TY - JOUR
T1 - Thrombocytopenia in Patients With Myelofibrosis
T2 - Pathogenesis, Prevalence, Prognostic Impact, and Treatment
AU - Sastow, Dahniel
AU - Mascarenhas, John
AU - Tremblay, Douglas
N1 - Publisher Copyright:
© 2022
PY - 2022/7
Y1 - 2022/7
N2 - Myelofibrosis (MF) is a clonal hematopoietic stem cell neoplasm, characterized by pathologic myeloproliferation associated with inflammatory and pro-angiogenic cytokine release, that results in functional compromise of the bone marrow. Thrombocytopenia is a disease-related feature of MF, which portends a poor prognosis impacting overall survival (OS) and leukemia free survival. Thrombocytopenia in MF has multiple causes including ineffective hematopoiesis, splenic sequestration, and treatment-related effects. Presently, allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curable treatment for MF, which, unfortunately, is only a viable option for a minority of patients. All other currently available therapies are either focused on improving cytopenias or the alleviating systemic symptoms and burdensome splenomegaly. While JAK2 inhibitors have moved to the forefront of MF therapy, available JAK inhibitors are advised against in patients with severe thrombocytopenia (platelets < 50 × 109/L). In this review, we describe the pathogenesis, prevalence, and prognostic significance of thrombocytopenia in MF. We also explore the value and limitations of treatments directed at addressing cytopenias, splenomegaly and symptom burden, and those with potential disease modification. We conclude by proposing a treatment algorithm for patients with MF and severe thrombocytopenia.
AB - Myelofibrosis (MF) is a clonal hematopoietic stem cell neoplasm, characterized by pathologic myeloproliferation associated with inflammatory and pro-angiogenic cytokine release, that results in functional compromise of the bone marrow. Thrombocytopenia is a disease-related feature of MF, which portends a poor prognosis impacting overall survival (OS) and leukemia free survival. Thrombocytopenia in MF has multiple causes including ineffective hematopoiesis, splenic sequestration, and treatment-related effects. Presently, allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curable treatment for MF, which, unfortunately, is only a viable option for a minority of patients. All other currently available therapies are either focused on improving cytopenias or the alleviating systemic symptoms and burdensome splenomegaly. While JAK2 inhibitors have moved to the forefront of MF therapy, available JAK inhibitors are advised against in patients with severe thrombocytopenia (platelets < 50 × 109/L). In this review, we describe the pathogenesis, prevalence, and prognostic significance of thrombocytopenia in MF. We also explore the value and limitations of treatments directed at addressing cytopenias, splenomegaly and symptom burden, and those with potential disease modification. We conclude by proposing a treatment algorithm for patients with MF and severe thrombocytopenia.
KW - Danazol
KW - Immunomodulators
KW - JAK inhibitors
KW - Pacritinib
KW - Ruxolitinib
UR - http://www.scopus.com/inward/record.url?scp=85125530314&partnerID=8YFLogxK
U2 - 10.1016/j.clml.2022.01.016
DO - 10.1016/j.clml.2022.01.016
M3 - Review article
C2 - 35221248
AN - SCOPUS:85125530314
SN - 2152-2650
VL - 22
SP - e507-e520
JO - Clinical Lymphoma, Myeloma and Leukemia
JF - Clinical Lymphoma, Myeloma and Leukemia
IS - 7
ER -