Hurricane Katrina barreled through New Orleans on August 29, leaving just three months to secure a new site, then fully plan and execute the ASH annual meeting. Thanks to the efforts of Ayuko Kimura-Fay, ASH Director of Meetings, and other dedicated ASH staff, the approximately 19,000 who attended the 47th ASH Annual Meeting were treated to the best annual meeting ever in Atlanta. "Rain checks" from all but eight of the scheduled speakers also contributed to the success of the meeting. Attendees celebrated the meeting's theme of translational research, and almost all of the 842 oral presentations and 2,860 poster presentations went off without a hitch. Our thoughts remained close to the city of New Orleans on Monday night as Katrina fund-raising efforts continued at the All-ASH Mardi Gras Partners in Relief Reception.
The Ham-Wasserman Lecture was presented by Dr. Frits Rosendaal from Leiden University in The Netherlands. Dr. Rosendaal gave an historical review of the etiology of venous thrombosis (VT), starting with the recognition of immobilization in the puerperium as a risk factor in medieval times to the current recognition that VT is a multicausal disease with interacting genetic, environmental, and behavioral risk factors. The identification of inherited deficiencies in antithrombin, protein C, and protein S as strong but rare risk factors for VT and genetic variants such as Factor V Leiden and prothrombin mutations as common but weak risk factors that cause disease only in the presence of other factors was discussed, as well as the roles of immobilization, pregnancy, oral contraceptives, and hormone replacement therapy as contributing factors. Dr. Rosendaal's take-home lesson was to forego costly laboratory evaluations for thrombophilia in patients with their first episode of VT, since they have not proven to be cost-effective.
It was most fitting that Dr. Rainer Storb, head of the Transplantation Biology program at the Fred Hutchinson Cancer Research Center, delivered this year's E. Donnall Thomas Lecture. Dr. Storb was recruited to Seattle by Dr. Thomas himself many years ago and has distinguished himself as a recognized authority on stem cell transplantation (SCT) and a pioneer in non-myeloablative or reduced intensity SCT. Dr. Storb gave an insightful review of work from his group showing that non-myeloablative SCT can be safely and effectively done in elderly patients and in patients with diseases such as multiple myeloma, for whom autologous SCT is not curative and myeloablative allogeneic SCT is prohibitively toxic. He also discussed emerging new data on non-myeloablative SCT in a variety of other diseases.
A Special Plenary Session highlighting the myeloproliferative disorders (MPDs) preceded this year's Plenary Scientific Session. Drs. Kenneth Kaushansky, Josef Prchal, Radek Skoda, and William Vainchenker discussed exciting events leading to the discovery earlier this year of the pathogenetic role of acquired V617F mutations in the JAK2 kinase in essential thrombocytosis (ET), polycythmia vera (PV), and idiopathic myelofibrosis (IMF). Translation of these findings to a rapid and reliable diagnostic test and the development of new drugs targeting the mutant JAK2 kinase provide new hope to patients with MPDs. Attendees were treated to a series of interesting and diverse presentations at the Plenary Scientific Session that followed. We heard about correlation of natriuretic peptide levels with pulmonary hypertension and mortality in patients with sickle cell anemia, and the prospect of improved care using this inexpensive non-invasive diagnostic test to guide earlier therapeutic interventions. The benefits of prophylactic Factor VIII infusions in preventing joint disease in young boys with hemophilia were presented, prompting questions about the cost of this approach. Attendees also heard about GATA1 mutations in X-linked gray platelet syndrome, providing the first evidence linking a specific gene mutation to this disease. Hype about the C-type lectin-like molecule-1 (CLL-1) antibody in distinguishing normal and AML stem cells was quickly tempered by the need to confirm the results in studies of many more patients. We heard results of the Phase III study on combination lenalidomide/ Dexamethasone, demonstrating that it is a well-tolerated and active oral regimen for patients with relapsed or refractory multiple myeloma. In a fascinating presentation, we also heard how c-MYC and BCL-6 form a complex in lymphoma cells leading to prolonged c-MYC half-life and oncogenic activation, synergistic suppression of p21 expression, and inhibition of BCL-6 acetylation and inactivation. The identification of this novel interaction provides a potential new pharmacologic target for therapeutic intervention.
The Presidential Symposium on "Translational Research in Hematology: From New Biologic Insights to Practice" gave attendees an additional opportunity to hear how new insights are being applied to improve patient care. Dr. Margaret Shipp of the Dana-Farber Cancer Institute and Dr. Maria Grazia Roncarolo of the San Raffaele Telethon Institute in Milan very eloquently discussed the application of novel insights in lymphoma and immunodeficiency disorders to guide the development of new treatments. Dr. Shipp discussed the use of whole genome arrays and multiple clustering methods to identify distinct subtypes of diffuse large B cell lymphomas (DLBCLs), as well as work from her laboratory using the unique transcriptional profiles of newly-diagnosed primary mediastinal large B cell lymphomas (MBCLs) and DLBCLs to detect differences in their NFκB target gene signatures. Their findings suggest that the NFκB pathway may be a potential therapeutic target in lymphomas. Dr. Michael Caligiuri from Ohio State University followed with a discussion of NK cell receptor biology and development. Dr. Roncarolo delivered an impressive review on gene therapy for primary immunodeficiencies, from the first successful gene transfer in murine hematopoietic stem cells (HSCs) over 15 years ago to the first successful clinical trials in humans with X-linked severe combined immunodeficiency (SCID-X1) and adenosine deaminase-deficient SCID (ADA-SCID). She discussed the efficacy of HSC gene therapy combined with non-myeloablative conditioning with busulfan in correcting both the immune and metabolic defects of ADA-SCID. She also addressed safety concerns with gene therapy, including the development of leukemia in three patients with SCID-X1 as a result of insertional activation of the LMO2 oncogene after receiving retroviral vector-based gene therapy. The use of lentiviral vectors as an alternative, potentially safer vector delivery system was discussed as well as targeted tissue-specific expression. This session was the perfect end to the meeting, giving attendees a wonderful opportunity to reflect on the essence of our work as researchers and clinicians in moving from "bench to bedside."
