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Erschienen in: Journal of Hematology & Oncology 1/2010

Open Access 01.12.2010 | Letter to the Editor

HLA-matched sibling transplantation with G-CSF mobilized PBSCs and BM decreases GVHD in adult patients with severe aplastic anemia

verfasst von: Sun Zi-Min, Liu Hui-Lan, Geng Liang-Quan, Wang Xin-Bing, Yao Wen, Liu Xin, Ding Kai-Yang, Han Yong-Sheng, Yang Hui-Zhi, Tang Bo-lin, Tong Juan, Zhu Wei-Bo, Wang Zu-Yi

Erschienen in: Journal of Hematology & Oncology | Ausgabe 1/2010

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Abstract

Background

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for severe aplastic anemia (SAA). However, graft failure and graft-versus-host disease (GVHD) are major causes of the early morbidity in Allo-HSCT.

Methods

To reduce graft failure and GVHD, we treated fifteen patients with SAA using high- dose of HSCT with both G-CSF mobilized PB and BMSCs from HLA-identical siblings to treat patients with SAA.

Results

All patients had successful bone marrow engraftment. Only one patient had late rejection. Median time to ANC greater than 0.5 × 109/L and platelet counts greater than 20 × 109/L was 12 and 16.5 days, respectively. No acute GVHD was observed. The incidence of chronic GVHD was 6.67%. The total three-year probability of disease-free survival was 79.8%.

Conclusion

HSCT with both G-CSF mobilized PB and BMSCs is a promising approach for heavily transfused and/or allo-immunized patients with SAA.
Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1756-8722-3-51) contains supplementary material, which is available to authorized users.

Competing interests

The authors declare that they have no competing interests.

Authors' contributions

SZM have made substantial contributions to conception and design; LHL, GLQ and WXB participated in the acquisition of data; WZY and ZWB participated in analysis and interpretation of data; YW and TJ drafted the manuscript; HYS, YHZ and LX revising it critically for important intellectual content; DKY and TBL performed the statistical analysis.
All authors have read and approved the final manuscript.
Abkürzungen
allo-HSCT
Allogeneic hematopoietic stem cell transplantation
SAA
severe aplastic anemia
GVHD
graft-versus-host disease
ANC
absolute neutrophil count
MSCs
mesenchymal stem cells
MPCs
mesenchymal (stroma) progenitor cells.

To the Editor

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a cure for patients with severe aplastic anemia (SAA). However, complications such as graft failure and graft-versus-host disease (GVHD) have limited the application of allo-HSCT[1, 2]. Increasing the number of donor blood stem cells decreases graft failure, however, high-dose of blood stem cell transplantation also increases the incidence of GVHD[3]. A combination of un-manipulated marrow and T-cell depleted PBSC as the stem cell source for SAA have shown rapid engraftment without increasing the risk of GVHD [4, 5]. Here, we report that transplantation of un-manipulated peripheral blood stem cells (PBSC) combined with bone marrow stem cells (BMSC) in patients with SAA to reduce the incidence of graft failure without negative effects on GVHD.
Fifteen SAA patients, received HLA- 6/6-identical sibling G-CSF-mobilized PB plus BMSC transplantation (Table 1). CY/ALG (12/15 patients) or Flu/CY/ALG (3/15 patients) were used as conditioning regimen for all of them. CsA-MMF regimen was used to prevent aGVHD. Other supportive treatment were also given, such as a cyclovir, intravenous rhG-CSF, and intravenous immunoglobulin. The engraftment of transplant cells was determined using the following methods: STR-PCR analysis, Y PCR analysis, and tests for hematopoietic reconstitution and GVHD.
Table 1
Outcome of 15 SAA patients who received the PB+BM transplantation
No.
Disease
Conditioning Regimen
GVHD Prophylaxis
Cell number
Engraftment (days)
    
    
NC × 108/kg
CD34 × 106/kg
ANC
PLt
    
    
PB/BM
PB/BM
> 0.5 × 109/L
> 20 × 109/L
> 50 × 109/L
Acute GVHD
chronic GVHD
Survival (Month)
Cause of death
1
VSAA-I
CY/ALG
CsA+MMF
5.95/3.06
3.07/0.89
11
15
18
N
skin
80+
 
