CXCR-4 is a chemokine receptor along with its ligand SDF-1 is a key regulator of the cross talk between the tumor microenvironment and the cancer cells. Its expression is associated with chemo resistance, increased relapse and poor survival in hematological and solid malignancies.
To determine the expression of CXCR-4 in patients and clinico- biological significance in patients with AML.
To determine its effect on overall survival .Event for OS was death due to any cause. Patients were censored
on the date of last contact or last to follow up.
116 patients diagnosed with de novo non-M3 AML treated with intensive chemotherapy (Cytarabine 100 mg/m2 for 7 days + Daunomycin 60 mg/m2 for 3 days) between 2016 to 2018 were enrolled. CXCR-4 expression was done by flow cytometry at diagnosis. For CXCR-4 detection anti CXCR-4 antibody in combination with anti-CD34, anti CD117 and anti CD-45 was used. Isotype control was used to better define the threshold of CXCR-4 positive-stained cells. If more than 20% of the blast population is stained, the AML sample is considered CXCR-4 positive. Patients were divided into groups based on CXR-4 expression Group A (<20%) and Group B (>20%). Karyotyping was done for all patients and risk stratified according to Modified MRC criteria. In patients with normal cytogenetics molecular testing for FLT-3 ITD, NPM-1 and CEBP-A mutations were done.
A total of 116 patients were included in our study with ages ranging from 18 to 54 years. 42% were in good risk, 21% in intermediate risk and 37% in high risk category. CXCR-4 expression was found in 72 patients (62%). CXCR-4 expression was associated with higher blasts (p = 0.001) and total leucocyte count (P = 01). CXCR- 4 expression was higher in unfavourable than favourable risk (77 % vs 38 % p = 0.046) and there was no difference between intermediate and unfavourable risk (76% vs &77% p = 1.00). Remission rate was lower in Group B (60% vs 85% p = 0.001). Count recovery followed induction chemotherapy was delayed in Group B (28 vs 21 days p = 0.04). After median follow up of fourteen months one year survival rate in group A was 78% and 45% in group B (p = 0.01). Median duration to relapse in group B was 8 months and 16 months in Group A (p = 0.02). Overall survival was 18 months and 10 months in group B (HR =0.34 p = 0.001). In multivariate analysis CXCR-4 expression > 20% (HR= 1.15, p = 0.01)and High risk cytogentics HR= 1.45 p = 0.01) were predictive of survival. Hemoglobin (p = 0.2), blast percentage (p = 0.06) and total leucocyte count (p = 0.07) were not predictive of survival.
CXCR-4 expression is a negative predictive and prognostic marker. in AML patients Its effect is independent of high risk cytogenetics. Since the molecular markers are expensive and not widely available in developing world CXCR-4 expression can be utilized for better characterization and prognostication of the disease at the time of diagnosis.