Tests Indicate Birth of New Immune System as Yale Hockey Player's Battle Continues
SEATTLE, Wash. – After spending six days in intensive care fighting her way through another life-threatening condition, Mandi Schwartz got some much-needed positive news in her battle with cancer this week. Tests have indicated that, nearly four weeks after her stem cell transplant, engraftment -- the birth of her new immune system -- appears to have taken place. This marks a major positive step, but challenges still remain for the Yale women's ice hockey center.
"The weeks since the transplant have been physically tough on Mandi, and there have been several scary moments, but she continues to fight," said her mother, Carol. "She remains focused on her goal of overcoming every challenge and getting her health back. We are all inspired by the support we have received from so many different people throughout this process."
Since receiving the stem cell transplant on Sept. 22, Mandi has been in the Seattle Cancer Care Alliance's inpatient unit at the University of Washington Medical Center. Recent engraftment test results indicate that the transplanted stem cells have begun to grow in her bone marrow and manufacture new blood cells and immune cells, which puts her in a better position to fight off any potential infections. She also now has a new blood type.
The results come after a harrowing period for Mandi and her family -- mother Carol, father Rick, brothers Jaden and Rylan and fiancé Kaylem Prefontaine have all spent time with her in Seattle -- that began shortly after the transplant took place.
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.
The chemotherapy also took a toll on Mandi's liver, and she began suffering from 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.
Out of intensive care, Mandi resumed her training regimen of riding on the exercise bike in her hospital room. She will receive a biopsy on Wednesday, and could be discharged within a day of that. She and her family are currently living in Seattle, 1,000 miles from her home in Saskatchewan, and must remain there for follow-up appointments with the Seattle Cancer Care Alliance.
As a transplant patient Mandi is still at risk for graft-versus-host disease, which involves the transplanted immune cells attacking the body and can be fatal. Acute graft-versus-host disease can occur up to 100 days after the transplant, while chronic graft-versus-host can appear later.
After Mandi is discharged from the hospital, she and her family will remain in Seattle for months of follow-up appointments. Complete recovery of Mandi's new immune system takes approximately a year, but could take longer if she develops any complications as a result of the transplant. 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, a native of Wilcox, Sask., has been battling acute myeloid leukemia for nearly two years. The stem cell transplant essentially gives her the new blood and immune system she needs to survive. Stem cells 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. She will require many transfusions for red blood cells and platelet cells as she recovers.
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.
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.
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.
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. The 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 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.
Yale Teammates Take Action
While Mandi's transplant utilized umbilical cord blood, the need for bone marrow donors for patients like her remains great. 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.
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. 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 last month. 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" (Mandi's uniform number), to raise awareness and funds. She brought in nearly $3,000.
Yale also plans to dedicate its game on Nov. 12 to Mandi. Details will be released on yalebulldogs.com shortly.
1. Send Mandi a card or letter showing your
Wilcox, SK S0G 5E0
2. Send donations (checks made out to "Yale University", with "Mandi Schwartz" in the memo line) to:
ATTN: Wayne Dean
20 Tower Parkway
New Haven, CT 06520
3. Become an umbilical cord blood donor:
4. Join the bone marrow donor registry:
For more information about Mandi and how you can help, visit http://www.yalebulldogs.com/mandi
Report by Sam Rubin '95 (firstname.lastname@example.org), Yale Sports Publicity