Bone Marrow Deficiency and Hematopoietic Cell Transplantation

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Hematopoietic cell transplantation (HCT) – the transplantation of multipotent hematopoietic cells, either autologous or allogeneic, is a standard treatment in various malignant and non-malignant conditions. An autologous transplant, where the person’s own hematopoietic stem cells are used, is intended to treat the chemotherapy-induced hypoplasia[1] and restore hematopoiesis. In an allogeneic transplant, hematopoietic stem cells from a donor are used, where the purpose is to replace the recipient’s immune system with the donor one[2]. Diseases treated with HCT can be either malignancies such as multiple myeloma, non-Hodgkin’s lymphoma, Hodgkin’s disease, and acute myeloid leukemia, or non-malignant such as autoimmune disorders[3],[4],[5]

According to the World Health Organization (WHO) more than 50,000 transplants are carried out annually worldwide and they are increasing each year with a global annual increase of >7%[6]. Coupled with the increased numbers of HCTs, there has been a steady improvement in transplant outcomes, related mainly to refinement in human leukocyte antigen (HLA) matching for allogeneic transplantations, improved supportive care, and advances in infectious disease therapy.

A successful HCT leads to hematopoietic recovery with full function of the bone marrow resulting in optimal or suboptimal blood count values. However, in a number of cases complete hematopoietic recovery is not reached, and patients have an increased risk of bleeding, infection, and poor general function. This can be due to graft failure (GF), which is caused primarily by graft rejection or poor graft function (PGF) that is characterized by persistent cytopenia in the presence of complete donor chimerism[7].

The current treatment for incomplete hematopoietic recovery is based on addressing the deficiencies in blood counts. It includes mainly hematopoietic growth factors with the administration of factors stimulating blood cell growth, such as granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF) and erythropoietin may be administered[8],[9] and the use of thrombopoietin receptor agonist, which was found to be effective in idiopathic thrombocytopenic purpura (ITP) and aplastic anemia, is currently under investigation[10],[11],[12].

However, the efficacy of these treatments is limited, and a significant proportion of patients do not respond to growth factors, remain cytopenic and require continued transfusion support[13] Transfusions expose the patients to transfusion-related risks such as iron overload, allo-sensitization and exposure to infective agents, without providing a curative solution. They are also associated with significant costs. Thus, there is an unmet medical need for additional treatment options for these patients.


[1] Maziarz, RT. and Slater, SS. 2015. Blood and marrow transplant handbook : comprehensive guide for patient care (Springer).

[2] Hatzimichael, E., and M. Tuthill. 2010. ‘Hematopoietic stem cell transplantation’, Stem Cells Cloning, 3: 105-17.

[3] Copelan, EA. 2006. ‘Hematopoietic stem-cell transplantation’, N Engl J Med, 354: 1813-26.

[4] Maziarz, RT. et al. 2015. ‘Single and multiple dose MultiStem (multipotent adult progenitor cell) therapy prophylaxis of acute graft-versus-host disease in myeloablative allogeneic hematopoietic cell transplantation: a phase 1 trial’, Biol Blood Marrow Transplant, 21: 720-8.

[5] Maziarz, Richard T., and Susan Slater. 2011. Blood and marrow transplant handbook : comprehensive guide for patient care (Springer: New York).

[6] Niederwieser, D, et al.  2019. One and Half Million Hematopoietic Stem Cell Transplants (HSCT). Dissemination, Trends and Potential to Improve Activity By Telemedicine from the Worldwide Network for Blood and Marrow Transplantation (WBMT). Blood, 134 (1): 2035.

[7] Chen, J. et al. 2020. Advances in the understanding of poor graft function following allogeneic hematopoietic stem-cell transplantation. Ther Adv Hematol. Aug 17;11:2040620720948743.

[8] Larocca, A. et al. 2006. Boost of CD34+-selected peripheral blood cells without further conditioning in patients with poor graft function following allogeneic stem cell transplantation. Haematologica. Jul;91(7):935-40.

[9] Fouillard, L. et al. 2007 Infusion of allogeneic-related HLA mismatched mesenchymal stem cells for the treatment of incomplete engraftment following autologous haematopoietic stem cell transplantation. Leukemia 21: 568–570.

[10] Mahat, U. Rotz, SJ and Hanna, R. 2020. Use of Thrombopoietin Receptor Agonists in Prolonged Thrombocytopenia after Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant. Mar;26(3):e65-e73.

[11] Halahleh, K. et al. 2021. Therapy of posttransplant poor graft function with eltrombopag. Bone Marrow Transplantation. 56:4-6.

[12] Giammarco, S. et al. 2021. Eltrombopag for the treatment of poor graft function following allogeneic stem cell transplant: a retrospective multicenter study. Int J Hematol. 2021 Apr 22. doi: 10.1007/s12185-021-03153-3.

[13] Stasia, A. et al. 2014. ‘CD34 selected cells for the treatment of poor graft function after allogeneic stem cell transplantation’, Biol Blood Marrow Transplant, 20: 1440-3.