Document Detail


Circulating levels of MCP-1, sIL-2R, IL-15, and IL-8 predict anemia response to pomalidomide therapy in myelofibrosis.
MedLine Citation:
PMID:  21442636     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cytokine-phenotype associations have recently been described in primary myelofibrosis and increased levels of IL-8, sIL-2R, IL-12, and IL-15 were found to be independently predictive of inferior survival. Pomalidomide therapy is effective for alleviating anemia in myelofibrosis; we examined the relationship between plasma cytokine/chemokine levels and response to treatment with pomalidomide. The study population included 32 Mayo Clinic patients (median age 66 years) who participated in two consecutive clinical trials of pomalidomide therapy for myelofibrosis-associated anemia. Ten (31%) patients achieved anemia response per International Working Group criteria. Anemia response was seen only in the presence of JAK2V617F (P = 0.04) and, in addition, predicted by lower circulating levels of MCP-1 (P = 0.003), IL-2R (P = 0.008), IL-15 (0.01), and IL-8 (P = 0.02). Marked splenomegaly and increased serum LDH level were associated with poor response (P = 0.02 and 0.03, respectively) and with each other (P = 0.02), but not with JAK2V617F. The aforementioned cytokines were not significantly associated with JAK2V617F but increased levels of sIL-2R (P = 0.01), IL-15 (P = 0.06), and MCP-1 (P = 0.07) clustered with marked splenomegaly. Current data suggest that, in the context of pomalidomide treatment, response is more likely in the presence of JAK2V617F and further predicted by the absence of marked splenomegaly or increased levels of proinflammatory cytokines.
Authors:
Animesh Pardanani; Kebede Begna; Christy Finke; Terra Lasho; Ayalew Tefferi
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Publication Detail:
Type:  Clinical Trial, Phase II; Journal Article; Randomized Controlled Trial    
Journal Detail:
Title:  American journal of hematology     Volume:  86     ISSN:  1096-8652     ISO Abbreviation:  Am. J. Hematol.     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-03-28     Completed Date:  2011-05-20     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  7610369     Medline TA:  Am J Hematol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  343-5     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Wiley-Liss, Inc.
Affiliation:
Division of Hematology, Department of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Anemia / blood,  etiology,  genetics,  prevention & control*
Chemokine CCL2 / blood
Cytokines / blood*
Female
Humans
Interleukin-15 / blood
Interleukin-8 / blood
Janus Kinase 1 / antagonists & inhibitors,  genetics
Janus Kinase 2 / antagonists & inhibitors,  genetics
Male
Middle Aged
Mutation
Predictive Value of Tests
Primary Myelofibrosis / blood,  complications,  drug therapy*
Receptors, Interleukin-2 / blood
Thalidomide / administration & dosage,  analogs & derivatives*,  therapeutic use
Treatment Outcome
Chemical
Reg. No./Substance:
0/CCL2 protein, human; 0/Chemokine CCL2; 0/Cytokines; 0/Interleukin-15; 0/Interleukin-8; 0/Receptors, Interleukin-2; 50-35-1/Thalidomide; D2UX06XLB5/pomalidomide; EC 2.7.010.2/JAK1 protein, human; EC 2.7.10.2/JAK2 protein, human; EC 2.7.10.2/Janus Kinase 1; EC 2.7.10.2/Janus Kinase 2

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