Back to Search
Start Over
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.
- Source :
-
Arthritis research & therapy [Arthritis Res Ther] 2019 Jan 22; Vol. 21 (1), pp. 30. Date of Electronic Publication: 2019 Jan 22. - Publication Year :
- 2019
-
Abstract
- Background: The effectiveness of autologous haematopoietic stem cell transplantation (auto-HSCT) in treating severe systemic sclerosis (SSc) is established; however, the necessity of purified CD34+ cell grafts and the appropriate conditioning regimen remain unclear. This study aimed to compare the efficacy and safety of CD34-selected auto-HSCT with unmanipulated auto-HSCT to treat severe SSc.<br />Methods: This study was a post hoc analysis of a phase I/II clinical trial conducted in Japan. Nineteen patients with severe SSc were enrolled. Peripheral blood stem cells (PBSCs) were mobilised with cyclophosphamide (4 g/m <superscript>2</superscript> ) and filgrastim (10 μg/kg/day). Following PBSC collection by apheresis, CD34+ cells were immunologically selected in 11 patients. All patients were treated with high-dose cyclophosphamide (200 mg/kg) monotherapy as a conditioning regimen and received CD34-selected (n = 11) or unmanipulated auto-HSCT (n = 8). Changes in skin sclerosis and pulmonary function were assessed over an 8-year follow-up period. Differences in the changes, toxicity, progression-free survival (PFS) and overall survival were compared between patients who had received CD34-selected auto-HSCT and those who had received unmanipulated auto-HSCT.<br />Results: Skin sclerosis progressively improved after transplantation over an 8-year follow-up period in both groups, and the improvement was significantly greater in the CD34-selected group than in the unmanipulated group. Forced vital capacity in the CD34-selected group continuously increased over 8 years, whereas in the unmanipulated group it returned to baseline 3 years after transplantation. Toxicity and viral infections, such as cytomegalovirus infection and herpes zoster, were more frequently found in the CD34-selected group than in the unmanipulated group. The frequency of severe adverse events, such as bacterial infections or organ toxicity, was similar between the two groups. No treatment-related deaths occurred in either treatment group. PFS of the CD34-selected group was greater than that of the unmanipulated group, and the 5-year PFS rates of the CD34-selected and unmanipulated group were 81.8% and 50% respectively.<br />Conclusions: CD34-selected auto-HSCT may produce favourable effects on improvement of skin sclerosis and pulmonary function compared with unmanipulated auto-HSCT. Use of CD34-selected auto-HSCT with high-dose cyclophosphamide monotherapy as a conditioning regimen may offer an excellent benefit-to-risk balance.
- Subjects :
- Adult
Cyclophosphamide therapeutic use
Disease-Free Survival
Female
Humans
Immunosuppressive Agents therapeutic use
Japan
Male
Middle Aged
Outcome Assessment, Health Care methods
Outcome Assessment, Health Care statistics & numerical data
Scleroderma, Systemic pathology
Severity of Illness Index
Transplantation Conditioning methods
Transplantation, Autologous
Antigens, CD34 blood
Hematopoietic Stem Cell Transplantation methods
Hematopoietic Stem Cells metabolism
Scleroderma, Systemic therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1478-6362
- Volume :
- 21
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Arthritis research & therapy
- Publication Type :
- Academic Journal
- Accession number :
- 30670057
- Full Text :
- https://doi.org/10.1186/s13075-019-1823-0