If there’s one single image that universally connotes death, it’s that of a skeleton. But in the living human body, bones are a beehive of activity that, at the cellular level, is as lively and intricate as any dance troupe could perform.
Within the hollows of the long bones dwells a spongy tissue called marrow, which hosts stem cells responsible for the production of both red and a variety of white blood cells. The latter are the warriors, messengers, sentries and medics that compose our immune system. White blood cells defend against microbial invaders and scour our bodies for suspicious cells showing signs of being cancerous. Without our immune systems we wouldn’t last a week.
Whether white or red, blood cells can become cancerous, giving rise to lymphomas and leukemias that, respectively, account for about 45,000 and 75,000 new cases annually in the United States. One effective method of treating these conditions is bone marrow transplantation. In this procedure, the patient’s own blood-forming stem cells are, as thoroughly as possible, wiped out, and then replaced with bone marrow from a donor. From the new bone marrow springs an entire new, cancer-free immune system.
There are two things to watch out for after a tranplant. The first is the possibility that not every single cancerous blood cell was destroyed. The second is the prospect that the new immune system, perceiving its new home in the patient’s body as foreign tissue, may turn its guns on the patient’s own organs – a condition called graft-versus-host disease, or GVHD.
The better the immunological match between donor and recipient, the smaller the chance of the recipient’s developing the unremitting, chronic, form of this syndrome (cGVHD). But when a male recipient gets bone marrow from a woman, there will always be a set of proteins produced from genes on the man’s Y chromosome that the immune cells from the female donor have never come across, says Stanford bone-marr0w-transplant researcher David Miklos, MD, PhD.
As I wrote in our release concerning Miklos’s recent discovery, just published in Proceedings of the National Academy of Sciences, of a blood-borne biomarker that predicts the onset of cGVHD after female-to-male bone marrow transplants, there’s a trade-off here that often justifies a male leukemia or lymphoma patient’s receiving marrow from a female donor:
While female-to-male bone-marrow transplants put the recipient at 40 percent higher risk of either acute or chronic GVHD than sex-matched transplants, they also reduce the male recipient’s risk of a cancer relapse by 35 percent. Cancer cells are, at heart, unstable and make all kinds of bizarre proteins, fragments of which they tend to display on their surface — a red flag to the immune system. The new immune system is therefore especially vigilant for cancerous cells that somehow survived the effort to destroy them, putting the patient at risk of a relapse.
Miklos has found that the presence of a very particular species of immune cell in the blood of men who’ve received marrow tranplants from women is a strong predictor of impending cGVHD. This early warning that the still asymptomatic condition is developing may may someday allow physicians to administer immune-suppressing drugs that nip cGVHD in the bud.