Thrombocytopenia in MDS: epidemiology, mechanisms, clinical consequences and novel therapeutic strategies.
Thrombocytopenia is commonly seen in myelodysplastic syndrome (MDS) patients, and bleeding complications are a major cause of morbidity and mortality. Thrombocytopenia is an independent factor for decreased survival and has been incorporated in newer prognostic scoring systems. The mechanisms of thrombocytopenia are multifactorial and involve a differentiation block of megakaryocytic progenitor cells, leading to dysplastic, hypolobated and microscopic appearing megakaryocytes or increased apoptosis of megakaryocytes and their precursors. Dysregulated thrombopoietin (TPO) signaling and increased platelet destruction through immune or nonimmune mechanisms are frequently observed in MDS. The clinical management of patients with low platelet counts remains challenging and approved chemotherapeutic agents such as lenalidomide and azacytidine can also lead to a transient worsening of thrombocytopenia. Platelet transfusion is the only supportive treatment option currently available for clinically significant thrombocytopenia. The TPO receptor agonists romiplostim and eltrombopag have shown clinical activity in clinical trials in MDS. In addition to thrombopoietic effects, eltrombopag can inhibit leukemic cell proliferation via TPO receptor-independent effects. Other approaches such as treatment with cytokines, immunomodulating drugs and signal transduction inhibitors have shown limited activity in selected groups of MDS patients. Combination trials of approved agents with TPO agonists are ongoing and hold promise for this important clinical problem.
Department of Medicine, Albert Einstein College of Medicine/Jacobi Medical Center, Bronx, NY, USA.
W
W
Li
Department of Pediatrics, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY, USA.
K
K
Morrone
Department of Medicine, University of Kansas Medical Center, Kansas City, KS, USA.
S
S
Kambhampati
Division of Hemato-Oncology, Department of Oncology, Albert Einstein College of Medicine, Bronx, NY, USA.
B
B
Will
Division of Hemato-Oncology, Department of Oncology, Albert Einstein College of Medicine, Bronx, NY, USA.
U
U
Steidl
Division of Hemato-Oncology, Department of Oncology, Albert Einstein College of Medicine, Bronx, NY, USA.
A
A
Verma
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001565:Benzoates / Q000627:therapeutic use; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D015972:Gene Expression Regulation, Neoplastic; D006470:Hemorrhage / Q000150:complications / Q000175:diagnosis / Q000453:epidemiology / Q000628:therapy*; D006801:Humans; D006834:Hydrazines / Q000627:therapeutic use; D008533:Megakaryocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009190:Myelodysplastic Syndromes / Q000150:complications / Q000175:diagnosis / Q000453:epidemiology / Q000628:therapy*; D017713:Platelet Transfusion; D011379:Prognosis; D011720:Pyrazoles / Q000627:therapeutic use; D011961:Receptors, Fc / Q000627:therapeutic use; D053628:Receptors, Thrombopoietin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D015398:Signal Transduction; D013921:Thrombocytopenia / Q000150:complications / Q000175:diagnosis / Q000453:epidemiology / Q000628:therapy*; D013926:Thrombopoietin / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use
D000970:Antineoplastic Agents; D001565:Benzoates; D006834:Hydrazines; D011720:Pyrazoles; D011961:Receptors, Fc; D053628:Receptors, Thrombopoietin; D011993:Recombinant Fusion Proteins; C082218:MPL protein, human; D013926:Thrombopoietin; C488777:romiplostim; C520809:eltrombopag