A multicentre, phase II, open-label, randomised controlled trial of repeated autologous infusions of granulocyte colony stimulating factor mobilised CD133 + bone marrow stem cells in patients with cirrhosis

Research output: Contribution to conference (unpublished)Abstract

Authors

Abstract

Background and Aims: Liver disease mortality and morbidity are rising and liver transplantation is limited by organ availability. Small scale human studies showed that autologous stem cell therapy whilst safe and readily available needed a well conducted randomised controlled trial. Methods: Patients with liver cirrhosis and MELD score 11.5-15.5 were randomised to Arm 1 - Conservative management; Arm 2 - Treatment with granulocyte colony stimulating factor (G-CSF) (Lenograstim) 15 mcg/kg od for 5 days or Arm 3 - Treatment with G-CSF 15 mcg/kg od for 5 days followed by leukapheresis, CD133+ cell isolation and infusion of freshly isolated CD133+ cells immediately and frozen doses at days 30/60 via peripheral vein (0.2 x 106 cells/kg). Co-Primary objectives were to demonstrate improvement in the severity of liver disease (change in MELD) at 3 months, and its trend over time, across Arms. To detect a 0.8 point reduction in MELD with a 2-sided alpha = 5% (alpha = 0.1 split equally) and 80% power required 27 participants per Arm (81 in total). Analyses were performed on a modified intention-to-treat basis. Results: Mean (SD) age was 55 (8.8), 53 were male, 37 had alcoholrelated liver disease and 10 had HCV. One patient with drew fully from Arm 1 (day 30) and two from Arm 3 (day 8 and 98). 19 (68%) Arm 3 patients received the intended dose of CD133+ cells. 27 (96%) Arm 3 patients and 24 (92%) Arm 2 patients received the intended dose of GCSF. The primary outcome measures were not met. Median (IQR) change in MELD for the control, GCSF, and GCSF + cell arms was -0.3 (-1.5,1.1), -0.5 (-1.4, 0.5) & -0.7 (-1.3,1.0) respectively. There was no evidence of a difference in change in MELD between control and Arm 2 (p = 0.78) or Arm 3 (p = 1.0). Moreover, there was no evidence of a difference in trend of change in MELD over time. None of the conclusions differed following a per-protocol analysis. No evidence of a difference was found in UKELD or the individual components of liver function (bilirubin, albumin, INR and creatinine). Median (IQR) change in Fibroscan (to day 90) were 0.0 (-1.6, 8.6), 0.0 (-13.0, 12.0), -0.1 (-6.6, 9.8). There was no evidence of a difference in change in Chronic liver disease questionnaire domains from baseline to day 90. Two Arm 1 patients, three Arm 2 and seven Arm 3 had 1 or more serious adverse events in the 90-day period. Conclusions: In this large, powered, randomised controlled trial GCSF and purified haematopoietic stem cells did not have an impact on liver function or fibrosis.

Details

Original languageEnglish
Publication statusPublished - 16 Apr 2016
EventThe International Liver Congress 2016 : 51st Annual Meeting of the European Association for the Study of the Liver - Barcelona, Spain
Duration: 13 Apr 201617 Apr 2016

Conference

ConferenceThe International Liver Congress 2016
CountrySpain
CityBarcelona
Period13/04/1617/04/16

Keywords

  • European, albumin, arm, autologous stem cell transplantation, bilirubin, cell isolation, cerebrospinal fluid, chronic liver disease, conservative treatment, creatinine, elastograph, fibrosis, granulocyte colony stimulating factor, hematopoietic stem cell, human, infusion, intention to treat analysis, international normalized ratio, lenograstim, leukapheresis, liver, liver cirrhosis, liver disease, liver function, liver transplantation, male, morbidity, mortality, patient, peripheral vein, questionnaire, randomized controlled trial