The Use of Donor Mesenchymal Stem Cells in the Treatment of Steroid Refractory Graft Versus Host Disease. Ten Years of Single Center Experience

Short Communication

During the years 2003-2012 there were 94 sibling allogeneic stem cell transplants (alloTx) performed at the National Cancer Institute, Bratislava, Slovakia. From them 43 (46%) patients were treated with reduced intensity conditioning (RI) and 10 (11%) patients received a HLA haploidentical graft. Eight patients (8.5%) developed steroid refractory graft versus host disease (GVHD). After obtaining a general approval from Ethics Committee, all 8 patients had been eligible for the infusion of freshly prepared ex vivo expanded mesenchymal stem cells (MSC). The MSC for ex vivo expansion were isolated from the bone marrow of the sibling donor and expanded according to Koç, et al. [1]. The patients’ characteristics are shown in the Table 1. The mean number of the MSC infused was 0.4x106 cells per kg of body weight. (Range 0.3-0.5x106 cells/kg). Two patients (No 5 and 7) received the MSC twice. Four patients died because of refractory GVHD. From the other 4 patients, two died because of the disease progression, one because of the fungal infection and one is alive up to 10 years after alloTxin complete remission without any signs of cGVHD. It should be noted that all patients were heavily pretreated but the last one who is alive, with more than 5 lines of chemotherapy including autologous stem cell transplantation. Nevertheless, the steroid refractory GVHD resolved in half (4) of them. Moreover it seems to be plausible to have the MSC “in stock” for rapid ex vivo expansion in order to use the cells freshly prepared (not frozen, thawed and immediately applied) [2].

  

    
Patient    No 
    
Gender 
    
Born 
    
Diagnosis 
    
Transplantation 
    
MSC    infusion 
    
Death 
    
Reason    of death 
    
Comment 
  
  

    
1 
    
M 
    
1971 
    
AML 
    
16.03.04 
    
d +206 
    
09.11.04 
    
cGvHD 
  
  

    
2 
    
M 
    
1976 
    
HD 
    
30.01.05 
    
d +1 
    
14.02.05 
    
aGvHD 
    
Haplo    Tx 
  
  

    
3 
    
M 
    
1971 
    
ALL 
    
13.12.05 
    
d +9 
    
05.04.06 
    
disease    progression 
  
  

    
4 
    
F 
    
1970 
    
Ph- CML 
    
26.04.07 
    
d +33 
    
- 
    
alive    (31.12.16) 
  
  

    
5 
    
F 
    
1978 
    
HD 
    
13.10.09 
    
d +60,    d+80 
    
23.02.10 
    
aGvHD 
    
RI    Tx 
  
  

    
6 
    
M 
    
1969 
    
ALL 
    
23.02.10 
    
d +168 
    
16.08.10 
    
cGvHD 
  
  

    
7 
    
F 
    
1973 
    
HD 
    
21.10.10 
    
d +92,    d+178 
    
22.09.11 
    
infection 
    
Haplo Tx 
  
  

    
8 
    
M 
    
1987 
    
HD 
    
18.10.11 
    
d    +43 
    
09.04.13 
    
disease    progression 
    
RI    Tx 
  

Table 1:  Patients‘characteristics, date of transplantation, MSC infusion, date of the patients’ death and the reason of death (Haplo Tx: HLA Haploidentical Transplantation;
RI Tx: Reduced Intensity Conditioning Transplantation).