Transplantation of Single Mismatch Hematopoietic Stem Cells with Third Party Mesenchymal Stem Cells for Severe Aplastic Anemia: A Case Report and Mini Review

Case Report

Ann Hematol Oncol. 2017; 4(5): 1150.

Transplantation of Single Mismatch Hematopoietic Stem Cells with Third Party Mesenchymal Stem Cells for Severe Aplastic Anemia: A Case Report and Mini Review

Keni N¹*, Kaynar L¹, Ünal A¹, Demir K¹, Ermis Turak E¹, Gönen ZB², Eser B¹, Sivgin S¹ and Çetin M¹

¹Department of Hematology, Erciyes Transplant Center, Turkey

²Genome and Stem Cell Center (GENKOK), Erciyes University, Turkey

*Corresponding author: Nermin Keni, Department of Hematology, Erciyes Transplant Center, Kayseri, Turkey

Received: March 14, 2017; Accepted: April 19, 2017; Published: May 10, 2017


While allogeneic hematopoietic stem cells transplantation (allo-HSCT)from HLA-identical siblings has high success rates for aplastic anemia, transplantation from HLA identical or mismatched unrelated donors carries a higher risk of engraftment failure and graft versus host disease (GVHD), remarkably reducing its success rate. A 36 year old woman was diagnosed with severe aplastic anemia and paroxysmal nocturnal hemoglobinuria. Immunosuppressive therapy failed and there was no available HLA compatible family donor. Allo-HSCT was performed using a 9/10 matched unrelated donor with the support of third party mesenchymal stem cells. On patient follow-up, successful engraftment was obtained and neither acute nor chronic graft-versus-host-disease was observed. Mesenchymal stem cells which have immunomodulatory, migratory and regenerative properties may increase the changes of success in unrelated HSCT.

Keywords: Mesenchymal stem cells; Hematopoietic stem cells; Paroxysmal nocturnal hemoglobinuria


Mesenchymal stem cells (MSCs) are non- hematopoietic, spindle-shaped fibroblastoid bone marrow progenitor cells. MSCs don’t express hematopoietic stem cells markers such as CD34 and CD45. Phenotypically they express CD44, CD73 (SH3/4), CD90, CD146, CD105 (SH2), vimentin, endoglin, SSEA-1 and SSEA-4. They have come to be preferred in clinical use because of their immunosuppressive, immunoregulatory and migratory properties and differentiation capacity for tissues such as muscle, bone, cartilage [1,2].

MSCs are a heterogeneous population of cells containing various stem cells which tend to decrease with increasing age. The main sources of MSCs are bone marrow, cord blood, peripheral blood and adipose tissue [3].

While HLA-I antigens are weakly expressed on the surface of MSCs, HLA-II antigens are not. Therefore MSCs can be used for the treatment of graft-versus-host-disease (GVHD) [4]. MSCs can synthesize cytokines and extracellular matrix proteins. It is though that MSCs show accelerating effect on neutrophil and platelet engraftments in autologous and allogeneic hematopoietic stem cells transplant (allo-HSCT) by supporting the placement, proliferation and differentiation of stem cells with their GM-CSF, G-CSF, SCF and IL-6 secreting properties. Via cytokines MSCs also display immunosuppressive properties by inhibiting the formation and activation of T lymphocytes and proliferation of CD4+ CD25+ T lymphocytes. Thus, MSCs can be used in allo-HSCT to reduce the risk of allograft rejection and GVHD [5,6].

It has been observed that MSCs accelerate the engraftment process and -also decrease the GVHD risk in patients with aplastic anemia (AA) who have a higher risk of primary and secondary graft failure and increased risk of GVHD after allo-HSCT [7,8]. MSCs can help improve tissue toxicity associated with allo-HSCT, by repairing the damaged tissue. MSCs also promise good results for the treatment of GVHD associated with HSCT [9,10].

A successful allo-HSCT was performed on our patient from an HLA- single mismatched unrelated donor, despite the increased risk of engraftment failure and GVHD. No MSC-induced toxicity was observed.

Case Presentation

Our 36 year old patient was diagnosed with severe aplastic anemia and paroxysmal nocturnal hemoglobinuria (PNH) at another health center in September 2012 (PNH clone rate was: 80%). Eculizumab was not administered for the treatment because the patient had no history of thrombosis and hemolysis associated with PNH; instead she was treated with cyclosporine and anti-thymocyte globulin (ATG) (horse origin). The patient’s situation did not improve

with the ATG treatment containing two doses at an interval of six months. The patient was still unresponsive in the following six month period after the last ATG dose. She had about two units of red blood cell transfusion requirement per month. The patient had to get hospitalization and treatment because of life threatening neutropenic colitis which repeated three times.

A single mismatched HLA-B locus unrelated donor was found for the patient who was unresponsive to immunosuppressive therapy which had been given twice and had no HLA matched related donor. The patient was admitted to our center for allo-HSCT. Her blood count and peripheral smear were compatible with sever aplastic anemia at admission (Table 1).