Donor stem cell transplantation may be an effective treatment for myeloma patients with certain chromosomal abnormalities, according to a recent retrospective analysis of patient data conducted in France.

In particular, the analysis showed that patients with a high risk for poor prognosis - those with the chromosomal abnormalities del(17p), t(4;14), or t(14;16) - achieved similar outcomes after receiving a donor stem cell transplant as patients without these abnormalities.

“Our retrospective analysis indicates for the first time that [donor stem cell transplantation] might overcome the poor impact of del(17p),” said the study’s lead author Dr. Damien Roos-Weil of the Pitié-Salpêtrière Hospital in Paris, France.

“These data could plead for [donor stem cell transplantation] in del(17) and t(4;14) myeloma patients,” he added.

The authors, however, noted that prospective studies are needed to better assess the efficacy of donor stem cell transplantation for high-risk patients.

“The best way to better evaluate the impact of chromosomal abnormalities and to avoid the bias of retrospective analysis is to design a prospective randomized study,” explained Dr. Roos-Weil.

In addition, the authors recommended clinical trials investigating the role of donor stem cell transplantation when administered in conjunction with novel agents.

Past studies have shown that chromosomal abnormalities, which result from changes in chromosome structure, may render myeloma patients less responsive to certain therapies.

The most common myeloma-related chromosomal abnormalities include deletions, translocations, and additions. A deletion, abbreviated “del,” occurs when part of a chromosome is missing. A translocation, abbreviated “t,” occurs when part of a chromosome is transferred to another, or when two chromosomes exchange parts. An addition, abbreviated “+,” occurs when a chromosome contains an extra part.

Historically, patients with a partial deletion of the long arm (q) of chromosome 13 or the short arm (p) of chromosome 17, del(13q) and del(17p), respectively, have experienced poor outcomes when treated with chemotherapy or autologous stem cell transplantation. Patients with a translocation between chromosomes 4 and 14, t(4;14), have also experienced poor treatment results.

A previous study has shown that while agents such as Revlimid (lenalidomide) may overcome the adverse prognoses of patients with del(13q) or t(4;14), they are not effective for patients with del(17p) (see related Beacon news).

According to the study authors, however, there is limited data regarding the impact of chromosomal abnormalities on donor stem cell transplantation, in which a patient receives stem cells from another individual.

“The role of [donor stem cell transplantation] in myeloma is still heavily debated,” said Dr. Roos-Weil. “It is of great importance to identify a potential subgroup of patients that might benefit [from it].”

Due to a high rate of complications following donor stem cell transplantation, the procedure is generally not recommended for low-risk myeloma patients who have a number of treatment options.  The role of donor stem cell transplantation for treating high-risk patients is still being investigated (see related Beacon news).

In order to shed light on this issue, the French researchers retrospectively analyzed the medical records of 143 patients who received a donor stem cell transplant between 1999 and 2008.

The median age of the patients included in the analysis was 51 years. They had received a median of two therapies before undergoing donor stem cell transplantation. All patients also had received at least one prior autologous stem cell transplant.

All patients were screened for at least two of the three major chromosomal abnormalities: del(13q), del(17p), and t(4;14).

Of the 143 patients included in the analysis, 74 percent had at least one of the following chromosomal abnormalities: del(13q) (59 percent), del(17p) (25 percent), t(4;14) (25 percent), t(11;14) (24 percent), and t(14;16) (4 percent).

The researchers found that the percentage of patients with either del(13q), del(17p), t(4;14), or t(11;14) who achieved at least a very good partial response was comparable to that of patients who did not possess each respective abnormality.

In addition, the progression-free survival, overall survival, and relapse rates after three years for patients with each chromosomal abnormality were comparable to patients without each respective abnormality.

The researchers did not analyze the data for patients with t(14;16) because the number of patients was too small. 

The researchers also divided the patients into a high-risk and a non-high-risk group, in order to assess the impact of the high-risk chromosomal abnormalities del(17p), t(4;14), and t(14;16).

The high-risk group included patients with at least one of these chromosomal abnormalities, and the non-high-risk group included patients without any of these abnormalities.

They found that the progression-free survival, overall survival, and relapse rates after three years for patients in the high-risk group (30 percent, 45 percent, and 53 percent, respectively) were comparable to that of patients in the non-high-risk group (17 percent, 39 percent, and 75 percent, respectively). 

Ninety percent of patients experienced graft-versus-host disease (GVHD), a condition in which white blood cells from the donor attack cells in the recipient. Acute GVHD, which develops within 100 days after the transplant, occurred in 47 percent of patients. Chronic GVHD, which develops more than 100 days after the transplant, occurred in 43 percent of patients.

Twenty-five percent of patients died within two years of transplantation from treatment-related causes.

Six percent of patients were not evaluable for results because of early death.

For more information, please see the article in the journal Haematologica (pdf).