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.
