HLA-matched sibling transplantation with G-CSF mobilized PBSCs and BM decreases GVHD in adult patients with severe aplastic anemia
Journal of Hematology & Oncology volume 3, Article number: 51 (2010)
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.
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.
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%.
HSCT with both G-CSF mobilized PB and BMSCs is a promising approach for heavily transfused and/or allo-immunized patients with SAA.
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. 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.
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.
Allogeneic hematopoietic stem cell transplantation
severe aplastic anemia
absolute neutrophil count
mesenchymal stem cells
mesenchymal (stroma) progenitor cells.
Remberger M, Naseh N, Aschan J: G-CSF given after haematopoietic stem cell transplantation using HLA-identical sibling donors is associated to a higher incidence of acute GVHD II-IV. Bone Marrow Transplant. 2003, 32 (2): 217-23. 10.1038/sj.bmt.1704108.
Storey JA, Rebecca F Connor, Zachary T Lewis, David Hurd, Gregory Pomper, Yi K Keung, Manisha Grover, James Lovato, Suzy V Toirti, Frank M Torti, Istvan Molnar: The transplant iron score as a predictor of stem cell transplant survival. Journal of Hematology & Oncology. 2009, 2: 44-
Dvorak CC, Gilman AL, Horn B: Primary graft failure after umbilical cord blood transplant rescued by parental haplocompatible stem cell transplantation. J Pediatr Hematol Oncol. 2009, 31 (4): 300-3. 10.1097/MPH.0b013e3181914a81.
Min CK, Kim DW, Lee JW: Supplemental peripheral blood stem cells to decrease marrow rejection in adult patients with severe aplastic anemia. Am J Hematol. 2002, 69 (1): 15-22. 10.1002/ajh.10015.
Cho BS, Eom KS, Kim YJ: HLA-matched sibling transplantation with BM and CD34(+)-purified PBSCs in adult patients with high-risk severe aplastic anemia to overcome graft rejection without an increase in GVHD. Bone Marrow Transplant. 2010, 11: 1-5.
We thank Lijun Xia from Oklahoma Medical Research Foundation for helpful suggestions.
The authors declare that they have no competing interests.
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.
Authors’ original submitted files for images
Below are the links to the authors’ original submitted files for images.
About this article
Cite this article
Zi-Min, S., Hui-Lan, L., Liang-Quan, G. et al. HLA-matched sibling transplantation with G-CSF mobilized PBSCs and BM decreases GVHD in adult patients with severe aplastic anemia. J Hematol Oncol 3, 51 (2010). https://doi.org/10.1186/1756-8722-3-51