Table 2.
Cardiovascular outcomes from studies of AHSCT for SSc.
| Author | Year | Mobilisation | Conditioning regimen | Patients n = | TRM n = (%) | Cardiac death n = (%) | Types of cardiac death (time point post-AHSCT) (mob = mobilisation; d = day) |
Other acute cardiovascular events | Long-term cardiovascular outcomes |
|---|---|---|---|---|---|---|---|---|---|
| Binks et al. 14 † | 2001 | CYC 4 g/m2 ± G-CSF or G-CSF alone | CYC 120–200 mg/kg ± ATG ± radiation ± anti-CD52 ± busulphan; carmustine/fludarabine/thiotepa | 41 | 7 (17.1)† | 3 (7.3)† | Ischaemic heart disease (mob), cardiac failure (mob), myocarditis (mob)† | Stable LVEF post-AHSCT Stable pulmonary pressures on echocardiogram Death from PAH (n = 1)† |
|
| Farge et al. 15 | 2002 | CYC 4 g/m2 + G-CSF (n = 1 BM stem cells) | CYC 200 mg/kg* | 11 | 1 (9.1) | 0 (0) | Transient cardiac failure due to hyperhydration (mob) Grade IV cardiac toxicity (n = 1) |
LVEF stable post-AHSCT | |
| McSweeney et al. 16 | 2002 | G-CSF | CYC 120 mg/kg + TBI + ATG | 19 | 3 (15.8) | 0 (0) | Transient fall in LVEF at 3 months post-AHSCT | ||
| Farge et al. 17 † | 2004 | CYC 4 g/m2 + G-CSF or G-CSF alone (n = 1 BM stem cells) | CYC 150–200 mg/kg ± irradiation ± ATG ± anti-CD52 BEAM; fludarabine; carmustine |
57 | 5 (8.8)† | 3 (5.3)† | Cardiac failure (d30), myocarditis (d8)† | Death from PAH (n = 1)† | |
| Nash et al. 18 | 2007 | G-CSF | CYC 120 mg/kg + TBI + ATG | 34 | 8 (23.5) | 1 (2.9) | Arrhythmia(0.5 months) | Supraventricular arrhythmias (n = 2), heart failure (n = 2) | Small decline in LVEF at 5–8 years |
| Oyama et al. 19 | 2007 | CYC 2 g/m2 + G-CSF | CYC 200 mg/kg + ATG | 10 | 0 (0) | 0 (0) | Fluid overload (n = 3), acute left ventricular failure (n = 1) | Stable LVEF and pulmonary pressures post-AHSCT | |
| Farge et al. 20 † | 2010 | CYC 1.5-4 g/m2 + G-CSF or G-CSF alone (n = 4 BM stem cells) | CYC 150-200 mg/kg; busulfan; BEAM ± ATG; TBI | 175 | 12 (6.9) | 1 (0.6) | Cardiac toxicity | ||
| Burt et al. 1 | 2011 | CYC 2 g/m2 + G-CSF | CYC 200 mg/kg + ATG | 10 | 0 (0) | 0 (0) | Arrhythmias(n = 2), volume overload (n = 2) | ||
| Henes et al. 21 | 2012 | CYC 2 g/m2 + G-CSF (n = 1 BM stem cells) | CYC 200 mg/kg # + ATG | 26 | 3 (11) | 0 (0) | Fatal arrhythmia at 23 months (n = 1) | ||
| Moore et al. 22 | 2012 | CYC 2 g/m2 + G-CSF | CYC 200 mg/kg + ATG | 10 | 0 (0) | 0 (0) | |||
| Burt et al. 23 | 2013 | CYC 2 g/m2 + G-CSF | CYC 200 mg/kg + ATG | 90 | 5 (5.6) | 4 (4.4) | Cardiac arrest (mob), cardiac failure (n = 2), constrictive pericarditis (during transplantation) | Volume overload (15.5%) | |
| Henes et al. 24 | 2014 | CYC 2 g/m2 + G-CSF | CYC 100 mg/kg + thiotepa 2x 5 mg/kg + ATG | 6 | 0 (0) | 0 (0) | Stable LVEF and troponin post-AHSCT Progressive PAH (n = 1) |
