By Peter W. Marks, MD, PhD

2009-12-08

The Late-Breaking Abstract Session will take place today from 7:30 to 9:00 a.m. in Hall F. Six papers that span the breadth of hematology from the genome to therapeutic interventions will be presented, and these should prompt lively discussions as participants prepare to head home from the annual meeting.

The introduction of imatinib for the treatment of chronic myeloid leukemia (CML) is often described as “revolutionary.” In looking to improve upon a good thing, Dr. Giuseppe Saglio will report initial results from the Evaluating Nilotinib Efficacy and Safety in Clinical Trials – Newly Diagnosed Patients trial (ENESTnd). ENESTnd is a randomized study in patients with newly diagnosed CML that compares the efficacy of two different doses of the more recently approved BCR-ABL inhibitor nilotinib with imatinib. Remarkably, even though imatinib is highly effective, it does look like improvement is possible with nilotinib. Dr. Richard Larson, a lead investigator on ENESTnd, notes, “Previous studies have shown that for newly diagnosed patients with chronic-phase CML, the risk of treatment failure and disease progression is greatest during the first one to two years after starting imatinib therapy.  In the large randomized trial being presented by Prof. Saglio, not only did patients receiving nilotinib achieve complete cytogenetic and molecular remissions more quickly than those receiving imatinib, there was also a significant reduction in the fraction of patients with an early progression event.”

The appropriate long-term management of patients with unprovoked venous thromboembolism (VTE) is an important area of debate among hematologists, in part because chronic use of vitamin K antagonists is cumbersome for patients and providers alike. On behalf of the EINSTEIN-Extension trial investigators, Dr. Harry Buller from the Academic Medical Center in Amsterdam will present the findings of a randomized trial of the oral direct factor Xa inhibitor rivaroxaban in patients with acute VTE.  Individuals who had completed six to 12 months of anticoagulation, yet did not have a clear indication for continued anticoagulation treatment, were randomized to rivaroxaban or placebo. A remarkable 82 percent relative risk reduction in recurrent VTE (7.1% absolute risk with placebo vs. 1.3% with rivaroxaban) was demonstrated in the 1,197 enrolled patients.

Moving on to the field of genomic medicine, Dr. Susanne Schnittger from Munich will present work examining the prevalence and significance of mutations in the IDH1 gene in acute myeloid leukemia (AML). This gene, coding for soluble isocitrate dehydrogenase 1, was previously identified by Dr. Mardis and colleagues as mutated in 8.5 percent of AML patients with a normal karyotype (New England Journal of Medicine, 2009; 361:1058-66). By examining a cohort of 999 comprehensively characterized AML cases, Dr. Schnittger and her colleagues confirmed the prevalence of IDH1 mutations in AML and demonstrated that these mutations are associated with an unfavorable prognosis in intermediate-risk AML.

Complications of transfusion therapy continue to be a clinical concern — particularly life-threatening complications such as transfusion-related acute lung injury (TRALI). The reason why some individuals sustain this complication has been somewhat mysterious. Though it has long been recognized that transfusion of products from multiparous donors is associated with a higher incidence of TRALI, the molecular basis for this observation was not understood. The work of Brian Curtis, technical director of the Blood Center of Wisconsin, and his colleagues sheds light on this by identifying a novel alloantigen system on leukocytes, the HNA-3a/b system carried on the choline-transporter-like protein CTL2, which appears to help explain this phenomenon.

Returning to the field of leukemia, Dr. Kristina Anderson from Lund, Sweden, will discuss the complexity of clonal architecture in childhood acute lymphoblastic leukemia (ALL). Upon examining single cells by multiplexed FISH analysis at diagnosis and relapse, a remarkable amount of sub-clonal diversity was detected. Interestingly, sub-clones detected at relapse had often evolved, diversifying further from the clones present at initial diagnosis. The investigators note that a major implication of their work is that leukemia stem cells in ALL (and potentially other cancers) are likely to be genetically diverse.

Finally, back in the arena of interventional clinical trials, Dr. Jeffrey Carson will present work on the Transfusion Trigger Trial for Functional Outcomes in Cardiovascular Patients Undergoing Surgical Hip Fracture Repair (FOCUS). If nothing else, the age of the subjects enrolled should catch our attention: 51 to 103 years (mean 81.6). This trial randomized patients with cardiovascular risk factors undergoing hip fracture surgery to a transfusion threshold of a hemoglobin less than 10 g/dL, or to transfusion for symptoms or a hemoglobin less than 8 g/dL. There were no significant differences in the ability of patients to walk across a room at 60-day follow-up or mortality between the two groups, indicating that a conservative transfusion strategy is most appropriate.

Running the gamut from reporting on state-of-the-art molecular analyses of leukemia to large interventional clinical trials, this session will cover a large swath of the discipline of hematology and should provide some topics for conversation on the journey home from the meeting. 

Dr. Marks indicated no relevant conflicts of interest.

back to top