After 3 Decades at MD Anderson, Leukemia Researcher Shows No Sign of Slowing Down

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I was fortunate to come to MD Anderson and work with giants like Emil Freireich, MD, Kenneth McCredie, MD, and others, all of whom had a tremendous influence on the way I approach oncology, both in the lab and at the bedside.

— Hagop M. Kantarjian, MD

Hagop M. Kantarjian, MD, Chair of the Department of Leukemia at The University of Texas MD Anderson Cancer Center, was born in Lebanon. The only member of his family to have pursued a career in medicine, he received his medical degree from the American University of Beirut (AUB), which was founded by American missionaries in 1866 and opened the doors of its School of Medicine a year later. AUB was an intensely egalitarian institution, and this quality was reflected in the university’s guiding principle:

This college is for all conditions and classes of men without regard to color, nationality, race or religion…white, black, or yellow, Christian, Jew, Mohammedan or heathen, may enter and enjoy all the advantages of this institution.…

During his medical education at AUB, Dr. Kantarjian spent 4 months in the United States as part of a visiting medical student elective at The University of Texas MD Anderson Cancer Center. “These elective periods are very influential and can have a profound effect on the lives and careers of medical students from outside the United States. For me, it was an eye-opening experience and a world I never thought existed. I fell in love with MD Anderson’s oncology program,” Dr. Kantarjian, said.

After returning to Lebanon, Dr. Kantarjian applied for a fellowship at MD Anderson. “I was accepted and joined the Department of Developmental Therapeutics in 1981. I never wanted to be at any other institution.”

Groundbreaking Work in Leukemia

Since his initial exposure to MD Anderson some 3 decades ago, Dr. Kantarjian’s work has markedly advanced the field of hematologic cancers, particularly in the areas of chronic myelogenous leukemia (CML) and acute lymphocytic leukemia (ALL). “In the Department of Leukemia, we’ve focused intensely on clinical translational research, and several lines of inquiry over the decades have made a significant impact on the prognosis of our patients,” Dr. Kantarjian said.

Early on, Dr. Kantarjian’s group focused their research efforts on the treatment of CML, starting with the original interferon studies. “I worked on this approach for about 2 decades until the first tyrosine kinase inhibitors came around. At that point, we expanded our research to include imatinib (Gleevec) and second-generation tyrosine kinase receptors to the point that today CML—which was once associated with an average survival of 3 to 6 years and a 10-year survival rate of less than 20%—has basically been transformed into a chronic indolent disease, as long as the patients adhere to their daily oral treatment and continue to be followed,” Dr. Kantarjian said.

Another encouraging development seen during Dr. Kantarjian’s career was led by a member of the Department of Leukemia, Michael J. Keating, MB, BS. Dr. Keating discovered the activity of fludarabine in refractory chronic lymphocytic leukemia (CLL). “Building on this discovery, we added cyclophosphamide and rituximab (Rituxan), constituting the FCR regimen. After the German randomized studies proved that it was more effective than the standard of care at the time, the FDA approved the FCR regimen in 2010 as the new standard of care. The combination has since improved survival in CLL. That was a major highlight in leukemia research,” Dr. Kantarjian said.

In 1992, Dr. Kantarjian was instrumental in creating the hyper-CVAD regimen for treating adult ALL. “We modified the regimen, added some components, and today we know that the hyper-CVAD regimen produces cure rates of about 40% to 50% in adults with ALL. Moreover, when we added tyrosine kinase inhibitors in Philadelphia chromosome–positive ALL, or rituximab for Burkitt’s leukemia and CD20-positive ALL, we markedly improved the survival of these patients,” Dr. Kantarjian noted.

Developing Previously Abandoned Drugs

Another distinction of Dr. Kantarjian’s career has been his instrumental work with drugs that had previously been abandoned by other researchers. “In 1991, I developed clofarabine (Clolar) through animal studies and phase I and II trials, which led to its FDA approval in 2006 for pediatric ALL. Another drug that everyone seemed to lose interest in was decitabine (Dacogen), which was originally developed in Europe. In 1992, I brought decitabine to the United States on an investigational new drug application, and together with Jean-Pierre Issa, MD, we developed the concept of epigenetic therapy. After continued work, we launched a trial in 1999 that led to FDA approval of the drug in the treatment of myelodysplastic syndromes,” Dr. Kantarjian said.

More recently, Dr. Kantarjian has been working on some promising new research. “A team in our group, led by Susan O’Brien, MD, is looking at B-cell receptor inhibitors in CLL. Another promising line of investigation is in monoclonal antibodies for ALL,” Dr. Kantarjian commented.

Encouraged by 30 Years of Progress

As Dr. Kantarjian looks back at the 30-year arc of his career, his optimism is bolstered by the increasing progress that he has witnessed and had a hand in. “I’ve been fortunate to have seen major advances in the prognosis of patients with subsets of leukemia. Those with CML who once had little chance of surviving more than a few years can now expect to live 25 to 30 years. In adult ALL, the cure rate has gone from less than 20% to about 50%, which is a remarkable achievement,” Dr. Kantarjian said.

Progress in oncology is built on incremental successes; similarly, the most fruitful academic oncology careers are built on the shoulders of predecessors. “I was fortunate to come to MD Anderson and work with giants like Emil Freireich, MD, Kenneth McCredie, MD, and others, all of whom had a tremendous influence on the way I approach oncology, both in the lab and at the bedside,” Dr. Kantarjian said.

High-level academic oncology is extremely taxing, but after 3 decades in the trenches Dr. Kantarjian shows no sign of slowing down. “I’m usually up around 6:00 AM, work out for a half hour, then get ready and head off to the Center for a 12-hour workday. I see patients 3 or 4 days a week, and I typically do 2 to 3 months of inpatient care. We see about 1,800 new leukemia patients per year in our group. The rest of my time is devoted to clinical translational research,” Dr. Kantarjian said.

Thriving in His Adoptive Home

When first making the transition from his native Beirut, known for its beauty and culture, to his new home in Houston, Dr. Kantarjian was warned that the Texas city was a bland and forgettable spot on the map. “Nothing could have been further from the truth,” he said, “I think Houston is one of the most beautiful, cosmopolitan cities in the country. I love it here,” Dr. Kantarjian enthused. Asked if he has any hobbies that allow him to decompress after his 12-hour days, Dr. Kantarjian answered, “Painting is my passion. I paint in the fauvist (from the French for ‘wild beasts’) style. I paint and take long jogs in the heat of Houston.” ■

Disclosure: Dr. Kantarjian reported no potential conflicts of interest.