Utilizing Y Chromosome FISH to Determine the Origin of Post-Transplant Lymphoproliferative Disease in Solid Organ Transplant Recipients

Background: Post-Transplant Lymphoproliferative Disease (PTLD) is a heterogeneous disease that arises as a complication after solid organ transplants (SOT) and unusually after bone marrow transplants (BMT). PTLD is generally of recipient origin in SOT patients and donor origin in BMT patients. Knowing the cellular origin of PTLD may provide insight into tumorigenesis and potentially guide treatment options.

Design/Methods: We identified gender mismatched SOT patients from our institutional databases who had PTLD tumor tissue for FISH analysis to determine the tumor origin (donor vs. recipient). From these samples, lesional and normal (when present) tissue was delineated by a hematopathologist (TG), and subsequent XY FISH studies were performed according to standard protocols for detection of the Y chromosome.

Results: Thirty-one gender mismatched PTLD patients were examined (20 were pediatric patients <18 yrs old). Transplants were: 8 isolated liver (L), 7 kidney (K), 3 small bowel (SB), 6 L/SB, 4 L/SB/pancreas (P), 2 K/L and one L/K/P. Of the 31 patients: 25 were 100% recipient origin; 5/31 demonstrated mixed chimerism; and 1 was 100 % donor origin. Of the 6 patients with chimerism (3 children), the percentage of donor cells ranged between 23% and 100%. Three of 31 had PTLD in the allograft, with 2 of 3 demonstrating mixed chimerism. One was a 2 y.o. F 3 months after a SB transplant and the other a 10 m.o. M 12 months after a L/SB/P transplant. Of the 28 with tumor tissue at other sites, 3 had mixed chimerism: a 60 y.o. M 9 months after a K/L transplant; a 7 m.o. M 8 months after a L/SB transplant; and a 64 y.o. F 3 months after a L transplant. The single patient with 100 % donor chimerism was a 27 year old female 5 months after a L/SB transplant. The 6 chimeric patients developed PTLD on average earlier than the 25 patients of recipient origin (6.9 months vs. 18.1 months). Of the 20 pediatric patient, 12 had transplants including small bowel and 3/12 demonstrated mixed chimerism. Mortality rate was similar between pediatric and adult populations (40% and 45% respectively).

Conclusion: As expected, the majority of patients in our series had tumors of recipient origin. However, 3/20 pediatric patients (15%) and 3/11 (27%) adult patients were chimeric in 23% to 100% of their tumor cells. Chimerism was more common in patients who received transplants that included L (4/5) and SB (3/5).