Bone marrow and haemathological evaluation of 62 xenografted cynomolgus monkeys

Background: Non-human primates (NHP) are used in pre-clinical studies, such as pig-to-NHP xenotransplantation. In this context, the evaluation of clinical-pathological data is essential for monitoring the post-transplantation period. Cytological examination of bone marrow (BM) is a helpful adjunct for a complete interpretation of haematological data. The aim of this work is to evaluate the cytology of BM and haematological data in immunosuppressed (IS) xenotransplanted NHP. Methods: Sixty-two xenografted NHP were included: 36 recipients of porcine renal xenograft (RX group) and 17 recipients of neuronal precursors (NPX group). Both groups received a maintenance immunosuppression with cyclosporine A, sodium mycophenolate and steroids. RX group received an induction therapy consistent of cyclophosphamide and/or GAS914, or rituximab, or IVIG or anti-CD154; NPX received cyclosporine A and GAS914. A complete CBC and femoral BM smears collected at euthanasia were obtained. BM cytological evaluation and differential counts of erythroid, granulocytic, megakaryocytic, lymphocytic and plasmacytic series were performed. The myeloid-to-erythroid ratio (M:E), the erythroid (E-MI) and myeloid (M-MI) maturation indices were calculated. Results: Compare to the reference range, 44 NHP showed an increased M:E ratio (>1.85) due to myeloid hyperplasia and erythroid hypoplasia. In 16 cases the M:E ratio was severely increased (>5.45). Both E-MI and M-MI were raised in 61 and 57 cases, respectively. The highest values of M:E and M-MI were recorded in the RX group. The main haemathological alterations observed were anemia (54/62 NHP), leucopenia (15/62) and lymphopenia (25/62). Cytoplasmatic and nuclear vacuolization, dysplastic changes in granulocytic and erythroid lineages were the main morphological alterations in BM probably due to toxic effects of IS therapy. In spite of IS therapy, xenografted NHP showed a myeloid hyperplasia, mainly in RX group probably due to the marked inflammatory status during acute rejection. Conclusions: The BM evaluation in xenografted IS NHP may provide the basis for a complete interpretation of hematological profiles and represent an important tool for a better design of IS strategies.