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 transplan tation is a serious and sometimes fatal complication. Lymphoproliferative d isorders 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 allog eneic bone marrow transplantation (alloBMT) from an HLA-identical sibling d onor. The abnormal lymphocytes showed CD31(low), CD4(+), CD8(-), CD2(+), CD 5(+), CD7(+), CD25(-), CD19(-), CD20(-), CD21(-), CD16(-), CD5610(low), T-c ell receptor (TCR)-alpha/beta- and TCR-gamma/delta(-) phenotypes, and no re arrangement of either TCR-C beta 1 or IG(H)JH was detected from the lymphoc ytes by Southern blot analysis. EBV was not found in the nuclei of lymphocy tes by an immunofluorescence antibody. The lymphoproliferation was resistan t against immunosuppressive drugs, administered for the treatment of chroni c GVHD, and it effectively inhibited aggravation of the chronic GVHD. Altho ugh antithymocyte globulin and cytosine arabinoside were administered later , the patient died of respiratory failure with bilateral pleural effusion a nd interstitial pneumonia. Because we found no evidence of monoclonality of the abnormal lymphocytes, we could not conclude that this patient had suff ered from malignant lymphoproliferation. To our knowledge, this is the firs t case report of proliferation of CD4(+) lymphocytes in a patient with chro nic GVHD following alloBMT. In this paper, we discuss the possible pathophy siology of the patient. Int J Hematol. 2000;71:389-393. (C) 2000 The Japane se Society of Hematology.