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Young, Unrelated Donors May Provide Better Transplant Outcomes In Older MDS Patients Than Sibling Donors

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Published: May 1, 2013 2:19 pm
Young, Unrelated Donors May Provide Better Transplant Outcomes In Older MDS Patients Than Sibling Donors

Results of a recent European study indicate that the age of matched unre­lated donors affects stem cell transplant outcomes in older myelodys­plas­tic syn­dromes patients.

Specifically, the researchers found that myelodysplastic syndromes (MDS) patients with younger, matched unrelated donors had lower relapse rates and higher overall survival rates than patients with either matched sibling donors or older, matched unrelated donors.

Younger donors were defined as those under the age of 30 years.

“The data suggest that if there is a completely matched, young (under 30 years), unrelated donor for an older MDS patient (over 55 years), the re­sults are better than using an HLA-identical sibling (who is usually as old as the patient),” said the study’s lead investigator Dr. Nicolaus Kröger from the University Hospital in Hamburg-Eppendorf, Germany.

However, Dr. Kröger emphasized to The Beacon that the better results with unrelated donors were only observed with younger unrelated donors.

”If the unrelated donor is older (for example, 45 or 50 years old), then the results are less encouraging and even worse than after HLA-identical sibling [stem cell transplantation],” he added.

Dr. Kröger and his colleagues also point out in their article that the study only included a relatively small number of patients who received transplants from young unrelated donors.  Thus, their findings need to be confirmed in a larger number of patients.

If the study results are confirmed in a larger group of patients, the researchers state that the finding could impact how searches are carried out for stem cell donors.

Currently, the initial search for a donor usually focuses on potential sibling donors.  If, however, the results of the current study are confirmed, it might be better to broaden searches from the outset to include both sibling and unrelated donors.

Background

The only potential cure for MDS is donor (allogeneic) stem cell transplantation. During the procedure, the patient receives chemotherapy and/or radiation treatment, which destroy the patient’s diseased stem cells as well as their healthy ones. The patient’s cells are then replaced by stem cells from a healthy donor.

One major risk of donor stem cell transplantation is graft-versus-host disease (GVHD), which occurs when donor immune cells recognize the patient’s healthy cells as foreign and attack them.

Immune cells determine whether other cells are foreign based on HLA proteins present on the surface of cells.  If donor and recipient cells have matched HLA proteins, they are less likely to consider each other as foreign.

The chances of finding an HLA-matched donor are higher among siblings of a patient than potential unrelated donors.

Another factor that affects transplantation outcome is the age of the donor. Previous research has shown that younger donor age is associated with better transplant outcome.

However, it is difficult to assess the effect of donor age for sibling donors because a sibling donor is usually close in age to the patient.

In the current study, the researchers sought to determine whether a young HLA-matched unrelated donor provides equal, or better, transplant outcomes as compared to an HLA-identical sibling donor in MDS patients who are over 50 years old.

Study Design

The researchers retrospectively analyzed data from 719 patients who underwent donor stem cell transplantation in Europe between 1999 and 2008.

All patients had advanced MDS and were older than 50 years. The median patient age was 58 years.

Patients were considered to have “advanced” MDS if they had refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, secondary acute myelogenous leukemia, or chronic myelomonocytic leukemia.

Overall, 77 percent of patients had HLA-identical sibling donors (median age of 56) and 23 percent had HLA-matched unrelated donors.

Results

To define the impact of age on transplantation outcome, the researchers divided patients into three groups based on donor type and donor age: patients with matched unrelated donors younger than 30 years old (59 patients), patients with donors with an age of 30 or more (105 patients), and patients with matched sibling donors (555 patients).

The HLA-identical sibling group was not divided by age since no difference in outcome was observed if the sibling donor was less than or more than 50 years old.

The researchers found that donor age significantly impacted patient survival, even after controlling for other factors which might also affect survival.

The five-year overall survival rate was 40 percent in patients with young, unrelated donors, compared to 33 percent for patients with sibling donors, and 24 percent for patients with older, unrelated donors.

Other factors associated with better survival at five years included a diagnosis of refractory anemia with excess blasts, normal chromosomal abnormalities, transplantation using stem cells from the circulating blood rather than bone marrow, and a complete response at the time of transplantation.

In addition, the researchers observed a trend for a reduced risk of relapse at three years following transplantation in patients with young, unrelated donors compared to patients with sibling donors (32 percent versus 38 percent, respectively).

Patients with young, unrelated donors also showed a trend for a lower non-relapse-related death rate one year following transplantation, compared to patients with sibling donors (16 percent versus 27 percent, respectively)

The rate of acute GVHD, which develops within 100 days following transplantation, did not differ significantly between patients with young, unrelated donors and patients with sibling donors (30 percent versus 25 percent, respectively).

The authors of the study note that there is not yet a widely accepted explanation for why stem cells from younger donors lead to better transplant outcomes.

One theory is that older donors may have, in comparison to younger donors, a higher share of immune system cells designed to protect against threats the body already has experienced in the past.

For a transplant to be effective, however, it may be better if donated immune system cells are oriented to more general protection of the body.

For more information about the European study, please see the study in the journal Leukemia (abstract).

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