Annals of Hematology

, Volume 88, Issue 3, pp 261–266 | Cite as

Mesenchymal stem cells for the treatment of refractory pure red cell aplasia after major ABO-incompatible hematopoietic stem cell transplantation

  • Baijun Fang
  • Yongping Song
  • Ning Li
  • Jing Li
  • Qin Han
  • Robert Chunhua Zhao
Original Article


Pure red cell aplasia (PRCA) is a well-known, although infrequent, hematological complication after allogeneic hematopoietic stem cell transplantation (HSCT). PRCA occurs in cases of major ABO mismatch between donor and recipient and is believed to be due to inhibition of donor erythroid progenitors by residual host isohemagglutinins. The purpose of our study was to further evaluate the efficacy of human adipose tissue-derived mesenchymal stem cells (AMSC) as the salvage therapy for refractory PRCA after major ABO-incompatible HSCT. Two patients with refractory pure red cell aplasia received intravenous infusions of AMSC at a dose of 1.5 × 106/kg of the patients’ weight, and rapid recovery from PRCA without any side effects was observed. We conclude that AMSC seems to be a promising therapeutic option in patients with PRCA after ABO-mismatched HSCT, in whom conventional treatment fails.


Hematopoietic stem cell transplantation Pure red cell aplasia Mesenchymal stem cell 



We want to thank the staff at the Center of Excellence in Tissue Engineering, Henan Tumor Hospital, Henan Institute of Haematology, Henan Medical School, Henan University, Zhengzhou, China. This study was supported by grants of National Development Plan of High Technology 863 (no. 2002AA205061) and Henan Outstanding Youth Foundation (no. 0612000900).


