The first featured iCMLf Prize nominee is Dr Ali Bazarbachi, American University of Beirut, Lebanon

“CML is predicted to become the most prevalent leukemia by 2040 and accordingly an intensive global effort with more international collaborations between clinicians and researchers is imperative to find a definitive cure for CML.”

Ali Bazarbachi, MD, PhD is a Professor of Medicine (Hematology and Oncology), Professor of Anatomy, Cell Biology and Physiological Sciences, and Director of the bone marrow transplantation program at the American University of Beirut-Medical Center. 

He received his MD and PhD degrees, residency and fellowship training at the University of Paris VII in France. Dr. Ali Bazarbachi’s basic and translational research focuses on targeted therapies for hematological malignancies as well as post-transplant pharmacological interventions. He has co-authored more than 350 articles in leading scientific journals including The New England Journal of Medicine, Science, Journal of Experimental Medicine, The Lancet Oncology, Journal of Clinical Oncology, Blood, Nature Communication, and Cancer Research. He is the Chairman of the EMBMT Leukemia Working Party, Chairman of the NCCN Lymphoma Group for Middle East and North Africa, past President of the Lebanese Society of Hematology, past President of the International Association for Comparative Research on Leukemia and Related Disorders, and Associate Editor of Bone Marrow Transplantation. He garnered multiple prestigious national and international awards including the 2008 award of the French National Academy of Medicine.

How has your research, or practice of CML changed or impacted CML management in your and perhaps other country(s)?

Clinical research and practice: I was the local PI in several international clinical trials including registration trials (Nilotinib 2005-2006; dasatinib 2019-2023; asciminib 2018-22) that allowed very early access of CML patients in Lebanon and the Middle East to the most innovative drugs at no cost and under state of the art monitoring. This is becoming even more crucial in the difficult economic situation that Lebanon and many Middle East countries are currently going through. I also played a seminal role in local registration of anti-CML medications. I was also the PI of an investigator-initiated trial that demonstrated that imatinib can maintain the cytogenetic and molecular disease control achieved after 1 year of nilotinib. This strategy allows a high rate of CML disease control while minimizing cost and long term cardiovascular and metabolic complications.

Basic research: TKIs have significantly prolonged the survival of CML patients with minimal side effects. However, despite the excellent progress made with CML management, major challenges remain. Interruption of treatment results in disease progression in most patients. Based on the increase in CML prevalence as a result of TKIs efficacy, the need for continuous therapy, and the high cost of this drug, CML treatment is currently becoming a tremendous financial burden on health systems, hence the need for the development of a curative approach to CML. At AUB, we have built a basic research team led by Rihab Nasr and focused on basic and translational approaches to the management of CML. Our in vitro studies have demonstrated that the anti-leukemic effects of arsenic trioxide and interferon alpha significantly prolongs the survival of primary T315I-CML mice and displayed a dramatic impairment of disease engraftment in secondary mice, reflecting a decrease in leukemia initiating cell activity (stemness). These findings provided clear evidence for the favorable preclinical efficacy of arsenic trioxide and interferon alpha in CML mice models, suggesting the investigation of this combination as a potential curative therapeutic strategy for CML. To pursue the search for other curative therapy for CML, we established, in collaboration with Rihab Nasr and Margret Shirinian, an expert in drosophila research, the first Drosophila model expressing the human BCR-ABL wildtype and BCR-ABL with T315I. Expression of both transgenes in the eyes of the fly yielded a transformative phenotype that was partially reversed upon the administration of some TKIs. This platform would address the need for a powerful, quick and cheap drug-screening platform, that can be validated as an in vivo method for high throughput drug screening in the CML field.

What do you consider as your biggest achievement or breakthrough in the research or management of CML?

1. The ability of imatinib to maintain the cytogenetic and molecular disease control achieved after 1 year of nilotinib. This strategy allows a high rate of disease control while minimizing cost and long term cardiovascular and metabolic complications
2. Preclinical efficacy of arsenic trioxide and interferon alpha in CML mice models, suggesting the investigation of this combination as a curative therapeutic strategy for CML
3. Development of the first Drosophila model expressing the human BCR-ABLwildtype and BCR-ABL with T315I

Have you encountered any challenges or discovered any limitations in your CML research and practices?

One big challenge is the lack of enough funding opportunities to support CML research. More recently, the dire economic situation that Lebanon is facing has deprived scientists of funding opportunities. Access to TKI has also become much more difficult for many patients since subsidized medications became very limited. We were able to overcome that so far mostly through active participation in multiple international clinical trials.

What are the major learnings from your research, or clinical practice that has impacted your views on CML?

1. The ability of imatinib to maintain the cytogenetic and molecular disease control achieved after 1 year of nilotinib. This strategy allows a high rate of disease control while minimizing cost and long term cardiovascular and metabolic complications
2. Preclinical efficacy of arsenic trioxide and interferon alpha in CML mice models, particularly through targeting CML leukemia initiating cells (stemness) suggesting the investigation of this combination as a curative therapeutic strategy for CML

What is your immediate hope for people with CML in your country?

Cancer is a disease of health inequity and disparity. I have witnessed CML patients struggling because of the shortage of medicine compounded with severe financial and political crises, the country has been facing during the last two years. My hope is that all patients whoever they are and wherever they live could access the best care they need.

What hematology associations do you work with?

In Lebanon, I was elected as president of the Lebanese Society of Hematology and has organized several prestigious national and regional scientific meetings. In the Middle East, I was appointed as the chairman of the lymphoma group for Middle East and North Africa by the United States National Comprehensive Cancer Network (NCCN) and chairman of the leukemia working party of the East Mediterranean Blood and Marrow Transplantation Group. At the global level, I am a co-founder of the International Academy for Clinical Hematology, I chaired several Task Forces for Guidelines of the Francophone Society for Bone Marrow Transplantation and was nominated member of the scientific committee of the European School of Hematology. Since 2018, I am the co-chair of the subcommittee on post-transplant pharmacological interventions of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. In 2019, I became president of the International Association for Comparative Research on Leukemia and Related Diseases.