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May primary liver cancer induce a graft-versus-tumor effect?

Bone Marrow Transplantation volume 31, pages 317–318 (2003)Cite this article

Preliminary results of nonmyeloablative stem cell transplantation in solid tumors provide some clinical evidence that allogeneic donor lymphocytes mediate a graft-versus-tumor (GVT) effect, which may be used for the immunotherapy of advanced solid tumors.1 Although the target antigens for the GVT effect are not defined, some tumors like renal cell cancer, breast cancer or, more recently, colorectal adenocarcinoma appear to be more responsive to this form of adoptive immunotherapy.2,3,4,5 As hepatocytes are known to be major targets for graft-versus-host disease (GVHD), one could speculate that cells from a hepatocellular carcinoma may be sensitive to the GVT reaction. We herein report an explosive progression of a previously unknown hepatocellular carcinoma in a patient who received allogeneic hematopoietic stem cells after a preparative regimen of reduced intensity for a myelodysplastic syndrome.

A 50-year-old male suffering from a refractory anemia was considered for a bone marrow transplant from his HLA-identical sister. Moderate biological hepatic disturbances had been noted for several years consisting of increased values of gamma-glutamyl transpeptidase (3–4 times normal value) and alkaline phosphatase (2–3 times normal value) with normal transaminases and bilirubin levels. Ferritin was increased to 865 μg/l and hepatitis serology was negative. Abdominal ultrasound performed 3 months prior to the graft did not detect any hepatic lesion. The patient received a reduced intensity conditioning regimen including total body irradiation (a 6 Gy total dose divided into three fractions), cyclophosphamide 60 mg/kg and antithymocyte globulin 10 mg/kg. Prophylaxis of acute GVHD consisted of the association of short-course methotrexate and cyclosporine. The early post-transplant course was uneventful. Successive studies of marrow or peripheral blood chimerism from day +30 post-transplant showed full donor origin. The patient developed a grade I acute GVHD that was spontaneously regressive. The previously known cholestasis syndrome progressively worsened during the second month after transplantation without any sign of GVHD or veno-occlusive disease. Ultrasound findings at the end of the second month consisted of a voluminous heterogeneous tumor in the segments VI and VIII of the liver. The suspected diagnosis of primary liver cancer was confirmed by a highly elevated level of serum alpha-fetoprotein (1841 μg/l). Thoracic and abdominal computerized tomography and bone scintigraphy did not reveal any metastasis. Cyclosporine was progressively tapered from day +115 and the patient was given regional chemoembolization because of a nonresectable tumor. Unfortunately, the patient died of tumor progression 6 months after transplantation. Since biological hepatic problems had been noted prior to transplantation, a retrospective serum alpha-fetoprotein dosage (950 μg/l) on serum stored immediately before conditioning regimen confirmed that the liver cancer was emerging before the bone marrow graft.

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  1. Service d'hématologie clinique Hôpital l'Archet 1 151, route de Saint-Antoine de Ginestière, Nice, 06202, Cedex 3, France

    A Sirvent-von Bueltzingsloewen, N Gratecos, J G Fuzibet & J P Cassuto

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  1. A Sirvent-von Bueltzingsloewen
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  2. N Gratecos
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  3. J G Fuzibet
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  4. J P Cassuto
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Sirvent-von Bueltzingsloewen, A., Gratecos, N., Fuzibet, J. et al. May primary liver cancer induce a graft-versus-tumor effect?. Bone Marrow Transplant 31, 317–318 (2003). https://doi.org/10.1038/sj.bmt.1703845

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