Unrelated donor (URD) transplantation has increased rapidly over the last 10 years. More than 700 unrelated donor bone marrow transplants and over 100 unrelated donor cord blood transplants have been performed at the University of Minnesota. Important issues regarding such transplants include:

On this page:

• Availability of Donors
• Outcomes of Unrelated Donor BMT
• Complications: Engraftment
• Complications: Graft vs. Host Disease
• Quality of Life Following Unrelated Donor BMT

Availability of Donors

The use of marrow from unrelated donors has expanded greatly since the first case reports of such procedures in the early 1980s. The development of this therapy has been made possible by the successful establishment and expansion of the National Marrow Donor Program (NMDP).

The NMDP now has more than 6 million potential donors registered, and through international agreements can facilitate access to more than 7 million potential donors worldwide.

Outcomes of BMT

Improvements in tissue typing, both in transplantation procedures and in supportive care of transplant recipients, have led to excellent outcomes in recipients of well-matched transplants. Data from the University of Minnesota and from others show that outcomes equivalent to those seen with matched sibling donor BMT can be achieved in optimal circumstances.

For example, in patients with early phase chronic myelogenous leukemia transplanted within one year of diagnosis with a six antigen matched donor, five-year survival is

• 76 percent in recipients of sibling donor marrow, and
• 70 percent in recipients of unrelated donor marrow (p=0.5)

Complications of BMT: Engraftment

Despite the excellent outcomes seen in optimal circumstances, achieving stable engraftment of marrow from an unrelated donor can present challenges.

An analysis of engraftment of URD bone marrow in 1,384 patients receiving transplants facilitated by the NMDP between November 1991 and August 1995, overall:

• 12 percent had delayed engraftment (or failure to reach an ANC of 5 x 10⁸/L by day 28).
• 5 percent of cases had primary graft failure (failure to achieve an ANC > 5 x 10⁸/L before death or second stem cell infusion in patients surviving at least 28 days).

Factors favoring myeloid engraftment were HLA A, B, and DR serologically matched marrow and higher cell dose.

A platelet count of >50 x 10¹⁰/L was achieved by 54 percent of surviving patients at day 100, 76 percent at one year, and 80 percent at 2 years. Conditional on survival to day 100, survival at two years was 71 percent in those with platelet engraftment at day 30, 62 percent in those engrafting between day 30 and day 100, and 39 percent in those not engrafted at day 100 (p < 0.0001).

Factors favoring platelet engraftment were higher cell dose, DRB1 allele match and recipient CMV seronegativity. Secondary graft failure occurred in 14 percent of cases achieving initial engraftment. Twenty-one percent of those cases survive.

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Complications of BMT: Graft vs. Host Disease (GVHD)

The major biological limitation on the success of unrelated donor BMT is graft versus host disease, in which the immune systems of the donor and recipient clash. While improvements in tissue typing have the potential to reduce GVHD, severe GVHD can still occur in donor and recipient pairs who appear well matched.

Host factors other than HLA-type can influence transplant outcome In a collaborative study with the University of Newcastle upon Tyne, England, we have examined the role of polymorphisms in TNF alpha and IL-10 on acute GVHD after BMT. In this study we demonstrated that recipients homozygous for TNFd allele, d3 were at increased risk of early death after BMT. Additionally, recipients with more dinucleotide repeats at the IL-10 promoter region-1064 polymorphism were at significantly higher risk of grade III-IV GVHD.

Studies in recipients of unrelated donor transplants, performed in collaboration with investigations in Bristol, England, also indicate that TNFd polymorphisms are important in outcomes of BMT and may be used in therapy planning in the future.

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Quality of Life After Unrelated Donor Transplant

To better characterize the outcome of this treatment, we have studied quality of life in patients surviving at least two years after URD tranplant. We have compared these outcomes with patients surviving at least two years after sibling donor transplants.

Thirty-nine patients surviving at least two years after unrelated donor transplant (URD) were identified. A computer program was used to identify sibling (related) donor transplant (RD) recipients surviving the same length of time. These recipients were matched individually with the URD recipients by patient age and by year of transplant (within two years).

Patients (or parents in the case of children under 18 years of age) were contacted by trained interviewers, who used a standardized questionnaire to ask about life after transplantation.

Eighty-three recipients answered questions, 31 URD recipients, and 52 matched RD controls.

Overall, patients in both groups judged their quality of life to be good. Related donor and URD recipients generally judged their quality of life to be good, with only one URD recipient and six RD recipients unable to carry on normal activity (measured as 70 percent or less on the Karnofsky scale).

Only two related donor recipients, and no URD recipients had been limited for more than three months in any of the physical activities mentioned in the questionnaire (sports, carrying groceries, walking uphill, bending and lifting, walking a block and personal hygiene).

Ninety percent of URD recipients and 77 percent of RD recipients fell they were limited in their social activities "a little of the time" or "none of the time," with only two related donor recipients and no unrelated donor recipients reporting being limited "all of the time."

The vast majority of URD (n=29) and RD (n=49) recipients described their general health as "good," "very good" or "excellent," with two URD and two RD recipients rating their health as "poor."

Overall, there were no significant differences between the two groups in their self-reported quality of life, though there was a trend (p=0.09) to a higher global health statement score (a measure of subjective well-being) in the URD recipients. Twenty-eight of the 31 URD recipients were in full-time work or attending school at a level appropriate for age.

Two URD recipients were not working by choice, and only one URD recipient remained unemployed as a consequence of his illness.

We conclude that successful URD BMT is compatible with a good quality of life, similar to that after RD BMT.

Therapy with URD BMT can be curative and also restore patients to normal physical and psychosocial function.

Taken together, these data indicate that BMT from an unrelated donor is a life-saving procedure for many patients and is associated with a high quality of life. While outcomes are excellent in optimal circumstances, further research is needed to improve outcomes for all patients.

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