TY - JOUR
T1 - Lymphocyte Phenotype during Therapy for Acute Graft-versus-Host Disease
T2 - A Brief Report from BMT-CTN 0302
AU - Bolaños-Meade, Javier
AU - Wu, Juan
AU - Logan, Brent R.
AU - Levine, John E.
AU - Ho, Vincent T.
AU - Alousi, Amin M.
AU - Weisdorf, Daniel J.
AU - Luznik, Leo
N1 - Funding Information:
Financial disclosure : Support for this study was provided by grant U10HL069294 from the National Heart, Lung, and Blood Institute , and the National Cancer Institute , along with contributions from Eisai, Hospira, Roche Laboratories, and Immunex Corporation, a wholly owned subsidiary of Amgen. Additional support was provided by the National Institute of Allergy and Infectious Disease for the ancillary studies “Analysis of Serum Biomarkers Related to aGVHD Treatment Responsiveness” and “Pharmacogenetics of Steroid Responsiveness in aGVHD.” The analyses were performed independent of any of the study sponsors.
PY - 2013/3
Y1 - 2013/3
N2 - 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.
AB - 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.
KW - Chronic graft-versus-host-disease
KW - Flow cytometry
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U2 - 10.1016/j.bbmt.2012.12.003
DO - 10.1016/j.bbmt.2012.12.003
M3 - Article
C2 - 23247045
AN - SCOPUS:84873591805
SN - 1083-8791
VL - 19
SP - 481
EP - 485
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 3
ER -