was 64.
8% ± 3.
0%, t(11; 19) The 5-year EFS of positive T-ALL (n=34) patients was 91.
2% ± 4.
9%.

Low EOI minimal residual lesions are associated with good EFS, and induction failure specifically predicts non-response to further treatment, relapse, and poor
EFS.
In addition, in t(4; 11) In patients with positive B-ALL (n=64 vs 51, p=0.
10) and 11q23/KMT2A rearranged T-ALL (n=16 vs 10, p=0.
69), allo-HSCT failed to significantly improve EFS
compared with chemotherapy.

Overall, patients with non-infant 11q23/KMT2A rearranged ALL have improved their prognosis compared with historical data, but allogeneic HSCT has failed to improve the prognosis
in these patients.
Therefore, targeted treatment is needed to reduce its relapse and treatment-related mortality
.

Original source:

Andishe Attarbaschi, et al.
Outcomes of Childhood Noninfant Acute Lymphoblastic Leukemia With 11q23/KMT2A Rearrangements in a Modern Therapy Era: A Retrospective International Study.
Journal of Clinical Oncology.
October 18, 2022.
https://ascopubs.
org/doi/abs/10.
1200/JCO.
22.
01297