For adults with acute lymphoblastic leukemia (ALL) that don’t respond to chemotherapy, the series of treatments that comes next can seem like the spin of a roulette wheel. Some patients receive a bone marrow transplant, which requires a lengthy testing process to ensure a good donor match, and months of recovery if everything goes well. Other patients instead begin with an immunotherapy, which can come with severe side effects and only helps quell disease in a fraction of people. If the first approach doesn’t work, their clinician may turn to the other. For a number of patients, their disease recurs even after both.

Now researchers and clinicians in the blood and marrow transplantation & cellular therapy division have developed a new option for ALL patients. Instead of trying a transplant followed by an immunotherapy—or vice versa—they have combined both therapies into one and added some new twists that could help improve the treatments’ success rates. The result: a single ALL treatment that integrates new avenues of research into the best way to fight the cancer.

“This new protocol really changes the paradigm. It combines multiple avenues of research that have been going on at Stanford for years,” says Lori Muffly, MD, associate professor of blood & marrow transplantation and cellular therapy. “We hope it’s a first step toward something really successful and exciting for our patients.”

This fall, Muffly and her colleagues enrolled the first ALL patients in a clinical trial to test the new combination approach, in which patients receive a customized cocktail of immune cells from a donor. The trial, she says, will advance the science of lymphoma and leukemia treatment, as well as give new hope to patients who have relapsed after chemotherapy.

“This trial is really showcasing Stanford’s strengths in both bone marrow transplantation and cell therapy,” says Muffly’s collaborator Melody Smith, MD, MS, an assistant professor of blood & marrow transplantation and cellular therapy.

If you don’t have high blood pressure, you probably have family, friends, colleagues, and acquaintances who do. Nearly half of all adults in the United States struggle with hypertension, and only one in four has their condition under control. Managing blood pressure often requires ongoing trial and error on the part of both clinicians and patients, making it difficult to fully treat with only occasional, short medical appointments.

To solve that problem, Stanford clinicians have designed a streamlined system that helps primary care physicians easily and quickly adjust their patients’ medications based on at-home blood pressure readings. The team, funded by a $2.5 million American Heart Association grant to Stanford Medicine’s Center for Digital Health in 2020, found that the new system could reduce patients’ blood pressure in a small pilot study. Now, they’re enrolling hundreds more patients in a larger clinical trial.

Their new program automatically calculates a two-week average blood pressure. If, at any point, that average blood pressure rises above a chosen threshold, the clinician receives a notification — along with information on the patient’s other medications, their allergies, and the preselected list of hypertension drugs, all in one place in the electronic health record. With a few clicks, the physician can order a new, adjusted prescription for the patient.

“What we’re trying to do with this project is to improve the way we monitor blood pressure,” says Division of Nephrology Chief Tara I. Chang, MD, an associate professor of medicine. “This technology has the potential to help us reach a broad community and level the playing field for typically underserved populations when it comes to hypertension.”

The interdisciplinary team at the Center for Digital Health wanted to make it easy for patients to track their blood pressure at home, upload the data directly to their primary care physician, and enable the physician to adjust the patient’s medications. In the past, this would have taken the clinician numerous steps — receiving an email or phone call from a patient and then accessing different electronic databases to review their medical history and other prescriptions.

“Most clinicians managing blood pressure already have a heavy burden due to the electronic health record,” says Wang. “Our insight is that by semiautomating the process, we can reduce the burden of blood pressure management, taking less effort but improving results.”

The system that the team settled on is one where a physician can preselect a list of blood pressure–lowering medications, in the order that they’d like a patient to try them. At an initial appointment, they start a patient on the first medication on the list. Then, using a blood pressure cuff and a connected smartphone app, patients track their blood pressure over the coming days and weeks.

“One value in the clinic doesn’t really tell a doctor the whole story of your blood pressure,” says Funes. “But in the past, the ability to get a longer time frame of data from patients was often unreliable; some patients might record their readings in a notebook and bring it to an appointment, but it wasn’t a streamlined process.”

“Some digital solutions create a separate workforce to manage chronic conditions,” adds Wang. “Although some of these efforts may be successful, they remove patient care from the primary care team, eliminating opportunities to better integrate care and save resources. Integrated approaches like ours aim to reduce disparities of care rather than increasing them.”

The Stanford Center for Digital Health already has other initiatives aimed at treating conditions as diverse as heart health, atrial fibrillation, migraines, and hyperactivity. The award from the American Heart Association is part of a $14 million grant to several institutions around the country for work on reducing health care disparities with the help of technology. In addition to Funes, the grant is funding fellowships for three Stanford cardiology trainees working on heart failure management. As virtual health moves mainstream and digital apps become routine tools in patient care, these fellows will continue to take the lead in innovating creative new ways for technology to help patients and doctors alike.

