Systemic sclerosis (SSc) patients showed reduced skin thickness and improved lung function after a hematopoietic stem cell transplant (HSCT) using blood progenitor cells positive for the CD34 marker, a study reports.
This finding suggests that CD34-selected autologous HSCT may have additional clinical benefits over conventional autologous HSCT.
The study, “CD34-selected versus unmanipulated autologous haematopoietic stem cell transplantation in the treatment of severe systemic sclerosis: a post hoc analysis of a phase I/II clinical trial conducted in Japan,” were published in the journal Arthritis Research & Therapy.
Autologous HSCT is a process in which a patient’s blood stem cells are collected and reintroduced back into the patient after a chemotherapy treatment course to eliminate faulty immune cells. The technique is often used in patients with cancer or autoimmune diseases, such as SSc, because it is thought to reset the immune system by removing autoreactive immune T-cells and B-cells.
Studies have shown that autologous HSCT can relieve skin symptoms and improve lung function in SSc patients, and lead to significant long-term and event-free survival.
In cancer patients, physicians often choose to select stem cells for HSCT based on the CD34 marker, which allows them to obtain highly purified tumor-free cell collections from patients with malignancies.
In SSc patients, though, it is not clear if the selection of CD34-positive cells prior to transplant affects HSCT outcomes.
To test if CD34-selected HSCT could offer additional clinical benefits to patients with SSc, researchers in Japan evaluated data from a non-randomized Phase 1/2 clinical trial assessing 19 SSc patients (mean age of 53.7 years), 11 of whom received a CD34-selected autologous HSCT, and eight who received a non-manipulated autologous HSCT.
All patients were treated with high-dose cyclophosphamide (200 mg/kg) monotherapy (chemotherapy regimen) before the stem cell transplant. Changes in skin sclerosis and pulmonary function were assessed over an eight-year follow-up period.
Most of the patients had moderate to severe skin sclerosis, established by a modified Rodnan skin score (mRSS; evaluating changes in skin thickness, a hallmark of SSc) of 15 or more (mean mRSS of 26.7). Higher mRSS values correlate with worse skin sclerosis.
Results showed a progressive improvement in mRSS after HSCT in both groups, with the mean mRSS decreasing from an initial 26.7 to 9.1 at the five-year mark. The CD34-selected group demonstrated significantly more improvement over the non-manipulated group.
To assess lung function, researchers measured forced vital capacity (FVC), which measures the amount of air forcibly exhaled from the lungs, and diffusing capacity of carbon monoxide (DCLO), which measures oxygen transfer from the lungs to bloodstream.
While DCLO levels were stable in both groups over the eight-year follow-up period, the researchers found a gradual improvement in FVC after the transplant in the CD34-selected group — from 71.5% at the start to 82.1% at five years and 84.8% at eight years.
In contrast, the non-manipulated group showed temporary FVC improvements at six months, which then returned to initial values three years after transplant.
The team also found that the CD34-selected group showed better progression-free survival (81.8%) at five years than the non-manipulated group (50%).
Results showed that the frequency of severe adverse events, such as bacterial infections or organ toxicity, was similar between the two groups. Viral infections were more common in the CD34-selected group (affecting nine patients), than in the non-manipulated group (two patients). Nonetheless, all patients were successfully treated with or without anti-viral medications. No treatment-related deaths occurred in either group.
The team concluded that “the results of this study show that improvements in skin sclerosis and pulmonary function due to CD34-selected [autologous] HSCT are maintained for at least 8 years, which is superior to results achieved with unmanipulated [autologous] HSCT.”
They suggest that given the fact that immune T-cells are “extremely deleted by the positive selection of CD34+ cells,” the use of CD34-selected autologous HSCT “has a benefit in that it prevents reinfusion of autoreactive [T-cells] that may be associated with SSc.”