Lifelong CLL Champion Continues Research For Improved Care
Michael J Keating: Striving to Make a Difference in CLL Patient's Lives
On a Friday afternoon creeping towards the end of most people’s workday, Michael J. Keating, M.D., breezes past the MD Anderson Leukemia Department’s small library conference room and in passing calls out, “Give me two minutes.” Keating undoubtedly needs an extra two minutes throughout the course of the day as he juggles patient care and research pertaining to Chronic Lymphocytic Leukemia (CLL) at MD Anderson, engages in his role as President and CEO of the CLL Global Research Foundation, a non-profit dedicated to furthering translational research for patients with CLL, mentors and fosters the pursuits of his teams, takes requests for speaking engagements and interviews, and in his spare time, acts as husband and father. “My wife ought to be nominated for canonization,” Keating insists when he is able to double back and start talking. The comment illustrates both his love for his family as well as the toll he understands an all-consuming career has taken on them.
Keating attended the University of Melbourne, Australia, where, as he explains, students finish one general year of study and head right into medicine for an additional five years. “At 23 I was a nervous doctor.” Three years after graduation, Keating was running the Oncology program at St. Vincent’s Hospital in Melbourne and studying leukemia and lymphomas. Keating made the decision five years later to move himself and his growing family to Houston, where he went from being an Assistant Professor to a First Year Fellow at MD Anderson. Initially, Keating worked in the acute myeloid leukemia (AML) group, but as he so candidly explains when asked about how he came to be a champion of CLL, “I was fired from the AML group.”
The comment is not intended to elicit judgment or sympathy, but as he seems to do with all aspects of his work and life, provide a clear and accurate assessment of the situation. Agree or disagree with him, a lifetime of purposeful work has granted Keating clarity and candor. The switch from AML to CLL turned out to be a fortuitous event for both Keating and CLL patients. Keating’s work with colleagues William K Plunkett, Jr., Ph.D., Varsha V Gandhi, Ph.D., both Professors in the Department of Experimental Therapeutics and Peng Huang, M.D., Ph.D., Professor in the Department of Molecular Pathology, led to the discovery that the drug fludarabine is the most active single agent against CLL and took remission rates from 5 to 30%. These collaborators, and the CLL group under Keating’s leadership, went on to illustrate fludarabine along with cyclophosphamide (FC), further benefited patients, and the FC combination in concert with rituximab (FCR), an anti-CD20 recombinant monoclonal antibody, was able to provide a 72% complete remission rate in previously untreated patients and a 60-80% improvement in 5-year survival rate when compared to chemotherapy alone.
CLL affects a relatively small number of patients; the National Cancer Institute estimates approximately 15,000 people will be diagnosed in 2010. Compared with lung, breast and prostate, which the NCI estimates will each exceed 200,000 cases in 2010, the disease receives much less attention. Most CLL patients are older, which Keating sees as another disadvantage for gaining research support. For those who work to improve CLL patient outcomes, however, the disease is no less important and the CLL research community has developed a small, tight-knit group who, according to Keating, celebrate each other’s successes as much as they do their own. The CLL research community as a whole also tends to concentrate on translational research to help patients. As institutions and government agencies grow, Keating and many of his CLL colleagues find it increasingly difficult to pursue research purely on behalf of the patient.
For that reason, Keating started the CLL Global Research Foundation, which is a non –profit supported by patients intent on improving care and control of CLL. The Foundation’s objective is to complement funding of translational research and thereby advance the rate of contribution to CLL treatment. Since December 2004 the Foundation has awarded more than $8 million to individual researchers, provided seed money to start the CLL Australian Research Consortium (CLLARC) and the CLL Israeli Research Consortium (CLLIRC) and provided more than $8million in funding to the Foundation’s U.S./European Alliance for the Therapy of CLL (Alliance). Keating believes global collaboration is critical for furthering CLL research without replicating efforts as a result of being unaware of current research worldwide. According to Keating, however, all disease might not benefit from a research foundation like CLL’s, “CLL researchers have compatible personalities enabling them to work together not against each other.”
Much of that compatibility is typified by Keating’s approach to research. “When most people talk about translational research, they talk about the science matching the science,” explains Keating. “But to me, research is much more like falling in love. It starts with inquisitiveness and interest. You attend a talk. You think of how that might apply to our work. You invite someone for coffee, learn their language and educate them on your language. You find the strongest relationships are not forced.” Rather they are complimentary, a sort of give and take where each researcher has something to contribute to the other. No matter the research discipline, Keating believes the common motivation has to be about curing patients, which is why the researchers involved in the Foundation work well together.
Whether it is through his work at MD Anderson or the Foundation, Keating views two areas of research as critical to improving care for patients with CLL; the genetic aspect of the disease and ridding the body of remaining leukemic cells after treatment. Over the past several years, Keating and others have employed fluorescence in situ hybridization (FISH) to detect genetic abnormalities in patients with CLL. These genetic differences have a significant impact on disease progression and outcomes for patients, but the reasons underlying the effects have yet to be elucidated. In addition, leftover leukemia cells, which are referred to as minimal residual disease and are the main cause of relapse in leukemia, continue to hinder curing CLL. Keating hopes research involving chimeric antigen receptors, which are receptors engineered to impart genetic material to a patient’s immune cells rendering them capable of detecting and eliminating leukemia cells, will increase remission as well as decrease relapse in CLL patients.
For a man who has worked in medicine for nearly a half century Keating exhibits no pining for times gone by, for a golden age passed. Instead his focus remains ever-forward and persistently aimed at the patient. “I have exceeded all expectations of what I could accomplish with my life,” Keating states rather matter-of-factly. “At this point it is about what I can do that other people are not in the position to do.” Keating makes no grandiose statements about curing a disease or achieving a particular definitive aim, but is simply dedicated to the work at hand and that our efforts either hinder or enable that work. For Keating, the work is to improve the lives of CLL patients through whatever mechanism possible.