Blood and Marrow Transplant Program Innovation. Compassion. Superior Outcomes.

In the Blood and Marrow Transplant (BMT) Program at University of Minnesota Medical Center, Fairview, we take great pride in providing patients with compassionate, expert and research‑driven care. With more than 40 years of transplant experience, including more than 6,000 transplants, we remain on the frontline of new developments in BMT. We are committed to providing each patient with high quality care and personalized attention in an academic medical center that offers access to the very latest BMT therapies through participation in clinical research trials.

We rely on our close relationships with referring physicians to integrate BMT into each patient's overall plan of care. In order to give the best possible chance of a cure through BMT, we need to evaluate patients early in their disease process. Research data from the National Marrow Donor Program and American Society of Blood and Marrow Transplant demonstrates a direct link between early referral for transplant and increased survival. We want to provide the best transplant option at the best possible time for your patients. If you would like to discuss a patient's case or ask a question about our BMT research, call us anytime at 612‑273‑2800.

Research conducted at the University of Minnesota has produced dramatic improvements in BMT patient survival rates and quality of life post‑transplant. The development of reduced intensity‑conditioning regimens allows us to safely provide BMT to patients who are older or have co‑morbid conditions. The use of double umbilical cord blood transplantation in adults, developed at the University of Minnesota, allows us to offer life‑saving BMT therapy to patients who do not have access to a matched related or unrelated donor.

In this report, you will learn about how our leading‑edge research results in superior patient outcomes. For example, Claudio Brunstein, MD, a nationally renowned expert in the field of umbilical cord blood transplant, talks about his research involving the use of specialized regulatory T‑cells from cord blood to reduce graft‑versus‑host‑disease after transplant. Erica Warlick, MD, relates her research efforts to understanding the biology and epidemiology of myelodysplastic syndrome and its potential treatment options, while Linda Burns, MD, discusses her research efforts to reduce the incidence of post‑transplant complications.

Over four decades, we have made great strides in the study and application of blood and marrow transplantation to provide the chance of cure for patients with advanced and life‑threatening marrow disorders. With your help, we can continue to increase survival and expand indications in order to make BMT a safe and available option for every patient who could benefit. We welcome the chance to share our exciting work with you, and would appreciate an opportunity to meet with you and your colleagues. Please give us a call at 612‑273‑2800 or 888‑601‑0787 (toll‑free) to schedule a visit or consultation.

 

w e lc o M e To T h e B lo o d a n d M a r r o w T r a n s P l a n T P r o G r a M

Daniel Weisdorf, MD director, adult Blood and Marrow Transplant Program

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we wanT To TalK To YoU!Your call will be answered by a registered nurse with years of Blood and Marrow Transplant (BMT) experience who can answer questions about our program, discuss open research protocols or put you in direct contact with one of our BMT physicians.

612‑273‑2800Blood and Marrow Transplant Program MMc 803 420 delaware st. se Minneapolis, Mn 55455

612‑273‑2800 or 888‑601‑0787 (toll‑free)

uofmbmt.org

U n Pa r a l l e l e d c a r e f o r T r a n s P l a n T PaT i e n T sUniversity of Minnesota Medical Center, Fairview, has provided innovative research, unmatched patient care and superior outcomes to blood and marrow transplant (BMT) patients for more than 40 years. Since performing the world's first successful BMT in 1968, specialists have performed more than 6,000 additional BMT procedures. Today, we have the largest umbilical cord blood program in the country, in addition to long‑standing programs in autologous and allogeneic transplantation. We have expertise in all available stem cell sources and conditioning intensities, which allows us to provide the best transplant options to patients of diverse ages, backgrounds and diseases.

Under the medical direction of Daniel Weisdorf, MD, our BMT program is regarded as one of the highest quality programs in the country. With an unwavering commitment to patient care and quality outcomes, we continue to improve survival rates for individuals with life‑threatening diseases. As these individuals age, we support them with long‑term follow‑up care to address their unique medical and emotional needs. We also offer these individuals an opportunity to participate in clinical studies that support our ongoing survivorship research.

from our pioneering research to our patient‑focused multidisciplinary care, the BMT team at University of Minnesota Medical center, fairview, is committed to providing experience, strength and leadership for BMT patients and their families.

