Over-Expression of CRLF2 By Flow Cytometry (FC) Impacts on Overall Survival (OS) in Mexican Patients with Acute Lymphoblastic Leukemia (ALL)

Abstract

Introduction: "Philadelphia like" ALL has been related to poor prognosis. CRLF2 over-expression (cytokine receptor like factor-2) has been found in up to 50% of patients with Philadelphia-like ALL and its expression can be measured by Flow Cytometry (FC). CRLF2 over-expression is more common in Hispanic population (45-68%) however, there is no current recommendation in using it as a prognostic marker. Objectives: Find the prevalence of CRLF2 overexpression measured by FC, in adult Mexican patients with treatment-naïve ALL Describe the outcomes of the patients who over-expressed CRLF2 by Complete Response (CR), Minimal Residual Disease (MRD), Leukemia-Free Survivale (LFS) and Overall Survival (OS). Methodology: This is a retrospective cohort study in adults with newly diagnosed ALL from two reference centers in Mexico City. We measured CRLF2 expression by FC in fresh bone marrow samples from treatment-naïve patients at one location; to define over-expression, samples were first analyzed by two different experts who grouped the cases in over-expression or no overexpression using Mean Fluorescence Intensity (MFI) between two populations, blasts and controls (normal B cells). Outcomes were compared using chi-square test for binary variables and log-rank test for time-to-event variables with a p value <0.05 as significant. Results: From April 2018 to January 2020 46 patients with treatment-naïve B-cell ALL were evaluable; the median age was 29.5 years, 38 (82.6%) were Adolescents and Young Adults (AYA), 22 (47.8%) had leukocytosis, 15 (53.5%) of the evaluable karyotypes, were assigned to high-risk group. The median time of follow-up was 24.5 months and 19 (41.3%) patients were positive for CRLF2-overexpression. For the follow-up cohort all of the patients were evaluable for outcomes. CNS disease was detectable in 11(24.5%) patients which was higher in CRLF2-overexpresed patients (15.5% vs 8.9%, p=0.015). We found no difference in Complete Remission (CR) in CRLF2 status but a high tendency for R/R (Relapse/Refractory) disease (83.3% in CRLF2-overexpression vs 60% in CRLF2 negative group; p=0.09) and dead (63.2% in CRLF2-overexpression vs 37% in CRLF2 negative group; p=0.07). MRD1, 2 and 3 (1=after induction, 2= week 16 and 3= before maintenance) was significantly worse in patients with CRLF2 overexpression (1=15.8% vs 58.3%, p<0.01; 2=7.1% vs 52.6%, p<0.01; 3=0% vs 55.6%, p<0.05). Overall Survival was significantly worse in patients with CRLF2 overexpression (Median Not Reached vs 11.05 months; p=0.04) (Figure 1); Disease-Free Survival (DFS) had a tendency towards worse outcome in patients with CRLF2 overexpression (18.48 vs 5.82 months, p=0.07) (Figure 2). Conclusion: Survival in patients who have CRLF2 overexpression is significantly worse when measured by FC, this might be related to early high-risk markers as MRD. CRLF2 overexpression in this hispanic sample was higher (41%) than other reports. CRLF2 measured as a prognostic factor by FC needs to be further considered due to the high availability of this technique across Latin-America. Figure 1 Figure 1. Disclosures Rangel-Patiño: Abbvie: Speakers Bureau; Bristol: Consultancy. Espinosa: Pfizer: Consultancy; Amgen: Speakers Bureau; Janssen: Consultancy. Demichelis: Novartis: Consultancy, Research Funding, Speakers Bureau; Gilead: Consultancy; Bristol/Celgene: Consultancy, Speakers Bureau; Jazz: Consultancy; ASH: Research Funding; Astellas: Consultancy; AMGEN: Consultancy, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau.

A modified CALGB 10403 in adolescents and young adults with acute lymphoblastic leukemia in Central America

“… 6 Another report in Mexico showed that 41.3% of adults diagnosed with ALL have CRLF2 overexpression, via flow cytometry, and this was associated with worse outcomes. 15 These results support the hypothesis that the population in Mexico and Central America has a more aggressive biology of the disease and could explain the increased risk of relapse in this population.…”