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Hematopoietic Growth Factor Therapy for Myelodysplastic Syndromes and Aplastic Anemia

  • Chapter
Hematopoietic Growth Factors in Oncology

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

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Abstract

Myelodysplastic syndromes (MDS) and idiopathic aplastic anemia (AA) are acquired bone marrow failure states. In AA, cytopenias are primarily caused by immune-mediated destruction of stem cells and concomitant severe compromise of hematopoiesis. In low-risk MDS, excessive intramedullary apoptosis of hematopoietic progenitors and ineffective hematopoiesis often account for the paradox of hyper-cellular marrows in the setting of chronic refractory cytopenias. Evolution to acute myeloid leukemia (AML) occurs in a proportion of patients with MDS and is frequently associated with reversion of marrow myeloid precursors to a leukemic phenotype. The development of recombinant cytokines has facilitated in vitro and in vivo analysis of the proliferative and differentiation defects involved in MDS and AA hematopoiesis. Cytokine therapy with recombinant human erythropoietin (rHuEPO) has resulted in clinically important erythroid responses in 20% of patients with MDS, which increases to 40% with addition of granulocyte colony-stimulating factor (rHuG-CSF). Identification of factors that predict response to these hematopoietic growth factors (HGFs) permits tailoring of these treatments to appropriate subsets of MDS patients. The rationale for using HGFs in AA has been to increase the pool of residual stem cells and to stimulate maturation of pre-existing progenitors in an attempt to ameliorate cytopenias; however, their prophylactic use as single agents has not been recommended. Instead, they have primarily been used as adjuncts to immunosuppressive therapy in the setting of clinical trials or in patients refractory to other therapies. Use of rHuG-CSF in AA has caused close scrutiny of the question as to whether the cytokine contributes to the increased risk of late clonal hematologic malignancies observed in a proportion of patients with AA.

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Authors
  1. Jason Gotlib MD, MS
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  2. Peter L. Greenberg MD
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Editors and Affiliations

  1. Amgen, Australia, Pty. Ltd., Monash University, Victoria, Australia

    George Morstyn MBBS, PhD, FRACP

  2. Amgen Inc., Thousand Oaks, CA, USA

    MaryAnn Foote PhD

  3. Ludwig Institute for Cancer Research, Royal Melbourne Hospital, Melbourne, Australia

    Graham J. Lieschke MBBS, PhD, FRACP

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Gotlib, J., Greenberg, P.L. (2004). Hematopoietic Growth Factor Therapy for Myelodysplastic Syndromes and Aplastic Anemia. In: Morstyn, G., Foote, M., Lieschke, G.J. (eds) Hematopoietic Growth Factors in Oncology. Cancer Drug Discovery and Development. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-747-5_17

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