The achievement of a mixed chimaerism, which eventually converts to full donor chimaerism, after a non-myeloablative allogeneic PBSCT, is thought to be responsible for a graft-versus-tumor effect to occur. Preliminary data from murine models and haematological malignancies suggest that anti-tumor response can be obtained despite loss of donor chimaerism but, to our knowledge, no such data exist on solid tumors.
On February 2004, V.P, affected by metastatic RCC, already pretreated with a-IFN and Vinorelbine, developed progressive disease in the lung and in the retroperitoneum. On July 2004 she was enrolled in a clinical protocol of reduced conditioning allogeneic PBSCT. Conditioning regimen was the following: fludarabine 30 mg/mq from day −4 to −1, and TBI (2 Gy) on day 0, when she also received 8.53x106 CD34+cells/kg from her sister, HLA-full matched, ABO compatible. aGvHD prophylaxis was performed with micophenolate mofetile 15 mg/kg bid, from day 0 to +27 and cyclosporine (Cys) 5 mg/kg bid, from day −2 to +36, followed by a tapering until +56. Chimaerism evaluation, performed on day +28 and +56, showed a full donor engraftment (>90% donor cells) on bone marrow (BM) samples, with 78% of donor CD3+ T cell on peripheral blood (PB). During follow-up, no signs of aGvHD were observed and CMV p65 and PCR remained negative. On day +90, peripheral pancitopenia occurred: WBC-190/mm3, PLT-8000/mm3, Hb-7.5 g/dL, associated with marrow aplasia. Chimaerism evaluation on both BM and PB showed a graft failure, (>95% recipient cells); serological tests were negative (HCV, parvovirusB19, EBV, CMV and adenovirus), no history of drug interaction could be identified. Because of febrile neutropenia she started a large spectrum antibiotic therapy, G-CSF 5 mg/die and an immunosuppressive therapy with metilprednisolone 1mg/kg plus Cys 5 mg/kg, After 5 days she had recovered the WBC while PLT normalization occurred after 45 days. Cys was continued and stopped at day +210. After a follow-up of 386 days from transplantation, she is still in good general condition, off treatment and with stable disease.
On the basis of murine models, the presence of a sustained SD in an otherwise fatal disease, despite loss of graft may suggest the presence of a host-versus-graftimmune response able to promote anti-tumor responses and may promote the development of novel transplant strategies without the risk of GVHD.