Table 3.
Clinical trials on liver insufficiency and T1D.
| Condition | Population | Study Design | Outcomes | Major Adverse Events | Ref |
|---|---|---|---|---|---|
| Liver Insufficiency | 5 pts (20–65 yrs old), chronic liver failure, abnormal serum albumin and/or bilirubin and/or pro-thrombin time, unsuitable for liver transplantation, WHO performance status < 2. | Phase I clinical trial. 3 pts received 1 × 106–2 × 108 autologous CD34+ cells via portal vein, 2 pts received 1 × 106–2 × 108 autologous CD34+ cells via hepatic artery. | Improvement in serum bilirubin in 3/5 pts at 60 days maintained by only 1 patient at 12 mo. Improvement in serum albumin in 4/5 pts at 60 days maintained at 12–18 mo. | No major procedure-related complications. | [153] |
| 9 pts (20–65 yrs old), chronic alcoholic liver failure, abnormal serum albumin and/or bilirubin and/or pro-thrombin time, unsuitable for liver transplantation, WHO performance status < 2. | Phase II clinical trial. Injection of autologous CD34+ cells (average 229.7 × 106) via hepatic artery. | Improvement in serum bilirubin at 12 weeks, transient improvement in ALT and AST. Improvement of Child–Pugh score in 7/9 patients and improvement of ascites in 5/9 patients at 12 weeks. |
No major procedure-related complications. | [156] | |
| 55 pts (18–70 yrs old), non-viral hepatic cirrhosis, MELD score > 14, requiring liver transplantation. | Phase II open-label non-randomized controlled CT. 22 patients unwilling for liver transplantation received autologous CD34+ cells via hepatic artery. 23 patients opted for regular inclusion in the institutional liver transplantation waiting list. | Transient improvement in serum albumin in treated pts (not sustained at 3 mo); improvement of serum creatinine and MELD score at 3 mo. | 3 deaths in ctrl group (2 due to sepsis, 1 to gastrointestinal bleeding), 1 death in treatment group on 88th day after CD34+ cell infusion (due to sepsis). No major procedure-related complications. | [157] | |
| T1D | 23 pts (12–35 yrs old), diagnosis of T1D within the previous 6 weeks. | Phase I/II clinical trial. Pts underwent immune ablation with cyclophosphamide and ATG, followed by infusion via peripheral vein of autologous CD34+ cells (10.52 × 106 cells/kg). |
Most pts showed a reduction in Hb1Ac levels and an increase in C-peptide levels after treatment. 20 pts experienced time free from insulin (12 until the end of follow up, up to 4 yrs). |
Bilateral nosocomial pneumonia (2 pts), posttransplant oligospermia (9 pts), Graves’ disease (1 pt), transient hypergonadotropic hypogonadism (1 pt), autoimmune hypoth-roidism (1 pt). | [159] |
| 24 pts (12–35 yrs old), diagnosis of T1D within the previous 6 weeks, sustained endogenous secretion of insulin and WHO performance status ≤ 2. | Phase II clinical trial. Pts underwent immune ablation with cyclophosphamide and ATG, followed by infusion via peripheral vein of autologous CD34+ cells (4.19 × 106 cells/kg). | General reduction in Hb1Ac levels and increase in C-peptide levels after treatment. 20 pts experienced time free from insulin (4 until the end of follow-up, up to 80 mo). |
ATG–related skin reaction/vasculitis (4 pts), neutropenic fever (12 pts), sepsis (4 pts, out of which 1 was fatal). | [160] | |
| 40 pts (14–27 yrs old), recent diagnosis of T1D with time from symptom onset to AHST 4–26 weeks | Phase II, parallel-assignment, non-randomized clinical trial. Treatment group pts underwent immune ablation with cyclophosphamide and ATG, followed by infusion via peripheral vein of autologous CD34+ cells. Ctrl group pts received regular insulin therapy. | Increase in C-peptide levels in treatment group and decline in ctrl group at 48 mo. Comparable reduction in Hb1Ac levels in both groups. 14 pts in treatment group experienced time free from insulin (3 until the end of follow up, up to 48 mo). One pt in ctrl group experienced transient insulin independence for 7 mo. |
Graves’ disease (2 pts on treatment, 1 pt in ctrl group), autoimmune thyroid disease (2 pts in ctrl group). | [161] |
Abbreviations: ASHT = allogeneic hematopoietic stem cell transplantation; ALT = alanine aminotransferase; AST = aspartate aminotransferase; ATG = anti-thymocyte globulin; CT = clinical trial; Hb1Ac = glycated hemoglobin; MELD = model for end-stage liver disease; PT = patient; T1D = type 1 diabetes; WHO = World Health Organization.