In the Clinic

On Cancer: New Treatment May Help Transplant Patients Recover Immune Function More Quickly

By Jim Stallard, MA, Writer/Editor  |  Friday, December 21, 2012
Pictured: Marcel R. M. van den Brink Physician-scientist Marcel R. M. van den Brink

Cancer patients who receive a stem cell transplant as part of their treatment undergo a temporary depletion of certain white blood cells known as T cells, which are critical to the proper functioning of the immune system. Until they can regenerate a sufficient number of T cells, these patients are at serious risk of infection by pathogens such as viruses, bacteria, and fungi — as well as of having their cancer return.

Now Memorial Sloan Kettering researchers have shown for the first time that administering a growth factor called interleukin-7 (IL-7) can help patients regenerate T cells more quickly after transplantation. The pharmaceutical version of IL-7, called CYT107, was developed by Cytheris, a clinical-stage biopharmaceutical company. Although the study involved only 12 people, it raises hopes for development of a therapy that would allow patients to regain full immune function faster and improve their chances of survival.

“IL-7 may be the T cell growth factor we’ve been looking for,” says physician-scientist Marcel R. M. van den Brink, head of Memorial Sloan Kettering’s Division of Hematologic Oncology and a member of the Sloan Kettering Institute’s Immunology Program. He led the research along with physician-scientist Miguel-Angel Perales, who conducted the phase I clinical trial, and they reported the results in the December 6 issue of the journal Blood.

Improving T Cell Recovery

Dr. van den Brink specializes in treating cancers and blood disorders using allogeneic stem cell transplantation, in which patients receive blood-forming stem cells from a donor to replace their own malfunctioning blood cells. In previous research in mice, Dr. van den Brink and colleagues had demonstrated that IL-7, a naturally occurring protein that carries signals between cells, could enhance the development and survival of T cells when given following allogeneic transplants.

Despite the promise shown by IL-7 in the laboratory, there was concern that boosting T cell recovery after a transplant could cause a complication known as graft-versus-host disease (GVHD), in which donor T cells attack the recipient. Risk of GVHD depends on the number of T cells present in the transplanted cells, with higher numbers of T cells bringing greater risk. Because of this threat, the researchers tested the IL-7 therapy in transplant patients receiving stem cells from which most of the T cells had been removed — an approach known as T cell depletion.

In the trial, 12 Memorial Sloan Kettering patients with blood cancers (acute myelogenous leukemia, myelodysplastic syndrome, or chronic myelogenous leukemia) who had received allogeneic transplants received injections of escalating doses of CYT107 once a week for three consecutive weeks. The trial was conducted mainly to demonstrate that the treatment was safe, although the researchers also looked for any evidence that IL-7 was having an effect on the transplanted T cells.

“To our surprise we already noticed increases in T lymphocyte counts even after the lowest dose of IL-7, which was not expected to have much effect,” says Dr. Perales.

No Toxicity

The treatment did not appear to have any toxic effects, and only one patient experienced GVHD.

In addition, subsequent analysis of each patient’s blood and lymph fluid showed that certain subsets of T cells had increased in number significantly — especially in a group known as effector memory T cells. These T cells fight off repeat infections and prevent a person from catching the same illness more than once.

The results suggest IL-7 holds promise as a treatment to help patients recover immune function after an allogeneic stem cell transplant.

“Although it’s a small trial, any therapy that shows a beneficial effect in people is a significant advance,” Dr. van den Brink says. “However, larger studies are needed to confirm the safety and success of this approach before it becomes part of a standard treatment for patients receiving an allogeneic transplant.”

Comments

I thought Drs. Barrett and Battiwalla at NIH/NHLBI were the only folks doing allogeneic t-cell depleted transplants in the US? I don't think they use Interlukin for GVHD control. Their GVHD control has been very successful.
Response rates have been great.

Thanks for your comment. According to Dr. van den Brink, Memorial Sloan-Kettering was the first center to perform a T cell depleted transplant. This happened in the 1980s, under the leadership of Richard O’Reilly, Chief of the Pediatric Bone Marrow Transplant Service. Within the United States, Memorial Sloan-Kettering currently performs more T cell depleted transplants than any other center. We also led a multi-center study (Biol Blood Marrow Transplant. 2011 Sep;17(9):1343-51), which demonstrated the effectiveness of this strategy for patients with acute myeloid leukemia.

This brings Hope!

My son had a stem cell transplant at MSKCC in June 2009 after a battle with ALL. I know he received 2 units of stem cells and although he had a very tough time, thanks to all those at MSKCC he is doing well!! He was under the care of Dr. Nancy Kernan and the entire BMT team. This study sounds very promising. This is exactly why one should go to MSKCC for cancer care. Thank you!

Thank you for your response on clarifying my understanding of t-cell depleted allo transplants. I had one 18 mos. ago for MCL at NHLBI/NIH.
I wasn't aware of Sloan Ketterings depth of experience in this area. God bless, and thanks for the great work that you do at SK.
Bill

DO YOU THINK THIS WOULD ALSO HELP PATIENTS WITH LUPUS, SJOGRENS AND SUCH ILLNESSES? THANKS FOR A REPLY

Thank you for your comment. This research is currently focusing on the treatment of patients who have received a stem cell transplant.

Will this work for pediatric (8 yr. old) autologuous transplant too? Will IL-7
regenerate T-cells more quickly or does it work only for allogeneic transplants?
Medulloblastoma brain tumor primary. Brain tumor gone, but small tumor in spine now. Chemo and then stem cell transplant recommended.

Hi, Judy, we spoke with Dr. van den Brink, who said, "IL-7 is currently not yet being tested in pediatric patients. As with many new drugs they are first tested in adults. However, based upon preclinical studies Il-7 is expected to be as effective in children as in adults." If you'd like to learn more about how Memorial Sloan-Kettering treats pediatric brain tumors, you can go to http://www.mskcc.org/pediatrics/childhood/pediatric-brain-tumors. To make an appointment with a pediatric oncology specialist, you can call 212-639-5954. Thanks for your comment.

I am diagnosed with T-cel Non Hodgkin Lymfoma and am proposed chemo (CHOP) as well as an autologous cell transplant. Could this new treatment be of use to me? Hartelijke groeten uit Nederland

Thank you for your comment. We are unable to answer personal medical questions on our blog. If you would like to make an appointment to discuss this with a Memorial Sloan-Kettering physician, please call 800-525-2225.

What an unnecessary formal reply. I am in the The Netherlands and an appointment is out of the question. I had to mention my disease because it is IN my T-cells and that prompts the question whether this treatment promotes the good regular production of t-cells or also of the malignant ones.

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