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“Mini” Unrelated Donor Stem Cell Transplantation May Be Feasible In Multiple Myeloma Patients

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Published: Mar 28, 2012 2:21 pm

“Mini” donor stem cell transplantation using stem cells from an unrelated donor may be feasible in multiple myeloma patients, according to the results of a recent small French study.

Results of the study showed that the estimated two-year overall and progression-free survival rates were similar between myeloma patients who received stem cells from a related donor and patients who received stem cells from an unrelated donor.

Based on these findings, the French researchers suggest that myeloma patients may benefit from a “mini” donor stem cell transplant in the absence of a suitable related donor.

Dr. William Bensinger of the Fred Hutchinson Cancer Research Center in Seattle, who was not involved in the study, agreed that these results suggest a feasible alternative for donor stem cell transplants when a related donor is not available.

He added, however, “This is a very small study [and] will not change the current approach to the treatment of myeloma. A much larger study using comparable groups of patients with a longer follow-up period (i.e. five years) [is needed].” 

The study investigators recommend prospective clinical trials in order to define the role of unrelated donor stem cell transplants in the current clinical setting.

Donor Stem Cell Transplantation

Donor, or allogeneic, stem cell transplantation is a procedure in which a patient receives high-dose chemotherapy followed by infusion of stem cells from a matched donor in order to replace the cells that were destroyed by the chemotherapy. These stem cells can be taken from either a related donor, such as a sibling or other relative, or from an unrelated donor.

Regardless of whether the donor is related or unrelated to the patient, the transfused stem cells must first be analyzed using tissue-typing proteins called human leukocyte antigens to ensure that they match the patient’s cells as closely as possible.

Once transfused into the patient, the donor stem cells eventually mature into immune cells which can recognize the patient’s cancer cells as abnormal cells and destroy them. This phenomenon is known as the graft-versus-tumor, or graft-versus-myeloma, effect.

Donor stem cell transplantation is different from autologous stem cell transplantation, in which a patient’s own stem cells are collected before receiving high-dose chemotherapy and then returned to the patient following chemotherapy. The graft-versus-tumor effect does not occur for patients receiving an autologous stem cell transplant because the patient’s own cells are unable to recognize and destroy the cancerous cells.

Although donor stem cell transplantation gives myeloma patients a better chance for a cure than autologous stem cell transplantation, it also carries a greater risk of complications. One of the most serious transplant-related complications is a condition called graft-versus-host disease (GVHD), in which white blood cells from the donor recognize the recipient’s cells as foreign and attack them.

To decrease the transplant-related complications and death rate, a new procedure known as non-myeloablative, or “mini,” donor stem cell transplantation has been introduced, which uses lower doses of chemotherapy and radiation than standard donor stem cell transplants. That makes the procedure less toxic and more tolerable, which is particularly important for myeloma patients who are elderly or have concurrent illnesses.

Study Motivation And Design

According to the French researchers, there are currently no clinical trials that have provided a direct comparison of “mini” donor stem cell transplants involving related and unrelated donors.

The researchers therefore retrospectively compared the outcomes of high-risk multiple myeloma patients treated with a “mini” donor stem cell transplant from a related or an unrelated donor.

The analysis included data from 40 multiple myeloma patients who had received a donor transplant between January 2007 and January 2011. The patients were divided into two groups based on their relationship to the donors: the related-donor group (57 percent) and the unrelated-donor group (43 percent).  The median age was 56 years in the related-donor group and 48 years in the unrelated-donor group.

Almost all patients (99 percent) in both treatment groups had received at least one prior autologous stem cell transplant. Patients in the related-donor group and the unrelated-donor group, respectively, had received similar prior treatments with the novel agents Velcade (bortezomib) (91 percent versus 94 percent), Revlimid (lenalidomide) (39 percent versus 41 percent), and thalidomide (Thalomid) (39 percent versus 24 percent).

Patients in both the related-donor group and the unrelated-donor group also had similar disease statuses before the donor transplant: Patients in the related-donor group and the unrelated-donor group, respectively, were either in at least very good partial remission (44 percent versus 35 percent), partial remission (52 percent versus 59 percent), or progressive disease (4 percent versus 6 percent).

As part of the “mini” donor stem cell transplant, 83 percent of patients in the related-donor group and 82 percent of patients in the unrelated-donor group received 30 mg/m2 of fludarabine daily for five days, 3.2 mg/kg of busulfan daily for two to three days, and 2.5 mg/kg of antithymocyte globulin daily for two days.

The remaining 17 percent of patients in the related-donor group and 18 percent of patients in the unrelated-donor group received 25 mg/kg of fludarabine daily for three days and 2 Gy total body irradiation.

The median follow-up time was 22 months.

Study Results

At the time of the most recent follow-up, 61 percent of patients in the related-donor group and 53 percent of patients in the unrelated-donor group were still alive. Of these patients, those in the related-donor group and unrelated-donor group, respectively, were in complete remission (79 percent versus 56 percent), partial remission (21 percent versus 22 percent), or progressive disease (0 percent versus 22 percent).

The researchers determined that patients in the related-donor group and the unrelated-donor group, respectively, had similar two-year progression-free survival (44 percent versus 42 percent) and overall survival rates (66 percent versus 59 percent).

The two-year treatment-related death rate was higher in the patients with related donors compared to patients with unrelated donors (22 percent versus 12 percent); however, the difference was not considered statistically significant.

The relapse rate was higher in patients with unrelated donors (40 percent versus 52 percent).

The rate of acute GVHD, which occurs within 100 days of the transplant, was lower in patients in the related-donor group (17 percent) than in patients in the unrelated-donor group (47 percent).

In contrast, the rate of chronic GVHD, which occurs at least 100 days after the transplant, was similar between the two treatment groups (24 percent versus 30 percent).

For more information, please see the article in the European Journal of Hematology (abstract).

Photo by Nissim Benvenisty on Public Library of Science – some rights reserved.
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One Comment »

  • Ed garbarino said:

    I am so grateful for the articles filled with such valuable information about my disease. I feel as though I have more options available to me. Do I head north to see Dr. Berlinger or do I head south and see Dr. Berrenson? I found out about theses experts who differ in their opinion on how they treat the disease. They both go at it with a passion. I need another opinion maybe two. I just don't know if I can afford it.