Note: This abstract was presented at the 2012 ASCO annual meeting in June 2012. The full abstract may be reviewed on the ASCO Annual Meeting Web site. Use the abstract number to access the full report.
Abstract # 6529
Myelodysplastic syndrome (MDS) is often a disease of advanced age with a majority of patients over the age of 65 years at the time of their diagnosis. Although some patients with MDS enjoy a long period of time with minimal symptoms or change in their disease, some patients experience a rapid progression to either bone marrow failure or acute myeloid leukemia (AML). For these patients, allogeneic stem cell transplantation is the only treatment that has demonstrated the ability to cure their disease. The term “allogeneic” refers to a transplant from a donor who is someone other than himself or herself; rather the donor is someone with a different immune system such as a sibling or an unrelated person. This type of transplant works by supplying the patient with effective blood-forming cells, improving their blood counts. Furthermore, the transplant provides a new immune system that can seek out and eliminate the patient’s MDS cells.
Transplantation is a rigorous process for any patient, but is especially challenging for the older patient. Although there is no age limit for transplantation, increasing age is frequently accompanied by decreasing function of organs such as the kidney, heart, and lungs, which can affect the success of transplantation. Since the time it was pioneered, much effort has been focused on reducing the toxicity experience due to the transplantation process. As it has become more tolerable, the number of allogeneic transplants in older patients has increased. According to the Center for International Blood and Marrow Transplant Research, 36% of patients who received an allogeneic transplant between the years 2005 and 2009 were older than 50 years, and 13% were over the age of 60 years.
The first step of any treatment plan involves a discussion between the health-care provider and patient. In addition to a patient’s unique values and circumstances, careful consideration must be given to whether the treatment would be actually be helping or potentially harming the patient. The concept of “help over harm” is central to the counseling and decision-making process of any individualized treatment plan, particularly when considering transplantation. With an increasing number of older patients undergoing transplantation for the treatment of MDS, the authors of this study sought to better understand the risks and benefits of transplantation in older patients.
Drs. Conter, de Lima, and their colleagues at the M. D. Anderson Cancer Center in Houston, Texas, summarized their experience in transplanting 182 patients over the age of 64 years with either MDS or more advanced disease (AML). The average age of the patients included was 67 years, with the oldest being 79. The primary focus of the study was to look at the effect of a transplant in older patients. The researchers found that at three years after transplantation, one in five patients had died as a result of the toxicities of transplantation. The patients in the study tended to have very aggressive disease that was resistant to chemotherapy, with only three in ten patients in remission (without evidence of disease) at the time of transplant. As a consequence, half of the patients experienced relapse after transplantation. However, the patients who went into transplant in remission were less likely to relapse after transplant as those with active disease prior to transplant. In looking specifically at the patients over the age of 69 years, there was no significant difference in survival after transplantation as compared to the patients between the ages of 64 and 69 years.
This study is a retrospective study that looks backwards over patients who have already been treated. It is important to understand when reading this study that there are some limitations to this research approach. In particular, the results can be inaccurate because there were no consistent rules determining which patients would undergo transplant; this is known as selection bias. Another point to keep in mind when looking at the results of this study is that the data was collected from patients who were treated with a transplant as far back as 1996. As mentioned before, over the past few decades, the transplantation process has steadily improved. Therefore, a patient transplanted in 1996 may have had a different outcome than a similar patient transplanted in 2012.
Despite these limitations, this study highlights several important points. One is that in the older patient, allogeneic stem cell transplantation is feasible with patients experiencing MDS-free survival despite an aggressive disease. This study also emphasizes that the less active disease a patient has prior to transplantation the more likely that patient is to experience long-term remission. Lastly, continued efforts and innovations are needed to reduce the risk of relapse and make transplantation even more tolerable for the older patient.