  1. 1.
    Worel N, Kalhs P, Keil F, Prinz E, Moser K, Schulenburg A et al (2003) ABO mismatch increases transplant-related morbidity and mortality in patients given nonmyeloablative allogeneic HPC transplantation. Transfusion 43:1153–1161 doi:10.1046/j.1537-2995.2003.00465.x PubMedCrossRefGoogle Scholar
  2. 2.
    Lee JH, Lee KH, Kim S, Lee JS, Kim SH, Kwon SW et al (2000) Anti-A isoagglutinin as a risk factor for the development of pure red cell aplasia after major ABO-incompatible allogeneic bone marrow transplantation. Bone Marrow Transplant 25:179–184 doi:10.1038/sj.bmt.1702121 PubMedCrossRefGoogle Scholar
  3. 3.
    Gmür JP, Burger J, Schaffner A, Neftel K, Oelz O, Frey D et al (1990) Pure red cell aplasia of long duration complicating major ABO-incompatible bone marrow transplantation. Blood 75:290–295PubMedGoogle Scholar
  4. 4.
    Lee JH, Lee JH, Choi SJ, Kim S, Seol M, Kwon SW et al (2002) Changes of isoagglutinin titres after ABO-incompatible allogeneic stem cell transplantation. Br J Haematol 120:702–710 doi:10.1046/j.1365-2141.2003.04128.x CrossRefGoogle Scholar
  5. 5.
    Badros A, Tricot G, Toor A, Morris C, Guo C, Munshi N et al (2002) ABO mismatch may affect engraftment in multiple myeloma patients receiving nonmyeloablative conditioning. Transfusion 42:205–209 doi:10.1046/j.1537-2995.2002.00027.x PubMedCrossRefGoogle Scholar
  6. 6.
    Mielcarek M, Leisenring W, Torok-Storb B, Storb R (2000) Graft-versus-host disease and donor-directed hemagglutinin titers after ABO-mismatched related and unrelated marrow allografts: evidence for a graft-versus-plasma cell effect. Blood 96:1150–1156PubMedGoogle Scholar
  7. 7.
    Gahrton G, Tura S, Ljungman P, Belanger C, Brandt L, Cavo M et al (1991) Allogeneic bone marrow transplantation in multiple myeloma. European Group for Bone Marrow Transplantation. N Engl J Med 325:1267–1273PubMedGoogle Scholar
  8. 8.
    Corcione A, Benvenuto F, Ferretti E, Giunti D, Cappiello V, Cazzanti F et al (2006) Human mesenchymal stem cells modulate B-cell functions. Blood 107:367–372 doi:10.1182/blood-2005-07-2657 PubMedCrossRefGoogle Scholar
  9. 9.
    Han Q, Liao L, You S, Deng H, Zhao RC (2005) Effects of allogeneic bone marrow-derived mesenchymal stem cells on T and B lymphocytes from BXSB mice. DNA Cell Biol 24:458–463 doi:10.1089/dna.2005.24.574 PubMedCrossRefGoogle Scholar
  10. 10.
    Fang B, Song Y, Zhao RC, Han Q, Cao Y (2007) Treatment of resistant pure red cell aplasia after major ABO-incompatible bone marrow transplantation with human adipose tissue-derived mesenchymal stem cells. Am J Hematol 82:772–773 doi:10.1002/ajh.20932 PubMedCrossRefGoogle Scholar
  11. 11.
    Cao Y, Sun Z, Liao L, Meng Y, Han Q, Zhao RC (2005) Human adipose tissue-derived stem cells differentiate into endothelial cells in vitro and improve postnatal neovascularization in vivo. Biochem Biophys Res Commun 332:370–379 doi:10.1016/j.bbrc.2005.05.034 PubMedCrossRefGoogle Scholar
  12. 12.
    Deng W, Han Q, Liao L, Li C, Ge W, Zhao Z et al (2005) Engrafted bone marrow-derived flk-(1+) mesenchymal stem cells regenerate skin tissue. Tissue Eng 11:110–119 doi:10.1089/ten.2005.11.110 PubMedCrossRefGoogle Scholar
  13. 13.
    Le Blanc K, Tammik L, Sundberg B, Haynesworth SE, Ringdén O (2003) Mesenchymal stem cells inhibit and stimulate mixed lymphocyte cultures and mitogenic responses independently of the major histocompatibility complex. Scand J Immunol 57:11–20 doi:10.1046/j.1365-3083.2003.01176.x PubMedCrossRefGoogle Scholar
  14. 14.
    Martelli M, Ponchio L, Beguin Y, Meloni G, Mandelli F, Cazzola M (1994) Pure red cell aplasia following peripheral stem cell transplantation: complete response to a short course of high-dose recombinant human erythropoietin. Haematologica 79:456–459PubMedGoogle Scholar
  15. 15.
    Ohashi K, Akiyama H, Takamoto S, Tanikawa S, Sakamaki H, Onozawa Y (1994) Treatment of pure red cell aplasia after major ABO-incompatible bone marrow transplantation resistant to erythropoietin. Bone Marrow Transplantation Team. Bone Marrow Transplant 13:335–336PubMedGoogle Scholar
  16. 16.
    Veelken H, Wäsch R, Behringer D, Bertz H, Finke J (2000) Pure red cell aplasia after allogeneic stem cell transplantation with reduced conditioning. Bone Marrow Transplant 26:911–915 doi:10.1038/sj.bmt.1702629 PubMedCrossRefGoogle Scholar
  17. 17.
    Sahovic EA, Flick J, Graham CD, Stuart RK (1991) Case report: isoimmune inhibition of erythropoiesis following ABO-incompatible bone marrow transplantation. Am J Med Sci 302:369–373 doi:10.1097/00000441-199112000-00009 PubMedCrossRefGoogle Scholar
  18. 18.
    Koç ON, Gerson SL, Cooper BW, Dyhouse SM, Haynesworth SE, Caplan AI et al (2000) Rapid hematopoietic recovery after coinfusion of autologous-blood stem cells and culture-expanded marrow mesenchymal stem cells in advanced breast cancer patients receiving high-dose chemotherapy. J Clin Oncol 18:307–316PubMedGoogle Scholar
  19. 19.
    Lazarus HM, Haynesworth SE, Gerson SL, Rosenthal NS, Caplan AI (1995) Ex vivo expansion and subsequent infusion of human bone marrow-derived stromal progenitor cells (mesenchymal progenitor cells): implications for therapeutic use. Bone Marrow Transplant 16:557–564PubMedGoogle Scholar
  20. 20.
    Le Blanc K, Rasmusson I, Sundberg B, Götherström C, Hassan M, Uzunel M et al (2004) Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet 363:1439–1441 doi:10.1016/S0140-6736(04)16104-7 PubMedCrossRefGoogle Scholar
  21. 21.
    Fang B, Song Y, Lin Q, Zhang Y, Cao Y, Zhao RC et al (2007) Human adipose tissue-derived mesenchymal stromal cells as salvage therapy for treatment of severe refractory acute graft-vs.-host disease in two children. Pediatr Transplant 11:814–817 doi:10.1111/j.1399-3046.2007.00780.x PubMedCrossRefGoogle Scholar
  22. 22.
    Le Blanc K, Samuelsson H, Gustafsson B, Remberger M, Sundberg B, Arvidson J et al (2007) Transplantation of mesenchymal stem cells to enhance engraftment of hematopoietic stem cells. Leukemia 21:1733–1738 doi:10.1038/sj.leu.2404777 PubMedCrossRefGoogle Scholar
  23. 23.
    Fang B, Song Y, Liao L, Zhang Y, Zhao RC (2007) Favorable response to human adipose tissue-derived mesenchymal stem cells in steroid-refractory acute graft-versus-host disease. Transplant Proc 39:3358–3362 doi:10.1016/j.transproceed.2007.08.103 PubMedCrossRefGoogle Scholar
  24. 24.
    Fang B, Song YP, Liao LM, Han Q, Zhao RC (2006) Treatment of severe therapy-resistant acute graft-versus-host disease with human adipose tissue-derived mesenchymal stem cells. Bone Marrow Transplant 38(5):389–390 doi:10.1038/sj.bmt.1705457 PubMedCrossRefGoogle Scholar
  25. 25.
    Verholen F, Stalder M, Helg C, Chalandon Y (2004) Resistant pure red cell aplasia after allogeneic stem cell transplantation with major ABO mismatch treated by escalating dose donor leukocyte infusion. Eur J Haematol 73:441–446 doi:10.1111/j.1600-0609.2004.00320.x PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Baijun Fang
    • 1
    • 2
  • Yongping Song
    • 1
  • Ning Li
    • 1
  • Jing Li
    • 2
  • Qin Han
    • 2
  • Robert Chunhua Zhao
    • 2
  1. 1.Henan Tumor Hospital, Henan Institute of Haematology, Henan Medical SchoolHenan UniversityZhengzhouChina
  2. 2.Institute of Haematology and Blood Diseases Hospital, Center of Excellence in Tissue EngineeringChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

Personalised recommendations