The MDS Beacon™

Dr. Sergio Giralt, Professor at the Stem Cell Tranplantation Department at the University of Texas M.D. Anderson Cancer Center in Houston, suggests that the development of reduced-intensity drug regimens and other novel transplantation technologies permit the consideration of stem cell transplantation for myelodysplastic syndromes (MDS) patients who are older than 55 years. His findings were published in the September 2009 supplemental issue of Clinical Lymphoma, Myeloma & Leukemia.

The most common form of bone marrow transplantation for MDS patients is allogeneic stem cell transplantation, also called allotransplantation. This procedure involves destroying patient bone marrow by chemotherapy or radiation, then replacing it with bone marrow from a matched donor. It is the only curative treatment currently available, but it does not guarantee full recovery.

Until recently, the risks of allogeneic stem cell transplants were considered too high for patients older than 50 years of age. Concerns about the inability of elderly transplant recipients to effectively fight graft vs. host disease resulted in limited recommendations for elderly MDS patients. Graft vs. host disease is a post-transplant threat caused by functional immune cells in the transplanted marrow. These immune cells view the recipient’s cells as foreign and attack them.

Due to the association between older age and a higher risk for graft vs. host disease, transplants have been largely recommended for younger patients only.

However, changes in transplantation technology are leading to better overall survival rates for elderly patients following stem cell transplantation.

Dr. Giralt states that reduced-intensity treatments involving lower doses of pre-transplant chemotherapy and radiation are improving survival rates in the elderly population. In addition, donor matching technology and supportive care have been developed to prevent a life-threatening immune response and delay relapse.

As a result, the number of older patients considered or recommended for transplants is increasing. From 1995 to 1997, only 23 percent of patients who reported to bone marrow transplant registries were older than 50 years of age. The number of patients who were reported to be over 50 increased to 35 percent from 2000 to 2006.

Dr. Giralt reviewed nine different studies investigating the survival and non-relapse mortality rates of elderly MDS patients who received reduced-intensity drug regimens before bone marrow transplants. The patients’ median age ranged from 52 to 60 years.

The results of these studies show that a large percentage of older patients survive or do not worsen when evaluated three years after treatment..

The average three-year survival rates ranged from 30 to 50 percent, while two to three-year mortality rates spanned from 10 to 30 percent.

Patients who received allogeneic stem cell transplants in first remission had even higher survival rates. At the three-year mark, these patients showed a 60 percent survival rate. Less than 15 percent had died from causes not related to relapse.

Though chemotherapy dose intensity varied significantly in the clinical trials he reviewed, Dr. Giralt did not make conclusions about an optimal dose. However, the dose is important for post-transplant disease control. A study reporting the transplant outcomes of 722 patients gives supporting evidence for the benefit of treating elderly MDS and acute myelogenous leukemia (AML) patients with reduced-intensity chemotherapy. While the mortality rate for patients who received normal-dose treatments was 32 percent, the proportion decreased to 18 percent for patients who underwent reduced-intensity treatments.

Dr. Giralt concludes that elderly patients should be offered transplantation options soon after diagnosis, based on the high risk of the disease getting worse quickly or progressing to AML and given the improved two or three-year survival rates for older patients.

He states that overcoming disease resistance and long-term administration of reduced-intensity follow-up regimens are important priorities in stem cell transplants for MDS patients. He adds that future clinical trials will investigate combination therapies and further develop transplant technologies to extend lives.

For more information, please see the article in Clinical Lymphoma, Myeloma & Leukemia (pdf).