Dasatinib After Allogeneic Stem Cell Transplantation in Philadelphia-Positive Leukemias.

Abstract 4304

Dasatinib is a second generation tyrosine kinase inhibitor for the treatment of Ph+ chronic myeloid leukemia. However many patients recieving dasatinib are candidates for an allogeneic transplantation and will receive a transplant eventually. The use of dasatinib after an allogeneic transplant is very controversial: First the allogeneic antileukemic immune effect should theoretically obviate the need for further tyrosine kinase inhibition. Second the considerable hematological toxicity of dasatinib might impair the fragile donor hematopoiesis, at least given at full dosage. And third there is evidence that dasatinib inhibits both effector and regulatory T-cells which might hamper the graft-versus-leukemia effect and/or inrease the risk for Graft-versus-host disease.

We report our experience with dasatinib in 3 patients with relapsing or persisting Ph+ leukemias after allogeneic stem cell transplantation.

Pat. 1 is a 66yr old female patient with an imatinib-resistant lymphoid blast crisis who responded to dasatinib and was transplanted from an unrelated donor. After achieving a complete molecular remission she experienced a molecular relapse and was started on dasatinib 20 mg daily. 3 months later she reached a complete molecular remission without any major changes in blood counts and continued on dasatinib 20 mg.

Pat. 2 is a 42yr old male with Ph+ CML and a paraspinal extramedullary lesion who responded to dasatinib after being resistant to imatinib. After an allogeneic transplant from his HLA-compatible brother he was in complete hematologocial and major molecular remission but relapsed 3 months later. Ciclosporin A was stopped and dasatinib introduced at 70 mg once daily. 2 months later he achieved a complete hematological and molecular remission. No hematological toxicity was found.

Pat. 3 is a 41yr old female patient with a Ph+ c-ALL with a history of liver cancer and a partial liver transplantation. After achieving a complete remission with chemotherapy with imatinib she reveived an allogeneic stem cell transplantation from her brother who also had donated the liver graft. She lost her remission 9 months after transplant and was retransplanted with the same donor but without immunospuppression. Due to the lack of a complete molecular remission she started dasatinib at 50 mg/d and became bcr-abl negative 3 months later. Blood counts improved during treatment with dasatinib.

In summary all patients showed stable responses to dasatinib at low doses without any major hematological toxicity. With a follow up of 8-12 months we did not observe any GvHD during dasatinib treatment. In our hands low dose dasatinib is a feasible treatment option for relapse after allogeneic transplantation in Ph+ leukemias.