Unveiling the Pathophysiological
Mysteries of Marrow Failure

On Saturday afternoon and Sunday morning,in a series of three very interesting presentations, marrow failure syndromes were discussed and dissected by four scientists who shared up-to-date classifications, diagnosis, management, and treatment of multiple diseases characterized by marrow failure. Dr. Grover Bagby (Oregon Health and Sciences University) and Dr. Jeffrey Lipton (Schneider Children’s Hospital) presented a comprehensive account of disorders associated with multilineage bone marrow failure and focused on four disorders that were chosen because of the level of understanding of their genetical and biochemical mechanisms. One of these four diseases is Fanconi anemia (FA) which is a rare autosomal recessive disease affecting patients from all racial and ethnic groups. Genetic instability is a hallmark of FA since a main function of FA proteins (to date, 11 complementation groups are known) is maintenance of chromosomal stability, although it is not yet well established how this is accomplished. A dual function of FA proteins in genetic stability and hematopoietic cell apoptosis may explain why selective dominance of stem cell clones may lead to leukemia in FA patients. Drs. Bagby and Lipton then discussed another disorder characterized by multilineage marrow failure, namely Dyskeratosis Congenita (DC). As with FA, the discussion of DC went through the clinical and hematologic features of the disease, pathogenesis, diagnosis, and management. They then moved on to describe two other inherited diseases which are associated with failure of single hematopoietic lineages in contradistinction to FA and DC. These two disorders are Diamond-Blackfan anemia and Shwachman- Diamond syndrome.

Dr. Elaine Sloand from the National Heart, Lung, and Blood Institute focused her talk on acquired aplastic anemia and followed a sequence similar to that in the previous presentations. Dr. Sloand described the pathophysiology of acquired aplastic anemia and compared the outcomes of bone marrow transplantation or immunosuppression as standard treatments of this disease. She also provided an algorithm for patient management and discussed treatment options for refractory cases as well as cases that progress to clonal evolution. Dr. Sloand concluded her presentation with a discussion of the results of matched-related and matched-unrelated allogeneic marrow transplantation in the treatment of aplastic anemia.

The final speaker in this Education Program was Dr. Charles Schiffer from Wayne State University who discussed the challenges of myelodysplasia. Given the confusion created by the use of varying definitions of the myelodysplastic syndromes (MDS) and agreed upon definitions of response, Dr. Schiffer spent some time covering the results of the recent standardization efforts by different international committees including the World Health Organization in the areas of the definitions of MDS, response to treatment, and the influence of prognostic factors. He then described in some detail some selected treatment approaches, including allogeneic stem cell transplantation. For the clinician seeking an in-depth analysis of diseases associated with marrow failure, this education program fit the bill exactly.