Findings from a recent retrospective study conducted at the Mayo Clinic in­di­cate that chromo­som­al abnormalities may influence which symptoms a multiple myeloma patient has at diagnosis.

For instance, the researchers found that newly diagnosed myeloma pa­tients with the chromo­some 14 translocation t(14;16) are more likely to have kidney damage, while patients with extra chromo­somes are more likely to have bone disease or anemia.

They also found that patients with t(14;16) who did not have kidney dam­age survived significantly longer (a median of 44 months) compared to those with kidney damage (9 months).  The researchers state that the high rate of kidney damage in patients with t(14;16), and the negative im­pact that kidney damage has on survival, may explain why patients with t(14;16) often have short survival.

Based on their results, the investigators conclude that the presence of chromo­som­al abnormalities not only plays a role in the prognosis of multiple myeloma patients, but also in the symptoms present at a patient's diagnosis.

They add that their findings may also support the notion that multiple myeloma should be considered a col­lec­tion of genetically diverse disorders, rather than a single disease entity.

However, they state that further studies are needed to confirm their findings.

Background

Chromosomal abnormalities are the result of structural changes in the chromo­somes of a patient’s mye­lo­ma cells.

These changes may occur through deletions, insertions, duplications, or movement of chromo­som­al re­gions.  Some patients also have missing or extra copies of entire chromo­somes.

Previous studies have shown that certain chromo­som­al abnormalities, in particular t(4;14) and del(17p), negatively affect the survival of myeloma patients who have these abnormalities (see related Beacon ^[1] news). Patients with these chromo­som­al abnormalities are considered to have high-risk myeloma ^[2] (see related Beacon ^[3] news).

However, according to the investigators, little is known about the relationship between these chromo­som­al abnormalities and the symp­toms – such as elevated calcium levels, kidney damage, anemia, or bone le­sions – that myeloma patients show at the time of diagnosis.

Therefore, the researchers decided to investigate the relationship between chromo­som­al abnormalities and myeloma-related symptoms at diagnosis.

Study Design

The investigators retrospectively analyzed the records of 484 newly diagnosed myeloma patients who were seen at the Mayo Clinic within 90 days of their diagnosis between January 2004 and December 2009.

All patients had chromo­som­al analysis performed via a technique known as fluorescent in situ hybridization ^[4] (FISH) either within one year preceding their myeloma diagnosis or within six months following diagnosis.

The researchers categorized the patients into four groups depending on the myeloma-related symptom or symptoms they showed at diagnosis: bone disease (34 percent of patients), anemia (15 percent), kidney failure (8 percent), and a combination of these symptoms (43 percent).

They explained that elevated calcium levels were not considered as a separate category because patients with elevated calcium levels almost always also have bone disease; these patients were therefore cate­go­rized into the bone disease group.

Study Results

Among the patients included in the analysis, 42 percent had trisomies (an extra copy of one or more chro­mosomes), 30 percent had chromo­some 14 translocations (rearrangement of a part of chromo­some 14 with part of another chromo­some, such as t(4;14) or t(11;14)), 15 percent had both, and 13 percent had no chromo­som­al abnormalities.

The researchers found that trisomies were more common in patients with anemia (45 percent), patients with bone disease (42 percent), and a combination of symptoms (44 percent), compared to patients with kidney failure (19 percent).

Chromosome 14 translocations, on the other hand, were much more common in patients with kidney failure (51 percent), compared to patients with a combination of symptoms (31 percent), patients with anemia (28 percent), and patients with bone disease (25 percent).

In particular, the t(14;16) translocation was present in only 5 percent of all the patients in the trial, but it was detected in nearly 14 percent of the patients with kidney failure.

When the researchers analyzed the data by the presence of individual chromo­som­al abnormalities, they found that 25 percent of patients with the t(14;16) translocation had kidney failure. Patients with t(14;16) and kidney failure had significantly shorter median overall survival (9 months) than patients with t(14;16) who did not have kidney failure (44 months).

As a result, the researchers contend that the reason why patients with the t(14;16) translocation have poor outcomes is because of the high share of patients with kidney failure. However, since a very small number of patients had this translocation in the study, they recommend a larger study comparing the presence of this translocation with the rate of kidney failure at diagnosis.

On the other hand, the share of patients with bone disease was high among patients with the translocation t(11;14) (35 percent).

Overall, patients with bone disease had a significantly longer median overall survival (59 months), com­pared to patients with kidney failure (42 months).  The researchers explained that patients with bone dis­ease may have longer survival because they may typically be diagnosed earlier in the course of their dis­ease.

For more information, please refer to the study in the journal Leukemia ^[5] (abstract).