Autologous stem cell transplantation with thiotepa-based conditioning in patients with systemic sclerosis and cardiac manifestations

Henes, Joerg; Koetter, I.; Horger, Marius; Schmalzing, Marc; Mueller, Karin; Eick, Christian; Bauer, Axel; Vogel, Wichard; Kanz, Lothar

doi:10.1093/rheumatology/ket464

Cited by 37 publications

(28 citation statements)

References 16 publications

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“…). Nine additional studies were identified by manual searching . We first removed 119 duplicates and then screened the abstracts before excluding an additional 226 studies because of irrelevance.…”

Section: Resultsmentioning

confidence: 99%

Efficacy and safety of autologous haematopoietic stem cell transplantation in systemic sclerosis: a systematic review of the literature

et al. 2018

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We aimed to assess the efficacy of autologous haematopoietic stem cell transplantation (HSCT) for skin sclerosis (SSc) and lung function in SSc. We performed a systematic literature review in the PubMed and Scopus databases from the earliest records to March 2016. We assessed study quality using the Cochrane tool for randomized studies, the Newcastle-Ottawa Scale for controlled cohort studies and an 18-item quality-appraisal checklist for case series. The primary outcome was the improvement of skin thickening using the modified Rodnan Skin Score (mRSS). The secondary outcome was efficacy on lung function, using diffusing capacity of the lungs for carbon monoxide and forced vital capacity (FVC). The safety of the procedure was evaluated. The literature search identified 431 citations. There were 38 studies involving a total of 344 patients who fulfilled our inclusion criteria. No meta-analysis was performed due to a high heterogeneity. There was a significant improvement in mRSS in the majority of the reports (P < 0·05), and the results were sustained for up to 8 years after autologous HSCT. The randomized studies and the four cohort studies each showed a slight but statistically significant improvement in FVC at 1 or 2 years. The treatment-related mortality calculated by pooling patients of 35 studies (336 patients with a follow-up up to 146 months) was 8·3% after autologous HSCT and 1% in cyclophosphamide-treated groups. Despite heterogeneity among the studies, we determined that autologous HSCT significantly improved cutaneous fibrosis and slightly improved FVC. Safety of autologous HSCT is acceptable given the severity of the disease. This systematic review was registered on PROSPERO, number CRD42016027951.

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Section: Resultsmentioning

confidence: 99%

Efficacy and safety of autologous haematopoietic stem cell transplantation in systemic sclerosis: a systematic review of the literature

et al. 2018

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“…Currently two studies are recruiting SSc patients eligible for autologous stem cell transplantation, one in Chicago, IL, USA and one in Tübingen, Germany (ClinicalTrials.gov NCT01445821; NCT01895244) [ 34 ]. These studies aim to reduce cardiac toxicity of the therapy regimen with effective use of stem cell transplantation [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

“…Standard treatment of SSc includes cyclophosphamide, which can be cardiotoxic [ 11 ]. In our patient group with severe scleroderma, CMR was part of a routine diagnostic work up in the course of preparation and risk stratification for autologous stem cell transplantation and escalation of potentially cardiotoxic therapy.…”

Section: Introductionmentioning

confidence: 99%

Cardiovascular magnetic resonance patterns of biopsy proven cardiac involvement in systemic sclerosis

Krumm

Mueller

Klingel

et al. 2016

Journal of Cardiovascular Magnetic Resonance

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BackgroundTo determine morphological and functional cardiovascular magnetic resonance (CMR) patterns in histopathologically confirmed myocardial involvement in patients with systemic sclerosis (SSc).MethodsTwenty patients (6 females; mean age 41 ± 11 years) with histopathologically proven cardiac involvement in SSc in the years 2008–2016 were retrospectively evaluated. Morphological, functional and late gadolinium enhancement (LGE) images were acquired in standard angulations at 1.5 T CMR. Pathologies were categorized: 1) Pericardial effusion; 2) pathologic left (LV) or right ventricular (RV) contractility (hypokinesia, dyssynchrony, and diastolic restriction); 3) reduced left (LV-EF) and right ventricular ejection fraction (RV-EF); 4) fibrosis and/or inflammation (positive LGE); 5) RV dilatation. 95 % confidence intervals (CI) were calculated for appearance of pathologic EF and RV dilatation.ResultsSeven patients (35 %) had positive CMR findings in three categories, 9 patients (45 %) in four categories and 4 patients (20 %) in five categories. The distribution of pathologic findings was: minimal pericardial effusion in 7 patients (35 %), moderate pericardial effusion >5 mm in nine patients (45 %); abnormal LV or RV contractility in 19 patients (95 %), reduced LV or RV function in 14 patients (70 %; 95 % CI: 51–88 %), pathologic LGE in all patients, RV dilatation in 6 patients (30 %; 95 % CI: 15–54 %).ConclusionsCMR diagnosis of myocardial involvement in SSc requires increased attention to subtle findings. Pathologic findings in at least three of five categories indicate myocardial involvement in SSc.Electronic supplementary materialThe online version of this article (doi:10.1186/s12968-016-0289-3) contains supplementary material, which is available to authorized users.

