[982]Leukemia and allogeneic transplantation of hematopoietic stem cells


1)    Area of clinical research on leukemia

An area of research of the work group is the investigation of new treatments for the management of leukemia or hematologic malignancies patients. This group is involved in multicenter protocols phase I-III both national and international for the management of patients with acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, chronic lymphocytic leukemia, myelodysplastic syndrome, myeloproliferative neoplasia, lymphoproliferative neoplasia.

Yves Chalandon is the principal investigator (PI) of a multicenter phase III study on acute lymphoblastic leukemia Philadelphia positive (GRAAPH 2014) and recently published the results of the previous GRAAPH 2005 for which he was also the PI (Chalandon et al. Blood 2015; 125: 3711). The group works in collaboration with the Clinical Research Unit of the HDFDL in the oncology center for the promotion of clinical research of patients with hematological malignancies and provides a platform for new therapies to patients in the Swiss French-speaking area suffering from these diseases. The group collaborates with the leukemia group and the lymphoma group of the SAKK (Swiss Cancer Research Group) and participates in the protocols of the latter.

2)    Area of clinical research on allogeneic transplantation of hematopoietic stem cells

This second axis focuses on clinical research and translational approach in allogeneic transplantation of hematopoietic stem cells. The group is particularly interested in developing strategies to reduce the incidence and severity of graft versus host disease while maintaining an immunotherapeutic graft-versus-tumor effect. This is based on a strategy of partial T-depletion of the graft with an addback of a lymphocyte load to retain a GVL effect. It evaluates prognostic scores allowing T-depletion to be used more targetedly with less risk of post-transplant relapse.

The group is also involved in national prospective multicentre studies with the SBST (Swiss Blood Stem Cell Transplantation) on conditioning, to perform bone marrow transplantation by decreasing toxicity while retaining a therapeutic effect. But also at an international level with the SFGM-TC (Francophone Society of Marrow Transplantation and Cell Therapy) and the EBMT (European Society of Blood and Marrow Transplantation) participating in both prospective and retrospective clinical studies.

At the prospective level, the group is interested in new strategies for preventing GvHD with cyclophosphamide in post-transplantation enabling the graft with haploidentific donors compared to other sources of stem cells (HLA-identical, matched related and unrelated donor mismatches). It is also involved in a national multicentre study on treatment of chronic steroid-resistant GvHD with IL-2.

At the retrospective level, the group is involved more specifically in transplantation and myeloproliferative neoplasia including myelofibrosis, chronic myeloid leukemia among others with graft evaluation within these indications, donor type, conditioning, complications and improvement strategies to reduce transplant-related mortality.

At the monocentric level, the group is interested in the post-transplant immune reconstitution, the markers of the latter and means to accelerate the latter while preserving the GvL effect without precipitating a GvHD effect. One of the ongoing projects is the selection of memory T cells and the elimination of prophylactically administered alloreactive lymphocytes in post-transplantation to accelerate immune reconstitution while preserving the risk of developing a graft-versus-host disease.

3)    Gene therapy of autologous stem cells to treat HIV

A new axis in development is gene therapy of stem cells and autologous lymphocytes followed by transplantation of these transfected cells "CCR5 knock-down" as a new treatment for HIV infection. This is a multi-center phase I-II study (Zürich-Geneva-Pretoria [South Africa]) using a very efficient miRNA vector for autologous HIV gene therapy. This work is carried out in collaboration with the infectious diseases groups of Zürich (Prof. R. Speck) and Geneva (Prof. A. Calmy, KH. Krause and B. Hirschel) and the Pretoria stem cell transplant group (Prof. M. S. Pepper).