Home monitoring of neutrophil counts by patients with cyclic and congenital neutropenia Free

Background: Currently most blood cell counts are performed at clinical laboratories which is time-consuming, costly and may expose immunosuppressed patients to the risk of infections. The Dale laboratory in Seattle worked with Stanford bioengineers on developing an automated differential cell counter (Athelas Home), a home monitoring device. The device uses a tiny drop of fingerstick blood evenly distributed and stained in a thin glass chamber (test strip). The strip is placed on the microscope stage and scanned mechanically. Serial images are analyzed via image analysis/artificial intelligence technology and reported as percentages of the total white blood cell count and absolute neutrophil counts (ANCs). The device is United States (US) Food and Drug Administration (FDA) approved for laboratory and professional use, but has had limited clinical application and has not yet been used to study chemotherapy-induced or severe chronic neutropenia.

Plan: The goal of this study was to determine if patients can easily learn to use the device and will consistently use it to do serial/daily counts to help with the diagnosis of cyclic versus severe congenital neutropenia. Patients on and not on treatment with granulocyte colony-stimulating factor (G-CSF) were recruited. We studied a sample of 20 patients with ELANE mutations because of the important dichotomy of risk and responsiveness to G-CSF for these patients: congenital patients generally require higher doses of G-CSF and have a greater risk of evolution to acute myeloid leukemia. The study required access to a smart device for remote analysis and reporting of results to the patient and the investigators.

After institutional review board (IRB) approval and with informed consent, the device was shipped to patients with written instructions, and patients trained via Zoom to collect and analyze their samples. Patients were requested to perform daily counts for 6 weeks/42 days at the same time each day, just before G-CSF injections. We also requested that they report adverse events, illnesses, and problems with the counter, ANC determination at medical laboratories during the study period or any questions.

Results: As of August 1, 2025, there are 20 enrolled patients all with ELANE mutations (9 with a clinical diagnosis of cyclic neutropenia (4 male, 5 female) and 11 severe congenital neutropenia (5 male, 6 female). Fourteen patients have completed 42 days of the study. There were no withdrawals; 1 patient had difficulty participating because of frequent illness and hospitalizations. There were no adverse events related to the finger sticks and patients uniformly like having access at home to their blood count information. For the patients who have completed the 42-day study, blood counts were done on 579 of 588 days (98% days with ANCs for analysis). Because all the patients so far studied were on clinically effective doses of G-CSF, ANC values less than 0.5 x 10⁹/L was reported in only one patient (3 ANCs of 0.4 x 10⁹/L). There were no illnesses except the one patient noted above.

Data were analyzed graphically and spectral analysis by periodogram by Montreal collaborators Craig, Côté and Mackey. The periodogram analysis detected that 5 of the 8 patients with a previous diagnosis of cyclic neutropenia showed statistically significant (p<0.05) oscillations in the current study. Surprisingly, less apparent but statistically significant oscillations were also observed in 4 of the 6 patients with a previous clinical diagnosis of severe congenital neutropenia.Conclusions: Home monitoring of ANCs is readily performed by patients themselves with written instructions, brief online coaching, and email follow-up to address issues with the device and to answer questions. Home monitoring of ANCs was well accepted by patients because they value the convenience and rapid reporting of their laboratory results. We observed consistency of the results between the home monitoring device and previously performed conventional laboratory testing. We also observed statistically significant oscillations in blood counts for patients with a previous diagnosis of severe congenital neutropenia, suggesting an overlap of cyclic and congenital neutropenia attributable to mutations in ELANE. We acquired this new information because serial blood counts for severe chronic neutropenia (as well as for other types of neutropenia) has previously been so difficult to obtain.