||
| Van Laar et al. 3 | 2014 | CYC 4 g/m2 + G-CSF | CYC 200 mg/kg + ATG | 79 | 8 (10.1) | 3 (3.8) | Cardiac failure (n = 2; d11, d35), myocardial infarction (d14) | No difference in LVEF at 2 years between AHSCT and CYC arms No cardiac death or cardiac failure in HSCT arm Grade III cardiac event (16.4%) in HSCT arm |
|
| Del Papa et al. 25 | 2017 | CYC 4 g/m2 + G-CSF | CYC 200 mg/kg + ATG | 18 | 1 (5.6) | 0 (0) | Transient fall in LVEF (n = 1) | Fatal arrhythmia at 34 months (n = 1) | |
| Sullivan et al. 2 | 2018 | G-CSF | CYC 120 mg/kg + TBI + ATG | 36 | 2 (6) | 0 (0) | ⩾Grade III cardiac disorders (8.8% in AHSCT vs 16.2% CYC arm, p = 0.1) | ||
| Nakamura et al. 26 | 2018 | CYC 4 g/m2 + G-CSF | CYC 200 mg/kg | 14 | 1 (7.1) | 1 (7.1) | Cardiac failure with cardiopulmonary arrest (during conditioning) | Cardiac failure (n = 1) | |
| Nair et al. 27 | 2018 | CYC 2 g/m2 + G-CSF | CYC 60 mg/kg + fludarabine 30 mg x2 + ATG | 4 | 0 (0) | 0 (0) | Stable LVEF post-AHSCT | ||
| Van Bijnen et al. 9 | 2020 | CYC 4 g/m2 + G-CSF | CYC 200 mg/kg + ATG | 92 | 10 (10.9) | 9 (9.8) | Not specified | Cardiac failure (n = 1) | |
| Henrique-Neto et al. 10 | 2021 | CYC 2 g/m2 + G-CSF | CYC 200 mg/kg $ | 70 | 3 (4.3) | 1 (1.4) | Acute cyclophosphamide cardiotoxicity (d60) | Cyclophosphamide-induced cardiac dysfunction (n = 4) | Pericarditis Fatal cardiac insufficiency (n = 2) |
| Henes et al. 8 | 2021 | CYC 1–4 g/m2 + G-CSF | CYC 50–240 mg/kg + ATG (n = 76) CYC 100 mg/kg + thiotepa 10 mg/kg + ATG (n = 4) |
80 | 5 (6.3) | 4 (5.0) | Acute cyclophosphamide cardiotoxicity (n = 3) (d1, d9, d61), AHSCT associated cardiac toxicity (d1) | Pericardial effusion Arrhythmias Myocardial infarction |
|
| Burt et al. 28 | 2021 | CYC 2 g/m2 + G-CSF | Fludarabine 120 mg/m2 + cyclophosphamide 60 mg/kg + ATG (±rituximab) | 42 | 1 (2.4) | 1 (2.4) | Myocardial infarction (during transplant hospitalisation) | Pericardial effusion with tamponade (n = 1) Atrial fibrillation (n = 2) |
Peripheral blood stem cells were used in all studies unless stated otherwise. *Melphalan 140 mg/m2 in n = 1 due to LVEF < 40%. #CYC 100 mg/kg + thiopeta in one patient with cardiac disease. $Fludarabine 120 mg/m2 and melphalan 120/m2 + ATG if cardiac disease. †Studies drawn from the same registry. Acute cardiovascular events were extracted from events reported during the transplant period or up to day + 100. BM bone marrow; BEAM carmustine, cytarabine, melphalan, etoposide; CYC cyclophosphamide; ATG anti-thymocyte globulin; TBI total body irradiation; LVEF left ventricular ejection fraction; PAH pulmonary arterial hypertension; TRM treatment-related mortality.