August 13, 2010

Mandi Schwartz Update: Breakthrough Procedure Holds Key to Transplant Success; More Chemotherapy Needed for Remission

Yale Women's Hockey Center Scheduled to Receive Stem Cell Transplant

NEW HAVEN, Conn. –The stem cell transplant that Mandi Schwartz needs to help win her battle with cancer will include a breakthrough procedure pioneered by one of her doctors at Fred Hutchinson Cancer Care Center. First, though, the 22-year old Yale women's ice hockey center must undergo more chemotherapy, as tests have indicated that she is no longer in remission.

Mandi, a native of Wilcox, Sask., is battling acute myeloid leukemia. This type of cancer starts inside the bone marrow and grows from cells that would normally turn into white blood cells -- cells of the immune system. Mandi was initially diagnosed in December of 2008, the first semester of her junior year at Yale. After multiple rounds of chemotherapy she was first declared to be in remission in the spring of 2009. She returned to Yale in January of 2010 and resumed practicing with the women's hockey team, but she was re-diagnosed this past April and had to return home for chemotherapy.

At that point it became clear that Mandi would need a stem cell transplant -- essentially, a new blood and immune system -- to survive. Stem cells have the ability to change into any of the body's cell types. In Mandi's case, they will be used to give her new blood cells and new immune cells.

The stem cells for transplants like the one Mandi needs can come from the bone marrow or peripheral blood of an adult donor or the blood left over in the umbilical cord after a baby is born. In order to limit the risk of complications, the stem cells must come from a donor who is a close genetic match to the patient.

For transplant purposes, genetic matches are judged by comparing proteins -- or markers -- found on most cells in the human body. The immune system uses these markers, known as human leukocyte antigens (HLA), to recognize which cells belong to that body and which do not. A close match between HLA markers can reduce the risk that the recipient's immune cells attack the donor's cells or that the donor's immune cells attack the recipient's body after the transplant. There are many different HLA markers, but transplant donors and patients are primarily compared for matches of eight to ten markers that are most important in transplant outcomes.

Mandi has been unable to find a bone marrow donor that is a genetic match -- 16,000 leukemia patients diagnosed each year cannot. None of her family members are matches. Inspired by Mandi, bone marrow donor drives have been held throughout her native Canada and the United States. The Yale Athletics Department has held drives each of the past two springs, adding more than 1,600 people to the National Marrow Donor Program's "Be The Match" registry. A series of drives in Canada added more than 2,600 people to Canadian Blood Services' "OneMatch" registry. The people that registered at these drives may be called upon someday to help save the life of a patient, like Mandi, with a life-threatening illness.

With no matching stem cell donor available, the best option is to get the stem cells for the transplant from umbilical cord blood. Cord blood has advantages as a stem cell source: fewer viral infections are transmitted with it, and -- because umbilical cord blood lacks well-developed immune cells -- there is less chance that the transplanted cells will attack the recipient's body (graft-versus-host disease). Using cord blood thus does not require the extremely close genetic matching of bone marrow transplants.

Because of the low volume of blood in umbilical cords, two cord blood units (from two different births) are typically used in transplants. The major disadvantage to using umbilical cord blood for a transplant is that each unit has fewer stem cells than other sources (approximately 1/10th). Because of this low number, engraftment (the generation of infection-fighting white blood cells of the new immune system following transplantation) in adults from a cord blood transplant takes about 26 to 28 days, compared to 15 for a bone marrow transplant. While waiting for engraftment patients run the risk of getting infections that can be fatal. That is where the breakthrough technique that will be part of Mandi's transplant protocol comes in.

When the Schwartzes were looking for a hospital for the transplant, they were drawn to Seattle Cancer Care Alliance, which is operated by Fred Hutchinson Cancer Care Center, University of Washington Medicine and Seattle Children's. As it turns out, they will now have the benefit of working with a doctor who has pioneered a way to speed up the process of engraftment and thereby limit the risk of infections. Dr. Colleen Delaney, an oncologist and researcher in Dr. Irwin Bernstein's Clinical Research Division lab, has been conducting a unique clinical trial using cord blood for the last four years.

In 2002, researchers in the Bernstein Lab found a way to increase the amount of stem cells in cord blood. They rapidly grow the cells on a protein called Delta, which activates a gene that keeps the cells from maturing into more specific cells. With the increased amount of stem cells involved in the transplant, engraftment is likely to happen more quickly.

The first human transplant using a cord blood unit whose stem cells had been "expanded" using this technique was performed in July of 2006. The technique has since shown promising signs of speeding up the time to engraftment.

