By James Foran, MD

2008-12-06

On the 50th anniversary of ASH, Dr. Bob Löwenberg of Erasmus University in Rotterdam, Netherlands, has been invited to present the Ham-Wasserman Lecture. He will be discussing “Challenges of Capturing Disease Variety” using the paradigm of acute myeloid leukemia (AML).

An ASH tradition, the Ham-Wasserman Lecture is named for two previous presidents of ASH who contributed greatly to the Society and worked together to initiate an Education Program at the annual meeting. Dr. Thomas Hale Ham focused on the pathophysiology of hemolytic anemias and won acclaim for his development of a diagnostic test (the Ham Test) for paroxysmal nocturnal hemoglobinurea (PNH). Dr. Louis Wasserman’s research in polycythemia vera did much to illuminate the understanding of myeloproliferative disorders, and under his leadership in the 1960s, the Polycythemia Vera Study Group established a standard of care for patients with this disorder and conducted one of the first clinical investigations involving a number of cooperative groups in both the United States and abroad.

Dr. Löwenberg is a fitting recipient of the prestigious lectureship, which is offered to an international hematologist who has made major contributions to the field of hematology. He is a founding member and past president of the European Hematology Association, and he has served as a founding member and chair of the Leukemia Trial Group in the Dutch-Belgian HOVON Cooperative Group. He has made important contributions in leukemia and hematopoietic stem cell transplantation over 30 years, and he has authored or co-authored more than 400 papers.

Dr. Löwenberg will discuss the unique challenges in diagnosis and management posed by the heterogeneity of AML, and he will outline the advances that have been made in molecular diagnostics of AML, including important contributions from his group. He will highlight what he calls the “art of distinction” in AML treatment through the recognition of unique subtypes of the disease, and he will discuss the evolution of treatment with an emphasis on individualizing treatment decisions.

The development of more powerful molecular tools has allowed remarkable insight into what Dr. Löwenberg calls the “dazzling heterogeneity” of AML, and he highlights as examples the role of the EVI1 gene and the “monosomal karyotype,” both associated with a particularly aggressive clinical course and poor prognosis. Beyond standard cytogenetics, gene expression studies have identified novel subtypes of AML and allowed investigation into unique forms of the silencing withadisease, such as those characterized by CEBP biphenotypic phenotype. MicroRNA expression profiling has identified new “signatures” and hopefully will also allow a more individualized approach to therapy. Together these have led to new prognostic models in AML, and the HOVON/SAKK (Dutch-Belgian Hemato-Oncology Cooperative Group and the Swiss Group for Clinical Cancer Research) groups have helped lead this effort.

A major challenge remains in developing optimal post-remission treatment for individual AML subtypes, but Dr. Löwenberg feels that, together with advances in allogeneic stem cell transplantation, an improved understanding of AML heterogeneity will allow investigation of transplantation in patients previously thought not to benefit from it. It will certainly allow us to explore “targeted therapy” as targets and subtypes become more apparent. Efforts are underway to individualize treatment approaches in AML, and to investigate (and hopefully overcome) mechanisms of resistance to therapy.

Dr. Löwenberg will note the remarkable advances in our understanding and treatment of AML since 1958, when morphology alone was the diagnostic tool and when one of the first comparative studies of treatment of acute leukemia with antimetabolites was published in Blood. The Ham-Wasserman Lecture is today at 12:30 p.m. in Halls B and C.

Dr. Foran indicated no relevant conflicts of interest.

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