Stem cells and multiple myeloma
Medical treatments with tissues and cells are increasing thanks to major advances in biotechnology. Today, there are more than 80 diseases and conditions that are treated with stem cells from umbilical cord blood, including multiple myeloma.
Myeloma, also known as multiple myeloma, is a type of blood cancer that develops from cells in the bone marrow called plasma cells1. Plasma cells are a type of white blood cells found mainly in the bone marrow. They are specialized in producing antibodies against viruses and bacteria2. In myeloma, a tumour transformation of one or more plasma cells takes place and they then begin to divide uncontrollably in the bone marrow1. As the myeloma cells grow in the bone marrow, they can crowd out the normal blood-making process that normally occurs there. As the disease progresses, bone pain, anaemia, kidney dysfunction and infections may occur3.
Each year, approximately 700 people are diagnosed with multiple myeloma.
The cause of multiple myeloma is unknown. Myeloma is a chronic disease, but most patients get better with treatment and can live a good life. Current treatment methods include stem cell transplantation as well as various combinations of chemotherapy and immunotherapy4. Several new treatments are being developed in clinical trials and will be important in the future. The first cell-based gene therapy for the treatment of multiple myeloma patients, who have tried other treatments but where none has had a good effect, has been approved by EMA (European Medicines Agency). The approval is based on study results that show a good and long-term treatment effect in the majority of the patients5,6. It is a CAR-T therapy that works in such a way that the patient´s own T cells, a type of white blood cells, are genetically modified so that they include a new gene that helps the body target and kill the myeloma cells.
For patients younger than 65 years, high-dose treatment with chemotherapy followed by stem cell transplantation is today the standard treatment for multiple myeloma4.
Hematopoietic stem cells are found in the bone marrow. They can produce all types of blood cells, including white blood cells, red blood cells and platelets7. In the treatment of multiple myeloma, hematopoietic stem cells from the patient himself (autologous stem cells) or from another person (allogeneic stem cells) can be used. There are several sources of stem cells such as bone marrow, peripheral blood, and umbilical cord blood. The patient with multiple myeloma first receives high-dose chemotherapy to kill the cancer cells. Then the healthy stem cells are infused into the blood. The procedure is similar to that of blood transfusion. The transplanted stem cells then reach the bone marrow, where they grow and develop into new mature blood cells, including red blood cells, white blood cells and platelets. In this way, a successful transplant can give the patient a healthy bone marrow.
The most serious side effect of allogeneic stem cell transplantation is graft versus host-reaction (so-called Graft-versus-Host disease, GvHD).
This occurs when the new immune cells, from the donor, recognize the patient´s tissues as foreign and attack them. GvHD is less common and less severe in patients following umbilical cord blood transplants compared with peripheral blood stem cells or bone marrow stem cells8. Stem cells from umbilical cord blood are also more immunologically immature than stem cells from bone marrow or peripheral blood. This means that the higher degree of differences in tissue types between donor and recipient can be tolerated than for bone marrow donors9.
Cord blood stem cells are therefore especially an option for patient where no tissue type match can be found.
- Joshua, D. E., Bryant, C., Dix, C., Gibson, J. & Ho, J. Biology and therapy of multiple myeloma. Med J Aust 210, 375-380, doi:10.5694/mja2.50129 (2019).
- Nutt, S. L., Hodgkin, P. D., Tarlinton, D. M. & Corcoran, L. M. The generation of antibody-secreting plasma cells. Nat Rev Immunol 15, 160-171, doi:10.1038/nri3795 (2015).
- Palumbo, A. & Anderson, K. Multiple myeloma. N Engl J Med 364, 1046-1060, doi:10.1056/NEJMra1011442 (2011).
- Offidani, M. et al. Stem Cell Transplantation in Multiple Myeloma. Curr Cancer Drug Targets 17, 769-781, doi:10.2174/1568009616666160920090236 (2017).
- Anderson, L. D., Jr. Idecabtagene vicleucel (ide-cel) CAR T-cell therapy for relapsed and refractory multiple myeloma. Future Oncol 18, 277-289, doi:10.2217/fon-2021-1090 (2022).
- Raje, N. et al. Anti-BCMA CAR T-Cell Therapy bb2121 in Relapsed or Refractory Multiple Myeloma. N Engl J Med 380, 1726-1737, doi:10.1056/NEJMoa1817226 (2019).
- Bujko, K., Kucia, M., Ratajczak, J. & Ratajczak, M. Z. Hematopoietic Stem and Progenitor Cells (HSPCs). Adv Exp Med Biol 1201, 49-77, doi:10.1007/978-3-030-31206-0_3 (2019).
- Gutman, J. A. et al. Chronic graft versus host disease burden and late transplant complications are lower following adult double cord blood versus matched unrelated donor peripheral blood transplantation. Bone Marrow Transplant 51, 1588-1593, doi:10.1038/bmt.2016.186 (2016).
- Goldstein, G., Toren, A. & Nagler, A. Transplantation and other uses of human umbilical cord blood and stem cells. Curr Pharm Des 13, 1363-1373, doi:10.2174/138161207780618759 (2007).