Transplants

When Sharon Hunt, MD, arrived at Stanford as a first-year medical student in the fall of 1967, it was just months before the late cardiac surgeon Norman Shumway, MD, and his team would perform the first adult human heart transplantation in the United States. Then just an observer, Hunt would eventually become a key player in transplantation – staying on at Stanford, caring for more than 1,500 heart transplant patients, and becoming a pioneer in the field of post-transplant cardiology.

Hunt recently received a lifetime achievement award from the International Society for Heart and Lung Transplantation. And in a Stanford Hospital piece today, my colleague John Sanford shares some of Hunt’s history and describes the significance of her early work:

“Even after the surgical technique for heart transplantation had been developed and operations had been done, the field was naïve in that people didn’t know how to manage patients,” said cardiologist Michael Pham, MD, MPH, a clinical associate professor of medicine at Stanford. “How do you manage patients who will be on immunosuppressive medications for the rest of their lives? How do you balance the benefit of these drugs with their toxicities in the long run? How do you identify and treat patients who reject their transplanted hearts? These are some of the questions that Sharon has done more than anyone to answer.”

…

“Without Sharon, who took care of these transplant patients after figuring out their medications and complications, there would be no successful cardiac transplantation at all,” said Alan Yeung, MD, chief of cardiovascular medicine at Stanford Hospital and the Li Ka Shing Professor in Cardiology.

Previously: First U.S. heart transplant among the top 50 breakthroughs in science
Photo by Norbert von der Groeben

Statistics don’t define twins Anabel Stenzel and Isabel Stenzel Byrnes, who were born with cystic fibrosis but are beating the odds at age 40. And yet there’s a staggering statistic attached to their story, as described in a STANFORD magazine feature:

A genetic disease familiar in people of Northern European descent, CF is extremely rare in Asia. [Anabel and Isabel's] papa, Reiner Stenzel, a physicist, did the math: The odds of having half-Japanese identical twins with CF were about one in 1.8 billion.

After undergoing aggressive treatments during childhood, the two graduated from Stanford in 1994 and from graduate school at Berkeley, received three sets of transplant lungs between them, wrote a double memoir in 2007, inspired a documentary film, and currently work at Stanford’s Lucile Packard Children’s Hospital. Following near-death experiences, they continue to advocate – and serve as inspiration – for other CF patients:

Dr. David Weill, [MD,] director of Stanford Hospital’s Center for Advanced Lung Disease and the Lung Transplant Program, describes the Stenzels as “mentors to a lot of people who are newly diagnosed with CF, have had transplants or are contemplating transplants and don’t know what to expect.” He met them six years ago and is part of the team that has cared for them at Stanford. “In all my years of doing transplants, I haven’t met anyone with this level of commitment and vigor to live their lives like each day could be their last. That’s what makes them such good ambassadors. They show the world what’s possible.”

Previously:  Life-threatening diagnosis leads to powerful friendship for two California teens and Transplant patients organize a boot camp

Chronic hypersensitivity pneumonitis, like other conditions that attack the lining of the lungs, has no known cure. Patient Jen Julian told me that when she was diagnosed, “I didn’t know if I was going to live or not. You face the reality of death.”

In the video above and in an article published today, we share the story of Julian, who was treated by physicians at Stanford’s recently established Center for Advanced Lung Disease. Julian received a transplant here and has since returned with gusto to all those things she did before – skiing, biking, hiking, golfing and scuba diving. Glenn Rosen, MD, director of the Interstitial Lung Disease program, said of his patient, “Jen has a unique attitude. She looks at the setbacks as challenges, tries new things and lives life to the fullest.”

At a recent luncheon on the Stanford medical school’s campus, a group of kidney-transplant recipients celebrated their freedom from a lifetime regimen of immune-suppressing drugs, thanks to a new protocol developed by immunologist Sam Strober, MD.

