Granulocyte-Colony Stimulating Factor GCSF Mobilizes Hematopoietic Stem Cells in Kasai Patients with Biliary Atresia in a Phase 1 Study and Improves Short Term Outcome
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In brief
In brief
Phase 1 trial demonstrates GCSF safely mobilizes hematopoietic stem cells in infants undergoing Kasai surgery for biliary atresia, with preliminary evidence of improved biliary drainage and reduced cholangitis at 6 months. Study supports advancement to Phase 2 efficacy trial of GCSF as adjunct therapy.
Written by the GCMD Library team from the article.
Abstract
Aims
In RCT of adults with decompensated cirrhosis, GCSF mobilizes hematopoietic stem cells HSC and improves short-term outcome. An FDA-IND for sequential Kasai-GCSF treatment for biliary atresia BA was approved. This phase 1 study examines GCSF safety in Kasai subjects. Preliminary short-term outcome was evaluated.
Methods
GCSF (Neupogen) at 5 or 10 ug/kg (n=3/group) was given in 3 daily doses starting on day 3 of Kasai surgery (NCT03395028). Serum CD34+ HSC cell counts, and 1-month of GCSF-related adverse events were monitored. The 6-months Phase 1 clinical outcome was compared against 10 subsequent post Phase 1 Kasai patients who did not receive GCSF.
Results
With GCSF, WBC and platelet count transiently increased, LFT and serum creatinine remained stable. Reversible splenic enlargement (by 8.5 to 20%) occurred in 5/6 subjects. HSC count increased 12-fold and 17.5-fold for the 5 μg/kg and10 ug/kg dose respectively; with respective median total bilirubin levels for GCSF vs no-GCSF groups of 55 vs 91 μM at 1 month, p=0.05; 15 vs 37 μM at 3 months, p=0.24); and the 6-months cholangitis frequency of 40% vs 90%, p=0.077.
Conclusions
GCSF safely mobilizes HSC in Kasai infants and may improve short-term biliary drainage and cholangitis. Phase 2 efficacy outcome of GCSF adjunct therapy for sequential Kasai and GCSF is pending.