title: Lymphocyte phenotype during therapy for acute graft-versus-host disease: a brief report from BMT-CTN 0302.
abstract: Although significant strides have been made in understanding the biology of graft-versus-host disease (GVHD) and its prevention over the last 4 decades, little is known about the different populations of lymphocytes and the changes in response to treatment for this condition. BMT-CTN 0302 was a randomized phase II clinical trial in the Blood and Marrow Transplant Clinical Trials Network that assessed the efficacy of combination therapy with steroids plus pentostatin, mycophenolate mofetil, etanercept, or denileukin diftitox in patients with acute GVHD. Patients enrolled in the study underwent blood analysis by flow cytometry on days 0, 14, and 28 of therapy to enumerate the number of total lymphocytes, T cells, B cells, and lymphocytes expressing activation markers. Baseline total lymphocyte counts and subpopulations were similar in the 4 treatment arms. Responding patients had a smaller decrease in total CD45(+) cell count (P = .005) compared with nonresponding patients at day 28. On univariate analysis, those who developed chronic GVHD had significantly higher CD8(+) cell counts at day 14 compared with those without it (P = .005). There was no significant association between baseline lymphocyte count and survival. On univariate analysis, among the patients with higher lymphocyte counts at days 14 and 28, there was a trend toward better survival at day 180, although this trend did not reach the predetermined threshold for significance. We found no significant differences in lymphocyte total or subpopulation counts among the 4 treatment arms, and no notable influence on outcomes.
authors.affiliation: Hematologic Malignancies, the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231, USA. Fbolano2@jhmi.edu
authors.forename: Javier
authors.initials: J
authors.lastname: Bolaños-Meade
authors.forename: Juan
authors.initials: J
authors.lastname: Wu
authors.forename: Brent R
authors.initials: BR
authors.lastname: Logan
authors.forename: John E
authors.initials: JE
authors.lastname: Levine
authors.forename: Vincent T
authors.initials: VT
authors.lastname: Ho
authors.forename: Amin M
authors.initials: AM
authors.lastname: Alousi
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weisdorf
authors.forename: Leo
authors.initials: L
authors.lastname: Luznik
mesh_terms: D000208:Acute Disease; D000328:Adult; D015703:Antigens, CD / Q000276:immunology; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology; D016026:Bone Marrow Transplantation; D004167:Diphtheria Toxin / Q000494:pharmacology / Q000627:therapeutic use; D000068800:Etanercept; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology / Q000627:therapeutic use; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D007376:Interleukin-2 / Q000494:pharmacology / Q000627:therapeutic use; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D015649:Pentostatin / Q000494:pharmacology / Q000627:therapeutic use; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000494:pharmacology / Q000627:therapeutic use; D016019:Survival Analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology; D014184:Transplantation, Homologous
chemical_list: D015703:Antigens, CD; D000970:Antineoplastic Agents; D004167:Diphtheria Toxin; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; C078456:denileukin diftitox; D015649:Pentostatin; D009173:Mycophenolic Acid; D000068800:Etanercept