The MDS Beacon™

Researchers in Germany showed that myelodysplastic syndromes patients have significantly higher rates of overall and relapse-free survival and lower rates of side effects when treated with a treosulfan-based chemotherapy than with a standard total body irradiation-based therapy before stem cell transplantation.

Stem cell transplants are currently the only curative treatment available for myelodysplastic syndromes (MDS). They require patients to be treated with chemotherapy or radiation to prepare their bodies for the procedure. However, these initial treatments are associated with severe side effects.

The majority of MDS patients are older people who commonly have other diseases in addition to MDS. Their age and the additional diseases can make older MDS patients ineligible for stem cell transplants since they are less likely to be able to tolerate the severe side effects associated with these regimens.

Researchers have been working to find less toxic alternatives as initial treatments prior to stem cell transplants.

Reduced-dose initial treatments have been introduced to allow older patients to undergo stem cell transplants. However, the reduced-dose treatments have been associated with an increased risk of relapse after stem cell transplantation.

The German researchers therefore investigated a treosulfan-based treatment as an alternative initial therapy for MDS patients prior to stem cell transplantation, since it shows high activity in other cancers and is associated with few side effects.

“The aim is to maintain the high anti-MDS activity without the negative toxic side effects of the standard-dose regimen,” said Dr. Jochen Casper, the study’s lead author in an email to The MDS Beacon.

Treosulfan is currently not approved in the United States. However, it is approved in Germany under the brand name Ovastat for the treatment of ovarian cancer.

In their study, Dr. Casper and his colleagues retrospectively analyzed data of 48 MDS patients who received stem cell transplants from a matched donor. The median age of the patients was 47.5 years, and 33 percent of the patients had high-risk disease.

Of the 48 patients, 29 (60 percent) received a standard total body irradiation-based therapy as initial treatment prior to stem cell transplantation. Nineteen patients (40 percent) were treated with a treosulfan-based therapy.

The researchers found that relapse was less common in patients who received the treosulfan-based initial therapy. One year after transplant, none of the patients who received the treosulfan-based therapy had relapsed compared to 14 percent of patients who received the standard initial treatment. Three years after transplant, 5 percent of patients who received treosulfan-based therapy had relapsed compared to 34 percent of patients on standard initial therapy.

The estimated three-year overall survival rate for patients in the treosulfan group was greater (57 percent) than for patients in the standard therapy group (34 percent).

Relapse-free survival after three years was significantly greater for patients on treosulfan-based therapy (57 percent) than for patients on standard initial therapy (31 percent).

For patients with an increased risk of severe side effects due to additional diseases, the difference in relapse-free survival was even more significant: 54 percent of patients who received the treosulfan-based therapy were still alive compared to 11 percent of patients who received the standard initial therapy.

The researchers also found that patients who received the treosulfan-based therapy developed fewer side effects than patients who received the standard initial therapy.

After the stem cell transplant, 21 percent of patients who received the standard initial therapy developed severe mucositis (ulceration of the digestive tract mucus membranes) compared to 11 percent of patients who received the treosulfan-based therapy.

Graft-versus-host disease, a common side effect of stem cell transplants, was also more common in patients who received the standard initial therapy (72.4 percent for acute disease and 72 percent for chronic disease) than in patients who received the treosulfan-based therapy (58 percent and 56 percent, respectively).

Dr. Casper and his colleagues concluded that treosulfan-based therapy shows high activity in MDS patients and is associated with fewer side effects than standard initial therapy and may therefore be a viable alternative to standard initial therapies prior to stem cell transplants.

They suggested larger studies be conducted to validate their findings.

For more information, please see the study in Bone Marrow Transplantation (abstract).