Reduced Toxicity Condition, Mixed Chimerism and Donor Stem Cells Infusion — A More Effective and Safely Model of Nonmyeloablative Allogeneic Stem Cell Transplantation (Seventy-Two Cases Report).

Background Recently, the development of nonmyeloablative allogeneic stem cell transplantation (NST) which are associated with lower toxicity and mixed chimerism has improved the survival of old and young patients with haematology diseases. Otherwise, donor lymphocyte infusion (DLI) that is associated with high immunological activity and more graft versus leukaemia effect has also improved the complete remission rate of relapsed patients after transplant. But there are remain of some problems to have resolved which includes how to prevent from graft-versus-hostdisease (GVHD) and leukaemia relapsed after NST. We conducted A more effective and safely model of nonmyeloablative allogeneic stem cell transplantation which haved successfully been used in the seventy-two cases of haematology diseases.

Methods Seventy-two parients (year range 17–61) with HLA-march donor in acute leukaemia(n=33), chromic leukaemia (n=23) and MDS or SAA(n=16) were received reduced toxicity condition (cyclophosphamide, fludarabine, anti-thymocyte gloubin and cytarabine or busulfan) following a allogenic perpheral blood stem cell transplantation. GVHD prophylaxis consisted of cyclosporine A and Mycophenolate mofetil (MMF) for 90 days. All cases who has no aGVHD were received the donor frozen mobilization and apheresis perpheral blood stem cells(DSI) in 35 to 55 days after NST.

Results All Seventy-two patients passed smoothly the hematopoietic suppression stage and achieved engraftment of the donor cells which included 42 cases of full donor chimerism FDC), 30 cases of mixed chimerism (MC) in which 27 cases converted to FDC in 1–16 monthes and 3 cases developed graft rejection. Among the all of Seventy-two cases, the incidence of aGVHD (grade I–II=18, and grade III–IV=3) was 29.2% (n=21) in which 5 cases of aGVHD was caused by the DSI and stopped CSA and MMF. There are much higher rate aGVHD in the FDC group (n=15) than the MC group (n=6) The incidence of cGVHD was 30.6% (n=22). Among the 33 cases of acute leukaemia patients, five cases died from leukaemia relapsed (15.2%). Follow-up 3 to 75 months, survive rate of patients is 77.8% (n=56) and the 3 year estimated disease-free survival is 41.7%.

Conclusions These results shown that new protocol of NST is a much more effective and safty strategy for haematology patients, the use of conditions with CTX, Flud, ATG, Ara-C/BU reduced toxicity of transplant, the mixed chimerism help to prevent from the aGVHD, use of DSI both improved the MC converted to FDC and GVL effect but only slightly GVHD and no hypocellular which is much better than the DLI.