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Auto-HSCT induces sustained responses in severe systemic sclerosis patients failing pulse cyclophosphamide

Bone Marrow Transplantation volume 47, pages 1486–1487 (2012)Cite this article

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Systemic sclerosis (SSc) is a heterogeneous autoimmune disease characterised by predominant T-cell activation, production of auto-Abs and cytokine release.1 Currently, no therapies have been proven to be effective in modifying the course of SSc. Oral CY has shown a marginal benefit in skin score and pulmonary function in a randomised trial.2 There is an urgency for more effective treatment strategies for this disease as patients with the more severe forms of the disease have a significantly reduced lifespan compared with the general population.3, 4 Autologous haematopoietic SCT (HSCT) has been suggested as a possible treatment modality in autoimmune diseases over the past 10 years. A consensus statement outlining areas for future research was released by the European Bone Marrow Transplant (EBMT) society and European League against Rheumatism (EULAR) in 1997.5 Since that publication, over 175 patients have undergone autologous transplant for SSc with encouraging results.6 The eagerly awaited results of phase III ASTIS and SCOT trials will provide more definitive data on the role of HSCT in this disease.7 Thus far, however, there have been heterogeneous patient groups in the initial phase II trials of HSCT in SSc. Previous studies have had few patients who have had pulse i.v. CY therapy before their autograft.8 As a result, the effect of HSCT on patients who have failed pulse CY therapy remains unknown. In this study, we present our experience of HSCT in 10 heavily pre-treated patients who had failed monthly i.v. CY.

Patients aged 18–65 years were eligible for this pilot study if they had rapidly progressive inflammatory diffuse scleroderma, within 3 years of onset, involving lungs and/or heart (myocarditis) that failed to stabilise with monthly i.v. CY (that is, no change in baseline skin score) and other antirheumatic agents. A total of 10 patients (8 female, 2 male) with a median age of 43 years (range: 23–46) were transplanted between October 2002 and November 2009 at St Vincent’s Hospital, Sydney, Australia. Baseline characteristics of patients are outlined in Table 1. All patients were antinuclear Ab-positive and six had pulmonary fibrosis. All patients had failed to stabilise with i.v. CY with a median dose of 3.75 g/m2 (1.5–6.5) with a minimum of two doses. After informed consent, a median of 7.37 × 106/kg (range: 2.14–77.2) CD34+ stem cells were collected after CY 2 g/m2 and G-CSF 10 μg/kg/day. Conditioning was with CY 200 mg/kg and equine antithymocyte globulin (Pfizer, Sydney, New South Wales, Australia). After the first patient developed a hypertensive crisis, all subsequent patients received captopril to a maximally tolerated dose to maintain systolic blood pressure of 100. Following engraftment, all patients received standard antimicrobial prophylaxis.

Table 1 Patient and disease characteristics
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Authors and Affiliations

  1. Department of Haematology and Stem Cell Transplantation, St Vincent’s Hospital, Sydney, New South Wales, Australia

    J Moore, S Milliken & D Ma

  2. Department of Rheumatology, Westmead Hospital, Westmead, New South Wales, Australia

    H Englert

  3. Department of Renal Medicine, St Vincent’s Hospital, Sydney, New South Wales, Australia

    T Furlong

  4. Department of Dermatology, St Vincent’s Hospital, Sydney, New South Wales, Australia

    T Poon

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  1. J Moore
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Correspondence to J Moore.

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Moore, J., Englert, H., Furlong, T. et al. Auto-HSCT induces sustained responses in severe systemic sclerosis patients failing pulse cyclophosphamide. Bone Marrow Transplant 47, 1486–1487 (2012). https://doi.org/10.1038/bmt.2012.67

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