Blood: Molecular classification can improve the risk assessment of BCR-ABL1-negative B-ALL adult patients

Central point: Genetic testing can improve the risk allocation of most adult patients with BCR-ABL1-B-ALL; when combined with genotype consideration, antigen profile can affect the outcome of B-ALL patients
.

Center point:

Genome classification improves the risk allocation of children with B-line acute lymphoblastic leukemia (B-ALL) , but has no optimization effect on adult patients with B-ALL
.

The international UKALLXII/ECOG-ACRIN E2993 (#NCT00002514) trial enrolled a total of 1,229 BCR-ABL1-B-ALL adolescent/adult patients (14-65 years old)

Children in this trial, although 93% of patients can get remission, 41% of patients relapse at a median time of 13 months (range: 28 days to 12 years).

Antigen expression of different molecular subgroups

Antigen expression of different molecular subgroups

Through transcriptome sequencing, gene expression profiling, cytogenetics, and fusion polymerase chain reaction, 282 patient samples were genotyped, of which 264 met the test conditions, accounting for 64.
5% of the E2993 test patients
.

Among patients with outcome information, 29.
5% of patients with good outcomes (5-year OS: 65%-80%) were considered standard risk (DUX4 rearrangement: 9.
2%; ETV6-RUNX1/-like: 2.
3%; TCF3) -PBX1: 6.
9%; PAX5 P80R: 4.
1%; hyperdiploid: 6.
9%) ; 50.
2% of patients have high-risk subtypes, and 5-year OS is 0%-27% (Ph-like: 21.
2%; KMT2A-AFF1: 12%; low hypodiploid/near haploid: 14.
3%; BCL2/MYC rearrangement: 2.
8%); 20.
3% of patients have the intermediate-risk subtype, and the 5-year OS is 33%-45% (PAX5alt: 12.
4 %; ZNF384/-like: 5.
1%; MEF2D rearrangement: 2.
8%)
.

29.
5% of patients with good results (5-year OS: 65%-80%) are considered standard risk (DUX4 rearrangement: 9.
2%; ETV6-RUNX1/-like: 2.
3%; TCF3-PBX1: 6.
9%; PAX5 P80R : 4.
1%; hyperdiploid: 6.
9%) 29.
5% of patients with good results (5-year OS: 65%-80%) are considered standard risk (DUX4 rearrangement: 9.
2%; ETV6-RUNX1/-like: 2.
3%; TCF3-PBX1: 6.
9%; PAX5 P80R: 4.
1%; hyperdiploid: 6.
9%) 50.
2% of patients have high-risk subtypes, and 5-year OS is 0%-27% (Ph-like: 21.
2%; KMT2A -AFF1: 12%; low hypodiploid/near haploid: 14.
3%; BCL2/MYC rearrangement: 2.
8%); 20.
3% of patients have intermediate-risk subtype, and 5-year OS is 33%-45% ( PAX5alt: 12.
4%; ZNF384/-like: 5.
1%; MEF2D rearrangement: 2.
8%)
.

20.

RFS and OS of patients in different molecular subgroups

RFS and OS of patients in different molecular subgroups

86% of patients with Ph-like mutations have IKZF1 variants, 54% of low hypodiploid patients and 33% of BCL2/MYC rearrangement patients have TP53 variants; there is no independent correlation between IKZF1 and TP53 variants and prognosis
.

Among high-risk patients assessed based on age and white blood cell count, 40% of patients had subtype-defining genetic changes associated with standard or intermediate-risk outcomes
.

In addition, the researchers also determined the different immunophenotypic characteristics of DUX4 rearrangement, PAX5 P80R, ZNF384-R/-like and Ph-like genotypes

immunity

In short, the study shows the prognostic significance of genomic analysis, which may translate into future treatment benefits

The study shows the prognostic significance of genomic analysis, which may translate into future therapeutic benefits.

Original source:

Elisabeth Paietta, et al.

Molecular classification improves risk assessment in adult BCR -ABL1-negative B-ALL in this message