Adult Stem Cell Current Clinical Applications – Hematological Disorders and Malignancies - Dipnarine Maharaj M.D. FACP

Current Clinical Applications – Hematological Disorders and Malignancies - Dipnarine Maharaj M.D. FACP

           

Dr. Dipnarine Maharaj M.D. - Medical Director - South Florida Bone Marrow Stem Cell Transplant Institute

 

Adult stem cells have been successfully used to treat blood disorders, blood cancers, and immune system disorders, for the last 50 years or so. Such treatments are routine medical procedures that provide curative protocols.

            An adult stem cell transplant, or hematopoietic stem cell transplant (HSCT), is a procedure in which progenitor cells that are capable of reconstituting normal bone marrow function are administered to a patient. HSCT is usually carried out to eliminate a bone marrow infiltrative process, such as leukemia, or to correct nonmalignant disorders. In order to carry out a HSCT the patient’s bone marrow is destroyed with high-dose chemotherapy and radiotherapy and the new stem cells are then transplanted into the patient.

            The stem cells which are used to replace the bone marrow and restore immune function are obtained from the patient (an autologous transplant), a donor (an allogeneic transplant), or from a genetically identical individual e.g. monozygotic twins (a syngeneic transplant). In order to conduct an autologous transplant the patient has to be in complete remission and the bone marrow has to be clean of tumor cells. In the case of allogeneic transplants, the donor and the recipient are not genetically identical, but they are histocompatible. There are several different types of allogeneic transplants: HLA (human leukocyte antigen)-matched sibling, HLA-matched unrelated donor, unmatched donor, and cord blood transplant.  A relatively new technique is a nonmyeloablative or “mini” allogeneic transplant. In this procedure the bone marrow is not ablated. Instead, lower doses of chemotherapy are used to create a space within the bone marrow. The donor stem cells from the normal donor are then infused into the space, thus creating a chimera – where both recipient and donor cells coexist within the bone marrow space. Ultimately, the normal cells will destroy the abnormal stem cells. Nonmyeloablative transplants are still somewhat experimental; however they are associated with a lower risk of transplant-related mortality and thus offer a potential cure to patients who are considered too high-risk for conventional allogeneic HSCT. Common indications for allogeneic HSCT include:

·         Malignant disorders:

• Acute myelogenous leukemia (AML)
• Non-Hodgkin’s lymphoma (NHL)
• Hodgkin’s disease
• Acute lymphoblastic leukemia (ALL)
• Chronic myeloid leukemia (CML)
• Multiple myeloma (MM)
• Chronic lympocytic leukemia (CLL)

·         Nonmalignant disorders:

• Aplastic anemia
• Thalassemia major
• Severe combined immunodeficiency
• Myelodysplastic syndromes
• Sickle cell anemia

            What about autologous transplants? Multiple myeloma remains the most common indication, followed by lymphoma, and then leukemia.  Autoimmune diseases are also considered for autologous transplant.

           

Figure 1. Indications for Hematopoietic Stem Cell Transplantation in North America (2005)

 

            Figure 1 illustrates data taken from the Center for the International Bone Marrow Transplant Registry. The green shows the number of allogeneic transplants that were carried out for different disease types and the yellow shows the autologous transplants. From this illustration it can be seen that the most common type of HTSC for multiple myeloma is an autologous transplant, whereas for acute lymphoblastic leukemia, the most common indication is for an allogeneic transplant.

 

Table 1. 5-Year Disease Free Survival Rate is Dependent Upon Transplant Type

5-Year Disease Free Survival
Disease		Autologous Transplantation	Allogeneic Transplantation
AML	1st Complete Remission	40%	55%
AML	2nd Complete Remission	30%	45%
Advanced AML		10%	20%
Multiple Myeloma		40%	35%
ALL	1st Complete Remission		40%
ALL	2nd Complete Remission		25%
HG Non-Hodgkin’s Lymphoma		50%	25%
Hodgkin’s Lymphoma		60%
CML	Chronic Phase 1st Year		68%
CML	Chronic Phase >1st Year		53%

 

            As can be seen in Table 1, different types of HTSC are better than others for specific diseases. For example, the 5-year survival rate of a patient with multiple myeloma is approximately 40% with autologous transplant. However, with allogeneic transplants it is approximately 35. So, for multiple myeloma, an autologous transplant is the treatment of choice.

            Research has shown that adult stem cells decline in function as we get older, but not in number. DNA damage and epigenetic modifications present in the older individual are known to limit the regenerative potential of adult stem cells. Thus, it is important to consider the age of a patient or stem cell donor, because even though we may be collecting large number of the cells many of them may be nonfunctional, and that will obviously have an impact upon the outcome of the transplant procedure. There is an obvious way around these problems, and that is to collect and store stem cells when we are young and healthy. The storage of healthy and functional adult stem cells provides biological insurance for the treatment of blood malignancies and for future regenerative therapies.