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coMPassionaTe. exPerT. innovaTive.The Blood and Marrow Transplant (BMT) team at University of Minnesota Medical Center, Fairview, is committed to sharing our experience, strength and leadership. With an unwavering commitment to patient care and quality outcomes, we continue to improve both survival and quality of life for individuals with life‑threatening diseases.

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ous

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Umbilical Cord Blood Transplant

Unrelated Donor Transplant

Related Donor Transplant

2012 BMTs by Stem Cell Source and Conditioning*

BMTs by Donor Type, 1974‑2012*

our BMT Program has led the nation in the development and implementation of new transplant modalities such as unrelated donor transplant and the use of umbilical cord blood.

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Diagnoses of Adult BMT Patients, 2007‑2012

University of Minnesota Medical center, fairview, has nearly 100 open BMT research protocols.

Acute lymphocytic leukemia (ALL)

Acute myelogenous leukemia (AML)

Chronic myelogenous leukemia (CML)

Chronic lymphocytic leukemia (CLL)

Myelodyplastic syndrome (MDS)

Non-Hodgkin lymphoma (NHL)

Hodgkin lymphoma (HL)

Multiple myeloma (MM)

Aplastic anemia (AA)

Fanconi anemia (FA)

Ewings Sarcoma Germ Cell tumor

Other malignancy Multiple Diseases

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Patient Age at Time of BMT

our team is dedicated to making transplant a safe and viable option for patients of all ages who might benefit from BMT.

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"I have new blood and a new outlook. I have a new life."

—Janice Haworth with Kathy Hodges, RN

Starting a New Lifein october 2004, Janice haworth passed out in a snowdrift while running a snow blower at her home in Bemidji, Minn. she was initially diagnosed as anemic, but further blood tests revealed a much more serious condition—multiple myeloma.

"i was overwhelmed," says haworth. "i was told i probably had two or three years to live and would die from this disease." But haworth was not one to back down from a fight.

in april 2005, haworth moved to Minneapolis for an autologous stem cell transplant. "By the time i was admitted to University of Minnesota Medical center, fairview, my myeloma had progressed from stage i to stage ii, which made me eligible for participation in a national trial that focused on the effects of double stem cell transplant."

her first transplant took place in May 2005 and her second two months later. surrounded by her mother and best friend, haworth spent several months laughing,

crying, figuring out pills, playing scrabble and eating ice cream. "i learned to fight with everything i had in me," she says. By october, haworth was ready to move home to Bemidji, and she returned to teaching in January 2006.

"on the day of my last weekly checkup with my oncologist, i asked him, 'what do i do now?' he said, 'Go out and live.'" Taking his advice to heart, haworth bought herself a scooter, learned to play the drums and moved to africa on a fulbright scholarship. "it was an opportunity to do something creative, interesting, crazily different and a lot of fun," she shares.

Today, at the age of 52, haworth is ready to leave africa and return to Minnesota where she will serve as chair of the music department at Bemidji state University. "i am determined to take things as they come," she reflects. "i have new blood and a new outlook. i have a new life."

Janice's Story

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a U To lo G o U s T r a n s P l a n TAutologous transplant can prolong the disease‑free interval in patients with hematologic malignancies, including lymphoma and multiple myeloma. Autologous transplant eliminates the risk of graft‑versus‑host‑disease, and provides fewer treatment‑related complications and lower mortality than allogeneic transplant.

Our Blood and Marrow Transplant Program offers many transplant options for patients with different disease and risk characteristics. Our researchers are engaged in multicenter national trials to further improve autologous transplant and improve survival.

M U K Ta a r o r a , M d : i M P r o v i n G PaT i e n T o U Tc o M e sMukta Arora, MD, is focused on developing new therapies to improve outcomes for transplant patients with multiple myeloma. Her work involves the use of medications to delay relapse following autologous transplant. "We are learning how to improve patient outcomes in the wake of new medications that have been discovered over the last decade," she says. "We are trying to determine the value of a single transplant or one with added consolidation treatment versus two transplants."

