High doses of mother's lymphocyte infusion to treat EBV-positive T-cell lymphoproliferative disorders in childhood

Abstract

AbstractDonor lymphocyte infusion is an alternative treatment for Epstein-Barr virus (EBV)–associated lymphoproliferative disorders (LPDs) but with risk of graft-versus-host diseases (GVHDs). According to the fetal-maternal microchimerism tolerance, we assumed that maternal lymphocyte infusion may be effective without causing GVHD. In 54 cases when a child required cytotherapy or hematopoietic stem cell transplantation, we studied the mother for child-mother microchimerism with use of insertion-deletion polymorphisms as allogeneic markers and a combination of nested polymerase chain reaction (PCR) and real-time quantitative PCR. Thirteen mothers were child-microchimerism–positive at the ratio of 10−5-10−3. Among them, 5 children had non–transplant-associated, EBV+ T-cell LPD. In these 5 cases, high doses of human leukocyte antigen–haploidentical maternal peripheral blood mononuclear cells (> 108/kg/infusion) were infused 1-4 times. Symptoms of all 5 patients improved between 3 and 10 days after the infusion; thereafter, 3 cases showed complete remission for 6-18 months without further therapy and 2 had partial remission. During the period of observation, none developed obvious GVHD. By quantitative PCR, in some patients maternal cells were found to be eliminated or decreased after infusions, indicating existence of host-versus-graft reaction. We suggest that high doses of mother's lymphocyte infusion may be an effective and safe treatment for non–transplant-associated EBV+ T-cell LPD.