The MDS Beacon™

The success of allogeneic stem cell transplantation for myelodysplastic syndromes (MDS) patients is determined by the stage of disease, rather than age or intensity of the pre-transplant regimen, according to a study published recently in the American Journal of Clinical Oncology.

Allogeneic stem cell transplantation, or allotransplantation, involves destroying patient bone marrow by chemotherapy or radiation and replacing it with healthy bone marrow from a matched donor.  Although this process is the only cure for MDS, it does not guarantee full recovery.

Transplants were previously not an option for older patients because of the increased risk for graft vs. host disease.  Graft vs. host disease is a potential threat for transplant patients where functional immune cells in the healthy transplanted marrow identify the recipient’s cells as foreign and attack them.

However, recent studies have shown that patients over 55 can successfully tolerate transplantation (see related Beacon article). 

The process has also become more feasible with the development of lower doses of pre-transplant chemotherapy and radiation, donor-matching technology, and supportive care (see related Beacon article). 

In this study, researchers analyzed the records of 1,333 MDS patients in the European Group for Blood and Marrow Transplantation registry who had received a bone or blood marrow transplant between January 1998 and October 2006.  The median age of the patients was 56, and all patients were over 50.

Forty two percent of patients had-early stage MDS, 52 percent had advanced stage MDS, and 6 percent of patients did not have blast percentage recorded.  Early-stage MDS was defined as having less than 5 percent blasts in the bone marrow, while advanced-stage patients had greater than 5 percent blasts. 

Records showed 38 percent of patients received the standard dose of chemotherapy in preparation for their transplants, while 62 percent received reduced-intensity conditioning.

The study compared the effects of patient age, stage of MDS, intensity of treatment, and relation of donor on rate of relapse and non-relapse mortality.  

Researchers found that patients in the 50 to 60 age group had higher relapse but similar non-relapse mortality rates as patients over the age of 60.

Patients who underwent transplantation in the advanced stage of MDS had significantly higher rates of both relapse and non-relapse mortality than patients with early-stage MDS. 

Patients on the low-intensity chemotherapy had a higher relapse but lower non-relapse mortality rate than patients on standard chemotherapy.

The researchers found that non-relapse mortality rates decreased significantly if older patients received bone marrow from a related donor.  However, transplants from both related and unrelated donors can be beneficial for patients over 60.

Upon further analysis of the study data, the researchers found that advanced disease stage at transplantation and low-intensity chemotherapy were associated with an increased relapse rate. They also found that advanced disease stage at transplantation and the use of unrelated donor were associated with non-relapse mortality. Advanced disease stage at transplantation was also associated with an inferior 4-year overall survival.

They concluded that disease stage at the time of transplantation was the single most important prognostic variable for the outcome of allogeneic stem cell transplantation.

The authors recommended considering alternative or novel treatment options for elderly patients with advanced disease at transplantation, including agents that modify MDS or interact with the immune system. 

In addition, they suggested future studies should try to find treatments that can prevent relapse, maintaining the post-transplant cure.

For more information, please see the American Journal of Clinical Oncology (abstract).