Blood cancer patients who are treated with allogeneic cell transplants are less likely to experience severe acute graft-versus-host disease (GVHD) if their donors take statins, a commonly-used class of cholesterol-lowering drugs, according to a study published in the journal Blood in December. Because they also found that statins don’t reduce the therapeutic effects of the transplant, the authors of the study suggested that statins may be an effective preventative treatment for acute GVHD.

Allogeneic transplants “may very well” increase in popularity after the Blood study’s data are confirmed by clinical trials, wrote Dr. Marco Mielcarek, the study’s lead scientist, in an e-mail to the Myeloma Beacon.

People with multiple myeloma are most often treated with autologous stem cell transplants, in which patients’ own stem cells are transplanted back into their bodies, rather than allogeneic stem cell transplants, in which a healthy donor’s stem cells are transplanted to the patient. Nevertheless, experts look to allogeneic transplants as a possible cure for multiple myeloma because the healthy donor cells can attack myeloma cells.

However, allogeneic stem cell transplants carry an increased risk compared to autologous stem cell transplants. 15 percent to 40 percent of allogeneic transplant recipients die from the treatment, compared to less than 3 percent of certain autologous transplant recipients, according to the National Cancer Institute.

One major cause of death is GVHD, which happens when the donated cells attack healthy cells in the recipient’s body. Scientists differentiate between acute GVHD, which normally occurs within the first 100 days after the transplant, and chronic GVHD, which is observed after 100 days of the transplant.

In their study, scientists analyzed the medical records of people with blood cancers who were treated with allogeneic cell transplants at the Fred Hutchinson Cancer Research Center in Seattle between 2001 and 2007. Fifty-seven of these people had marrow cell donors who were taking a statin, and 12 were taking a statin and had a donor who was taking a statin. Scientists compared these groups’ reactions to their allogeneic transplants with the reactions of 464 people who did not take a statin and whose donors did not take a statin. 

Patients whose donors took a statin, and who received the immune system treatment cyclosporine after their transplant, were less likely to have severe acute GVHD in the stomach and intestines. However, patients who received the post-transplant immune system treatment tacrolimus did not see any protective effects against acute GVHD from their donors’ statin use.

When both the patients and their donors took statins, the patients were also less likely to have severe acute GVHD, but because the number of these patients was small, the results didn’t reach statistical significance.

The scientists also examined the medical records of 16 blood cancer patients who were taking a statin and had a donor who was not taking a statin. They found that these patients did not have a reduced risk of developing acute GVHD.

The scientists also found that patient or donor statin use did not decrease the risk of chronic GVHD or significantly lower cancer reoccurrence or mortality rates.

In their paper, Dr. Mielcarek’s research team presented some possible explanations for how statins may reduce GVHD. Statins, which are commonly prescribed to people with high cholesterol, heart disease or diabetes, lower cholesterol levels by blocking a cholesterol precursor. This precursor is also important to certain immune responses. Additionally, statins have immune system effects that are independent of its cholesterol-lowering effects. Combined, these effects may reduce the immune response that is the main cause of GVHD. “Statins seem to dampen ‘excessive’ immune responses through a variety of mechanisms,” wrote Dr. Mielcarek to the Beacon. “Which of these mechanisms is most relevant remains to be seen.”

Statin use seems to be relatively safe for donors, and donors who do not need statins for other conditions may be able to take them just for the donation. However, many questions remain. “Statins are among the most widely prescribed drugs worldwide; thus, they have a well established safety profile even though rare but serious adverse effects are known,” wrote Dr. Mielcarek. However, he added, scientists don’t yet know how much statin donors should take, or for how long. His research also did not address what kinds of statins are the most effective, as the study included donors who were taking different statins, including Lipitor (atorvastatin), simvastatin (Zocor) and Crestor (rosuvastatin).

“Our data provide strong evidence that donor or donor/recipient statin use confers protection against severe acute GVHD without compromising” the curative effects of an allogeneic transplant, the study’s paper concluded. The Fred Hutchinson scientists wrote that their results “might motivate” the creation of clinical trials, but suggest some questions for further research to answer first.

For more information, please see the study in Blood (abstract).