There are few procedures in medicine more complex, dangerous, and remarkable than stem cell transplantation. This procedure has enabled us to successfully treat cancers that were previously uniformly fatal. For certain types of acute myeloid leukemia, for example, stem cell transplant increases 5-year survival from less than 15% to about 44%.
But the full story of stem cell transplant is much more complicated. The data are complicated and the research is full of fits and starts, new questions and dead-ends.
There is, for example, the story of stem cell transplant (SCT) for breast cancer, a therapy which persisted despite data showing its ultimate inutility. There is the pioneering use of SCT for the treatment of autoimmune disorders such as lupus and multiple sclerosis, something still being investigated. And there is a great deal of promise in the treatment/cure of genetic blood diseases such as sickle cell anemia.
When we talk about stem cell transplants we are talking about something very different from the stem cell research controversy. Stem cell transplants (and previously, bone marrow transplants) involve harvesting and transplanting the immature cells that develop into mature blood and immune cells. The procedure is generally referred to as "hematopoietic stem cell transplantation (HSCT)". These transplants can come from the person being treated (autologous) or from someone else (allogeneic). The difference can be quite important.
To understand how SCTs can be used therapeutically, we need a little biology. Hematopoietic stem cells normally reside in the bone marrow. They are the precursors to our blood/immune cells. They are very, very sensitive to chemotherapy and radiation, and the death of these cells often limits how aggressively a cancer can be treated. If you give a patient enough chemotherapy or radiation, you can kill off a patient's stem cells permanently. This is usually a bad thing. Except when it isn't.
Since bone marrow toxicity often limits how much therapy we can deliver to fight cancer, what would happen if we took bone marrow out of the picture? This is what we do for certain cancers. Before delivering otherwise-deadly doses of chemotherapy and/or radiation, stem cells are harvested from either the patient or a matched donor. Once this is done, the patient can be exposed to higher doses of therapy than would otherwise be possible. As you might imagine, though, HSCs and cancer cells aren't the only ones killed off by chemotherapy, and HSCT is often an arduous and dangerous procedure. More about this below.
An even simpler idea (at least on paper) is the cure of certain genetic diseases using HSCT. Sickle cell disease (SCD), a painful and life-shortening genetic illness that primarily affects Africans and African Americans, has been successfully treated with HSCT. In SCD, a mutation in the gene which codes for hemoglobin causes red blood cells to "sickle", blocking of blood vessels and damaging vital organs. If a suitable donor can be found, the patient's own marrow can be (mostly) killed off by radiation and chemotherapy, and the donor stem cells transplanted. If it all works just right, the donor stem cells will seed the marrow and start to produce normal red blood cells in sufficient quantity to eliminate the symptoms of sickle cell disease. This complex and dangerous treatment is not yet widely available, but the word "mostly" may turn out to be a solution, as in the paper cited below.
Back to a little biology. Stem cells, like all cells, have markers on their surfaces that tell other cells who they belong to. If I were to just toss a new liver into someone, host immune cells would notice the markers on the liver cells that say "not me" and reject them, which is a nice way of saying "kill them". Stem cells come with a slightly different problem. Blood stem cells grow up to become immune cells, immune cells marked as belonging to the donor. This is all well and good if the donor and recipient are the same person (an autologous transplant), but if they are different (allogeneic), the stem cells can actually attack the recipient causing "graft vs. host disease (GVHD)". This is usually treated with drugs that suppress the immune system, forcing doctor and patient to balance GVHD and opportunistic diseases caused by immune suppression. And this is where it gets really interesting.
If we are treating a leukemia, for example, an allogeneic stem cell transplant allows us to do two really cool things. First, it allows us to deliver enough chemo and radiation to kill the malignant cells. When the donor cells implant, they will recognize any residual leukemia cells as "other" and take them out. This is called the "graft vs leukemia effect" and puts the transplanted stem cells to work in maintaining remission.
But HSCTs are serious medicine, with a high rate of complications and mortality. While they have theoretical benefit for many conditions, data must drive the use of this procedure. In the 1990s, SCT was used to treat advanced breast cancer, but the data showed that this treatment was not delivering the anticipated benefit. Data is growing for the use of "mini-transplants" in which the marrow is only partly killed, reducing the chances of the patient dying of infections and other complications while waiting for the new cells to implant.
This is a fascinating field, one that is decades old and continues to evolve, and that will likely give us plenty of interesting news to talk about in the future.
Hsieh, M., Kang, E., Fitzhugh, C., Link, M., Bolan, C., Kurlander, R., Childs, R., Rodgers, G., Powell, J., & Tisdale, J. (2009). Allogeneic Hematopoietic Stem-Cell Transplantation for Sickle Cell Disease New England Journal of Medicine, 361 (24), 2309-2317 DOI: 10.1056/NEJMoa0904971