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Cancer, Patient Care, Stem Cells, Transplants

The inside scoop on bone marrow transplants

The inside scoop on bone marrow transplants

blood-156063_1280Your bones harbor blood manufacturing factories. Those factories, packed in the bone marrow, produce stem cells that develop into red blood cells, white blood cells and platelets. Cancers such as leukemia and a few genetic conditions can weaken the bone marrow, necessitating a bone marrow transplant.

Witold Rybka, MD, director of the Bone Marrow Transplantation Program at Penn State Hershey, fielded questions recently in this Q&A on the procedure. An excerpt:

What are the most common types of bone marrow transplants?

For an autologous transplant, the patient can bank his or her own stem cells before undergoing intensive treatment for certain diseases such as lymphoma, Hodgkin’s lymphoma or multiple myeloma. The patient’s body can then use its own banked stem cells to regenerate healthy marrow once treatment is complete. Other transplants are allogeneic, meaning that the patient must receive matching stem cells from a sibling, family member or unrelated donor.

What are the odds of finding a match within one’s own family?

The chance of finding a full match is one in four, so the larger your family, the better chance you have of finding a match among your relatives. Given the size of most American families, most donors must use an unrelated match from a registry of more than 17 million living donors worldwide.

Unfortunately, it’s possible that a patient who needs a bone marrow transfusion won’t get one. Most banked stem cells are from donors in North America and Europe, making it easier for white patients to find a match. For patients of other ethnicities, the chance of finding a donor is only 60 percent, Rybka said.

To learn more about bone marrow transplants, visit Be The Match.

Previously: Bone marrow transplantation: The ultimate exercise in matchmaking, Bone marrow transplantation field mourns passing of pioneer Karl Blume and One (blood stem) cell to rule them all? Perhaps not, say Stanford researchers
Image by OpenClipartVectors

Cardiovascular Medicine, Patient Care, Pediatrics, Stanford News, Transplants

NBC Dateline to explore the “extraordinary situation” facing one Packard Children’s transplant family

NBC Dateline to explore the "extraordinary situation" facing one Packard Children's transplant family

Bingham family - 560

It’s a story that seems a bit hard to believe.

Stacy and Jason Bingham of Haines, Oregon, have five beautiful children — Sierra, Megan, Lindsey, Hunter, and Gage. Unfortunately, as written about on Scope previously, three of the kids have been hit with cardiomyopathy, a life-threatening disease of the heart muscle that reduces the heart’s ability to pump blood effectively. Two other children are being monitored for heart irregularities.

The result? The eldest, 16-year-old Sierra, has received two heart transplants at Lucile Packard Children’s Hospital Stanford, one in 2006 and a replacement in 2015. Lindsey, 12, had a heart transplant in 2013. Gage, 7, was recently placed on a Heartware ventricular assist device in order to support his failing heart. He is now awaiting placement on the transplant list. Meanwhile, cardiologists are keeping an eye on any potential problems that could be faced by Megan, 14, and Hunter, 9.

“This is an incredibly strong and wonderful family, and they’re facing an extraordinary situation,” said David Rosenthal, MD, director of the pediatric heart failure program at Packard Children’s.

This Sunday, January 17, at 9 PM Pacific, Dateline NBC will be presenting their second national broadcast looking at the personal and medical journey the Binghams have faced, along with the many challenges ahead. In addition, the program will reveal some of the advanced therapies for heart failure offered by the Heart Center at Stanford Children’s Health.

The first Dateline NBC program on the Bingham family, which aired in 2013, can be viewed here.

Robert Dicks is senior director of media relations for Lucile Packard Children’s Hospital Stanford.

