Proliferation of CD4+ lymphocytes in a patient with chronic graft-versus-host disease after allogeneic bone marrow transplantation.

Expansion of donor-derived lymphocytes after allogeneic stem cell transplantation is a serious and sometimes fatal complication. Lymphoproliferative disorders are reportedly caused mainly by reactivation of Epstein-Barr virus (EBV) and non-EBV-associated secondary lymphoma or leukemia. In this paper, we report massive proliferation of CD4+ lymphocytes in peripheral blood of a patient with chronic graft-versus-host disease (GVHD) following allogeneic bone marrow transplantation (alloBMT) from an HLA-identical sibling donor. The abnormal lymphocytes showed CD3low, CD4+, CD8-, CD2+, CD5+, CD7+, CD25-, CD19-, CD20-, CD21-, CD16-, CD56low, T-cell receptor (TCR)-alpha/beta- and TCR-gamma/delta- phenotypes, and no rearrangement of either TCR-C beta 1 or IG(H)JH was detected from the lymphocytes by Southern blot analysis. EBV was not found in the nuclei of lymphocytes by an immunofluorescence antibody. The lymphoproliferation was resistant against immunosuppressive drugs, administered for the treatment of chronic GVHD, and it effectively inhibited aggravation of the chronic GVHD. Although antithymocyte globulin and cytosine arabinoside were administered later, the patient died of respiratory failure with bilateral pleural effusion and interstitial pneumonia. Because we found no evidence of monoclonality of the abnormal lymphocytes, we could not conclude that this patient had suffered from malignant lymphoproliferation. To our knowledge, this is the first case report of proliferation of CD4+ lymphocytes in a patient with chronic GVHD following alloBMT. In this paper, we discuss the possible pathophysiology of the patient.