A major randomized national trial, led by Arora and other researchers at the University of Minnesota's Masonic Cancer Center, is currently underway examining the role of lenalidomide (Revlimid®) in patients with multiple myeloma. "We have seen encouraging outcomes with this drug when given post‑transplant," she says. "It prolongs disease‑free intervals and survival."

University of Minnesota researchers, including Arora, are investigating the incorporation of protease inhibitors into cancer treatments. Early clinical trials suggest this approach may yield fewer side effects and higher response rates for patients with myeloma, leukemia and lymphoma.

Arora stresses the importance of timing, especially for national trials. "These trials need early referrals," she explains. "We want to see patients immediately after diagnosis, not after they have tried other therapies. The sooner we see them, the better."

Arora clearly is optimistic about the future of autologous transplant, especially for patients with hematologic malignancies such as multiple myeloma. "There is a lot of research going on in the area of myeloma—it is an exciting time."

Nurse coordinators

every blood and marrow transplant (BMT) patient works with one designated nurse coordinator from his or her very first visit through transplant and follow‑up care. The nurse coordinator is a vital link to the entire BMT team, serving as a direct contact for answering medical questions and addressing concerns.

"having one contact makes it more personal for the patients," says carol rose, rn, nurse coordinator. "we act as a point person so patients reach a live person every time they call." nurse coordinators provide patients with in‑depth education about the BMT process. They also help patients understand their symptoms, obtain medication refills, make appointments, and coordinate procedures and lab tests.

"The most rewarding element of my job is developing a trusting relationship with a patient," states Kathy hodges, rn, nurse coordinator.

"Patients know they can count on us. we are their advocates."

"This is a world‑class program that provides comprehensive care for our patients," continues rose. "it is so interesting to see the research take place and patients survive when five years ago that might not have been the case. we continue to see improved results, and that is pretty exciting."

hodges agrees. "There are so many new and exciting protocols, medications and therapies. i learn something new every day."

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An Unbelievable Miraclein 2009, musician dean Magraw was on what he described as "the greatest tour of my life." Traveling through europe with a five‑person band, he basked in the sights, sounds and energy of the experience—he had no idea the music would turn discordant upon his return.

a blood test during a routine physical revealed that Magraw had myelodysplastic syndrome (Mds), which can only be cured through blood and marrow transplant (BMT). neither his brother nor sister was a match so on august 25, 2009, dean received a cord blood transplant at University of Minnesota Medical center, fairview.

working with experts from University of Minnesota Physicians, Magraw embarked upon the toughest journey of his life. "This experience has changed my spiritual outlook and given me a new perspective on what is important and what is not," he explains.

after his transplant, Magraw returned to his music. as a guitar player, there were times during his recovery when he could not play. "The guitar was too heavy on my knee," he says. "and my hands would cramp up. My wife encouraged me to play more simply and let the instrument hold the notes." it seemed to work. in april 2011, Magraw performed an original composition called "BMT Blues" at a concert for the BMT program staff and their families.

Today, he has nothing but thanks for his caregivers. "The doctors and nurses were top notch," says Magraw. But it is his wife for whom he has the most gratitude. "she was my primary caregiver when i went home. she flushed my lines every day and did a thousand other things for me."

despite the stress of the experience and setbacks along his way, Magraw appreciates the medical advances that gave him back his life. "it was an unbelievable miracle," he says.

"This experience has changed my spiritual outlook, and given me a new perspective on what is important and what is not."

—Dean Magraw, musician and BMT patient

Dean's Story

Photography by Manfred Pollert

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Social workers

Blood and marrow transplant (BMT) patients are never alone. a clinical social worker supports every patient and their family from the first appointment through the entire transplant process.

The adult BMT program at University of Minnesota Medical center, fairview, has four licensed social workers, all of whom hold a master's degree in clinical social work. "while we work as a team with nurse coordinators, our role is to assist patients and families with nonmedical needs," explains leah otterlei, BMT social worker.

