Donor cell reaction to OKT3 as predictor of chronic graft-vs-host disease in hematopoietic stem cell recipients

• Published in: Experimental hematology Vol. 34; no. 12; pp. 1753 - 1758
• Main Authors: Lindemann, Monika, Ottinger, Hellmut D., Elmaagacli, Ahmet H., Trenschel, Rudolf, Rebmann, Vera, Beelen, Dietrich W., Grosse-Wilde, Hans
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.12.2006
• Subjects: Adolescent; Adult; Aged; Cell Proliferation - drug effects; Chronic Disease; Cohort Studies; Female; Follow-Up Studies; Graft vs Host Disease - immunology; Graft vs Host Disease - prevention & control; Granulocyte Colony-Stimulating Factor - administration & dosage; Hematopoietic Stem Cell Transplantation - adverse effects; Humans; Lymphocyte Activation - drug effects; Male; Middle Aged; Muromonab-CD3 - pharmacology; Predictive Value of Tests; Reproducibility of Results; Retrospective Studies; Risk Factors; Sensitivity and Specificity; Severity of Illness Index; Tissue Donors; Transplantation, Homologous; Treatment Outcome
• ISSN: 0301-472X; 1873-2399
• DOI: 10.1016/j.exphem.2006.08.003

In the hematopoietic stem cell transplantation setting, granulocyte colony-stimulating factor (G-CSF) administration can reduce donor cell reactivity in vitro, but the clinical significance of this phenomenon was only sparsely defined. We performed lymphocyte transformation tests in 28 related stem cell donors pre and 5 days post G-CSF treatment, respectively, and correlated proliferative responses of donor peripheral blood mononuclear cells with clinical parameters in the corresponding recipients. In vitro reactions towards 4 mitogens and 12 recall antigens at day 5 post G-CSF administration were predictive for the occurrence of chronic graft-vs-host disease (cGVHD). Here, proliferative responses towards the mitogen anti-CD3 monoclonal antibody (OKT3) above median were most informative; this threshold could be determined by discrimination and receiver operating curve (ROC) analyses. In the whole cohort (18 human leukocyte antigen [HLA]-identical and 10 partially mismatched donor-recipient pairs), OKT3 responses predicted cGVHD with an odds ratio of 33.0, a sensitivity of 79%, and a specificity of 90%. A subgroup analysis of HLA-identical pairs even yielded an odds ratio of 85.0. Furthermore, bivariate analysis defined HLA compatibility and responses towards OKT3 as independent risk factors for cGVHD ( p = 0.02 and p = 0.0007, respectively). The proliferative capacity of G-CSF-mobilized donor cells appears as a graft factor that determines the future incidence of cGVHD in the corresponding recipient.