A recent retrospective study by researchers at the M.D. Anderson Cancer Center in Houston shows that multiple myeloma patients with the chro­mosomal abnor­mality t(11;14) have better outcomes after stem cell trans­plan­ta­tion than patients with high-risk chromosomal abnormalities.

However, the progression-free and overall survival of patients with the t(11;14) abnormality were not as good as those of patients with normal chromosomal profiles.

According to the study investigators, these findings are consistent with other studies that have shown that patients with any chromosomal ab­nor­mality have worse outcomes than those with normal chromosomal pro­files.

Also consistent with previous research, the M.D. Anderson study found that a high beta-2 microglobulin level and relapsed disease at the time of transplantation are independently associated with poorer survival out­comes.

The study investigators argue that their findings may be useful for more accurately classifying patients into different prognostic groups.

Dr. Rafael Fonseca from the Mayo Clinic in Arizona, who was not involved in the study, advised that the results of the new study should be interpreted cautiously.  He pointed out that the study had several limi­ta­tions.

For example, the share of patients carrying the t(11;14) chromosomal abnormality was very small, and one-third of patients with the t(11;14) abnormality in this study also had high-risk chromosomal abnormalities. “I worry now that folks who have t(11;14) detected by FISH only will think they have a more aggressive multiple myeloma,” explained Dr. Fonseca.

Background

Chromosomes are the genetic material inside cells, and chromosomal abnormalities are changes in the number or structure of the chromosomes in cells.  These changes can include deletions, insertions or gains, duplications, or movement of chromosomal regions.

Multiple myeloma patients frequently have chromosomal abnormalities in their myeloma cells.  The pres­ence or absence of such abnormalities is often a signal of how well a patient's myeloma will respond to treat­ment.

As a result, chromosomal analysis is routinely performed on multiple myeloma patients.  Two forms of chro­mo­somal analysis are commonly used: conventional cytogenetic (chromosomal) analysis, and fluo­res­cence in situ hybridization (FISH), which is newer and more sensitive.

A number of chromosomal abnormalities detected by conventional cytogenetic analysis and FISH are con­sidered signs that a myeloma patient has high-risk (treatment-resistant) disease. Approximately 15 percent of myeloma patients are estimated to have high-risk disease, and their median overall survival of two to three years is noticeably lower than the survival of patients in other risk groups.

According to the authors of the current study, myeloma patients with the chromosomal abnormality t(11;14) are not generally classified as having higher-risk disease.  One previous study found that the abnormality has a somewhat negative impact on treatment outcomes; two studies have found a somewhat positive impact of the abnormality; and two other other studies have found no meaningful impact.

The authors note, however, that few studies have investigated the impact of the t(11;14) abnormality in patients who have undergone autologous (own) stem cell transplantation.

The authors of the current study therefore sought to determine the impact of the abnormality on treatment outcomes in multiple myeloma patients who have had a transplant.

Study Design

The researchers retrospectively analyzed the records of 993 multiple myeloma patients who underwent an autologous stem cell transplant at M.D. Anderson between 2000 and 2010.

They divided the patients into three groups based on their chromosomal profiles: 869 of the patients had chromosomal profiles that were considered normal, 27 had translocation t(11;14), and 97 had what the researchers defined as high-risk chromosomal abnormalities (but without the t(11;14) abnormality). Nine patients of the 27 patients with t(11;14) had concurrent high-risk chromosomal abnormalities.

The researchers classified patients as having high-risk abnormalities if, based on conventional cyto­ge­net­ics, they had either a deletion of the short arm on chromosome 13 (del13q), absence of chromosome 13 (monosomy 13), or 44 or fewer chromosomes overall (hypodiploidy).

Patients also were classified as high-risk if, based on either conventional cytogenetics or FISH, they had a deletion of a segment on the short arm of chromosome 17 (del17p13) or if they had one of the follow­ing translocations (switches in parts of different chromosomes): t(4;14), t(14;16), and t(14;20).

At the time of transplantation, 15 percent of patients had relapsed disease (13 percent of the normal group, 7 percent of the t(11;14) group, and 37 percent of the high-risk group).

The median follow-up time was 37 months.

Study Results

The median progression-free survival from the time of transplantation was highest for patients with normal chromosomal profiles, at 33 months, compared to 23 months for patients with t(11;14) and 9.7 months for patients with high-risk chromosomal abnormalities.

Click on image to view a larger version of it.

Likewise, the median overall survival from time of trans­plan­ta­tion was highest for the normal group at 87 months, compared to 51 months for the t(11;14) group and 21 months for the high-risk group (see overall sur­vi­val curves in the figure to the right).

The results also showed that the presence of t(11;14), high-risk abnormalities (without t(11;14)), and re­lapsed disease at time of transplantation were independently associated with shorter progression free-survival and shorter overall survival.

In addition, a beta-2 microglobulin level of 3.5 mg/L or higher at the time of transplantation was associated with shorter overall survival. Beta-2 microglobulin is a protein commonly found on the surface of cells, and its levels are generally elevated in multiple myeloma.

For more information, please refer to the study in the journal Biology of Blood and Marrow Transplantation (abstract).