A search of the umbilical cord blood registries located two umbilical cord blood units that were identified as "5-out-of-6" matches based on Mandi's HLA type. Because umbilical cord blood stem cells require less strict matching criteria, transplants can be performed even with 4-out-of-6 matches.

The cord blood units that will be used in Mandi's transplant came from two separate donors who are, and will remain, anonymous. They were donated to public cord blood banks and located by a registry search performed by the Seattle Cancer Care Alliance.

The chemotherapy that Mandi underwent back home at the Allan Blair Cancer Centre in Pasqua Hospital in Regina put her in remission, which is necessary in order for her to be able to receive the transplant, for a second time. She was found to be in remission on June 9, and she was discharged from Pasqua Hospital on July 11. Mandi, her parents and her fiancée Kaylem Prefontaine then made the trip to Seattle from her home in Saskatchewan by RV. They then met Dr. Delaney and their transplant team. Her attending physician is Dr. Rainer Storb, a longtime Hutchinson Center transplant physician and researcher.

In between medical appointments, Mandi and her family have taken time out for some other activities, including hiking. On Sunday Aug. 8, Mandi threw out the first pitch at the Seattle Mariners' game vs. Kansas City at Safeco Field.

Mandi's transplant had been scheduled for Aug. 27, but was postponed once it was learned on Aug. 11 that the cancer had returned for a third time. She will have to undergo more chemotherapy to put her back in remission, and then a date for the transplant can be finalized.

As has been the case throughout her battle, Mandi's reaction to the news of her relapse was inspiring. She had to undergo a procedure on Wednesday that took approximately five hours, but she did not let that stop her from her continuing efforts to build up her strength.

"Carol and I came back to make supper for Mandi, but she texted me telling us to hold off with supper because she wanted to go work out first when she got out," Rick said. "What a kid! Still wants to work out even after hearing the bad news."

In preparation for her transplant, Mandi will have to undergo more chemotherapy and total-body radiation starting the week before the transplant. This part of the procedure is designed to ensure that all of the existing cancerous cells are eliminated and to further suppress Mandi's immune system to prevent her from immediately rejecting the new donor cells.

The transplant itself is similar to a transfusion and takes a few hours. The stem cells are placed in the body through a vein, and find their way to the bone marrow to create new blood cells and immune cells.

After the procedure, the next milestone that everyone will be watching for is known as "engraftment": the transplanted stem cells beginning to grow in Mandi's bone marrow and manufacture new blood cells and immune cells. This signifies the birth of Mandi's new immune system, and could happen within a few weeks of the transplant.

Complete recovery of Mandi's new immune system takes approximately a year. Following the transplant, she will be monitored regularly through blood tests to confirm that new blood cells are being produced. She will spend several months in Seattle before she can return home to Saskatchewan.

While Mandi's transplant will utilize cord blood, the need for bone marrow donors for patients like her remains great. Just two weeks ago, another donor who registered at a Yale bone marrow donor drive was called upon and donated stem cells to help save a 55-year old man with a life-threatening illness. This was the second confirmed donation from one of the Yale bone marrow donor drives. Mandi and her family continue to encourage all adults to sign up as bone marrow donors, and for expectant mothers to sign up as cord blood donors.

In order to raise awareness of the need for bone marrow donors and umbilical cord blood donors in general, and to help the Schwartz family with expenses, Mandi's Yale teammates have been organizing several events. Rising junior forward Aleca Hughes (Westwood, Mass.) raised more than $6,000 and added approximately 70 people to the bone marrow donor registry at the Chowder Cup Tournament last month. Rising senior defenseman Samantha MacLean (Mississauga, Ont.) is organizing a bike ride from Toronto to New Haven, "The Ride for 17" (Schwartz' uniform number), to raise awareness and funds at the end of August.

Report by Sam Rubin '95 (sam.rubin@yale.edu), Yale Sports Publicity

 

HOW YOU CAN HELP  

1. Send Mandi a card or letter showing your support:

Mandi Schwartz
Box 308
Wilcox, SK S0G 5EO
Canada   

2. Send donations, checks made out to "Mandi Schwartz", to the above address.

3. Become an umbilical cord blood donor:

  • Click here to visit the U.S. National Marrow Donor Program's page with information about umbilical cord blood donation.

4. Join the bone marrow donor registry:

  • Click here to visit the U.S. National Marrow Donor Program's "Be The Match" website to learn how you can request a bone marrow donor testing kit or find a bone marrow donor testing drive near you.
  • Click here to visit the DKMS Americas bone marrow donor page.
  • Click here to visit the Canadian Blood Services page.
  • Click here for the U.S. National Marrow Donor Program's list of International donor centers if you are not in the U.S. or Canada.

 

 

For more information about Mandi and how you can help, visit http://www.yalebulldogs.com/mandi

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