Table 2.
Adverse Effects Reported in Controlled Clinical Trials of Bone Marrow-Derived Cell Therapy for Myocardial Repair
| |
|
|
Cardiovascular death |
In-stent restenosis or target vessel PCI |
SVT |
VT |
Recurrent MI/angina |
|
|||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Cell type | Follow-up (months) | T | C | T | C | T | C | T | C | T | C | Comments | |
| A. Cells harvested from the bone marrow | |||||||||||||
| ASTAMI (58, 59) | BMMNC | 12 | 0/50 | 0/50 | 11/50 | 9/50 | NR | NR | 2/50 | 1/50 | 1/50 | 0/50 | No difference in signal- averaged ECG variables |
| Hendrikx et al. (34) | BMMNC | 4 | NR | NR | NA | NA | NR | NR | 6/9 (induced) | 0/5 (induced) | NR | NR | |
| Karpov et al. (41) | BMMNC | 6 | NR | NR | 4/22 | 3/22 | NR | NR | NR | NR | 4/22 | 3/22 | Incidence of arrhythmia was similar in both groups |
| Meluzin et al. (63, 64) | BMMNC | 12 | NR | NR | 9/40 | 3/20 | NR | NR | NR | NR | 1/40 | 2/20 | |
| Mocini et al. (67) | BMMNC | 12 | 0/18 | 0/18 | NA | NA | 8/18 | 6/18 | 6/18 | 9/18 | NR | NR | Cardiac NMR scan did not reveal any abnormal tissue or calcification |
| Penicka et al. (76) | BMMNC | 4 | 2/17 | 0/10 | 24% | 40% | NR | NR | NR | NR | 1/17 | NR | Major adverse events in cell therapy group occurred prior to BMMNC injection |
| Perin et al. (77, 78) | BMMNC | 12 | 2/11 | 0/9 | NA | NA | 0/11 | 0/9 | 0/11 | 0/9 | NR | NR | No change in signal-averaged ECG parameters, BNP level, and WBC count |
| PROTECT-CAD (102) | BMMNC | 6 | 0/19 | 1/9 | NA | NA | 0/19 | 0/9 | 0/19 | 0/9 | 0/19 | 2/9 | Cardiac MRI did not reveal any tumor or calcification |
| REPAIR-AMI (25, 90, 91) | BMMNC | 12 | 2/101 | 5/103 | 16/101 | 26/103 | NR | NR | 5/101 | 4/103 | 0/101 | 6/103 | Combined cardiovascular events were significantly reduced in treated patients |
| Strauer et al. (97) | BMMNC | 3 | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | No side effects were observed at any point of time |
| Strauer et al. (98) | BMMNC | 3 | NR | NR | 1/18 | 0/18 | 0/18 | 0/18 | 0/18 | 0/18 | NR | NR | |
| TCT-STAMI (29) | BMMNC | 6 | 0/10 | 0/10 | NR | NR | 0/10 | 0/10 | 0/10 | 0/10 | 0/10 | 0/10 | |
| TOPCARE-CHD (7) | BMMNC CPC |
6 | 0/35 (BMC) 0/34 (CPC) |
1/23 | 4/35 (BMC) 3/34 (CPC) |
0/23 | NR | NR | 0/35 (BMC) 1/34 (CPC) |
1/23 | 0/35 (BMC) 2/34 (CPC) |
0/23 | |
| BOOST (66, 92, 106) | BMC | 18 | 0/30 | 1/30 | 5/30 | 4/30 | 0/30 | 0/30 | 1/30 | 1/30 | 1/30 | 0/30 | Echocardiography did not reveal any tumor or calcification; no case of cancer was diagnosed during follow-up |
| Janssens et al. (37) | BMC | 4 | NR | NR | 0/33 | 1/34 | 5/33 | 6/34 | 0/33 | 3/34 | 2/33 | 1/34 | No late potential noted |
| Ruan et al. (87) | BMC | 6 | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | |
| Bartunek et al. (10) | AC133 + BMC | 4 | NR | NR | 9/19 | 4/16 | NR | NR | 2/19 | 0/16 | NR | NR | |
| Chen et al. (17) | MSC | 6 | NR | NR | NR | NR | 0/34 | 0/35 | 0/34 | 0/35 | NR | NR | |
| Chen et al. (16) | MSC | 12 | 2/24 | 4/24 | NR | NR | NR | NR | NR | NR | NR | NR | |
| Katritsis et al. (42) | MSC and EPC | 4 | NR | NR | NR | NR | 0/11 | 0/11 | 0/11 | 0/11 | NR | NR | |
| B. Mobilized progenitor cells | |||||||||||||
| Choi et al. (18) | PBSC | 24 | 0/10 | 7/63 | 1/10 | 8/63 | NR | NR | 0/10 | 0/63 | 0/10 | 4/63 | |
| Erbs et al. (24, 45) | CPC | 3 | NR | NR | 3/12 | 3/11 | NR | NR | NR | NR | NR | NR | |
| Li et al. (55) | PBSC | 6 | 0/35 | 0/35 | 0/35 | 0/35 | NR | NR | 1/35 | NR | 1/35 | 2/35 | |
| Losordo et al. (57) | CD34+ cells | 12 | 0/18 | 0/6 | NA | NA | 2/6 | 2/18 | 1/6 | 0/18 | 3/6 | 7/18 | |
| MAGIC Cell-3-DES (40) | PBSC | 6 | 0/41 | 1/41 | 0/41 | 4/41 | NR | NR | NR | NR | 0/41 | 1/41 | No significant increase in coronary restenosis in cell-treated patients |
| Tatsumi et al. (101) | PBMNC | 6 | 0/18 | 0/36 | 4/18 | NR | NR | NR | NR | NR | NR | NR | The incidence of recurrent MI and in-stent restenosis was similar between groups |
| TOPCARE-CHD (7) | BMMNC CPC |
6 | 0/35 (BMC) 0/34 (CPC) |
1/23 | 4/35 (BMC) 3/34 (CPC) |
0/23 | NR | NR | 0/35 (BMC) 1/34 (CPC) |
1/23 | 0/35 (BMC) 2/34 (CPC) |
0/23 | |
BMC, unfractionated bone marrow cell; BMMNC, bone marrow mononuclear cell; C, control; CPC, circulating progenitor cell; EPC, endothelial progenitor cell; MSC, mesenchymal stem cell; NA, not applicable; NR, not reported; PBMNC, peripheral blood-derived mononuclear cell; PBSC, peripheral blood-derived stem cell; SVT, supraventricular tachycardia; T, BMC-treated; V, ventricular tachycardia.