Nicotinamide (NA) Treatment Improves Response to G-CSF in Severe Congenital Neutropenia (SCN) Patients

Background: SCN is an inherited bone marrow failure syndrome with markedly reduced granulocyte numbers and functions that often manifests with life-threatening bacterial infections. G-CSF treatment is the primary therapeutic approach, yet some SCN patients require high doses of G-CSF which increases the risk of acute myeloid leukemia development, or do not respond to GCSF at al. We have demonstrated that nicotinamide (NA) treatment increases granulocyte numbers in healthy volunteers.

Aim: To asses the effect of NA treatment in SCN and cyclic neutropenia (CyN) patients.

Methods: 15 SCN and three CyN patients ages 0.5 to 31 (M-5.47) years were orally treated with 20 mg/kg/day of NA in addition to G-CSF therapy. G-CSF dose varied between 0.6 and 50.8 µg/kg/day before start of NA treatment.

Results: After three months of NA treatment, absolute neutrophil counts (ANC) increased from median 0.80 x 10⁹/l (Q1 0.61, Q3 1.29 x 10⁹/l) to 1.77 x 10⁹/l (Q1 1.49, Q3 2.33 x 10⁹/l) (p < 0.001). This allowed G-CSF dose reduction from 15 µg/kg/day (Q1 5, Q3 25 µg/kg/day) to 10 µg/kg/day (Q1 1.77, Q3 15.16 µg/kg/day) in 17 patients, and complete G-CSF tapering in one patient. After one year of observations, ANC were 1.50 x 10⁹/l (Q1 0.99, Q3 2.86 x 10⁹/l), median increase of ANC from start of therapy was 0.89 x 10⁹/l fold (Q1 0.39, Q3 1.57; р = 0.004). NA was well tolerated, without severe adverse events. We also observed a marked reduction of the frequency and severity of bacterial infections upon combination of NA and G-CSF.

Conclusions: In our group of SCN/CyN patients, NA treatment led to increased neutrophil counts and decreased required G-CSF doses with continuous clinical and laboratory responses. We also observed a reduction of the frequency and severity of bacterial infections. Therefore, the use of NA in combination with a reduced dose of G-CSF for the treatment of SCN and CyN patients is promising and should be further investigated in a larger cohort of patients.