Horomanski is a principal investigator in research supported by a grant from the Maternal & Child Health Research Institute. This aligns with her deep interest in how vasculitides affect young women, their fertility, and their decisions regarding if and when to have children.

“We’re actually talking about a collection of pretty heterogeneous diseases. Because vasculitides are all different, they affect very different populations. One of the vasculitides is Takayasu arteritis, for example. More than 80% of patients with Takayasu arteritis are women, and most of those women are under the age of 40, so it primarily affects people in their childbearing years. We don’t know enough about the maternal and fetal outcomes associated with pregnancy in vasculitis patients. A component of our current research involves the use of large databases to help answer such questions about these rare diseases,” Horomanski says.

Horomanski also has a particular interest in ultrasound and performs musculoskeletal ultrasound to evaluate for various rheumatologic and other joint musculoskeletal complaints in the Immunology and Rheumatology Clinic. In the past 20 years, specialists have recognized the value of vascular ultrasound to both diagnose and monitor large vessel vasculitis, and Horomanski received additional training in August 2022 to perform vascular ultrasound for patients with large vessel vasculitis.

“The best part about ultrasound is that it is noninvasive. Frequently these conditions need to be diagnosed by biopsy, and often temporal artery biopsy, which can be challenging to coordinate and schedule. And of course, it is an invasive procedure. If we can quickly and accurately diagnose people by ultrasound, it is a huge benefit to the patients,” she says.

As the clinic grows, greater involvement in clinical trials is expected, too.

Currently, Horomanski is working under principal investigator Matthew Baker, MD, assistant professor of immunology and rheumatology, on several trials related to IgG4-related disease and sarcoidosis, both of which can present with vasculitis. Horomanski, who did additional training during her fellowship on clinical trial design and management, is very interested in pursuing other vasculitis trials as the clinic continues to expand.

“That was one of the main objectives of this clinic. Stanford has a robust infrastructure to run these types of clinical trials, and we are looking forward to great things in the future,” she says.

Referrals come from throughout California, Oregon, Nevada, Hawaii, and even the East Coast, but most patients live in California’s Central Valley, where providers do not have extensive experience with these rare illnesses. Horomanski tries to share care with each patient’s local rheumatologist, which allows the patient to see their nearby physician, while also getting the care they need from a large academic center.

She fell in love with hematology on her first day of medical school. Hematologist May Chien, MD, remembers feeling that she had “found her dream.”

Chien, who is clinical assistant professor, pediatrics–hematology & oncology, and medicine–hematology, recalls that “I loved all the mechanisms of blood diseases and all the thought processes hematology involves.” Today, she’s living her dream.

Chien is board-certified in both internal medicine, hematology, and pediatric hematology-oncology, which gives her an unusually broad perspective from which to manage patients with classical (nonmalignant) blood disorders.

“Until recently, patients with blood diseases such as hemophilia and thalassemia did not survive past childhood,” she notes. “But today, with improved treatment options, many children born with these diseases grow into adulthood.” And since hematologists who treat adults don’t always have a lot of training in childhood diseases, her breadth of skills enables her to care for patients with blood disorders and follow them from birth through adulthood.

For example, she may help a woman with a bleeding disorder get through pregnancy and birth, and then find that the child has inherited the same disease. Chien can help them both manage their conditions and has done so numerous times.

often present options you didn’t know existed. I went to medical school at the University of Southern California Keck School of Medicine. Some colleagues I most admired there were doing a combined internal medicine (IM) and pediatrics residency. I applied for that program and got in.”

Four years later, she came to Stanford for fellowship training. “Stanford was wonderful for allowing me to create my own combined fellowship program in both IM and pediatrics. It was the perfect answer to finding a place where my intellectual and clinical interests could intersect,” she says.

Chien was the first fellow in the Stanford Department of Medicine to complete two fellowships concurrently. “One of the best things about Stanford is that if you dream it, people can make it happen,” she says. “I had an idea and found complete support for it here.”

Not only did she need faculty approval for the combined fellowship, but also she had to secure consent from the two board-certifying organizations involved: the American Board of Internal Medicine and the American Board of Pediatrics, both of which approved her proposed fellowship program.

A native of Southern California, Chien graduated from Amherst College in Massachusetts before returning home to pursue what she thought would be a career in laboratory research. “I was not living my best life at a laboratory bench,” she says. “I realized I was more interested in working directly with people.” So, she applied to medical school and found her “best life.”

