Differences in Neutrophil Counts Between African and Non-African Countries in 2 International Clinical Trials.

BACKGROUND

Differences in absolute neutrophil count (ANC) between African and non-African populations have been reported. Neutropenia has also been reported during rifamycin use. ANC values in current tables that assign severity grades to clinical or laboratory events (National Cancer Institute Common Terminology Criteria for Adverse Events [CTCAE] and the National Institute of Allergy and Infectious Diseases Division of AIDS [DAIDS]) might not consistently be applicable among different populations.

METHODS

During 2 international tuberculosis treatment trials, 337 participants received 10 mg/kg of rifampin, and 3 groups of 361, 81, and 81 participants received 10, 15, and 20 mg/kg of rifapentine, respectively, for 2 months of daily treatment. ANC was measured at baseline and after 2, 4, 6, 8, and 12 weeks of treatment. CTCAE versions 2.0-4.0 and DAIDS version 2.0 define neutropenia grade 3 as ANC 500-999 cells/μL and ANC 400-599 cells/μL, respectively. We analyzed factors associated with neutropenia.

RESULTS

Baseline median ANC was lower in Black African participants than in Black non-African participants (P = .004). CTCAE-defined grade 3 or higher neutropenia occurred in 32 (28 in Africa) participants. Proportions did not differ between rifapentine doses. Only 4 events would have been reported by DAIDS criteria. All neutropenia events resolved spontaneously without interrupting treatment. Enrollment in an African country was an independent factor associated with the development of neutropenia.

CONCLUSIONS

Differences in baseline median ANC can result in misclassification of adverse events or inappropriate clinical management. Development and use of population-specific normal values of ANC could improve guidance for research and clinical management.