I was there, too, and a few of those patients shared with me their experiences, as reported here today. The man shown in the photo with his adorable and very happy (I can attest to that) 2-year-old daughter is Daniel Bitner, one of the success stories.

In the three-and-a-half years since his kidney transplant, Bitner has been able to go without anti-rejection medications – which cost between $12,000 and $15,000 a year; can come with side effects such as high blood pressure, diabetes and higher risk of cancer and infection; and sometimes just don’t work. As I reported last October, the new protocol carries a total expense estimated to range from $20,000 and $40,000, so it has the potential to pay for itself within a few years. And it requires no additional hospital time.

Those seeking relatively simple scientific details of how the treatment works can find it here; a fuller explanation is provided in this release. And the latest and most-detailed description of the since-expanded trial, entitled “Tolerance and Withdrawal of Immunosuppresive Drugs in Patients Given Kidney and Hematopoietic Cell Transplants,” is scheduled for publication in the American Journal of Transplantation this week.

Previously: Might kidney-transplant recipients be able to toss their pills?
Photo by Norbert von der Groeben

Diagnosed early in childhood with cystic fibrosis, Emma Greene and Tiffany Senter were for several years able to lead relatively normal lives by managing their disease with medication and machines to help them breathe. But both were eventually sidelined by their condition, which can result in life-threatening lung infections and serious digestion problems. The California teens, who at the time didn’t know each other, sought treatment at Lucile Packard Children’s Hospital and, as the above KGO-TV segment explains, their time there led to a strong friendship.

Previously: Building a new lung, one cell at a time?, A story from the edge of medical possibility: Operatic soprano sings after double lung transplant and Image of the Week: First heart-lung transplant

Twitter has launched a great looking new site, Twitter Stories, to show how people are using the service. One story, about @ChrisStrouth, chronicles how Twitter helped him connect with a kidney donor:

. . .He needed a transplant. Not knowing what else to do, he turned to Twitter and wrote:

“Sh*t, I need a kidney”

Within a few days, 19 people offered to find out if they might be a match…

The rest is over at Twitter Stories.

Up to 30 per day. That’s how many pills a typical kidney-transplant recipient can expect to have to ingest every day for the rest of his or her life. Not that it’s not worth swallowing them – the life expectancy of someone receiving an immunologically matched kidney from a living donor is 25 to 30 years, double the life expectancy for a patient who remains on dialysis instead of getting a kidney tranplant.

Still, even the best of immunological matches, unless the donor is your identical twin, will leave your immune system scratching away at the new organ until, over time, it weakens and fails. This erosion can be vastly slowed by keeping your immune system in a constant state of suppression, via a stiff daily regimen of drugs that do just that.

But a medical advance developed by Stanford’s Sam Strober, MD, appears to be allowing kidney-transplant patients to get weaned off of these drugs. In a letter to the New England Journal of Medicine, Strober, nephrologist John Scandling, MD, and other Stanford researchers  describe a new post-transplant protocol involving radiation treatment and injections of blood-forming stem cells from the donor as well as antibodies targeting the recipient’s own immune system. As my release states:

Eight of the 12 patients discussed in the small study have now been off of immunosuppressant drugs for at least one year, and in some cases for longer than three years, without any apparent damage to their new kidney — unheard-of in patients undergoing standard transplantation procedures. None of the 12 patients has experienced kidney transplant failure or serious side effects.

The new brew seems to suppress the kidney receiver’s immune system long enough for the donor’s stem cells to differentiate into a complementary set of immune cells, with a resulting balance between donor and recipient immune systems.

It took more than 30 years of mouse research on Strober’s part to get just the right mix of ingredients to achieve this balance, he says. But it has finally started paying off for us people.

The study is actively recruiting new subjects and is now being expanded to include less-than-perfectly matched donor/recipient pairs. Patients considering enrolling can learn more about it by contacting the study coordinator, Asha Shori.

