Prognostic Significance of Neutrophil-to-Lymphocyte Ratio in Relapsed/Refractory Acute Myeloid Leukemia

Abstract Background The inflammatory and immune response in tumor microenvironment plays a critical role in cancer progression. Neutrophil-to-lymphocyte ratio (NLR) has been reported as a prognostic factor in solid and lymphoid malignancies. We explored the association of NLR with response to chemotherapy and overall survival (OS) in patients with relapsed/refractory acute myeloid leukemia (RR-AML). Methods A single-center retrospective study was conducted, including 63 adult RR-AML patients who underwent salvage therapy at the University of Wisconsin from 2009 to 2018. Demographic, clinical and pathologic factors were ascertained at the time of RR-AML diagnosis. Refractory AML was defined as failure to achieve remission and Results The study included 63 patients with relapsed (57%) or refractory (43%) AML. Median age was 58 years and 59% of patients were male. AML was classified according to WHO 2016 guidelines as AML with recurrent genetic abnormalities (25%), myelodysplasia (MDS)-related AML (25%), therapy-related AML (6%) and AML not otherwise specified (43%). Cytogenetics were good (5%), intermediate (68%) and poor (27%) with normal (46%), complex (17.5%) and trisomy (14%) being common karyotypes. Frequent molecular abnormalities were NPM1 (21%), FLT3-ITD (17.5%), FLT3-TKD (8%), DNMT3A (6%) and CEBPA (5%). AML risk status was good (19%), intermediate (36.5%) and poor (44.5%), based on cytogenetic and molecular abnormalities as defined by the ELN 2017 and NCCN 2018 guidelines. Extramedullary disease was present in 11% of patients. Prior hematopoietic stem cell transplant (HSCT) was performed in 13% of patients. Median values for clinical factors were: hemoglobin 9.2 g/dL, platelets 43 K/uL, leukocytes 1.7 K/uL, neutrophils 262 /uL, lymphocytes 820 /uL and LDH 211 U/L. Median bone marrow cellularity was 50% with 35% myeloblasts. Median NLR was 0.22 (mean 1.54) and 11% patients had NLR of 3 or more. Salvage chemotherapy included MEC (71%), CLAG-M (24%) and CLAG (5%). Complete remission (CR) was noted in 36.5% patients, 8% of patients had CR with incomplete hematologic recovery (CRi) and 55.5% patients were refractory. Thirty patients (48%) received HSCT, of which 40% (n=12/30) were refractory or relapsed. After index salvage regimen, about half of patients received one (33%) or two (16%) lines of further chemotherapy. At last follow-up, 32% of patients were in CR and 62% had relapsed or refractory disease. Nineteen (30%) patients were alive at last follow-up with a median OS of 8.1 months (95% CI 5.0-11.1). Significant correlates of poor OS included MDS-related AML (HR 2.19, 95% CI 1.13-4.27, P=0.021) and therapy-related AML (HR 4.02, 95% CI 1.16-13.90, P=0.028) compared to de-novo AML, poor-risk AML (HR 3.09, 95% CI 1.18-8.10, P=0.022) compared to good-risk AML, refractory to salvage chemotherapy (HR 7.04, 95% CI 3.51-14.14, P Conclusion High NLR independently predicts poor OS in RR-AML patients. Our findings warrant further studies with a large prospective cohort to explore the prognostic significance of NLR and incorporate it in AML risk assessment. Disclosures Atallah: BMS: Consultancy; Abbvie: Consultancy; Novartis: Consultancy; Jazz: Consultancy; Pfizer: Consultancy.