Scleroderma is an autoimmune disease where the immune system mistakenly attacks healthy tissues. This triggers the overproduction of collagen, causing hardened scar-like tissue to form. The more severe systemic scleroderma results in damage to internal organs, leading to a range of problems.

Research is ongoing to test whether stem cell transplants can be an effective treatment for scleroderma. Hematopoietic stem cells are one type of stem cells that have been investigated in several clinical trials in scleroderma.

How hematopoietic stem cell therapy works

Stem cells are a specific type of cell that has the potential to develop into a range of other cells. Hematopoietic stem cells are precursors to blood cells, including the white blood cells of the immune system. Once transplanted inside the body, the therapy aims to replace the patient’s immune cells and reset the autoimmune response.

The transplant can be autologous or allogeneic. Autologous stem cells are harvested from the patient themselves and have a lower risk of being rejected by the body. Allogenic stem cells are harvested from a healthy matching donor.

Before the transplant, the patient will undergo conditioning treatment where they are given immunosuppressant medication or radiotherapy. This is to allow the stem cells space to grow in the patient’s body and to prevent the immune system from immediately rejecting them. 

Hematopoietic stem cells in clinical trials for scleroderma

A U.S. and Canada-based Phase 2/3 clinical trial (NCT00114530) funded by the National Institutes of Health (NIH), called SCOT, was completed in January 2018.

It aimed to assess the safety and effectiveness of autologous hematopoietic stem cell transplants in scleroderma, following myeloablation conditioning. The cells were harvested from the patient’s own peripheral blood.

Myeloablation involved chemotherapy and total body irradiation to eradicate the bone marrow cells, including immune cells, of the patient. The transplanted stem cells could then rebuild the bone marrow and immune system and “reset” the auto-immune response. 

The trial randomly assigned 75 adults with severe systemic scleroderma to receive either the myeloablative stem cells or a monthly dose of the immunosuppressant, cyclophosphamide, a common treatment in scleroderma.

Results, published in the New England Journal of Medicine, showed that the myeloablative stem cell transplantation was superior to immunosuppression alone. Significant long-term benefits included higher event-free survival and higher overall survival.

In the transplant group, 79 percent of patients had seen no disease progression after 4.5 years, compared to only 50 percent of cyclophosphamide-treated patients. The overall survival rate was 86 percent in the transplantation group compared to 51 percent in the immunosuppressant group after six years. However, the myeloablation was associated with an increase in treatment-related mortality. Two patients out of 36 (6 percent) died due to the transplant, compared to none in the cyclophosphamide group.

A completed Phase 1/2 clinical trial (NCT00622895), run by the Fred Hutchinson Cancer Research Center, aimed to examine the safety and effectiveness of an allogeneic hematopoietic stem cell transplant following a reduced intensity conditioning regime to prepare the body for the transplant.

This conditioning does not eliminate all the bone marrow as in myeloablation but can result in significantly reduced blood cell levels (cytopenia). A lower chemotherapy and total body radiation dosage aimed to reduce the toxic side effects.

In total, three systemic scleroderma patients received a transplant of hematopoietic cells harvested from the bone marrow of a healthy matched donor. Patients were monitored for up to five years. At the two-year follow-up, one patient out of three had survived with no disease worsening. The two deaths were thought to be treatment-related, and not related to disease progression.

The Fred Hutchinson Cancer Research Center is currently enrolling patients for a second Phase 2 clinical trial (NCT01413100) called STAT. The trial aims to recruit 30 patients with systemic scleroderma at several sites in the U.S. and Canada. 

The hematopoietic stem cells will be harvested from the patient’s own peripheral blood. Patients will be given high a dose of cyclophosphamide and anti-thymocyte globulin to condition the body for the transplant. Patients will be monitored for side effects for five years.

The efficacy of the treatment will be assessed primarily as event-free survival. Other measures will include heart, kidney, and lung function tests, quality of life, and overall survival. The study is expected to be completed by September 2019.

There are several other clinical trials investigating different hemopoietic stem cell transplantation regimes, which are still recruiting participants. These include:

  • The autologous stem cell systemic sclerosis immune suppression study (DIScl2011), a Phase 3 clinical trial (NCT01445821) aiming to recruit up to 160 patients with systemic scleroderma at Northwestern University in Illinois;
  • The autologous stem cell transplant for progressive systemic sclerosis study (AST-MOMA), a Phase 2 clinical trial (NCT01895244, EudraCT: 2011-002434-40) recruiting up to 44 patients with progressive systemic scleroderma at the University Hospital Tuebingen in Germany.

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