The social worker's support begins at the new transplant consultation, at which time patients receive detailed information about the BMT process. "BMT social workers have access to multiple grants to help patients and their families with the ongoing out‑of‑pocket costs they will face," says otterlei. "we are aware of all the criteria, as grant eligibility varies based on diagnosis and donor source. Many patients fear the financial burdens of complex care almost as much as the risks of therapy. we work hard to help them find all available resources."

BMT social workers also provide patients and their families with information and advocacy for caregiver needs, employment and disability concerns, temporary housing needs, family medical leave and health care directives. caregiver and patient support groups provide opportunities for ongoing group counseling.

"BMT social workers play a unique role," says otterlei. "we can be a wonderful resource for the patient and his or her family during this journey."

U M B i l i c a l c o r d B lo o d T r a n s P l a n TUmbilical cord blood (UCB) transplant requires less stringent matching, which extends the option of transplant to patients who do not have a matched related or unrelated donor. In addition, UCB is more rapidly available and offers a lower incidence of graft‑versus‑host‑disease as compared to unrelated donor stem cells.

At University of Minnesota Medical Center, Fairview, we have the nation's largest adult UCB transplant program. Experts from University of Minnesota Physicians continue to lead the field in cord blood research and transplantation. Their depth of experience allows us to find a suitable transplant option for nearly all patients who could benefit from transplant.

claUdio BrUnsTein, Md: new Uses for UMBilical cord BloodClaudio Brunstein, MD, clinical director of the Blood and Marrow Transplant (BMT) Program at University of Minnesota Medical Center, Fairview, is a nationally renowned expert in the field of umbilical cord blood transplant for adult patients. "We can find cord blood grafts for almost everybody," says Brunstein. "On the other hand, only one‑third to one‑half of adults are able to find an adult donor because of issues with tissue matching." In addition, cord blood transplant is associated with a lower incidence of graft‑versus‑host‑disease (GVHD), a serious complication of allogeneic transplant.

"For most adults, a single cord blood unit is not large enough," continues Brunstein. "The double cord transplant provides the quantity of hematopoietic stem cells an adult needs and also enhances the immune system." Today, more than 400 double cord transplants have taken place at the medical center, and the protocol has been adopted worldwide.

"Looking ahead, there are two areas of research that hold great interest for us," says Brunstein. "We are involved in a study to evaluate the safety and tolerability of using expanded umbilical cord blood hematopoietic stem cells in patients with hematological malignancies." Brunstein, along with Margaret MacMillan, MD, are principal investigators studying the use of specialized regulatory T‑cells from cord blood to reduce GVHD after a transplant. "Initial results of a study found reduced incidence of grade II‑IV acute GVHD with no increased risk of infection, relapse or early mortality," says Brunstein. Researchers are now giving higher doses of the cells to patients.

"The treatment of high risk and advanced hematologic malignancies is still suboptimal," Brunstein reports. "But the results today are better than they were 10 years ago. It is critical that we continue to investigate and invest in new methodologies such as cord blood transplant, which make it possible for every patient who needs a transplant to find a donor."

we have a l l of The P i eces!Our expert team works together to provide all of the pieces, ensuring that every blood and marrow transplant patient receives superior care and support before, during and after transplant.

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The Gift of HopeTerry connor was no stranger to health problems. living with multiple sclerosis and crohn's disease, she was used to routine blood draws, transfusions and hemoglobin levels as low as 5.3. however, a bone marrow biopsy in June 2010 confirmed a new diagnosis—myelodysplastic syndrome (Mds).

"My doctor said if i did not do something now, i would not make it to christmas," says connor. "That was difficult to hear."

chemotherapy failed to control her disease, and complications landed connor in the intensive care unit. "i was in a grave situation. My kidneys were shutting down, and my heart was enlarging. it was touch and go."

