%0 Journal Article
%T Transplantation for Congenital Bone Marrow Failure Syndromes
%A Kenji Morimoto
%A Theodore B. Moore
%A Gary Schiller
%A Kathleen M. Sakamoto
%J Bone Marrow Research
%D 2011
%I Hindawi Publishing Corporation
%R 10.1155/2011/849387
%X Congenital bone marrow failure syndromes (BMFSs) are relatively rare disorders characterized by aberrant development in one or more hematopoietic lineages. Genetic alterations have now been identified in most of these disorders although the exact role of the molecular defects has yet to be elucidated. Most of these diseases are successfully managed with supportive care, however, treatment refractoriness and disease progression¡ªoften involving malignant transformation¡ªmay necessitate curative treatment with hematopoietic stem cell transplantation. Due to the underlying molecular defects, the outcome of transplantation for BMFS may be dramatically different than those associated with transplantation for more common diseases, including leukemia. Given recent improvements in survival and molecular diagnosis of bone marrow failure syndrome patients presenting at adult ages without physical stigmata, it is important for both pediatric and adult hematologists to be aware of the possible diagnosis of BMF syndromes and the unique approaches required in treating such patients. 1. Introduction Bone marrow failure syndromes (BMFSs) are a constellation of disorders characterized by abnormal hematopoiesis and often accompanied by assorted physical findings and a strikingly increased risk for hematologic malignancy. Historically, patients presented with significant cytopenias and physical stigmata during childhood. However, it is now evident that BMFS posses a broad range of phenotype penetrance and an increasing number of patients are being identified in adulthood, occasionally presenting with leukemia or aplastic anemia. Some BMFS disorders are associated with defective DNA repair or maintenance pathways and possess increased sensitivity to DNA-damaging agents including chemotherapy and radiation. These sensitivities have been clearly demonstrated by the significantly increased chemotherapy-related and stem cell transplant-related morbidity and mortality in BMFS patients. It is therefore important for both pediatric and adult hematologists to be aware of the presentation, management, complications, and approaches to treat BMFS. We review here transplantation approaches and outcomes in patients with Fanconi Anemia, Diamond-Blackfan anemia, dyskeratosis congenita, severe congenital neutropenia, and Shwachman-Diamond syndrome to illustrate their relative risks for malignancy and reported utility of varying transplant regimens. The reporting of cumulative transplant outcomes will hopefully add clarity to the indications for transplantation in these disorders. 2. Fanconi
%U http://www.hindawi.com/journals/bmr/2011/849387/