Results from a recent study indicate that collecting more stem cells prior to a myeloma patient’s first transplant may be beneficial for future trans­plants.

Specifically, relapsed patients who received a second transplant with cells that had been collected prior to their first transplant, rather than those collected following the first transplant, had a lower risk of later developing myelodysplastic syndromes (MDS).

MDS is a group of blood disorders marked by ineffective production of blood cells.  MDS often progresses to acute myeloid leukemia, an ag­gres­sive blood cancer in which the body overproduces abnormal white blood cells.

The authors of the current study also found that low platelet counts prior to stem cell collection significantly lowered the chance of a successful stem cell collection.

Based on the results, the investigators recommend that enough stem cells for at least two transplants be collected prior to the first transplant.

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

Background

Autologous stem cell transplantation is commonly used as part of the treatment process for myeloma patients, particularly those who are younger and otherwise healthy. The procedure involves collecting a patient’s own stem cells prior to high-dose chemotherapy. The stem cells are then re-infused back into the patient to replace the healthy cells destroyed by chemotherapy.

Patients can undergo stem cell transplantation soon after initial therapy is completed or wait until relapse.  Some patients even undergo two back-to-back transplants to make sure as much of the cancer is destroyed as possible.

Studies have also shown that patients who undergo stem cell transplantation while in their first remission may benefit from a second transplant after they relapse, particularly if they achieved a long remission after their first transplant (see related Beacon ^[1] news).

However, many patients only collect a sufficient number of stem cells for one transplant, which means that they need to collect more stem cells after their first transplant if they decide to have a second transplant later.

The current study was designed to assess the feasibility of stem cell collection after a prior transplant as well as to identify factors that were associated with unsuccessful stem cell mobilization.

Due to concerns that certain myeloma therapies may increase patients’ risk of developing second cancers ^[2], particularly other blood cancers such as MDS, the current study also investigated whether the use of stem cells collected after transplantation increases a patient’s risk of developing MDS.

Study Design

Investigators from the University of Arkansas for Medical Sciences retrospectively analyzed the records of 221 myeloma patients who had undergone stem cell mobilization after having received at least one prior autologous stem cell transplant at their institution between January 2000 and January 2012. The median patient age was 56 years.

The median time from stem cell mobilization to their last autologous stem cell transplant was 4.2 years. Approximately half of the patients (51 percent) had received one prior transplant, 40 percent had received two, and 9 percent had received three or more.

One quarter of all the patients received the stem cell mobilization agent Mozobil ^[3] (plerixafor) to increase their stem cell collection.

Among those with information available about their chromosomal abnormalities, 64 percent showed no chromosomal abnormalities, 34 percent had chromosomal abnormalities that are associated with multiple myeloma, and 2 percent had abnormalities that are associated with MDS.

Of the 221 patients who underwent stem cell mobilization, 154 subsequently underwent stem cell trans­plan­ta­tion.

These patients were separated into three different groups based on the source of the stem cells used during transplantation: Group 1 (29 percent) used cells collected solely prior to their first transplant; Group 2 (56 percent) used cells collected after their first transplant; and Group 3 (15 percent) used a mix of both pre- and post-transplant stem cells.

Results

Overall, 74 percent of patients were able to collect a sufficient number of stem cells (2.5 million cells/kg) after their first transplant for at least one additional transplant. The patients collected a median of 4.7 million cells/kg within a median of four days.

The researchers found that the timing of the mobilization was associated with the success of the collection.

Specifically, the median number of cells collected before the first transplant (12.5 million cells/kg) was significantly higher than the median number of cells collected after transplantation (4.7 million cells/kg).

Patients who received a mobilization regimen consisting of conventional chemotherapy plus granulocyte colony-stimulating factor (G-CSF) had the highest yield during the collection process (median of 6.8 million cells/kg).

Mozobil improved the stem cell yield in patients who previously were not able to collect enough stem cells for transplantation, from 1.8 million cells/kg to 3.4 million cells/kg.

They researchers found that patients with low platelet counts or who only received G-CSF for mobilization were at the highest risk of not collecting enough stem cells for a second transplant.

When the researchers compared transplant outcomes across the three groups of patients who underwent an additional stem cell transplant, they found that the stem cell source had no significant impact on progression-free and overall survival.

Specifically, the median progression-free survival was 5.8 months and the median overall survival was 14.7 months for all patients and did not differ significantly across the three groups.

However, the researchers found that patients who used stem cells that were collected after a transplant took significantly longer to achieve platelet engraftment, in which the transplanted stem cells make sufficient levels of new platelets.

Among the 154 patients who underwent transplantation during the study period, 8 percent subsequently acquired chromosomal abnormalities associated with MDS and 5 percent developed MDS.

The researchers found that patients who used stem cells that were collected after a transplant were at a noticeably higher risk of acquiring chromosomal abnormalities associated with MDS and eventually developing MDS.

In particular, patients transplanted with stem cells collected after a transplant were more than 10 times more likely to develop chromosomal abnormalities associated with MDS, and 3.5 times more likely to develop MDS itself, than patients transplanted with stem cells collected prior to their first transplant.

Patients who had chromosomal abnormalities linked to MDS before stem cell mobilization, as well as those with low levels of the protein albumin, were also found to be at a higher risk of acquiring chromosomal abnormalities associated with MDS.

For more information, please refer to the study in the journal Leukemia ^[4] (abstract).