Research in Classical Hematology

“Classical hematology is about intricate pathways,” says Chien. “Finding the correct diagnosis is like solving a fascinating puzzle, since there are numerous mechanisms for coagulation and other beneficial events to occur and possibly go wrong.”

Stanford researchers are pursuing new and novel treatments for conditions classified as classical hematological disorders, including hemophilia, thalassemia, pyruvate kinase deficiency, and sickle cell disease. Some of these involve gene therapy or stem cell transplantation.

“Inherited blood diseases are especially amenable to treatments like these,” says Chien. “Some are currently in clinical trials, but we have a way to go before they can be universally applied.”

For example, hemophilia A is an inherited genetic disease that results from a gene mutation that prevents the liver from making enough of a clotting factor called factor VIII. The result is excessive bleeding.

“Research in hemophilia is very exciting right now,” says Chien. “Gene therapy is starting to show promise in providing a potential cure for the disease.” Hemophilia is an ideal candidate for gene therapy because it arises from mutations of a single gene and because a patient doesn’t need a lot of the clotting factor to bring about a change from severe disability to wellness.

“Unlike stem cell replacement, successful gene therapy would entail one infusion into the liver to stimulate production of factor VIII,” Chien explains. “This not only would add years to patients’ lives but also could actually cure the disease.”

She is also interested in thalassemia, a type of anemia in which the entire hemoglobin portion of the blood is abnormal. Currently, blood transfusions are the main therapy used to treat thalassemia. The challenge with this approach is the possibility of overloading the liver with more iron than it can handle. A clinical trial underway at Stanford is exploring the potential of an oral drug that could extend the lifespan of a red blood cell, thereby boosting red blood cell levels and reducing or possibly eliminating the need for transfusions.

Looking forward, Chien is eager to continue her work in decreasing the burden of inherited blood disorders such as hemophilia, thalassemia, and sickle cell disease. “My goal is to continue to improve life expectancy and quality of life for adults and children with these conditions,” she says.

Ten years ago, Miriam Gutierrez, 47, was diagnosed with lupus. “Though I took medication for that condition,” she recalls, “my kidneys started to fail, and I was put on home dialysis.” She had a catheter attached to her abdomen, which enabled nightly cleansing of her blood.

Gutierrez was told she had about a 1% chance of getting a donated kidney because of the complex nature of her case, which included elevated antibodies, a blood type that would be difficult to match, and having had many blood transfusions.

In 2020, after eight years on dialysis, her physician referred her to Stanford for evaluation. Using the parameters of the Transplant Readiness Assessment Clinic (TRAC), she began monthly visits to monitor her compatibility with potential donated kidneys. Two years later, she remembers, “I received a phone call on a Friday night saying I had matched with a donor kidney. I went to Stanford Hospital on Saturday morning and had the transplant surgery that day.”

“I’m very grateful,” she says. “Now my life is back to normal, and I’m looking forward to visiting my family in Mexico soon.”

“It may be any time, day or night, far or near. And if a potential recipient is found, he or she must get to Stanford immediately for an updated physical and psychosocial evaluation.”

If it’s been a long time since the patient’s most recent clinical assessment, they may have experienced illness or other physical challenges that could affect their likelihood of success with a donor kidney. “By the time the evaluation is completed,” notes Cheng, “the kidney may no longer be viable, or we may have found out that the patient and the organ are not a good match.”

Pre-transplant Readiness Improves Kidney Transplant Rate

Cheng and the kidney transplant team began reviewing the Tier 2 patients. They wanted to determine if, by reevaluating those patients before a kidney became available, they could prepare the patients to be ready for surgery with very short notice. This involved doing all the necessary medical workups and education needed in advance of a donor kidney becoming available.

In making these assessments, Cheng and the transplant team rely on the Kidney Allocation Score (KAS) to determine a patient’s priority for kidney transplant according to national allocation policies. The KAS is a composite of the amount of time the patient has been on dialysis, the amount and kind of antibodies the patient has, the patient’s blood type, and other factors.

Using the KAS, Cheng and her colleagues established wider parameters for eligibility for a kidney transplant. Doing this kind of evaluation for every person on the waiting list would be very time-consuming and not necessarily result in an organ match. But when focusing on the patients who would more likely be offered a donor kidney based on their KAS, even one that is not considered “perfect,” the pool of possible recipients becomes more manageable and results in a group of patients that is more likely to succeed.

“Our team meets weekly to review the patients who were seen that week who may qualify for this proactive management. With input from transplant surgeons, we can see trends developing so we can predict who on our lists might be eligible for an organ and ask those patients to come in for a clinical workup so they’re ready if an organ does become available.”