Analysis of overall survival in a large multiethnic cohort reveals absolute neutrophil count of 1,100 as a novel prognostic cutoff in African Americans

Abstract

Although absolute neutrophil counts (ANC) below 1.5x103/uL are used to define neutropenia as a marker of increased susceptibility to infections, their relationship with survival has not been examined. Since low counts trigger extensive investigations, determining prognostic cutoffs especially for different ethnicities and races is critical.A multiethnic cohort of 27,760 subjects, 65 years old and above, was utilized to evaluate the association of neutropenia with overall survival in different ethnicities and races.The mean ANC was 4.6±1.51x103/uL in non-Hispanic whites, 3.6±1.57x103/uL in non-Hispanic blacks and 4.3±1.54x103/uL in Hispanics (p<0.001). An ANC below 1.5x103/uL was associated with significantly shorter overall survival among whites (HR 1.74; 95% CI 1.18 - 2.58; p<0.001), but not in blacks (HR 0.89; 95% CI 0.86 - 1.17; p=0.40) or Hispanics (HR 1.04; 95% CI 0.76 - 1.46; p=0.82), after adjustment for age, sex, comorbidities, anemia and thrombocytopenia. Using Cox regression multivariable models, an ANC below 1.1x103/uL in blacks was found to be associated with increased mortality (HR 1.86; 95%CI 1.21 - 2.87; p<0.01). We found no association between neutropenia and mortality at any ANC cutoff in elderly Hispanics. In conclusion, neutropenia was found to be an independent prognostic variable in the elderly, when determined in race-specific manner. Most importantly, a cutoff of 1.1x103 neutrophils/uL may be a more prognostically relevant marker in elderly blacks and could serve as a novel threshold for further evaluation and intervention in this population.

Age‐related prevalence and clinical significance of neutropenia ‐ isolated or combined with other cytopenias: Real world data from 373 820 primary care individuals

“…In conclusion, this study provides a basis for stratification of the clinical investigation of a person presenting with NP, alone or combined with anemia and/or thrombocytopenia, irrespective of if this occurs in the setting of primary or secondary care. It also supports the notion that a cut‐off value for ANC at 1.5 G/L (ie, the most common ANC limit for defining NP) is of significance for morbidity and mortality …”

Lower Total Leukocyte and Neutrophil Counts in Healthy Young Africans from Uganda

“…Also, the expected leukocytosis during infections in these individuals may be blunted with resultant underestimation of the severity of infection. A multiethnic cohort study of 27,760 elderly (C65 years) subjects has recommended that instead of a TLC cut off of 1.5 9 10 9 /l, values below 1.1 9 10 9 /l may be regarded as neutropenia in the black population [17].…”

Prospects for targeting ACKR1 in cancer and other diseases

“…ACKR1-mediated DANC neutropenia affects patient care by impeding administration of drugs like clozapine or azathioprine and leading to potentially unwarranted bone marrow biopsies ( 165 – 167 ). Patients with FyES phenotype are at increased risk of side effects from chemotherapy but using the same neutropenic cutoff values may unnecessarily delay initiation and prolong duration of cancer treatment ( 168 – 172 ). Adapting standard of care for patients with DANC could provide an opportunity to address disparate treatment outcomes with a precision medicine approach.…”