Previously: Ventricular assist device helps teen graduate from high schoolStem cell medicine for hearts? Yes, please, says one amazing family and Packard Children’s heart transplant family featured tonight on Dateline
Photo by Norbert von der Groeben

Cancer, Immunology, Research, Science, Stanford News, Stem Cells, Transplants

One (blood stem) cell to rule them all? Perhaps not, say Stanford researchers

One (blood stem) cell to rule them all? Perhaps not, say Stanford researchers

4294019174_3f269b3f38_oThe blood stem cell, or hematopoietic stem cell, is a cell that’s believed to give rise to all the components of the blood and immune system. Nestled in our bone marrow, it springs into action as necessary and is a key component of bone marrow transplantation procedures (more accurately called hematopoietic stem cell transplantation) conducted to save patients with blood diseases or whose immune systems have been wiped out by large doses of chemotherapy or radiation.

But new research published today in Stem Cell Reports by research associate Eliver Ghosn, PhD, and colleagues in the laboratory of geneticist Leonore Herzenberg suggests that, at least in laboratory mice, this stem cell may not be as omnipotent as previously thought. In particular, it seems unable to give rise to an important subpopulation of B cells, a type of immune cell. As Ghosn explained to me in an email:

Briefly, our findings challenge the idea that a single blood, or hematopoietic, stem cell (HSC) can fully regenerate all components of the immune system. We’ve shown that transplantation with highly purified HSCs fails to fully regenerate the B lymphocyte compartment, which is needed to protect against infections such as influenza, pneumonia and other infectious diseases, and also to respond to vaccinations.

Further studies conducted by the researchers suggest that these B cells may arise from an alternative fetal progenitor cell distinct from the HSC — perhaps as an evolutionary effort to separate what’s known as innate immunity from adaptive immunity. They urge further research into the clinical outcomes of the transplantation of purified HSC in humans. As Ghosn said:

From a clinical standpoint, these findings raise the key question of whether human HSC transplantation, widely used in human regenerative therapies to restore immunity in immune-compromised patients, is sufficient to regenerate human tissue B cells that help protect transplanted patients from subsequent infectious diseases. This is specially relevant today considering that the field is moving toward using highly purified human HSCs in clinical settings. 
More research is needed to confirm the findings in humans, however. If you’re interested in learning more about this, Ghosn expanded upon the idea earlier this month with a review in the Annals of the New York Academy of Sciences.

Cardiovascular Medicine, Pediatrics, Transplants

Unusual bridge-to-transplant method helps teen get new heart and lungs

Unusual bridge-to-transplant method helps teen get new heart and lungs

bridge-to-transplant device
Earlier this year, Oswaldo Jimenez’s heart and lungs were failing. He needed a combined heart-lung transplant, but his doctors at Lucile Packard Children’s Hospital Stanford were worried that the 14-year-old from Salem, Oregon might not survive the wait for donor organs.

Stanford physicians have lots of experience with using external and implanted pumps that can support a patient’s failing heart. A few years ago, for instance, an 8-year-old patient spent 229 days with a Berlin Heart pump that moved blood through her body while she awaited a heart transplant.

Oswaldo’s case was different. Although his heart failure was significant, his failing lungs posed the biggest risk to his health. His doctors were concerned that his poor lung function would immobilize him – yet to benefit from transplanted lungs, he needed to stay fairly fit and mobile while he waited.

So the doctors decided to try an unusual bridge-to-transplant procedure called a “pulmonary to left atrial shunt,” which connected Oswaldo’s heart to a portable box outside his body that oxygenated his blood. Essentially, the team gave Oswaldo a temporary, artificial lung.

A press release from the hospital explains how it worked:

The procedure involved the insertion of a tube that redirected blood away from Oswaldo’s lungs into the oxygenator. This, in turn, provided oxygen to the blood and then returned it to his body, with his own heart providing the pump. Reports on this shunt device being able to sustain patients’ lives range from several weeks to six months, depending mostly on being able to prevent the blood from clotting while avoiding complications such as bleeding or stroke.

On July 12, Oswaldo made history by becoming the first child in the western United States to undergo this treatment — it saved his life and bought him time. Then, just one week after receiving the shunt, donor organs became available. Oswaldo received his heart and lung transplant on July 19.

Oswaldo is still recovering at the Ronald McDonald House, and his doctors think he’ll be able to go home close to the New Year. He’s looking forward to being a kid again, and his grateful family is thinking about how his case might benefit other kids in similar situations. “Now the doctors can use this therapy to treat other patients,” said Oswaldo’s mom, Carmen Hernandez.

