Autologous Hematopoietic Stem Cell Transplantation for Refractory Autoimmune Diseases

Phase I/II Open-Label Monocentric Clinical Trial for Induction of Tolerance With CD34-Enriched Autologous Hematopoietic Stem Cell Transplantation After High-Dose Chemotherapy With Cyclophosphamide and Rabbit-Antithymocyte Globulin for Refractory Autoimmune Diseases

While glucocorticoids and immunosuppressants ameliorate manifestations of autoimmune diseases in many patients, current therapies are insufficient to control the disease in a subset of patients, and their clinical prognosis remains poor due to the development of vital organ failure, cumulative drug toxicity and to the increased risk of cardiovascular disease and malignancy. Immunoablative chemotherapy followed by autologous hematopoietic stem cell transplantation (ASCT) has recently emerged as a promising experimental therapy for severely affected patients, providing them the potential to achieve treatment-free, long-term remission. The rationale for applying ASCT to autoimmune diseases has been the hope that immunoablation could eliminate inflammation-driving pathogenic cells from the immune system, and that regeneration of the patients' immune system from hematopoietic precursors could re-establish immunological tolerance.

Inclusion Criteria:

• Autoimmune disease
• Active disease with inadequate response to standard protocols (glucocorticoids and at least two different regimens of immunosuppressive drugs, such as intravenous cyclophosphamide 800-1000mg/application)
• Provision of informed consent by subject

Exclusion Criteria:

• Active or chronic infections
• Uncontrolled arrhythmia or congestive heart failure (ejection fraction below 50% determined by echocardiogram)
• Lung fibrosis (transfer factor for carbon monoxide [TLCO] <45%)
• renal insufficiency (glomerular filtration rate below 40 ml/min)
• Pulmonary arterial hypertension (>40mmHg)
• History of malignancy
• Women who are pregnant or breastfeeding
• Use non-reliable methods of contraception