Terry's doctor referred her to erica warlick, Md, at University of Minnesota Medical center, fairview. "My initial doctors had been very negative," continues connor. "They did not think i would be a good transplant candidate because of the Ms and crohn's disease. dr. warlick changed all of

that. she said i was a strong young woman, and there was no reason not to have a transplant. she gave me hope."

connor's siblings were not a match so an unrelated donor was found through the national Marrow donor Program. "The transplant itself felt like a big transfusion of blood," says connor, who remained in the hospital for a couple of weeks. after discharge, her family and friends provided round‑the‑clock care to her at home.

"This experience has changed my perspective about life," she says. "i thank God every day that i wake up. i am thankful for my donor. smaller things in my life mean more than bigger things now. i have learned to let go. having been told i was going to die changed everything."

connor reports that life today is a little slower as she continues to regain her strength. "But every day is a blessing. i am so grateful to dr. warlick for saving my life."

"I thank God every day that I wake up. I am thankful for my donor."

—Terry Connor with Erica Warlick, MD

Terry's Story

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U n r e l aT e d d o n o r T r a n s P l a n TIf a human leukocyte antigen (HLA)‑matched relative is not available, a transplant using stem cells from an unrelated donor may be an option. The Blood and Marrow Transplant (BMT) Program at University of Minnesota Medical Center, Fairview, has a long‑standing and collaborative relationship with the National Marrow Donor Program (NMDP), which maintains a database of nearly 10 million potential volunteer donors and direct connections to other donor registries worldwide.

At the medical center, we have one of the oldest and most respected unrelated donor transplant programs in the nation. Many of the physicians in our program hold leadership positions within the NMDP and Center for International Blood and Marrow Transplant Research that allow them to shape the future of research.

e r i c a wa r l i c K , M d : UndersTandinG MYeloPlasTic sYndroMeErica Warlick, MD, medical director of the Blood and Marrow Transplant Clinic, devotes her research efforts to understanding myelodysplastic syndrome (MDS), its progression and potential treatment options. She is a key member of the Masonic Cancer Center team that is heading up the largest study of its kind to identify factors that may increase the risk of developing MDS. Researchers are comparing clinical and genetic data from 700 MDS patients with data from 700 individuals without MDS.

"This study is very exciting," says Warlick. "It will better our understanding of who gets MDS and why—and why it progresses to acute leukemia in some. Knowing that information will help us develop more effective treatments."

In March 2012, University of Minnesota researchers were awarded a $1.35 million grant for projects that aim to identify genes that may be important in both MDS development and progression to leukemia. "The identification of certain genes will lead us to predictors of who is most vulnerable to leukemia," states Warlick. She is particularly excited about using the grant money to develop a clinical trial that will test the feasibility of enhancing a patient's own immune system with natural killer (NK) cells. "Giving patients NK cells from healthy individuals may help to reduce the number of MDS cells and control progression of the disease."

Warlick believes the next breakthrough in MDS research will come from having a better understanding of the genetic basis of the disease and its progression to acute leukemia, enabling physicians to identify therapies to target those genetic defects.

"Focusing on genetic testing will enable us to identify patients who best respond to treatment and develop therapies directed toward new treatment targets."

Finding the best match – donor search process

for patients in need of allogeneic transplant, it is critical to quickly identify an acceptable source of stem cells. The use of dna‑based tissue typing has increased the accuracy of human leukocyte antigen (hla) matching, resulting in improved survival, reduced graft‑versus‑host‑disease (Gvhd) and improved rates of engraftment.

"when there is not an appropriate family match, the search goes to unrelated donors or cord blood," says Kathy french, rn, unrelated donor search coordinator at University of Minnesota Medical center, fairview. "we are learning more all of the time, and our process changes as the situation changes."

search coordinators must consider many patient and disease factors when identifying the best graft source from among the 10 million donors and 165,000 umbilical cord blood units listed through the national Marrow donor Program (nMdP) and worldwide registries.

"it is a privilege to work with families, referring physicians and doctors from University of Minnesota Physicians to gather information and keep all parties informed during the search for a donor," Kathy adds. "The turning point for families is when we find a suitable graft allowing the patient to proceed. our goal is to have the best donor graft ready and available when it is needed, and to help facilitate a successful transplant."

