Table 5 Considerations for HSCT in systemic sclerosis.
Inclusion criteria | Exclusion criteria | Concerns | Specific disease assessments |
|---|---|---|---|
• Age: Recommended age limit is 60 years [39], certain patients >60 years may be considered along with co-morbidity assessment and the agreement of the MDT (level III) • Patients with diffuse progressive SSc fulfilling the 2013 ACR/EULAR classification criteria [104] • Optimal time-point: disease duration <5 years (level I); in case of severe progressive disease, HSCT can be considered after 5 years of disease duration, according to local experience (level III) • Second-line option for patients with evidence of sustained disease activity after 6 months of first-line therapy or intolerance of treatment (level I) • mRSS >15 and visceral involvement with at least 1 organ manifestation OR mRSS >20 without visceral organ involvement but evidence of inflammatory disease (increased CRP >10 mg/L without evidence for infection or other cause) (level I) • Patients with progressive ILD confirmed by chest CT may be eligible in case of mRSS <15 and limited SSc [39] or even sine scleroderma [105] (level III) • HSCT can be considered as first-line option for patients with high risk profile (see red flags above) and rapid progression (study underway) [106] (level III) • In highly active and severely affected patients with transient contraindications (e.g. active myocarditis), data support pretreatment with RTX and MMF [57] | • General contraindications (Table 2) • Cardiac: absolute contraindications for all protocols are cardiac MRI with septal bounce, constrictive pericarditis or cardiac tamponade • Cardiac: absolute contraindications for standard protocols using high-dose cyclo-phosphamide (200 mg/kg) are PASP >40 mmHg at rest or >45 mmHg with fluid challenge, or mPAP >25 mmHg at rest or >30 mmHg with fluid challenge (RHC) according to EBMT reommendations [21] • Cardiac: absolute contraindications for cardiac-safe protocols like the CAST-regimen [39] are LVEF <40%, mPAP >30 mmHg or PASP >50 mmHg in RHC without fluid challenge. • Pulmonary: absolute contraindications are FVC <45% and DLCO-SB <40% • Renal: active renal crisis or creatinine clearance <30 ml/min (for standard protocols); in fludarabine-based regimens dose adjustment in patients with GFR <80 ml/min or according to centre policy • Active smoking | • Caution is required for patients with pulmonary hypertension • Right heart catheterization after 10 days cessation of endothelin-receptor antagonists or calcium channel blockers with fluid challenge (1000 cc normal saline in 10 min i.v. is recommended for exclusion • Reassessment of cardiac function between mobilization and conditioning is recommended, at least by echo-cardiography and ECG, if more than 3-month interval • Caution is required for patients with GAVE | • Blood monitoring should include cardiac biomarkers (CK, NTpro-BNP, troponin hs) • EBV/CMV PCR (at least every two weeks for the 100 days after HSCT (level III) • Skin-score: mRSS [107] • S-HAQ [108] score • Echocardiography with measurement of PAP, LVEF biannually for 2 years, yearly thereafter • Lung function test including FVC, DLCO biannually for 2 years, yearly thereafter • Chest CT scan in case of ILD: annually for the first three years, to be adapted thereafter according to individual involvement • Serology, ANA/ENA, disease-specific, i.e. anti-topoisomerase or anti-RNA polymerase III antibodies, C3, C4 • Consider nailfold capillaroscopy, joint count, range of motion, cardiac MRI, Holter monitor, endoscopy, and oesophageal manometry |