2
VSAA-I
CY/ALG
CsA+MMF
2.47/1.9
2.39/0.7
11
14
18
N
N
62+
 
3
SAA-II
CY/ALG
CsA+MMF
2.91/2.6
2.33/1.48
15
47
53
  
7
Late graft
         
N
N
 
Rejection
4
VSAA-I
CY/ALG
CsA+MMF
2.46/2.21
5.66/0.95
14
22
34
N
N
54+
 
5
SAA-I
CY/ALG
CsA+MMF
6.47/1.88
5.3/0.47
10
20
50
N
N
9
Infection
6
SAA-I
CY/ALG
CsA+MMF
4.54/3.87
2.81/1.1
12
20
32
N
N
46+
 
7
VSAA-I
CY/ALG
CsA+MMF
6.17/1.0
1.54/0.3
14
30
35
N
N
30+
 
8
SAA-I
CY/ALG
CsA+MMF
4.64/1.86
4.45/0.71
11
15
18
N
N
30+
 
9
SAA-II
Flu/CY/ALG
CsA+MMF
5.05/1.14
1.36/0.33
12
17
20
N
N
29+
 
10
SAA-II
Flu/CY/ALG
CsA+MMF
3.75/1.47
4.2/0.66
12
15
16
N
N
28+
 
11
SAA-I
CY/ALG
CsA+MMF
2.98/1.77
6.62/0.9
10
15
20
N
N
26+
 
12
VSAA-I
CY/ALG
CsA+MMF
7.80/2.6
5.7/0.85
12
14
15
N
N
26+
 
13
SAA-II
Flu/CY/ALG
CsA+MMF
5.86/2.1
5.03/0.92
13
16
16
N
N
20+
 
14
VSAA-I
CY/ALG
CsA+MMF
2.15/1.9
0.49/1.14
23
27
35
N
N
5
Infection
15
SAA-I
CY/ALG
CsA+MMF
8.3/0.77
1.66/0.17
16
29
48
N
N
7+
 
Median (range)
  
4.64(2.15-8.3)/1.9(0.77-3.87) × 108/kg
3.07(0.49-6.62)/0.85(0.17-1.48) × 106/kg
Day 12 (10-23)
Day 16.5 (14-47)
Day 20 (15-53)
  
Month 27 (7-80)
 
CY: cyclophosphamide; ALG: antihuman T-lymphocyte globulin; MMF: mycophenolate mofetil; CsA: cyclosporine A; N: without any acute GVHD or chronic GVHD
All fifteen patients receiving allo-HSCT had successful bone marrow engraftment except for one of them had a late rejection. The incidence of acute and chronic GVHD was 0% and 6.67%. The reasons for the decreased incidence may be multifactorial, the use of G-CSF mobilized PBSC + BMSCS as the source of grafts, usage of ALG in conditioning regimen and CsA/MMF for the prophylaxis of GVHD. No recipients died from treatment-related complications within the first 100 days after transplantation. There were twelve disease-free survivals. The total three-year probability of disease-free survival was 79.8% (Figure 1).
Our data indicate that high- dose of HSCT with both G-CSF mobilized PB and BMSCs resulted in a quick engraftment, low graft rejection, a relatively low incidence of acute GVHD, and good DFS, although larger scale, prospective, and randomized studies are required to confirm these benefits.

Acknowledgements

We thank Lijun Xia from Oklahoma Medical Research Foundation for helpful suggestions.
Open AccessThis article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://​creativecommons.​org/​licenses/​by/​2.​0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Competing interests

The authors declare that they have no competing interests.

Authors' contributions

SZM have made substantial contributions to conception and design; LHL, GLQ and WXB participated in the acquisition of data; WZY and ZWB participated in analysis and interpretation of data; YW and TJ drafted the manuscript; HYS, YHZ and LX revising it critically for important intellectual content; DKY and TBL performed the statistical analysis.
All authors have read and approved the final manuscript.

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Metadaten
Titel
HLA-matched sibling transplantation with G-CSF mobilized PBSCs and BM decreases GVHD in adult patients with severe aplastic anemia
verfasst von
Sun Zi-Min
Liu Hui-Lan
Geng Liang-Quan
Wang Xin-Bing
Yao Wen
Liu Xin
Ding Kai-Yang
Han Yong-Sheng
Yang Hui-Zhi
Tang Bo-lin
Tong Juan
Zhu Wei-Bo
Wang Zu-Yi
Publikationsdatum
01.12.2010
Verlag
BioMed Central
Erschienen in
Journal of Hematology & Oncology / Ausgabe 1/2010
Elektronische ISSN: 1756-8722
DOI
https://doi.org/10.1186/1756-8722-3-51

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