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Here for a Reasonin 2002, leah arnold was newly married, had graduated from college and was preparing to take the Medical college admissions Test (McaT) when she noticed a lump on her neck. doctors told her it was related to stress, but over the next several months, the lump kept growing, and she began having trouble breathing and swallowing. a tumor stretching from her neck to her heart was discovered—arnold was diagnosed with non‑hodgkin lymphoma.

arnold immediately began chemotherapy and radiation, but it did not stop new tumors from forming in her kidney, liver and lungs. she needed a blood and marrow transplant, and was referred to University of Minnesota Medical center, fairview. human leukocyte antigen testing revealed that her younger brother, Justin, was a perfect match, and arnold was transplanted with his donated stem cells in July 2003.

"i was basically out of it for the next 80 days," says arnold. "My father and father‑in‑law were both retired so they became

my caregivers so that my husband could continue to work. My mother and mother‑in‑law came up on the weekends."

arnold had a few rough spots in her recovery. following transplant, she dealt with graft‑versus‑host‑disease, infection, scleroderma and fractures, including a broken rib from rolling over in bed. "My doctors just kept searching for solutions. They never gave up. i had an amazing transplant team."

in 2011, arnold received her forensic science certificate, and she currently is interning at the Minnesota Bureau of criminal apprehension. she is grateful for the medical staff that surrounded her. "i would not be here without dr. Burns. she is more than a doctor. i consider her almost family and will always be grateful to her."

arnold has a special reason for staying strong now. "My dad was diagnosed with lymphoma after my transplant, and he did not make it. we drew strength from each other. now, i want to live for him. i am here for a reason."

"My doctors just kept searching for solutions. They never gave up. I had an amazing transplant team."

—Leah Arnold with Linda Burns, MD

Leah's Story

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r e l aT e d d o n o r T r a n s P l a n TThe first step to a successful transplant is the identification of a histocompatible source of donor stem cells. The search process typically begins with the human leukocyte antigen (HLA) typing of a patient's siblings. Since HLA types are inherited, siblings who genetically share a mother and father have a 25 percent chance of being an identical HLA match.

All related donors are cared for by our expert blood and marrow transplant team. They receive a thorough medical screening and information to ensure that they are both medically eligible and fully informed about the donation process. Our goal is to provide a safe, convenient and rewarding experience for the donors who choose to make a lifesaving donation for their family member in need.

l i n da B U r n s , M d : redUcinG coMPlicaTions of Blood and Marrow TransPlanTaTionImproving outcomes for patients with hematologic malignancies is the focus of research led by Linda Burns, MD. "Our research efforts are focused in three major areas," she says. "We conduct novel studies through the University of Minnesota's Masonic Cancer Center; we work with large, well‑recognized U.S. centers of transplant excellence; and we conduct pharmaceutical studies with drugs we are considering."

"Clinical trials can really move the field forward and change the course of treatment," continues Burns. "I can remember a time before we used hematopoietic growth factors hormone for autologous transplant donors. Now, thanks to insights uncovered in clinical trials, this is the standard of care."

Burns cares deeply about reducing complications of blood and marrow transplantation, including infections, second cancers and late effects. Burns' former patient, Leah Arnold, was responsible for launching Burns into a new career focus on late complications.

"Leah began experiencing spine and rib fractures following her transplant," says Burns. "Working with her led me to think more about helping patients survive the cure itself." Burns just concluded a study aimed to prevent bone loss during the first year after an allogeneic transplant. "The results have been very positive."

She also is studying patients who require multiple blood transfusions during therapy, paying special attention to iron overload. Burns and her team want to know if patients with high levels of iron are especially prone to deleterious effects such as graft‑versus‑host‑disease or infections.

Looking to the future, Burns would like to see more patients enter into transplant while in clinical remission. "The less disease a patient has, the better the outcome," she says.

