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

• Published in: Journal of pediatric surgery Vol. 56; no. 7; pp. 1179 - 1185
• Main Authors: Holterman, AiXuan, Nguyen, Hoa Pham Anh, Nadler, Evan, Vu, Giap H, Mohan, Parvathi, Vu, Megan, Trinh, Thuy Thi, Bui, Huong Thuy Thi, Nguyen, Binh Thanh, Quynh, Anh Tran, Pham, Hien Duy
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2021
• Subjects: Biliary atresia; Cholangitis; GCSF; Global health; IND; Kasai; Low middle income country; Phase 1 study; Safety; Global health; Biliary atresia; Low middle income country; Cholangitis; Phase 1 study; Kasai; Safety; GCSF; IND
• ISSN: 0022-3468; 1531-5037; 1531-5037
• DOI: 10.1016/j.jpedsurg.2021.03.038

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 in biliary atresia BA was approved. This phase 1 study examines GCSF safety in Kasai subjects. Preliminary short-term outcome was evaluated. GCSF (Neupogen) at 5 or 10 μg/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. With GCSF, WBC and platelet count transiently increased, LFT and serum creatinine remained stable. Reversible splenic enlargement (by 8.5–20%) 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. 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.