Photo by psyberartist

The latest issue of AARP The Magazine has a nice round-up of “amazing medical discoveries” that could benefit older adults. Among the advances that made the cut were artificial retinas, transcranial magnetic stimulation for depression and, perhaps the coolest-sounding, “grow your own” organs:

[Anthony] Atala’s lab, in the Wake Forest Institute for Regenerative Medicine, in Winston-Salem, North Carolina, was the first to build functioning organs from scratch — bladders that were reconstructed in nine children whose own organs did not function properly. In those cases researchers built a biodegradable scaffolding shaped like a bladder, seeded it with bladder and muscle cells from the patient, and implanted it into the child’s body. One of the children — now a college junior — was in kidney failure when he got his new bladder 10 years ago. He went on to become captain of his high school wrestling team.

The lab has since expanded its experiments to include more than 30 tissues and body parts…

Growing the organs is a slow and painstaking process, and investigators also need to follow patients over time to confirm the organs’ safety and durability. It will likely be a decade or more before these bioengineered organs are commonplace, but Atala is committed: “I’ve made it my mission to get this technology to patients.”

Via: Kaiser Health News
Previously: Regenerating organs from scratch and 3D printer uses living cells to produce a human kidney

In the most recent issue of Inside Stanford Medicine, my colleague tells the almost-difficult-to-believe story of Milton Gilmer, a man who literally drove himself to the hospital while having a heart attack.

Gilmer had been diagnosed with pulmonary hypertension, a disease that causes abnormally high blood pressure in the lungs and heart, in 2006. In 2010, his condition had reached a critical point, and it became clear that he would need a heart and lung transplant. Gilmer’s health insurance initially refused to pay for the operation, since the cost exceeded the medical plan’s lifetime dollar limit for this kind of procedure. Luckily for him, the Affordable Care Act that passed in March 2010 eliminated lifetime benefit limits.

Health-care reform was something of a deus ex machina for Gilmer – and it didn’t come a moment too early. In early February 2011, days before Gilmer was scheduled for a heart-lung transplant at Stanford Hospital, a pre-transplant coordinator received a phone call from Gilmer informing her that he was having a heart attack. When she told him to hang up and call 911, Gilmer told her that he was already at the hospital. True to his independent Montana roots, he had driven himself in his truck. (Don’t try this at home, kids.)

Gilmer successfully underwent surgery on February 8. He’s happy to be back on his Montana ranch home with his wife, Donna.

Earlier this spring, my colleague wrote about a group of Stanford organ transplant patients who created an informal exercise group to help with their recovery. Now, in an article made available online today, the San Francisco Chronicle has taken a closer look at the efforts of these “boot camp” participants and at the thoughts of their physician:

Dr. David Weill, medical director of the Stanford Lung and Heart-Lung Transplant Program, treats many of the patients who participate in boot camp. He applauds their efforts, noting that the hospital provides pulmonary rehab only for the first three months after a patient’s lung transplant. After that, it’s up to the patients to start their own exercise routines.

…

“In the past, I had modest expectations for transplant recipients,” Weill added. “I don’t have that anymore. I’ve seen several hundred patients, and I’ve seen them do the most amazing things: run races, ski, hike, climb mountains. I don’t think there’s anything they can’t do.”

Previously: Transplant patients organize a boot camp

Emily Fennell lost her right hand after it was crushed in a roll-over car accident five years ago. But last month she underwent a 14-hour hand-transplant surgery at Ronald Reagan UCLA Medical Center. In this video, Fennell talks about the emotional experience of receiving the life-changing surgery and UCLA medical staff explain this experimental procedure.

Via UCLA Medical Center

This is remarkable stuff: A group of transplant patients from Stanford Hospital & Clinics have organized a “Transplant Boot Camp.” According to an SHC release:

The Transplant Boot Camp at Stanford began as an offshoot of workouts attended by several athletes training for the 2008 U.S. Transplant Games. Two competitors, identical twins Anabel Stenzel and Isabel Stenzel Byrnes, decided last year to organize similar workouts open to all members of the local transplant community.

