Dr. Mielcarek is the medical director of the Adult Blood and Marrow Transplant Program and an oncologist who cares for patients who receive stem cell transplants for treatment of hematologic cancers.
Dr. Mielcarek believes that individualizing treatment according to the patient's needs and philosophy, combined with incorporating up-to-date research knowledge, are key ingredients for excellent patient care.
- Blood stem cell and bone marrow transplantation for hematologic malignancies
- Graft-versus-Host Disease (GVHD)
- Medical Director, Adult Blood and Marrow Transplant Program, Seattle Cancer Care Alliance
- Member, Clinical Research Division, Fred Hutch
- Professor of Medicine, Department of Medical Oncology, University of Washington
- MD: Freie Universität Berlin, 1986
- PhD: Freie Universität Berlin, 1987
- Residency: Freie Universität Berlin, Internal Medicine, 1987-1993
- Research Fellowship: Fred Hutchinson Cancer Research Center, 1994-1999
- Residency: University of Washington, Internal Medicine, 1999-2000
- Fellowship: University of Washington, Medical Oncology, 2000-2003
“The plan was to do two years of research and then go back to Germany,” said Marco Mielcarek, MD, the medical director of the Adult Blood and Marrow Transplant Program at Seattle Cancer Care Alliance (SCCA) and Fred Hutch.
That was 20 years ago when Dr. Mielcarek left his native Berlin and took a translational research fellowship in the laboratory of Beverly Torok-Storb, PhD, at the Hutchinson Center.
“As you can see, I’m still here,” he said.
Clinician in a lab coat
Moving to Seattle required more than one type of cultural transition.
“I was not a laboratory person,” he said. “I was a board-certified internal medicine doctor from Germany with hematology/oncology experience. The research was interesting. I learned a lot. It was a good collaboration. But when I decided to stay, I still wanted to take care of patients, so I did a second residency in internal medicine and fellowship in medical oncology at the University of Washington (UW) and the Hutch.”
Ever since then, Dr. Mielcarek has divided his time between patient care and research while staying focused on his specialty of stem cell and bone marrow transplantation (BMT) for hematologic malignancies.
He currently holds positions as professor of medicine in the department of medical oncology at the UW School of Medicine and associate member of the Clinical Research Division at the Hutch.
A Focus on Graft-Versus-Host Disease
Dr. Mielcarek’s research is aimed at preventing graft-versus-host disease (GVHD) and making treatments for this immune-triggered inflammatory syndrome more tolerable. Over the past decade, advances in donor selection, typing technology, supportive care, and preventive drugs have all helped to reduce the number of patients who suffer the dire consequences of GVHD. But 10 to 15 percent of patients with matched grafts still develop severe acute GVHD (grades III or IV). And half end up with the late-developing chronic GVHD.
“Severe acute GVHD is potentially life-threatening,” said Dr. Mielcarek, “and it may not respond well to our standard treatment, which is prednisone. Those patients with chronic GVHD may need to take immunosuppressive drugs for years, putting them at risk of infection and compromising their quality of life.”
Dr. Mielcarek and his research colleagues are testing whether statin treatment of stem cell donors has the potential to prevent GVHD in recipients. Animal studies and retrospective studies show that these widely used cholesterol-lowering agents appear to weaken T-cell function in a way that reduces GVHD.
“In our large retrospective studies,” said Dr. Mielcarek, “we found that if the donor was taking statins then grades III-IV GVHD were almost nonexistent.”
Dr. Mielcarek has initiated two SCCA prospective trials to determine if giving atorvastatin (Lipitor) to donors for the two weeks leading up to their final stem cell collection will reduce GVHD rates. He is also working with basic scientists to determine how statins alter immune cells and whether the molecular effects triggered by statins might synergize with agents such as calcineurin inhibitors to enhance anti-GVHD effects.
In other studies, Dr. Mielcarek is evaluating whether low-dose prednisone might be a less toxic yet effective treatment for GVHD and whether the use of carefully timed infusions of high-dose cyclophosphamide after transplantation is safe and effective at preventing GVHD.
Dramatic changes in BMT over the past 10 years
All the advances in transplantation made over the past decade—many of them initiated or refined right here in Seattle—have led to major changes in the typical BMT procedure and outcome.
“Our reduced-intensity conditioning regimens are effective even for many advanced diseases and yet relatively well tolerated by most patients, even by older patients and younger patients with comorbidities,” said Dr. Mielcarek. “These patients couldn’t tolerate the old-fashioned high-dose treatments. We are now at the point where we can deliver transplant care to most of the population with the highest need—the older patients in their 60s or 70s. This is who tends to get leukemia and lymphoma.”
The procedures using less toxic moderate-dose conditioning, sometimes called mini-transplants, are changing who gets a transplant and where the transplant is done. Many patients who get these transplants today spend very little time in the hospital. Some do not even require admission to the hospital unless there are complications.
“At SCCA in 2013 more than 40 percent of all our allogeneic transplants were mini-transplants done on an outpatient basis. This is a dramatic change,” said Dr. Mielcarek.
The future of transplants: Reduced toxicity, increased targeting
Looking ahead, Dr. Mielcarek sees a continuation of the two key trends that have defined BMT over the course of his career: first, further reduction in the intensity of pre-transplant conditioning and, second, increasingly effective treatments targeted at the leukemia or lymphoma itself.
These two trends, he said, are not only accelerating but also starting to be woven together in powerful new combination regimens that hold the promise of much better and more durable outcomes.
“Transplantation is evolving to reduce the toxicity by giving less chemotherapy and radiation up front,” he said. “And at the same time we are introducing more targeted treatments to take out the cancer itself without causing wholesale damage to other healthy tissues. Combining these new disease-targeted treatments with the new transplantation protocols can make the procedure safer and reduce relapse rates. This is the future of transplantation.”
Dr. Mielcarek emphasizes that clinical research remains essential to achieving that future. That’s why he first stepped into the lab 20 years ago, and it’s why he stepped up to assume leadership of the adult transplantation group as medical director in 2013.
“Research is the backbone for improving cancer care,” he said. “And for this we rely on our patients and our referring physicians. By participating in appropriate clinical trials, patients help us increase our understanding of diseases, improve our treatments, and achieve better cure rates.”
Dr. Mielcarek enjoys living in Seattle with his wife, Bessie Young Mielcarek, MD, a nephrologist and clinical researcher at the Veteran’s Affairs Puget Sound Health Care System. They enjoy hiking and traveling to Germany to visit his family. Dr. Mielcarek also plays guitar and soccer with his Hutchinson Center teammates.