ESMO Asia Congress 2022

Abstract 218P

Background

Acute Lymphoblastic Leukemia (ALL) is a disease of rapid cell proliferation. Onset and development of ALL has also been linked to a reduction in the rate of apoptosis. We aimed to study the rate of in vivo spontaneous apoptosis at baseline in predicting induction outcome for newly diagnosed ALL.

Methods

Newly diagnosed ALL, age 1-39 years, were prospectively enrolled during the study period (December 2020- December 2021) and clinical course was followed till end of induction. Whole blood samples were obtained and assessment of Apoptotic Index (AI) was done using two-parameter Flowcytometry by Annexin- Propidium Iodide staining. The AI was expressed as ratio of Annexin V-positive blast cells divided by total blast cells in the gate.

Results

Total of 70 patients were enrolled, median age was 12.5 years (range, 1-39). Baseline characteristics and induction outcomes are summarized in the table. In the entire cohort, median AI in the blasts was 11.89 (0-87). Patients with high risk had a significantly low AI (median=11) compared to standard risk (median AI=16.9): p=0.026. Post induction, patients who attained CR had a significantly high AI (median=11.8) compared to patients with refractory disease (median AI=3.21): p=0.031. A cut-off of 12 was taken to define high AI (>12) and low AI (<12) for analysing post induction outcomes. In patients with high AI(N=28) and low AI(N=35), CR was 100%(n=28/28) and 85%(n=30/35), while refractory disease was 0% vs 14.3%(n=5/35) respectively. Thus, high AI at baseline was significantly associated with attainment of CR(p=0.037). No association of AI was found with baseline characteristics, D8 response and MRD. Table: 218P

Baseline characteristics and Induction outcomes

Characteristics (N=70)	N(%)
Age
1-18 years	49 (70)
19-39 years	21 (30)
Gender
Male	47 (67.1)
Female	23 (32.9)
Subtype
B-ALL	57 (81.4)
T-ALL	13 (18.6)
NCI Risk group
HR	48 (68.6)
SR	22 (31.4)
Protocol
BFM-95	26 (37)
ICiCLe	44 (63)
D8 steroid response
Good response	55 (78.6)
Poor response	13 (18.6)
Unknown (early death)
BM Remission statusCR	58 (82.9)2 (2.9)
Refractory	5 (7.1)
Unknown/death	7 (10)
MRD Positive	9 (12.9)
Negative	53 (75.7)
Unknown	2 (2.9)

Conclusions

Low baseline AI in blast is associated with poor remission rates post induction. Validation of the prognostic role of AI in larger/alternate patient population and for survival outcomes can guide inclusion of apoptosis directed therapy for these high risk subsets.