December 22, 2010

Mandi Schwartz Update: More Chemo Required after Relapse

Yale Hockey Player's Battle with Cancer Continues

SEATTLE, Wash. – After results of a recent biopsy indicated that her cancer has returned, Mandi Schwartz has begun additional chemotherapy in an effort to get back into remission. Mandi has started the treatment under the supervision of doctors at the Fred Hutchinson Cancer Research Center in Seattle. She is scheduled to return home at the end of December to continue the treatment at the Allan Blair Cancer Centre in Pasqua Hospital in Regina, Saskatchewan.

It has been more than two years since Mandi, a center on the Yale women's ice hockey team, was first diagnosed with cancer (acute myeloid leukemia) while in the first semester of her junior year at Yale. She and her family have been living in Seattle -- 1,000 miles from their home in Wilcox, Saskatchewan -- for the last five months as she has undergone treatment at the Fred Hutchinson Cancer Research Center. The latest biopsy results came less than three months after Mandi received a stem cell transplant that was designed to give her the new blood and immune system she needs to survive.

Acute myeloid leukemia is a type of cancer that starts inside the bone marrow and grows from cells that would normally turn into white blood cells -- cells of the immune system. The stem cells used in the transplant have the ability to change into any of the body's cell types. In Mandi's case, they are being used to give her new blood cells and new immune cells. Her old immune system, along with the cancerous cells, was eliminated by chemotherapy and radiation prior to the transplant.

The birth of Mandi's new immune system after the transplant, known as "engraftment", was confirmed in mid-October, and she was in remission. The results of the recent biopsy indicate that she has relapsed, her third relapse this year.

Mandi is now being treated with Azacitidine, also known as Vidaza, as part of a research program to study that drug's effectiveness against acute myeloid leukemia. The drug has been used primarily as treatment for another type of blood disorder, myelodysplastic syndrome (MDS). The goal is to eliminate the cancerous cells and to help Mandi's bone marrow grow normal blood cells. Doctors also began tapering the postgrafting immunosuppression to take the "brakes off" the donor immune cells and eventually allow for graft-versus-tumor effects to deal with any residual leukemic cells.

Mandi's treatment with Azacitidine consists of seven straight days of injections each month over a period of six to eight months. Treatment started last Friday, Dec. 17. The injections take approximately 30 minutes, and hospitalization is not required. She will have regular blood checks and may also require transfusions for red blood cells and platelet cells.

Mandi and her family had been expecting to leave Seattle with her still in remission, with the hope that she would continue gradually regaining her strength while still battling through the side effects of the transplant and the many medications required as part of the treatment. She had recently overcome graft-versus-host disease (GVHD), a potentially fatal condition in which the transplanted cells attack the recipient's body. Acute graft-versus-host disease can occur up to 100 days after the transplant, while chronic graft-versus-host can appear later. She was hospitalized for acute graft-versus-host disease on Dec. 3 and released on Dec. 5.

The latest biopsy was performed on Dec. 13. The results were a serious setback for Mandi and her family. Her mother Carol, father Rick, brothers Jaden and Rylan and fiancé Kaylem Prefontaine have all spent time with her in Seattle.

"The results of the biopsy caught us off guard, because we had hoped to be done with this part of the battle," said Carol. "Mandi remains committed to fighting this disease, and we are going to continue doing everything in our power to help her. We are so grateful for all the support we have received throughout this ordeal. We know how many families have been affected by cancer, and we know that the efforts to raise awareness of this cause that have been made on Mandi's behalf are making a difference for her and for so many other patients in need. That gives us the strength to keep going."

Mandi had been making gradual progress since the transplant, despite having many challenges to overcome. Prior to the transplant, in order to ensure that all of the existing cancerous cells in her body were eliminated -- and to suppress her immune system to prevent her from immediately rejecting the new donor cells -- Mandi received chemotherapy and radiation treatment. Fatigue, fevers, hallucinations, nausea and the condition known as mucositis (painful inflammation and ulceration of the mucous membranes lining the digestive tract) were among the many immediate consequences of Mandi's treatment and the drugs required afterwards.

Mandi also spent six days in intensive care in early October fighting her way through another life-threatening condition, veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS). In this condition, which is potentially fatal, veins in the liver become blocked, leading to an increase in weight and liver size. Mandi retained approximately 35 extra pounds of body fluid due to VOD, and her breathing became labored. Medication, along with green tea and vitamin E, eventually helped her overcome the condition.