Previously: Stem cell medicine for hearts? Yes please, says one amazing family, “Liberated from LVAD support”: One patient’s story and Image of the Week: First heart-lung transplant
Image of pulmonary to left atrial shunt courtesy of Lucile Packard Children’s Hospital Stanford

Cancer, Research, Sleep, Stanford News, Stem Cells, Transplants

Sleep deprivation affects stem cell function, say Stanford scientists

Sleep deprivation affects stem cell function, say Stanford scientists

sleepy mouseWe all know that sleep is important for many biological functions. But I’m still surprised at the breadth of its influence. Today, a former postdoctoral scholar at Stanford, Asya Rolls, PhD, published a fascinating study in Nature Communications showing that blood-forming stem cells from drowsy mice perform more poorly when transplanted into recipient animals. In particular, they are less able to home to the bone marrow, and they generate a smaller proportion of a type of immune cell called a myeloid cell than do stem cells from well-rested mice.

Although the researchers studied only laboratory mice, the possible implications for human transplant recipients (in humans, these procedures are called hematopoietic stem cell transplants, or sometimes bone marrow transplants) are intriguing. As Rolls, who is now an assistant professor at the Israel Institute of Technology, said in our release, “Considering how little attention we typically pay to sleep in the hospital setting, this finding is troubling. We go to all this trouble to find a matching donor, but this research suggests that if the donor is not well-rested it can impact the outcome of the transplantation.”

At Stanford, Rolls worked in the laboratory of psychiatrist and sleep medicine specialist Luis de Lecea, PhD, and she collaborated with Wendy Pang, MD, PhD, and Irving Weissman, MD, director of the Stanford Institute of Stem Cell Biology and Regenerative Medicine, to conduct the research.

Despite the fact that sleep deprivation in the donor reduced the efficacy of their stem cells by about 50 percent, all is not lost. From our release:

Although the effect of sleep deprivation was stark in this study, Rolls and her colleagues found that it could be reversed by letting the drowsy mice catch up on their ZZZs. Even just two hours of recovery sleep restored the ability of the animals’ stem cells to function normally in the transplantation tests.

“Everyone has these stem cells, and they continuously replenish our blood and immune system,” said Rolls. “We still don’t know how sleep deprivation affects us all, not just bone marrow donors. The fact that recovery sleep is so helpful only emphasizes how important it is to pay attention to sleep.”

Previously: In mice, at least, uninterrupted sleep is critical for memory and Bone marrow transplantation: The ultimate exercise in matchmaking
Photo by Eddy Van 3000

Immunology, Infectious Disease, Precision health, Research, Stanford News, Transplants

A blood test that monitors for post-lung-transplant rejection and infection

A blood test that monitors for post-lung-transplant rejection and infection

lungsA team under the direction of Stanford bioengineer Steve Quake, PhD, has shown that a noninvasive blood test can accurately diagnose lung-transplant rejection. The test also simultaneously detects infections by patient-imperiling microbes.

About 3,500 lung transplant procedures are performed annually worldwide. But median survival after the graft barely exceeds five years, trailing the outcomes for kidney, heart, liver and other solid organ transplants. Chronic organ rejection is the biggest single factor. Infection (for which recipients are at high risk due, ironically, to their post-transplant regimen of immune-suppressing drugs given to reduce the likelihood of organ rejection) is another leading contributor.

In a study published in Proceedings of the National Academy of Sciences, Quake and his associates demonstrated that the test, which involves high-throughput sequencing of DNA, flags organ rejection by detecting increasing amounts of donor DNA in a recipient’s blood. The relatively low-cost test doesn’t require the highly invasive removal of lung tissue, and it can also screen for myriad bacterial, viral and fungal pathogens.

In another study in 2014, Quake and Stanford colleagues had come up with a similar blood test to determine whether a heart-transplant recipient was headed for organ rejection. The new study expands the test’s applicability to lung transplantation – and suggests that its utility may extend to solid organs in general, including more-frequently performed procedures such as kidney transplantation (more than 17,000 in the United States alone in 2014).

