Unrelated Donor Hematopoietic Stem Cell Transplantation for Treatment of High-Risk Leukemia

objective: To investigate the efficacy of unrelated donor hematopoietic stem cell transplantation(URD-HSCT) for high-risk leukemia.

Methods: From June 2001 to July 2008, 62 patients of high-risk leukemia underwent HSCT with unrelated donor. The median age was 24(6~49)years. There were 21 unrelated donor’s grafts came from Buddhist Tzu Chi Stem Cells center in Taiwan, and 41 unrelated grafts came from Red Cross Society of China Hematopoietic Stem Cell Marrow Donor Program Administration Center. Seventeen patients received bone marrow transplantation and another 45 patients received peripheral blood stem cell transplantation. Fifty patients were fully matched with their donors for HLA loci A and B as well as for HLA-DRB1. Eight of 62 patients had 1 molecular loci mismatch and 4 of 62 patients had 2 molecular locus mismatch. The conditioning regimen consisted of modified BU/CY or modified total body irradiation(TBI) plus CY. Eleven patients received cyclosporine (CSA), short-term methotrexate (MTX) and mycophenolate mofetil (MMF) as the regimen of prophylaxis of GVHD. Forty |four patients received CSA, MTX and MMF plus ATG/ALG for GVHD prophylaxis. The combination of CSA, MTX, MMF,ATG/ALG and CD25 monoclonal antibody for preventing GVHD in 4 patients. Other two patients received Tacrolimus, short-term MTX and ATG to prevent GVHD.

Results: The incidence and severity of regimen-related toxicity were mild. The median number of MNC and CD34 positive cell was 4.48×10⁸/kg and 4.06×10⁶/kg respectively. The median time of the engraftment of neutrophil and platelet was 13 days and 16 days posttransplant respectively. The incidence of infection posttransplant was 48%. The complicated pneumonitis occurred frequently (67%), The incidence of grade I–II and grade III–IV acute GVHD was 17% and 23% respectively. Limited chronic GVHD occurred in 17% patients and extensive cGVHD presented in 14% patients. Median follow up was 6 (range 1 `85) months after transplantation. 83% patients achieved full donor chimerism(FDC) detected by STR-PCR and FISH. While 17% patients presented mixed chimerism (MC) and 10 of them converted to unstable MC. Among them 4 patients presented graft rejection and 6 patients suffered from relapse. Decreasing values of donor chimerism were detected prior to the relapse of disease. Furthermore the treatment related mortality (TRM) was 16%(10/62), The incidence of relapse was 10%. Until now 37 patients are still alive. The 5-years expected survival was 52.2%.

Conclusion: URD-HSCT can be an effective and curable approach for high risk leukemia with higher incidence of GVHD and infection. The treatment for the severe and deadly GVHD and pulmonary infection are still major problems need to be resolved in the future.