Non Myeloablative Allogeneic Stem Cell Transplantation as Adjuvant Treatment in Patients With Pancreatic Adenocarcinoma

Background Cancer of the pancreas is one of the most common cancer forms in Sweden. Nine-hundred persons receive this diagnosis every year. The 5-year survival is very low, between 5 and 15%, even in the cases where radical resection of the tumor can be performed. This is probably due to minimal residual disease that cannot be diagnosed at the time of surgery. It has recently been shown that micrometastases of pancreatic adenocarcinoma can be detected in tissue samples from lymph nodes and bone marrow, using new sensitive immunohistological methods. When radical resection of the tumour is performed, no microscopically visible tumour is left, but even in this situation, local recurrence of the disease is the most common cause of death in these patients. None of the so far studied adjuvant treatments, irradiation or chemotherapy, has substantially improved the survival in patients with pancreatic adenocarcinoma.

Allogeneic hematopoietic stem cell transplantation (HSCT) is an established curative treatment for malignant blood diseases, mainly leukemia. Using the conventional form of HSCT, where the patient undergoes a myeloablative conditioning with chemotherapy and irradiation, will diminish the amount of malignant cells, but also create space in the bone marrow for the donated stem cells. The myeloablative conditioning induces severe toxic effects, but the patient is rescued by the transplantation of the donated hematopoietic stem cells. The new stem cells will mature into an immune system that will react with the patient's cells, an effect called graft-versus-host reaction (GVHD). It has been shown that the graft-versus-host reaction correlates well with the curative anti-tumor effect. A mild GVH reaction will diminish the risk of relapse, while a severe GVH reaction might be mortal. This anti-tumour effect is mediated by white blood cells of the T-cell type. From this knowledge, the HSCT technique has been developed and nowadays it is possible to use reduced intensity conditioning (RIC). With reduced intensity conditioning using milder forms of chemotherapy, the toxic effects can be reduced, but the immunosuppressive effect is enough to make sure that the hematopoietic stem cells will engraft. Using RIC has lead to treatment of older patients and the anti-tumor effect is just as efficient as with the myeloablative conditioning.

Recently, RIC with HSCT has been used as adjuvant treatment against solid tumours, mainly kidney cancer, colon cancer and breast cancer. An important part of the treatment consists of additional infusion of donor lymphocyte infusions (DLI) after the transplantation to maintain or increase the anti-tumour effect. At our clinic, we have treated about 50 patients with solid tumours using RIC with HSCT. Most of our patients had kidney or colon cancer (19 and 16 patients, respectively), but also two patients with prostate cancer have been treated. About ten patients with primary liver cancers have been treated with liver transplantation combined with RIC with HSCT. The transplantation-related mortality in these patients is about 10-15%.

Aim:

To study the antitumour effect of RIC with HSCT in patients with pancreatic adenocarcinoma after radical resection of the tumour and adjuvant treatment with standard chemotherapy.