With better than half of all lung-transplant patients suffering organ rejection in just the first year after their operation, this advance holds great clinical potential. Quick, accurate diagnosis is the first step toward appropriate treatment.

Previously: A simple blood test may unearth the earliest signs of heart transplant rejection, Step away from the DNA? Circulating *RNA* in blood gives dynamic information about pregnancy, health and Might kidney-transplant recipients be able to toss their pills?
Photo by Lorraine Santana

Cancer, Patient Care, Stanford News, Transplants, Videos

Immunosuppression brings higher risk for skin cancer – and need for specialized care

Immunosuppression brings higher risk for skin cancer – and need for specialized care

An estimated 50 million Americans must take immunosuppressants to treat more than 80 autoimmune disorders, according to the National Institutes of Health. These medications are particularly vital to the survival of people who have undergone organ transplants to prevent their bodies from rejecting their donor organ.

While immunosuppressants can be life-saving, their very action of reducing the body’s innate defense systems can have negative side-effects. One particularly dangerous concern is an increased risk for skin cancer, particularly for those individuals with fair skin or an inherited tendency to develop skin cancers. (My colleague Tracie White told the story of one transplant patient’s struggle here earlier this summer.)

To address the specialized needs of patients taking immunosuppressants or with compromised immune function, Stanford dermatologists recently launched the High-Risk Skin Cancer Clinic.

In this Stanford Health Care video, the clinic’s Carolyn Lee, MD, PhD, explains the particular vulnerabilities of transplant patients to aggressive skin cancer and the importance of a dedicated clinic to meet their needs. “What we hate to see — and it’s easily preventable — is someone who’s been waiting for a transplant to finally get it, only to be felled by skin cancer,” she says.

 

Previously: Rebuilding Cassie’s smile: A lung transplant patient’s struggle with skin cancer and This summer’s Stanford Medicine magazine shows some skin

Genetics, Pediatrics, Transplants, Women's Health

Rare African genes might reduce risks to pregnant women and their infants

Rare African genes might reduce risks to pregnant women and their infants

Khoe-SanWhen Hugo Hilton began working at Stanford as a young researcher several years ago, his supervisor set him to work on a minor problem so he could practice some standard lab techniques. His results, however, were anything but standard. His supervisor — senior research scientist Paul Norman — told him to do the work over, convinced the new guy had made a mistake. But Hilton, got the same result the second time, so Norman made him do it over again. And then again.

“This was Hugo’s first PCR reaction in our lab and I gave him the DNA,” recalled Norman, “and the very first one he did, he pulled out this mutation. I was convinced that he’d made a mistake.” Norman even quietly redid the work himself. But the gene variant was real.

Norman and colleagues had been studying the same group of immune genes for decades and he knew them like the back of his hand. Yet he was astonished by what Hilton had stumbled on — a mutation that switched a molecular receptor from one protein target to another. It would be as if you bent your house key ever so slightly and discovered it now opened the door to your neighbor’s apartment — but not yours.

And the mutation, far from causing some illness, might contribute to healthier mothers and babies. Parallel research at another institution suggests the odd gene most likely changes the placenta during early pregnancy, leading to better-nourished babies and a reduced risk of pre-eclampsia, a major cause of maternal death.

The surprising finding grew out of a long-term effort to understand how immune system genes make us reject organ transplants. A big part of that puzzle is understanding how much immune genes can vary. On the surfaces of ordinary cells are proteins called HLAs. Combinations of these proteins mark cells in a way that makes each person’s cells so nearly unique that the immune system can recognize cells as either self or not self. When a surgeon transplants a kidney, the recipient’s immune system can tell that the kidney is someone else’s — just from its cell surface HLA proteins. The patient’s immune system then signals its natural killer cells to attack the transplanted kidney. The key to all that specificity is the huge variation in the genes for the HLA proteins.

