New research from Japan indicates that low levels of the blood protein ferritin are associated with better outcomes in myelodysplastic syndromes (MDS) patients who undergo stem cell transplantation.

“In both [standard- and high-risk] MDS, elevated ferritin has a negative effect on the outcomes of transplantation,” said study author Dr. Takayoshi Tachibana of the Yokohama City University Medical Center in Yokohama, Japan.

Dr. Tachibana pointed out that patients with elevated ferritin levels should nevertheless undergo stem cell transplantation because “We think transplantation is the most promising therapy [for MDS patients].”

Instead he suggested that “The mechanism or nature of ferritin must be explored and a novel [approach] for reducing pre-transplant ferritin must be devised.”

Patients with MDS frequently have low red blood cell counts, a condition known as anemia. Red blood cell trans­fusions can be used to increase the cell counts. However, receiving repeated red blood cell trans­fusions can lead to excess iron in the blood, also known as iron overload.

Ferritin is an iron storage protein that can be used as an indicator for the amount of iron in a patient’s blood. “In most MDS patients, elevated ferritin [in the blood] is related to red blood cell trans­fusion,” explained Dr. Tachibana.

According to the Japanese researchers, elevated ferritin levels prior to stem cell transplantation have been shown to have a negative impact on outcomes in patients with higher-risk MDS.

“Elevated ferritin [in the blood] seems to be associated with a higher risk of complication after transplantation,” said Dr. Tachibana.

However, little is known about the effects of ferritin levels in lower-risk patients who undergo a stem cell transplant.

In this study, the researchers retrospectively analyzed data from 261 patients with different blood cancers of varying severity to determine the impact of pre-transplant ferritin levels on outcomes.

Of the 261 patients included in the analysis, 36 (14 percent) had MDS. The rest of the patients had either acute myeloid leukemia (AML) or acute lymphoid leukemia (ALL). (Unless otherwise specified, all results discussed in the rest of this article will be for patients with any of the three blood cancers covered by the study — not just for patients with MDS.)

The median age of the patients in the study was 43. All patients were treated at three hospitals in Japan between January 2000 and December 2008.

For their analyses, the authors of the study divided patients into two groups based on their disease severity: standard-risk and high-risk.

One quarter of the 36 MDS patients included in the analysis were categorized as having standard-risk disease, and three quarters were categorized as having high-risk disease.

Ferritin levels were measured one month before the patients began preparative chemotherapy for their stem cell transplants.

Patients were placed in the low ferritin group if they had less than 1,000 ng/mL ferritin in their blood or in the high ferritin group if they had 1,000 ng/mL or more ferritin in their blood.

The median ferritin level was 970 ng/mL. The researchers found that high-risk patients were significantly more likely to have high ferritin levels.

After five years, more patients with standard-risk disease were alive (60 percent) than patients with high-risk disease (25 percent).

Similarly, more patients in the low ferritin group were alive (54 percent) than patients in the high ferritin group (36 percent) after five years.

When the researchers divided the patients by disease-risk groups, they found that low ferritin levels had a positive impact on outcomes in both standard-risk and high-risk patients.

Standard-risk patients with low ferritin levels had significantly better overall survival after five years (64 percent) compared to standard-risk patients with high ferritin levels (54 percent).

In the high-risk group, patients with low ferritin levels also had significantly better overall survival compared to patients with high ferritin levels (35 percent versus 16 percent).

High-risk patients with low ferritin levels were also significantly less likely to experience disease relapse (50 percent) than high-risk patients with high ferritin levels (72 percent).

The impact of ferritin levels on survival remained statistically significant when the researchers controlled for a number of patient characteristics that also could affect survival.

In addition, the effect of ferritin levels stayed significant even when the analysis focused only on the 36 patients in the study who had MDS.

As the researchers explain in their article, “When subgroup analysis was done for the underlying diseases, pre-transplant [ferritin level] was a significant predictor of the outcome for patients with AML or MDS …”

Acute graft-versus-host disease, a transplant-related complication that develops within 100 days after transplantation, occurred in 107 of the 261 patients patients. The development of acute graft-versus-host disease was not found to be related to a patient’s ferritin levels.

Patients who developed chronic graft-versus-host disease, which occurs more than 100 days post-transplant, had better overall five-year survival (67 percent versus 51 percent) than patients who did not have chronic graft-versus-host disease.

A total of 141 patients died during the study’s five years follow-up time; 43 percent died of disease relapse or disease progression and 57 percent died of other causes, including infection, organ failure, graft-versus-host disease, pneumonia, and transplant rejection or failure.

For more information, please see the study in the journal Leukemia & Lymphoma (abstract).

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