Graft versus tumor effect has been described in solid metastatic tumor. We reported here the case of a patient treated for an acute myeloid leukemia with reduced-intensity conditioned allograft and the effect of this procedure on concomitant of renal localised cancer. The effect of immune-mediated cytotoxicity on renal cancer is the more consistent explanation to understand the necrosis of this tumor. Any case of RIC allograft has been reported before to treat localised renal tumor.
The effect of immune-mediated cytotoxicity on renal cancer has been clearly outlined in the last decades by several lines of evidence. We reported here a patient with bone marrow failure treated with RIC allograft and the effect of this procedure on a concomitant localised renal cancer.
A 52-year-old man was referred in 1980 in our department because of severe pancytopenia (platelets: 8 G/L; hemoglobin: 8.3 g/d; MCV: 87 fl, reticulocytes: 0.5% (14000/microL); WBC : 2.1 G/L; Neutrophils: 16%; Lymphocytes: 70%; Monocytes: 4%). Bone marrow was aplastic on histological examination. He was then treated with packed red cells and platelets transfusions and horse antithymocyte globulin with a full response. The disease relapsed in 1997 with the same presentation. After an ineffective course of ciclosporin, a partial response was obtained with a second course of rabbit antithymocyte globulin and high dose androgen therapy. Subsequently, myelodysplasic features appeared with chromosome 7 monosomy, which evolved to a smouldering transformation in AML 6 in April 2004.
At the same time, a left kidney tumor (46
CT scan showing left renal tumor before RIC HSCT.
Prevention of graft versus host disease was based on ciclosporine 3 mg/kg/day started at day 1 and switched on day 6 on mycophenolate mofetil 15 mg/kg twice a day and prednisone 1 mg/kg/day because of an increasing plasma creatinine.
The immediate course was uneventful with a complete full donor-type haematological reconstitution on day 42. At this time, prednisolone was decreased; on day 85, a skin and gut grade II acute graft versus host disease developed which was treated with high dose methylprednisolone and mycophenolate mophetil. At that time, the left kidney tumor measured 50 mm and his aspect remained unchanged on CT scan. Acute GVHD quickly resolved and in May 2006 chronic skin and pulmonary GVHD developed. Subsequent scans showed stability of the renal tumor.
Finally, in September 2006, as the patient has recovered a good clinical and haematological status (haemoglobin: 13.1 g/dL; platelets: 110 G/L; leucocytes: 5.1 G/L with normal differential count), a left nephrectomy was performed. The tumor size was 60 mm
In this case, we could not document precisely the histological type of this kidney cancer, as it was completely necrosed at time of nephrectomy. However, the aspect on the CTscan is favoring the diagnosis of renal cell carcinoma with a strong evidence.
The mechanism accounting for the tumor regression deserves discussion. The tumor necrosis was delayed nine months after the administration of the allograft conditioning regimen.
Spontaneous tumor regression can be hypothesised, but the true incidence of this phenomenon is probably less than 1% and the majority of documented spontaneous regressions involve metastasis spread of renal cell carcinoma, not primitive tumor.
An immune-mediated necrotic process of the kidney cancer is a more consistent explanation in this case. This phenomenon has been clearly illustrated by several lines of evidence in the past. Rosenberg et al. [
Brouwenstijn et al. [
Similarly, there is some evidence that bone marrow transplant could reverse the spread of metastatic renal cell carcinoma [
Posttransplant DLI and chronic GVHD improved the patient’s survival. TRM was 16%, patients with less than three metastatic locations and a Karnofsky score
A direct cytotoxic effect involving donor lymphocytes issued from the graft is a consistant hypothesis. Harlin et al. [
In our patient, such a mechanisme remains the more consistent explanation. To our knowledge, a complete necrosis of a localised renal tumor in relation with RIC allograft effect has not been previously reported.