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.
Adult
Antigens, CD34
/ blood
Cyclophosphamide
/ therapeutic use
Disease-Free Survival
Female
Hematopoietic Stem Cell Transplantation
/ methods
Hematopoietic Stem Cells
/ metabolism
Humans
Immunosuppressive Agents
/ therapeutic use
Japan
Male
Middle Aged
Outcome Assessment, Health Care
/ methods
Scleroderma, Systemic
/ pathology
Severity of Illness Index
Transplantation Conditioning
/ methods
Transplantation, Autologous
CD34
Haematopoietic stem cell transplantation
Scleroderma
Systemic sclerosis
Journal
Arthritis research & therapy
ISSN: 1478-6362
Titre abrégé: Arthritis Res Ther
Pays: England
ID NLM: 101154438
Informations de publication
Date de publication:
22 01 2019
22 01 2019
Historique:
received:
10
11
2018
accepted:
14
01
2019
entrez:
24
1
2019
pubmed:
24
1
2019
medline:
17
3
2020
Statut:
epublish
Résumé
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. 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 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. 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.
Sections du résumé
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.
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
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.
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.
Identifiants
pubmed: 30670057
doi: 10.1186/s13075-019-1823-0
pii: 10.1186/s13075-019-1823-0
pmc: PMC6341635
doi:
Substances chimiques
Antigens, CD34
0
Immunosuppressive Agents
0
Cyclophosphamide
8N3DW7272P
Types de publication
Clinical Trial, Phase I
Clinical Trial, Phase II
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
30Subventions
Organisme : Japan Society for the Promotion of Science
ID : JSPS KAKENHI 16K19603
Pays : International
Organisme : Japan Society for the Promotion of Science
ID : JSPS KAKENHI 15K09527
Pays : International
Organisme : Ministry of Health, Labour and Welfare
ID : H24-Jitsuyoka-Kokusai-004
Pays : International
Organisme : Japan Agency for Medical Research and Development
ID : the Practical Research Project for Rare/Intractable Diseases
Pays : International
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