Article
Hematopoietic stem cell transplantation for autoimmune diseases – a 20 years single-centre experience
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Authors
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Tobias Alexander
- Charité – Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und Klinische Immunologie, Berlin
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Lars Templin
- Charité – Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und Klinische Immunologie, Berlin
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Andreas Grützkau
- Deutsches Rheuma-Forschungszentrum (DRFZ), Berlin
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Heike Hirseland
- Deutsches Rheuma-Forschungszentrum (DRFZ), Berlin
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Andreas Thiel
- Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité – Universitätsmedizin Berlin, Berlin
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Gerd-Rüdiger Burmester
- Charité – Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und Klinische Immunologie, Berlin
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Renate Arnold
- Charité – Universitätsmedzin Berlin, Hämatologie und Onkologie, Berlin
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Falk Hiepe
- Charité – Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und Klinische Immunologie, Berlin
| Published: | February 5, 2019 |
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Outline
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Background: Over the past 20 years, haematopoietic stem cell transplantation (HSCT) has emerged as promising treatment option for severe cases of autoimmune diseases (ADs). The goal of this therapy is to induce durable remissions by eradicating the pathologic autoreactive memory and restoration of self-tolerance. Here, we summarize the clinical outcomes of AD patients receiving HSCT at the Charité – University Medicine.
Methods: In this prospective study, outcomes of 22 patients with various ADs (SLE, n=10, SSc, n=4, vasculitis, n=4, MS, n=2, inflammatory polyneuropathy, n=1 and autoimmune haemolytic anaemia, n=1) were analysed after receiving a CD34-selected autologous HSCT. Multiparamteric flow cytometry was used to characterize peripheral blood lymphocytes subsets including analysis of the TCR-Vbeta repertoire on CD4+ T-cells, CD31-expression (as marker for recent thymic emigrants) and Siglec-1 expression as well as RNA-expression profiling by microarray to analyse type-1 interferon activity. Autoantibodies were investigated with ELISA.
Results: With a median follow-up of 138 months, overall survival (OS) was 76.5% and progression-free survival (PFS) 67.9%, respectively. 3 deaths were regarded as treatment related (TRM). All patients went into remission, but 4 relapses occurred (autoimmune anaemia at 1mo and SLE at 18, 36 and 80 months, respectively). Remaining patients are in stable clinical remissions for up to 20 years despite withdrawal of chronic immunosuppression. HSCT was associated with significant reduction or even normalization of autoantibody levels and a profound reconfiguration of the adaptive immune system, the latter characterised by a re-emergence of naïve T cells with markers of recent thymic emigrants and renewed TCR repertoire, including Foxp3+ Tregs and regeneration of naïve B cells. In SLE patients, Siglec-1 expression on monocytes completely normalized and transcriptome analysis revealed an abrogation of type I interferon signalling in responding patients.
Conclusion: Our data provide the „proof-of-concept“ that a chronic autoimmune system can be reset into a naïve and self-tolerant state by immunoablation and HSCT. In view of accumulating positive results form phase II and RCT in major indications and gradually improved TRM, HSCT may be considered earlier in the treatment algorithm for ADs, especially in young patients with poor prognosis and live-threatening disease.