This video, which was produced by Todd Holland and John Sanford, tells their story.

Few things are probably as scary as learning you need a heart transplant. But then picture hearing that, after a suitable organ has been identified and transplanted, you’ll need to undergo regular heart biopsies, in which surgeons snip off pieces of your new healthy organ for testing. Says cardiologist Hannah Valantine, MD:

Patients are very fearful of the biopsies; they hate having them done. They are also very expensive and carry risks of medical complications.

Now Valantine and bioengineer Stephen Quake, PhD, have come up with a new way to assess the health of a transplanted heart through a simple blood test. This is the second such blood test devised by Valantine; last year she published results showing that a blood test she help develop called AlloMap could be used to assess the health of transplanted hearts. The new technique, however, plays on a novel concept – that of looking for increasing levels of DNA from the donor in the blood of the recipient. It’s interesting because it springs from a unique way of looking at organ transplants, according to Quake:

Basically, when you get a new organ, you’re also getting a genome transplant. Someone else’s genome is put into your body, packaged in the donated tissue. So now we can use advances in genetic sequencing to identify which bits of DNA in the blood come from the recipient and which come from the donor.

The research will be published this week in the Proceedings of the National Academy of Sciences. The hope is that this type of ‘genome transplant dynamics’ study can be used in conjunction with the AlloMap to eliminate the need for invasive biopsies and – by diagnosing rejection in its very early stages – the use of high doses of immunosuppressants to treat advanced rejection episodes of nearly every organ.

You might remember Quake from previous news reports in which he first (in 2009) used technology he invented to sequence his own genome quickly and cheaply, and then (in 2010) collaborated with Euan Ashley, MD, at Stanford to come up with clinical recommendations for himself based on that sequence. He has also published widely covered research showing that it’s possible to identify fetal genetic abnormalities from a maternal blood sample. It was that research that attracted Valantine’s attention:

When I saw that, I thought wow, this could probably be applicable to monitoring rejection. After all, transplanted organs are a completely foreign tissue. If he can detect DNA from a fetus, maybe we can use the same technique to find donor DNA in the patient’s blood.

The researchers have now received a three-year, $2 million NIH grant to prospectively study heart and lung transplant recipients. Quake, Valantine and Thomas Snyder, PhD, (the paper’s first author) have filed for a patent on the use of this technique.

Previously: Blood test reduces biopsies in heart-transplant patients and Whole genome sequencing data vaults into clinic

Today, we take a moment to reflect on an important milestone in modern medicine. On this date thirty years ago, Stanford surgeon Bruce Reitz, MD, and the late Norman Shumway, MD, PhD, performed the world’s first successful combined heart-lung transplant.

During the four-hour operation, the heart and lungs of an anonymous donor were implanted into the chest of a Mary Gohlke, a 45-year-old newspaper executive from Mesa, Arizona. This was made possible by the use of the immunosuppressive drug cyclosporine, and previous laboratory research performed at Stanford.

In the past three decades, more than 150 patients have received a heart-lung transplant and more than 120 patients have received either a single-lung or double-lung transplant at Stanford.

Photo by Stanford School of Medicine

An estimated 110,460 people are currently waiting for an organ transplant and each day 18 people die waiting for transplants, according to statistics from the U.S. Department of Health and Human Services. But early-stage research at the Wake Forest Institute for Regenerative Medicine offers the potential to significantly reduce this organ donor shortage.

Researchers at the institute have developed a technique and equipment for printing transplantable organs. The seven-hour process begins with collecting 3-D images of the organ that needs to be replaced. Next, a small tissue sample is taken from the patient and used to seed a specially-designed printer. The printer then replicates the tissue layer by layer to create a new organ.

In the just-posted video above, institute director Anthony Atala, MD, explains the organ-printing process in detail and shows the audience a completed model.

Although the printed kidney structures are early prototypes and years away from clinical use, the research is an exciting look at the possibilities of regenerative medicine.