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Cancer, Chronic Disease, Dermatology, Stanford News, Surgery, Transplants

Rebuilding Cassie’s smile: A lung transplant patient’s struggle with skin cancer

lung patientWhen I first met Cassie Stockton, she was seated in an exam chair in Stanford’s dermatology clinic, getting cosmetic skin treatments. Lovely and young, just 21 years old, it seemed a bit silly. How could she possibly need injectable lip fillers or laser skin treatments?

I knew Stockton had a lung transplant at 15 and that the immunosuppressant drugs she was required to take to keep her body from rejecting the donated lungs had made her susceptible to skin cancer. But it wasn’t until I researched her story in depth that I truly understood how she ended up needing regular cosmetic treatments here.

As I explain in my recently published Stanford Medicine article, her story began at birth:

Born premature, [Cassie] was intubated the first two weeks of life, then sent home with her mother and an oxygen tank. She remained on oxygen 24 hours a day for the first two years of her life. Eventually, she was diagnosed with bronchopulmonary dysplasia, a chronic lung disorder …

Sixteen years later, the donated gift of new lungs saved her life – but it left scars, both emotional and physical:

The day Stockton woke up out of the anesthesia six years ago after a 13-hour surgery at the Transplant Center at Lucile Packard Children’s Hospital Stanford, she breathed in oxygen with newly transplanted lungs, and breathed out sobs. Tears streamed down her face. “At first, I thought she was in pain,” says her mother, Jennifer Scott, who stood by her side. But that wasn’t it. Stockton was overwhelmingly sad because she now knew her new lungs were the gift of a child. It was Dec. 6, 2009, just before Christmas. The death of someone else’s child had given her a whole new life.

And now:

Every four months, she and her fiancé make the four-hour drive from their home in Bakersfield, California, past the oil rigs and cattle farms to Stanford’s Redwood City-based dermatology clinic for her skin cancer screening. It’s been two years of treatments: freezings, laserings, a total of eight outpatient skin surgeries — the most significant resulting in the removal of the left half of her lower lip. The dermatologic surgeon removes the skin cancers, and then gets to work to repair the damage. “It’s heart-breaking to have to remove the lip of a 21-year-old woman,” says Tyler Hollmig, MD, clinical assistant professor of dermatology and director of the Stanford Laser and Aesthetic Dermatology Clinic, who leads Stockton’s treatment and keeps her looking like the young woman she is, restoring her skin, rebuilding her lip, making sure she keeps her smile.

Stockton doesn’t complain about any of the struggles she’s had post transplant. She knows she got a second chance at life. And, she tells me, it’s her job to take care of the lungs given to her by that child who died.

Previously: This summer’s Stanford Medicine magazine shows some skin
Photo by Max Aguilera-Hellweg

Cardiovascular Medicine, Chronic Disease, In the News, Research, Stanford News, Transplants

Are donor hearts getting wasted?

Are donor hearts getting wasted?

heart choiceI wrote a press release recently on a study that showed a high percentage of donated hearts were not being used, raising concerns that some were getting wasted when they could be used to save lives. This made me curious about the process of just how a donor heart, which ideally has about a two-hour window before it gets transplanted to a patient with heart failure, gets matched.

The result is a Stanford Medicine magazine story titled “Heart Choices” that describes this process, the tough decisions that family members make when a loved one donates a heart, and the excruciating waiting that patients in need of a new heart go through.

Most importantly the article asks the question: Should more “high-risk” donor hearts be used? An estimated 20,000 people across the country are waiting for new hearts, and only a few thousand transplants happen on average per year. My story explains the dilemma:

The general assumption is that there simply are not enough donor hearts available to meet a growing demand. But new research is questioning that assumption. Some researchers and surgeons claim that thousands of donor hearts that could be used are turned away each year. The hearts are considered marginal because they come from older, sicker or riskier donors, but many argue they are safe for transplant, and could be saving lives.

“As patients wait longer, they often get sicker, and we often lose patients,” says Stanford cardiologist Kiran Khush, MD, whose research reports that 65 percent of available heart donations are discarded because of stringent acceptance criteria. Yet the criteria have not been critically evaluated, she says. “Increasing the supply of donor hearts is, of course, a great concern of mine.”

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