Saving his sister's life, in a heartbeat

Justin Johnson was only 22 years old when he offered to donate bone marrow to his sister, leah arnold. "My brother and i were tested to see if we were a match," he says. "i lucked out. leah was very sick. There was only so much we could do for her, but this would give her a chance."

Johnson was given growth factor injections to increase the number of stem cells in his circulating blood. he then spent an afternoon at University of Minnesota Medical center, fairview, hooked up to an apheresis machine that collected his stem cells for transplant.

"i watched a movie and ate a cheeseburger while this was happening," he recalls. "it was the easiest thing i have ever done. it is really all relative. You watch your sister go through that and ..." his voice trails off. "when i was younger, i used to think we were invincible. This experience has made me come to terms with life and death."

Johnson is happy with the progress his sister is making and care she has received. "leah is the best i have ever seen her," he says. "she will give a lot back to society. her doctors were lifesavers. There is no way i can repay them."

when asked if he would he consider donating bone marrow again someday, Johnson replies without hesitation, "in a heartbeat."

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NK Cellular Therapy

Natural killer (NK) cells enhance immune responsiveness and attack cancer cells. "The most promising NK therapy right now is in patients with refractory acute myeloid leukemia (AML)," continues Miller. "We have been studying this for nearly 10 years using AML patients for whom standard therapy has not worked. We give them a preparatory regimen of chemotherapy and/or radiation therapy to blunt their immunity and make space for transferred donor NK cells."

In the last 10 years, more than 100 patients have been treated with NK cell therapy at University of Minnesota Medical Center, Fairview. Now, Miller and other researchers are looking for better ways to stimulate the NK cells so they can be more effective.

"Earlier studies used Interleukin‑2 (IL‑2)," says Miller. "Now we are expanding our research into more novel approaches such as Interleukin‑15 (IL‑15)." The first in‑human study using IL‑15 to stimulate donor‑NK cells for refractory AML is taking place at the medical center. "It is a dose escalation study," adds Miller. "We are the only site outside of the National Cancer Institute using IL‑15."

"We have the infrastructure in place to pair scientists with clinical investigators and people familiar with cancer drugs to devise strategies that can bring a basic laboratory idea to the clinic."

—Jeffrey Miller, MD, Masonic Cancer Center director

n e w d i r e c T i o n s i n B lo o d a n d M a r r o w T r a n s P l a n T r e s e a r c hIn their effort to expand blood and marrow transplant (BMT) options for patients and improve outcomes, scientists at the University of Minnesota's Masonic Cancer Center foster discovery and innovation through their ongoing research initiatives. These dedicated researchers translate hours of painstaking work in the laboratory into novel treatments that can provide patients with more effective and safer treatment options.

16Pictured at left: Jeffrey Miller, Md

Researchers at the Masonic Cancer Center are exploring the use of NK cells to attack other diseases. Veronika Bachanova, MD, and Miller are targeting lymphoma. Melissa Geller, MD, is focusing on ovarian cancer. Erica Warlick, MD, is working on therapies for myelodysplastic syndrome. Researchers also have completed a clinical trial using NK cells from cord blood and are looking at ways to combine NK treatment with BMT in a single procedure.

"What is unique about our effort is that we are trying to enhance all the potency of NK cells and targeting them to the tumors," says Miller. "Others are trying to get the same effect with regulatory T‑cells."

Regulatory T‑cell Research

Regulatory T‑cells (T‑regs) are a type of white blood cell that has been shown to reduce graft failure and prevent graft‑versus‑host‑disease (GVHD), a serious complication of transplantation. GVHD results when donor T‑cells attack a patient's normal tissues. T‑regs, given soon after transplant, can suppress the immune reactions and reduce the potential for GVHD.

University of Minnesota researchers conducted the first in‑human clinical trial using T‑reg cells from umbilical cord blood. "T‑regs blunt the immune response," says Miller. "A dose escalation study is one of several T‑reg projects now underway at the University of Minnesota." Initial results of one study led by Claudio Brunstein, MD, found reduced incidence of grade II‑IV acute GVHD with no increased risk of infection, relapse or early mortality. Efforts are currently underway to improve T‑reg longevity and expansion.

