Autologous Hematopoietic Stem Cell Transplantation Improves Long-Term Survival

Data From a National Registry

Norbert Blank; Marc Schmalzing; Pia Moinzadeh; Max Oberste; Elise Siegert; Ulf Müller-Ladner; Gabriela Riemekasten; Claudia Günther; Ina Kötter; Gabriele Zeidler; Christiane Pfeiffer; Aaron Juche; Ilona Jandova; Jan Ehrchen; Laura Susok; Tim Schmeiser; Cord Sunderkötter; Jörg H. W. Distler; Margitta Worm; Alexander Kreuter; Gernot Keyẞer; Hanns-Martin Lorenz; Thomas Krieg; Nicolas Hunzelmann; Jörg Henes


Arthritis Res Ther. 2022;24(258) 

In This Article

Abstract and Introduction


Background: Current recommendations on the management of systemic sclerosis (SSc) suggest that autologous hematopoietic stem cell therapy (HSCT) can be a rescue therapy for patients with rapidly progressive SSc.

Objectives: To assess the safety and efficacy of HSCT for patients with SSc and to compare these with non-HSCT patients in a control cohort with adjusted risk factors.

Methods: A retrospective analysis of data from the multicentric German network for systemic scleroderma (DNSS) with 5000 patients with SSc. Control groups consisted of all patients with diffuse cutaneous (dc)-SSc (group A) and an adjusted high-risk cohort of male patients with Scl70-positive dc-SSc (group B).

Results: Eighty SSc patients received an HSCT 4.1 ± 4.8 years after SSc diagnosis. Among them, 86.3% had dc-SSc, 43.5% were males, and 71.3% were positive for Scl70 antibodies. The control group A (n=1513) showed a significant underrepresentation of these risk factors for mortality. When the survival of the control group B (n=240) was compared with the HSCT group, a lower mortality of the latter was observed instead. Within 5 years after HSCT, we observed an improvement of the mRSS from 17.6 ± 11.5 to 11.0 ± 8.5 (p=0.001) and a stabilization of the DLCO. We did not see differences in transplant-related mortality between patients who received HSCT within 3 years after SSc diagnosis or later.

Conclusion: Our analysis of real-life data show that the distribution of risk factors for mortality is critical when HSCT cohorts are compared with non-HSCT control groups.


Systemic sclerosis (SSc) is a complex multisystem autoimmune disease, which affects the skin and internal organs, such as the lung, heart, gastrointestinal tract, musculoskeletal system, and kidneys.[1] Until today, effective treatment options are very limited. Immunosuppression, especially in early disease (<2 years from first non-Raynaud phenomenon), is recommended using methotrexate or cyclophosphamide.[2] A randomized controlled trial showed equivalent efficacy of mycophenolate and cyclophosphamide in patients with SSc-associated interstitial lung disease (ILD).[3] Nintedanib was effective in reducing the progression of SSc ILD as an antifibrotic treatment.[4] Very recently, tocilizumab showed some benefit with regard to the lung involvement but not for the skin sclerosis.[5] Furthermore, an observational study of rituximab showed some benefit for the skin sclerosis but not for the lung function parameters.[6] Currently, no biologic treatment option has been approved for SSc skin sclerosis.

Risk factors for the progressive disease have been identified during the last years, and male patients with early diffuse cutaneous skin manifestations and anti-topoisomerase I (Scl70) antibodies are at high risk for disease-related mortality.[7,8]

Autologous hematopoietic stem cell transplantation (HSCT) is a very effective and meanwhile well-established treatment option for SSc patients with a severe course of the disease. Therefore, HSCT was included in the current EULAR management guidelines.[2] Three randomized controlled trials proved its superiority over standard treatment with cyclophosphamide pulses in severe cases,[9–11] and a recent non-interventional trial showed its effectiveness also in a real-life setting.[12] The aim of the treatment strategy is improvement of long-term survival by eliminating the auto-aggressive immune system using high-dose chemotherapy in combination with lymphoablative antibodies or myeloablative radiation. Major points of criticism are side effects, especially the treatment-related mortality (TRM) between 5 and 10%.[9–12] Therefore, it is very important to discuss and compare the risk for disease-related mortality with TRM. To investigate long-term survival in a subgroup of patients with a high risk for disease-related mortality, we compared data of patients with and without HSCT from the registry of the German Network for Systemic Scleroderma.