Bone Marrow Failure and Hematopoietic Cell Transplantation

Hematopoietic cell transplantation (HCT), is a standard treatment in various malignant and non-malignant conditions. The hematopoietic cells for HCT can come from a donor (allogeneic) or from the patient (autologous), and can be harvested from peripheral blood, bone marrow or umbilical cord blood. Diseases commonly treated with autologous HCT include malignancies such as multiple myeloma, non-Hodgkin’s lymphoma, Hodgkin’s disease, and acute myeloid leukemia, as well as non-malignant diseases and autoimmune disorders. The majority of allogeneic HCTs are performed to treat hematologic malignancies, but they may also be performed for other diseases, such as aplastic anemia or thalassemia. Transplant patients require extensive care and monitoring, and sometimes need intensive treatment for complications.

In the U.S, approximately 22,000 HCTs were performed in 2013, including both autologous and allogeneic transplantations, and the annual rate of transplantations continues to rise. 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. More patients now survive the first months after transplantation, but in a number of cases complete hematopoietic recovery is not reached, and patients have an increased risks of bleeding, infection, and poor general function.

The current treatment for incomplete hematopoietic recovery includes administration of factors stimulating blood cell growth, such as granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and erythropoietin. However, a significant number of patients do not respond to growth factors and may require frequent transfusions, which expose them to transfusion-related risks such as allo-sensitization and infections, without providing a curative solution. They are also associated with significant costs. Thus, there is an unmet need for additional treatment options for these patients.