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“…Moreover, a correlation between peak concentration and cardiac toxicity has been reported, possibly indicating a role of infusion rate in side effects [ 72 ]. A recent study could show, that a therapy regimen with adding thiotepa, an alkylating agent, that is used in haematological malignancies for aSCT and has no known cardiotoxicity, could be used successfully in patients with SSc and cardiac involvement [ 73 ]. The time to haematological recovery was was longer compared to CYC treatment and infectious complications were described.…”

Section: Discussionmentioning

confidence: 99%

Clinical and Histopathological Features of Patients with Systemic Sclerosis Undergoing Endomyocardial Biopsy

Mueller

Eppler

et al. 2015

PLoS ONE

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BackgroundCardiac involvement in systemic sclerosis (SSc) is associated with a variable phenotype including heart failure, arrhythmias and pulmonary hypertension. The aim of the present study was to evaluate clinical characteristics, histopathological findings and outcome of patients with SSc and a clinical phenotype suggesting cardiac involvement.Methods and Results25 patients with SSc and clinical signs of cardiac involvement were included between June 2007 and December 2010. They underwent routine clinical work-up including laboratory testing, echocardiography, left and right heart catheterization, holter recordings and endomyocardial biopsy. Primary endpoint (EP) was defined as the combination of cardiovascular death, arrhythmic endpoints (defined as appropriate discharge of implantable cardioverter defibrillator (ICD)) or rehospitalization due to heart failure. The majority of patients presented with slightly impaired left ventricular function (mean LVEF 54.1±9.0%, determined by echocardiography). Endomyocardial biopsies detected cardiac fibrosis in all patients with a variable area percentage of 8% to 32%. Cardiac inflammation was diagnosed as follows: No inflammation in 3.8%, isolated inflammatory cells in 38.5%, a few foci of inflammation in 30.8%, several foci of inflammation in 15.4%, and pronounced inflammation in 7.7% of patients. During follow up (FU) (22.5 months), seven (28%) patients reached the primary EP. Patients with subsequent events showed a higher degree of fibrosis and inflammation in the myocardium by trend. While patients with an inflammation grade 0 or 1 showed an event rate of 18.2%, the subgroup of patients with an inflammation grade 2 presented with an event rate of 25% versus an event rate of 50% in the subgroup of patients with an inflammation grade 3 and 4, respectively (p=0.193). Furthermore, the subgroup of patients with fibrosis grade 1 showed an event rate of 11%, patients with fibrosis grade 2 and 3 presented with an event rate of 33% and 42% respectively (p = 0.160).ConclusionsPatients with SSc and clinical signs of cardiac involvement presented with mildly impaired LVEF. Prognosis was poor with an event rate of 28% within 22.5 months FU and was associated with the degree of cardiac inflammation and fibrosis.

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Autologous stem cell transplantation with thiotepa-based conditioning in patients with systemic sclerosis and cardiac manifestations

Cited by 37 publications

References 16 publications

Efficacy and safety of autologous haematopoietic stem cell transplantation in systemic sclerosis: a systematic review of the literature

Efficacy and safety of autologous haematopoietic stem cell transplantation in systemic sclerosis: a systematic review of the literature

Cardiovascular magnetic resonance patterns of biopsy proven cardiac involvement in systemic sclerosis

Clinical and Histopathological Features of Patients with Systemic Sclerosis Undergoing Endomyocardial Biopsy

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