KIR and Transplant Research

Sarah Cooley, MD, in collaboration with Miller and Daniel Weisdorf, MD, is leading a national clinical trial to examine the killer immunoglobulin‑like receptor (KIR) gene typing of donors as a way to improve patient transplant outcomes.

KIRs represent one family of receptors on the surface of NK cells. "In trying to understand how NK cells attach to tumors, we have to understand the interactions between NK cells and tumor cells," explains Cooley. "The NK cells are covered with dozens of receptors that can either be activating and stimulating the NK cells to kill their targets or inhibitory to calm the cell. Every interaction between NK cells and tumor cells is a net balance of how many activation signals stimulate versus how many inhibitory signals quiet the immune attack. The result determines whether or not the target is destroyed." Inherited KIR genes determine whether a person's NK cells are more likely to attack or not; immune activity which in a transplant donor might lead to better prevention of cancer recurrence or not.

In a 2010 article published in the journal Blood, Cooley reported encouraging data that justified opening a national study led by researchers at the Masonic Cancer Center that entailed using the inherited KIR genetic data to choose who might be a better donor for transplants. This ongoing clinical trial involves 20 transplant centers around the country that perform unrelated transplants for patients with acute myeloid leukemia (AML).

Right now, the greatest benefit of this donor KIR gene research appears to be for patients with AML. "They seem to be uniquely susceptible to NK cell‑mediated attack," says Cooley. "Our goal is to be able to select donors with favorable KIR profiles and achieve better outcomes for these patients."

Looking to the Futurenever content to rest on their laurels, researchers at the University of Minnesota are constantly searching for ways to drive the field of blood and marrow transplantation forward. "we are all trying to understand how to muster the successes we have seen in transplantation for hematologic malignancies and bring them to solid tumor settings," says Miller. "we are starting at the cellular level. Maybe we will find an effective immune cell therapy and will not need to perform a blood and marrow transplant after all."

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Daniel Weisdorf, MDDirector, Adult BMT Program 612‑624‑3101weisd001@umn.edu

Mukta Arora, MD612‑626‑4105arora0005@umn.edu

Veronika Bachanova, MD, PhD612‑625‑5469bach0173@umn.edu

Nelli Bejanyan, MD612‑624‑6982nbejanya@umn.edu

Claudio Brunstein, MD612‑625‑3918bruns072@umn.edu

Linda Burns, MD 612‑624‑8144burns019@umn.edu

Sarah Cooley, MD612‑625‑8474cool0023@umn.edu

Dan Kaufman, MD, PhD612‑624‑0922kaufm020@umn.edu

Aleksandr Lazaryan, MD612‑626‑4253 alazarya@umn.edu

Brian McClune, DO612‑625‑7101bmcclune@umn.edu

Philip McGlave, MD612‑624‑5422mcgla001@umn.edu

Jeffrey Miller, MD612‑625‑7409mille011@umn.edu

Arne Slungaard, MD612‑624‑9210slung001@umn.edu

Celalettin Ustun, MD612‑624‑5109custun@umn.edu

Gregory Vercellotti, MD612‑626‑3757verce001@umn.edu

Erica Warlick, MD612‑625‑5467 ewarlick@umn.edu

Tim Krepski, RN BMT program supervisor

we wanT To TalK To YoU!• Refer a patient• Ask questions about our BMT

Program • Inquire about open BMT

research protocols• Request a callback from a BMT

physician

612‑273‑2800Blood and Marrow Transplant Program MMc 803 420 delaware st. se Minneapolis, Mn 55455

612‑273‑2800 or 888‑601‑0787 (toll‑free)

uofmbmt.org

"Patients with leukemia or other blood diseases who can be cured by transplant do better if they are referred early and transplanted while in remission."

—Sarah Cooley, MD

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Blood and Marrow Transplant ProgramUniversity of Minnesota Medical center, fairview MMc 803420 delaware st. seMinneapolis, Mn 55455

uofmbmt.org