Lymphocyte subsets may discern treatment effects in children and young adults with post-transplant lymphoproliferative disorder.
To identify potential alternatives to Epstein-Barr virus (EBV)-specific cytotoxic T-cell responses, peripheral lymphocyte subsets (PLS) (CD4+, CD8+, CD3+, CD19+, CD56+) were measured by flow cytometry in children with abdominal transplants (n = 22) and heart transplants (n = 2), with (n = 14) and without (n = 10, group C) post-transplant lymphoproliferative disorder (PTLD). PTLD resolved with reduced immunosuppression and antiviral therapy in eight children (group B). Recalcitrant PTLD was observed in six children (group A). Recalcitrant PTLD followed prior antilymphocyte therapy [monoclonal anti-CD3 antibody (OKT3) and thymoglobin (n = 3) and thymoglobin (n = 1)] for refractory rejection in four of these six children, and resolved after treatment with rituximab (anti-CD20 monoclonal antibody). Ten children without PTLD served as a control group (group C). Between group comparisons showed a numeric increase in CD8 + cells and significantly lower CD4:CD8 ratios in both PTLD groups (A and B) compared with group C. Group A children also demonstrated significant depletion of natural killer (NK) cells, and post-rituximab depletion of B-cells compared with group B (no rituximab treatment). We conclude that NK cell depletion with a reversed CD4:CD8 ratio may represent a persistent immunosuppressed state, which may result from prior antilymphocyte therapy and may predispose to recalcitrant EBV-PTLD. Clinical remission with rituximab is accompanied by B-cell depletion. Serial monitoring of PLS from the time of diagnosis of PTLD will be necessary to confirm these observations.
LeVasseur
Ryan
R
Department of Pediatric Transplantation, Children's Hospital, University of Pittsburgh, Pittsburgh, PA 15217, USA.
Ganjoo
Jessie
J
Green
Michael
M
Janosky
Janine
J
Reyes
Jorge
J
Mazariegos
George
G
Sindhi
Rakesh
R
D000293:Adolescent; D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology*; D002469:Cell Separation; D002648:Child; D002675:Child, Preschool; D005434:Flow Cytometry; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007223:Infant; D007694:Killer Cells, Natural / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000276:immunology*; D008232:Lymphoproliferative Disorders / Q000209:etiology* / Q000276:immunology; D016377:Organ Transplantation / Q000009:adverse effects*; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000276:immunology*; D014181:Transplantation Immunology