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Experts Recommend Against Donor Stem Cell Transplantation For Multiple Myeloma Patients Until Safety And Efficacy Is Improved

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Published: Sep 13, 2010 3:11 pm

The International Myeloma Working Group, a group of leading myeloma specialists, recently published a report establishing recommendations regarding the use of donor stem cell transplantation as a treatment option for multiple myeloma. The myeloma experts came to the conclusion that due to the risks associated with donor stem cell transplantation and limited data supporting its efficacy, it should only be recommended to multiple myeloma patients during clinical trials.

Over the past decade, the life expectancy of multiple myeloma patients has improved. Currently, most multiple myeloma patients are projected to live 7 to 10 years with good quality of life. Multiple myeloma remains, however, an incurable disease for most patients.

Allogeneic (donor) stem cell transplantation is currently the only treatment option that has the potential to cure multiple myeloma. In donor stem cell transplantation, patients undergo chemotherapy to kill off the myeloma cells and then receive stem cells from a donor to replenish their blood cells.

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Despite its therapeutic potential, the use of donor stem cell transplantation is highly debated in the medical field due to the safety risks and rate of relapse. After a stem cell transplant, patients may experience bleeding, infection, and graft-versus-host disease, a complication when transplanted stem cells attack the patient’s body.

In its recently published report, the International Myeloma Working Group (IMWG) made recommendations based on the review of stem cell transplant registries and studies that used several different transplant protocols.

Full Donor Stem Cell Transplants

The IMWG reviewed three transplant registries that contain data on patients who received myeloablative allogeneic (full donor) stem cell transplants. The goal of this type of transplant is to eradicate all myeloma cells before donor stem cells are transplanted into the patient to re-grow new blood cells.

The IMWG also reviewed several clinical trials that compared full donor transplants to autologous transplants. In an autologous transplant, a patient’s own stem cells are collected before intense therapy to kill the myeloma cells, and then the patient’s stem cells are transplanted back afterward. Because the patient’s own stem cells are used in an autologous transplant, it is associated with fewer complications than a donor transplant.

A review of these registries and studies revealed that full donor stem cell transplants were associated with high treatment-related mortality. The lowest reported percentage of treatment-related mortality among these registries and studies was 30 percent, though most groups reported at least 40 percent. The IMWG wrote that a 30 percent or higher mortality rate is “unacceptably high.”

The experts concluded that although myeloablative therapy proved effective for a small percentage of patients, it is not a good option for patients with multiple myeloma who can be treated with autologous stem cell transplantation.

Since treatment-related mortality is improving for full donor stem cell transplants, the IMWG suggested that these transplants could be further studied in well-designed clinical trials.

Reduced-Intensity Donor Stem Cell Transplants

As compared to full donor transplants, the IMWG found that non-myeloablative (also called mini or reduced-intensity conditioning) donor stem cell transplantation, either alone or preceded by autologous transplantation, was associated with a lower treatment-related mortality, as low as 9 percent in two studies. However, patients undergoing the reduced-intensity regimen were twice as likely to relapse (54 percent versus 27 percent).

The IMWG did not find convincing evidence during its review to suggest that donor stem cell transplantation improved survival compared to autologous stem cell transplantation. The group recommended that reduced-intensity donor transplants only be used in clinical trials.

Donor Transplantation In High-Risk Myeloma Patients

Likewise, the IMWG did not find convincing data to support the use of donor stem cell transplantation for patients with high-risk myeloma. However, many of the studies included small numbers of patients.

The IMWG wrote that a full donor transplant may be considered for “exceptional cases” in which the patients are “aware of their unfavorable prognosis and accept the risks of myeloablative conditioning.” The group suggested further studies in patients with chromosomal abnormalities t(4;14), t(14;16), and 17p- as well as patients who do not achieve at least a very good partial response after autologous transplantation.

Improving Donor Transplants

The IMWG stressed that future studies of donor stem cell transplantation be aimed at improving the efficacy and safety of the procedure.

They highlighted the need to better understand the graft-versus-myeloma effect to improve efficacy and the need to better manage graft-versus-host-disease to improve safety.

They also suggested that novel agents, such as thalidomide (Thalomid), Revlimid (lenalidomide), and Velcade (bortezomib), might improve the efficacy of donor stem cell transplantation. They cautioned, however, that the optimal timing and dosage of such protocols has not yet been determined.

For more information, please see the study in the Journal of Clinical Oncology (abstract).

Nissim Benvenisty on Public Library of Science – some rights reserved.
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