After overcoming VOD and GVHD, Mandi had regained enough strength to start doing things like volunteer coaching with a local girls' hockey team. She was behind the bench on Saturday Dec. 11 helping the Western Washington Female Hockey Association's Phoenix defeat the Kent Valley boys' team 3-0. The Phoenix have played all season with a patch on their jerseys bearing Mandi's uniform number, 17, and they have retired their own No. 17 jersey for the season.

In addition to chemotherapy, Mandi must also continue to await complete development of her new immune system, which takes approximately a year. She will be monitored regularly through blood tests to confirm that new blood cells are being produced.

Mandi's transplant on Sept. 22 utilized stem cells from two umbilical cord blood units donated anonymously to public cord blood banks. The procedure lasted 32 minutes and was similar to a transfusion. The stem cells were placed in Mandi's body through a vein so that they could find their way to her bone marrow to create new blood cells and immune cells.

Mandi and her family continue to encourage all adults to sign up as bone marrow donors, and for expectant mothers to sign up as umbilical cord blood donors. Yale has held two bone marrow donor testing drives in Mandi's honor in the last two years, and those drives have identified at least four genetic matches for patients in need. That includes Lexy Adams (Lancaster, Pa.), a sophomore on the Yale field hockey team.

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 organized several events. Junior forward Aleca Hughes (Westwood, Mass.) raised nearly $6,000 and added approximately 70 people to the bone marrow donor registry at the Chowder Cup Tournament over the summer. On Aug. 26, senior defenseman Samantha MacLean (Mississauga, Ont.) completed a five-day, 500-mile bike ride from Toronto to New Haven, "The Ride for 17", to raise awareness and funds. She brought in nearly $3,000.

Yale also held a fundraiser at its game vs. RPI on Nov. 12, known as the "White Out for Mandi". The Bulldogs sold white t-shirts for fans to wear at the game. With no admission charge, donations were accepted at the door and the Bulldogs also lined up donors who pledged donations based on the attendance count. A record crowd of 1,066 wound up attending. Combined with the money from a silent auction of sports memorabilia, the event brought in approximately $15,000.

On Nov. 6 the Yale and Quinnipiac Athletic Departments combined to support the Yale Club of New Haven's "March for Mandi", held before the Yale-Quinnipiac men's ice hockey game. The March utilized the Farmington Canal Rails-to-Trail path between Quinnipiac's TD Bank Sports Center and Yale's Ingalls Rink, and the fundraiser generated more than $4,000 for Mandi and her family.

In addition to the work they have been doing on Mandi's behalf, her Yale women's ice hockey teammates have also adopted a nine-year old brain tumor patient through a new program at Yale-New Haven Hospital known as "Bulldog Buddies". The patient, Giana, was introduced to the crowd at Ingalls on the night of the White Out for Mandi and dropped the ceremonial first puck.

 

 

Here is a look at some of the key elements to Mandi's battle:

 

About Acute Myeloid Leukemia

Acute myeloid leukemia is a type of cancer that starts inside the bone marrow and grows from cells that would normally turn into white blood cells -- cells of the immune system.

 

Treatment Back Home in Saskatchewan

Mandi was initially diagnosed with acute myeloid leukemia in December of 2008, near the end of the first semester of her junior year at Yale. She returned home to Saskatchewan for treatment at the Allan Blair Cancer Centre in Pasqua Hospital in Regina. 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 in April 2010 and had to return home for more chemotherapy. At that point it became clear that she would need a stem cell transplant to survive, and her family chose to have the transplant through the Seattle Cancer Care Alliance. Her chemotherapy in Saskatchewan put her in remission, which was necessary in order for her to be able to receive the stem cell transplant, for a second time. She was found to be in remission on June 9, and was discharged from Pasqua Hospital on July 11. That enabled her and her family to make the trip to Seattle and begin preparing for the transplant.

 

Attempts to Find a Genetic Match for Mandi

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 10 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 organized by former Yale men's ice hockey player Brennan Turner '09, a Schwartz family friend, 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.

To date, four people are known to have been identified as matches from the Yale bone marrow donor drives. That includes Yale sophomore field hockey player Lexy Adams (Lancaster, Pa.), who was found to be a match for a cancer patient in need.

 

 

The Umbilical Cord Blood Option

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.

The 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.

 

 

Seattle Cancer Care Alliance, Mandi's Doctors

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. The transplant was overseen by Dr. Colleen Delaney, an oncologist and researcher in Dr. Irwin Bernstein's Clinical Research Division lab.

