[1229] The Immune Microenvironment in Post-Transplant Lymphoproliferative Disorders (PTLDs): Composition and Relationship to Outcome.

Amy Chadburn, Anmaar Abdul-Nabi, Beverly Nelson, David Myerson, Howard Shulman. Northwestern University Feinberg School of Medicine, Chicago, IL; Seattle Cancer Care Alliance, WA

Background: The prognosis of immunocompetent patients with B-cell lymphomas is not only related to tumor cell characteristics but also to the associated immune microenvironment (ME) composed of subtypes of T cells (i.e. regulatory T cells, follicular T helper cells, cytotoxic T, etc.) and macrophages. Post-transplant lymphoproliferative disorders are predominately EBV+ B cell proliferations that arise in the setting of an altered immune milieu. However, whether the alterations caused by an iatrogenically manipulated immune ME is associated with prognosis, EBV status, type of transplant (solid organ vs bone marrow) or histogenic origin of the B cells is not known.
Design: Tissue microarrays (2 cores/case) composed of 28 bone marrow PTLDs (BMT) from 27 patients (14M:13F; 2-64 yrs) and 21 solid organ PTLDs (SOT) from 18 patients (9M:9F; 19-79 yrs) were examined for CD20, ME marker expression (CD3, CD4, CD8, CD57, TIA1, FOXP3, PD1, KP1), EBV status (EBER, LMP1, EBNA2) and histogenic origin (CD10, BCL6, MUM1). Cases were scored as percent positive, except for KP1 scored as 1-4+. ME marker expression was compared with outcome, EBV status, histogenic category (germinal center [GC] vs. non-GC) and PTLD type (SOT vs. BMT).
Results:

Histogenic Origin, EBV Status, ME Marker Expression
 GCEBV+ Lat 2/3CD3>/=30%CD4>/=20%CD8>/=30%FOXP3+PD1+
BMT0/28100%25%3%26%032%
SOT1/2183%57%19%5%81%48%


2/3 SOT EBV Latency (Lat) I had higher numbers of CD4+ and PD1+ cells. Only 2/18 SOT patients died; both had lesions with 90% CD20+ and rare to no CD4+, CD8+, FOXP3+, and/or PD1+ cells. All BMT PTLD patients with >/=30% CD20+ cells died of PTLD. Only 1 BMT had >/=10% CD4 cells (died of PTLD); 30% of BMT patients who died of PTLD and 29% who died of other causes had >/=30% CD3/CD8+ cells. Expression of TIA1, CD57, FOXP3, KP1+ did not correlate with outcome in SOTs or BMTs.
Conclusions: Although the composition of the immune ME in immunocompetent B NHLs appears to influence disease behavior, the lack of a general immune response seems to be more predictive of outcome in PTLD. Thus, the nuances of the immune response contributed by specialized ME cell subpopulations appear to play more of a role in disease behavior when the immune system is intact.
Category: Hematopathology

Wednesday, March 2, 2011 9:30 AM

Poster Session V # 174, Wednesday Morning

 

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