Over-Expression of CRLF2 By Flow Cytometry (FC) Impacts on Overall Survival (OS) in Mexican Patients with Acute Lymphoblastic Leukemia (ALL)
Authors: Almanza Huante Emmanuel , Rangel-Patiño Juan , Córdova-Serrano Rosana Daniela , Espinosa Karla Adriana , Demichelis Roberta 
Published: November 2021

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 &lt;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&lt;0.01; 2=7.1% vs 52.6%, p&lt;0.01; 3=0% vs 55.6%, p&lt;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.