title: Increased adenosine triphosphate production by peripheral blood CD4+ cells in patients with hematologic malignancies treated with stem cell mobilization agents.
abstract: Hematopoietic stem cell (HSC) transplantation is an important therapeutic option for patients with hematologic malignancies. To explore the immunomodulatory effects of HSC mobilization agents, we studied the function and phenotype of CD4(+) T cells from 16 adult patients with hematologic malignancies undergoing HSC mobilization treatment for autologous transplantation. Immune cell function was determined using the Immuknow (Cylex) assay by measuring the amount of adenosine triphosphate (ATP) produced by CD4(+) cells from whole blood. ATP activity measured in G-CSF-treated patients was significantly higher than that measured in healthy individuals or "nonmobilized" patients. In patients treated with G-CSF, CD4(+) T cells were predominantly CD25(low)FOXP3(low), consistent with an activated phenotype. However, T-cell depletion did not abrogate ATP production in blood samples from G-CSF-treated patients, indicating that CD4(+) myeloid cells contributed to the increased ATP levels observed in these patients. There was a significant correlation between ATP activity and patient survival, suggesting that efficient activation of CD4(+) cells during mobilization treatment predicts a low risk of disease relapse. Monitoring immune cell reactivity using the Immuknow assay may assist in the clinical management of patients with hematologic malignancies and optimization of HSC mobilization protocols.
authors.affiliation: Department of Pathology, Columbia University Medical Center, New York, New York, USA.
authors.forename: Kiran
authors.initials: K
authors.lastname: Manga
authors.forename: Geo
authors.initials: G
authors.lastname: Serban
authors.forename: Joseph
authors.initials: J
authors.lastname: Schwartz
authors.forename: Ronit
authors.initials: R
authors.lastname: Slotky
authors.forename: Nita
authors.initials: N
authors.lastname: Patel
authors.forename: Jianshe
authors.initials: J
authors.lastname: Fan
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Bai
authors.forename: Ajai
authors.initials: A
authors.lastname: Chari
authors.forename: David
authors.initials: D
authors.lastname: Savage
authors.forename: Nicole
authors.initials: N
authors.lastname: Suciu-Foca
authors.forename: Adriana I
authors.initials: AI
authors.lastname: Colovai
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D003115:Colony-Stimulating Factors / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology / Q000627:therapeutic use; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology / Q000627:therapeutic use; D019337:Hematologic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy*; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D007958:Leukocyte Count; D008213:Lymphocyte Activation / Q000187:drug effects; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D012372:ROC Curve; D012727:Sex Characteristics; D013234:Stem Cells / Q000166:cytology
chemical_list: D003115:Colony-Stimulating Factors; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D010835:Phytohemagglutinins; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000255:Adenosine Triphosphate