Post-transplant survival: A study of the gap between ethnic groups

African-American patients who receive stem-cell transplants from tissue-matched family members or unrelated donors have significantly poorer survival rates than Caucasians and other racial and ethnic groups, according to a recent Clinical Research Division study.

In an analysis of data from 1992 to 2000 on more than 3,500 patients with blood cancers treated at Fred Hutchinson Cancer Research Center and the Veterans Affairs Puget Sound Health Care System, researchers found that African Americans had a 70 percent higher mortality rate compared to Caucasians. Asian, Hispanic and Native-American patients fared similarly to Caucasians. For autologous transplants, which do not require a donor and use the patient's own stem cells, survival was comparable among all of the groups.

The results appear in the March issue of the journal Biology of Blood and Marrow Transplantation.

The new findings — the first to look at race as a survival factor for Hutchinson Center patients since a smaller study was published in 1986 — contribute to a growing body of evidence of poorer survival for African Americans compared with Caucasians after cancer diagnosis.

The underlying reasons for the survival differences in this study, which may stem from health-care delivery issues, biological factors or both, did not seem related to Seattle-based transplant care or socioeconomic issues.

"The mortality problem occurred beyond 100 days from transplant, at a time when most patients had been discharged from the Center," said Dr. Marco Mielcarek, lead author on the study. "So this raises the question about whether there is some kind of drop-off of medical care once patients are sent back to their referring physicians."

Post-transplant care is complex and requires long-term monitoring. "Inadequate monitoring for graft-vs.-host disease (GVHD) and the consequent failure to adjust immunosuppressive treatment could be factors that play out longer term," Mielcarek said. "It is unclear why this would be particularly true for African-American patients. It does imply, however, that we need to be very vigilant in trying to keep track of these patients and to develop a better understanding of possible differences in quality of post-transplant care."

The researchers also looked at socioeconomic factors like education, annual household income, employment status before transplant and health-care coverage and did not find that these indicators differed between African American and Caucasians patients treated at the Center. This may be related to the fact that the Hutchinson Center is a highly specialized care center, which may not attract a true cross-section of the population.

Diagnosis-to-transplant delay

There were, however, significant time differences between diagnosis and treatment for African Americans and Caucasians. Transplantation within a year of diagnosis, for example, is known to be beneficial for patients with chronic myeloid leukemia (CML).

"Comparing African Americans vs. Caucasians with CML, it took twice as long for the sibling-donor transplants — almost one year compared to six months — and three times as long for the unrelated donor transplants — three years vs. one year, for African Americans to come to transplant," Mielcarek said.

The researchers speculate that the diagnosis-to-transplant time delay for African Americans may be due to patient, physician and/or cultural factors like infrequent doctor visits, medical-insurance issues, or skepticism about the medical system. Whatever the reason, the delay leads to more advanced disease in African Americans.

The study showed that the lower survival rate among African Americans after unrelated-donor transplant was largely related to severe GVHD, which is attributed in part to the difficulty in finding suitable unrelated donors. GVHD is a sometimes-serious complication that occurs when donor cells attack healthy tissue in the patient. It is more likely to occur when tissue type between donor and recipient is imperfectly matched. According to the National Marrow Donor Program, the likelihood of finding an unrelated-donor match is 80 percent for Caucasians and only 30 percent for African Americans. This can be partly attributed to the fact that fewer African Americans have registered as potential donors. In general, a smaller donor pool makes finding a match for diverse populations more challenging. But even among patients with tissue-matched family donors, 37 percent of African-American patients experienced severe GVHD versus 21 percent of Caucasians.

Transplant center collaboration

"Certain drugs used for prophylaxis against and/or treatment of GVHD may be less effective in African Americans," said Dr. Beverly Torok-Storb, one of the study co-authors. "There's evidence in the literature of ethnic differences in drug metabolism and immune responsiveness. Certain immune-response genes or the way drugs are metabolized can have a huge impact on outcomes."

Mielcarek cautions that the Hutchinson Center's study may not reflect the experience of other transplant centers, in part because of the Center's low number of non-Caucasian patients. Studies conducted by the International Bone Marrow Transplant Registry looking at multiple transplant centers found only a moderately increased mortality risk among African Americans compared to Caucasians, and poorer outcomes for Hispanic patients than Caucasians.

Though it is difficult to pinpoint clear answers in retrospective studies related to differences in outcomes, Mielcarek hopes to pursue further research in this area. "I would like to collaborate with other transplant centers that have a higher representation of non-Caucasian patients," he said. "We would like to understand why African Americans are doing worse and what can be improved to equalize racial outcomes."

Center co-authors included Drs. Ted Gooley, Paul Martin, Thomas Chauncey and Rainer Storb. Dr. Bessie Young of the University of Washington also contributed.