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Grand Rounds | Clinician's Corner

Targeting Immune Dysregulation in Myelodysplastic Syndromes

Matthew J. Olnes, MD, PhD; Elaine M. Sloand, MD
JAMA. 2011;305(8):814-819. doi:10.1001/jama.2011.194.
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Myelodysplastic syndromes (MDS) are a heterogeneous group of bone marrow disorders characterized by ineffective hematopoiesis and a tendency to develop leukemia. In some patients, laboratory and clinical evidence supports a role for the immune system in the pathogenesis of early MDS. Many younger patients who respond to immunosuppressive therapy with drugs such as antithymocyte globulin and cyclosporine have clonal expansions of cytotoxic CD8+ T cells that suppress normal hematopoiesis, as well as expansion of CD4+ helper T-cell subsets that promote and sustain autoimmunity. Immunosuppressive therapy can produce hematologic responses in some patients and may improve survival and halt leukemic progression. In this report, we describe a 56-year-old woman who presented with fatigue and easy bruising, eventually became pancytopenic, and was diagnosed with MDS. After treatment with a clinical protocol using alemtuzumab, an anti-CD52 antibody, her blood cell counts returned to normal and she has remained in complete remission for more than 2 years of follow-up. In this article, we review the pathobiology of immune dysregulation in MDS and summarize the role of immunosuppressive therapy in MDS.

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Figure 1. Morphologic Findings of Myelodysplastic Syndromes (MDS)
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A, Bone marrow aspirate morphology from a patient with MDS demonstrates small mononuclear megakaryocytes; B, bilobed nuclei; C, nuclear budding; and D, granulocyte dyspoiesis with an increased nucleus to cytoplasmic ratio and nuclear hypolobulation.

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Figure 2. Hematologic Responses to Alemtuzumab in a Patient With Myelodysplastic Syndromes (MDS)
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Transfusion independence for red blood cells is defined according to the International Working Group Criteria for MDS49 as a stable hemoglobin level of at least 9 g/dL without transfusions for at least 8 weeks, and for platelet count as a stable platelet count greater than 10 000/μL for at least 8 weeks without transfusions.




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