The MDS Beacon™

A recent study of myelodysplastic syndromes patients who received a donor stem cell transplant showed that the percentage of donor versus patient stem cells in the bone marrow or blood may be able to predict relapse.

Stem cell transplants for myelodysplastic syndromes (MDS) patients are usually performed by giving the patient stem cells from a healthy donor. This is the only known cure for MDS.

Ideally, the patient’s blood-forming stem cells are destroyed and replaced by the donor’s healthy stem cells. The donor’s cells then grow in the patient and produce healthy blood cells.

However, the donor’s stem cells often do not completely replace the patient’s stem cells. The patient’s unhealthy cells continue to grow alongside the donor cells and can cause the disease to relapse.

In this study, Swedish researchers monitored post-transplant MDS patients to determine if remaining patient stem cells could predict relapse in MDS.

They analyzed stem cells in the peripheral blood and in the bone marrow of patients after stem cell transplantation to determine what percent of cells were donor cells versus recipient cells. Having more than five percent of the patient’s own stem cells remaining is known as “mixed chimerism.”

The study included 75 patients who were monitored for a median of 34 months. During that time, 35 percent died from transplant complications. Another 25 percent relapsed after a median of five months. Patients who had chromosomal abnormalities or who received low-dose chemotherapy or radiation to destroy their cells were significantly more likely to relapse. The estimated 5-year overall survival rate was 45 percent.

Of the patients whose stem cell composition was evaluated, 27 percent had mixed chimerism in the peripheral blood and 54 percent had mixed chimerism in the bone marrow at some point after transplantation.

Among the patients who relapsed during the study, 44 percent showed mixed chimerism in the peripheral blood a median of 1 month before relapse and 71 percent showed mixed chimerism in the bone marrow a median of 2.5 months before relapse.

Although mixed chimerism in the bone marrow, as compared to the peripheral blood, was more likely to predict a patient who was about to relapse, it was also more likely to inaccurately predict relapse in patients who did not relapse. This is often referred to as a “false positive” and can lead to unnecessary treatment and emotional stress for the patient.

Therefore, the researchers suggested that physicians should monitor chimerism in both the peripheral blood and bone marrow to predict which patients should begin treatment to prevent relapse.

They concluded that patients without mixed chimerism in the bone marrow were unlikely to relapse and did not require treatment, while mixed chimerism in the peripheral blood “should undoubtedly lead to initiation of treatment owing to the very high risk of relapse.”

For patients with mixed chimerism in the bone marrow but not in the blood, they should begin treatment if there are any clinical signs of relapse, such as low blood cell counts or deformed cells. Otherwise, chimerism should be re-tested in four weeks. Patients with stable chimerism or an increasing amount of their own cells should begin treatment.

Four patients who had mixed chimerism in the peripheral blood received an infusion of additional donor white blood cells to prevent relapse. Three of these patients (75 percent) were still alive at the time of analysis three to seven years after transplantation. In comparison, more than 90 percent of the patients who did not receive pre-emptive donor white blood cells relapsed.

Although the use of pre-emptive donor white blood cells is promising, these results are based on a very small number of patients. The researchers suggested further studies should evaluate pre-emptive treatments, including Vidaza (azacitidine) and Dacogen (decitabine).

For more information, please see the study in Bone Marrow Transplantation (abstract) or Beacon resource articles about stem cell transplantation.