Bone Deep: Generating New Knowledge to Benefit Our Patients
Next Generation is a Brigham Clinical & Research News column penned by students, residents, fellows and postdocs. If you are a Brigham trainee interested in contributing a column, email us. This month’s column is written by Heardley “Moses” Murdock, MD, a second-year resident in Internal Medicine.
The first days of intern year — the first year of being a doctor — can be terrifying. All the lectures and simulations of medical school pale in comparison to real patients who are sick and in need of support through incredibly trying circumstances. One of my early rotations was on the bone marrow transplantation service, where high doses of chemotherapy are administered to eliminate a patient’s immune system. This treatment will make room for donor bone marrow to fight cancer and support the production of new blood. Often, a bone marrow transplant represents the best hope for a cure for patients with leukemias or lymphomas. The road to that cure can be harrowing. Yet medical advances empower us to support patients, allowing them to leave the hospital and enjoy life, with time for loved ones and hobbies. This bone marrow transplant rotation was the highlight of my intern year, as being on the front lines of clinical care and research reinforced the unique resources available at the Brigham and Dana-Farber to improve the prognosis of patients with cancer.
During my bone marrow transplant rotation, I admitted several patients to the hospital who had high-risk disease. For many, their leukemias had mutations and other molecular alterations that made their cancer resistant to conventional chemotherapy. When I walked into their room to ask them about their medical history and medications, I was struck by their courage. Many had endured several rounds of chemotherapy and were now signing up for another month in the hospital. They did so despite knowing that infections, graft-versus-host disease and leukemia relapse after transplantation can cause devastating complications. Clinician-scientists at the Dana-Farber Brigham Cancer Center are investigating ways to modify the chemotherapy patients receive in preparation for a bone marrow transplant, with the goal of more effectively eliminating leukemic cells and improving outcomes. For example, in addition to high doses of chemotherapy, medical oncologist Jacqueline Garcia, MD, is studying the addition of venetoclax to transplant regimens to prevent the re-emergence of leukemia after transplantation, and I’ve been lucky enough to be part of her team studying this treatment strategy.
Venetoclax is a small molecule that targets the apoptotic system – the cellular machinery responsible for controlling when and how a cell dies. As an intern, I cared for patients enrolled on a phase 1 clinical trial of adding venetoclax to transplant regimens. On the clinical side, I witnessed the day-by-day drop in the blood counts of patients, and the near-miraculous re-emerge of red cells, white cells and platelets as the donor’s bone marrow settled in and produced new blood. As a research trainee under the mentorship of physician-scientist R. Coleman Lindsley, MD, PhD, I tracked leukemia-associated mutations over time after transplantation. These mutations sometimes disappeared, corresponding to leukemia eradication and remission. Sadly, I also saw mutations persist, often at very low levels, only to later come roaring back as relapse.
I never thought that as an intern, I would have the opportunity to simultaneously live in the world of day-to-day clinical care and early phase clinical research. The Brigham is an exceptional training institution precisely because it fosters exposure to experts in their fields – encouraging trainees to engage not as passive observers of novel work but as active participants in the generation of new knowledge to benefit patients. I aspire to work as a leukemia specialist and clinical trialist who advances novel treatment strategies while gleaning insights into the biology of leukemia alongside basic scientists. This goal was shaped in no small part by witnessing the resiliency and courage of patients undergoing transplants, the humanism of clinical mentors and the curiosity of researchers unsatisfied with the status quo.