 

 

The Family in Seattle

Mandi, her parents Carol and Rick, and her fiancée, Kaylem Prefontaine, made the trip to Seattle from their home in Saskatchewan by an RV donated by Traveland RV in Regina. Mandi's younger brothers, Jaden and Rylan, have both spent time visiting her in Seattle as well. They are hockey players at Colorado College, and Jaden was recently selected in the first round of the NHL Draft by the St. Louis Blues. He has also been selected to be on Team Canada's roster for the International Ice Hockey Federation's World Junior Championships in Buffalo, N.J., Dec. 26 through Jan. 5.

 

The Cord Blood Selected for Mandi's Transplant

The cord blood units that were 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 units are each identified as "5-out-of-6" genetic matches for Mandi. Because umbilical cord blood stem cells require less strict matching criteria, transplants can be performed even with "4-out-of-6" matches.

 

Changing the Initial Transplant Date

On Aug. 11 -- just 16 days before her originally scheduled transplant date -- a biopsy indicated that Mandi's cancer had returned. The transplant had to be postponed as she underwent another round of chemotherapy.  After being discharged from the hospital when that round finished on Aug. 19, tests indicated that she was in remission.

 

Changing the Initial Transplant Plan

The original plan was to have Mandi receive cord blood that had its number of stem cells "expanded", or increased, in order to speed up the time to engraftment. Because of the results of a biopsy on Sept. 13, she instead received a transplant from units that did not have their number of stem cells expanded. That biopsy indicated 2.5 to seven percent blast cells in Mandi's bone marrow. Blast cells are immature cells in bone marrow that mature into white blood cells or red blood cells. They normally account for up to five percent of the cells in bone marrow, so a higher ratio than that can indicate a problem.

 

Words to Her Yale Teammates

Prior to the Sept. 22 transplant, Mandi took the time to write to her Yale women's ice hockey teammates, who have been among her most active supporters throughout her ordeal.

"I'm praying every day for everything to work out, and I know you all are thinking about me and praying for me - thank you very much - your support means the world to me. I think about the team, your workouts, the busy school day, and the beautiful feeling of stepping out onto that ice every day."

 

The Transplant

The transplant procedure on Sept. 22 lasted 32 minutes and took place at the Seattle Cancer Care Alliance's inpatient transplant unit at the University of Washington Medical Center.  It utilized stem cells from two umbilical cord blood units donated anonymously to public cord blood banks. The procedure was similar to a transfusion. The stem cells were placed in Mandi's body through a vein so that they could find their way to her bone marrow to create new blood cells and immune cells.

That capped a whirlwind 10-day span, because up until receiving the results of a biopsy on Sept. 13 it was unclear whether Mandi would be cleared for the transplant. She had been battling a series of infections, but when the biopsy results that day indicated that she was still in remission her medical team acted quickly to begin her conditioning for the transplant. The radiation treatment began Sept. 14, and was followed by chemotherapy.

 

Complications after the Transplant: VOD

After the transplant Mandi spent six days in intensive care in early October fighting her way through another life-threatening condition, veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS). In this condition, which is potentially fatal, veins in the liver become blocked, leading to an increase in weight, liver size, and blood levels of bilirubin (a byproduct of the degradation of heme, part of the hemoglobin that is the principal component of red blood cells).

Mandi retained approximately 35 extra pounds of body fluid due to VOD, and her breathing became labored. Doctors were hesitant to use the experimental drug defibrotide to treat her VOD due to concerns about one of its side effects, internal bleeding. A CT scan had shown an inflammation in Mandi's lungs, and a bronchoscopy later confirmed that this was blood. Thus, using a drug with internal bleeding as one of its side effects was ruled out and Mandi was treated with a different drug along with green tea and vitamin E.

Mandi was moved to the intensive care unit on Monday, Oct. 4. Her breathing and vitals showed improvement on Thursday, Oct. 7, and she was released from intensive care on Saturday, Oct. 9. By Wednesday, Oct. 13, she had dropped 30 of those extra pounds. The bilirubin count in her blood was down to 3.4, and subsequently dropped to 2.3 on Monday Oct. 18, with the goal of getting it down to the 1.4 range. Doctors had to be careful to keep her from eliminating too much weight at once so as not to put too much of a strain on her kidneys; she did lose 10 pounds in one day.

 

 

 

HOW YOU CAN HELP  

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

Mandi Schwartz
Box 308
Wilcox, SK S0G 5E0
Canada   

2. Send donations (checks made out to "Yale University", with "Mandi Schwartz" in the memo line) to:

Yale Athletics
ATTN: Wayne Dean
20 Tower Parkway
New Haven, CT 06520

 

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

 

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

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