HLA-Mismatched Hematopoietic Stem Cell Transplantation for Treatment of Chronic Myelogenous Leukemia.

Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is still the only curative treatment for Chronic Myelogenous Leukemia (CML) at present. For only few patients having suitably matched donor, transplantations with stem cells from HLA mismatched related family donors have been increasingly used. But Used of HLA mismatched HCT involves crossing histocompatibility barriers, it has been limited by high risk of severe graft-versus-host disease (GVHD), graft rejection and delayed or incomplete immune reconstruction. The inducing immune tolerance and modulate allogeneic reaction may play a role in avoiding severe GVHD in HLA-mismatched HSCT. Our goal in this study was to investigate the feasibility and clinical value of this approach in the treatment of CML. From February 1999 to February 2008, 55 patients with CML, aged 8 to 52 years (median age 29 years), received HSCT from HLA two or three loci mismatched donor, 18 were in chronic phase, 19 were in accelerated phase, 18 were in blast crisis. The outcome were compared with related HLA matched hematopoietic cell transplantation performed during the same time period. As a control, 41 patients with CML, aged 13 to 52 years (median age 31 years), received HLA-matched HSCT, 21 were in chronic phase, 12 were in accelerated phase, 8 were in blast crisis. All of patients received combined transplantation of the G-CSF primed bone marrow and peripheral blood stem cell without T cell depleted, and the prophylaxis regimen for acute GVHD consisted of CSA, short-term MTX, and MMF, but ATG (Fresenius S) and CD25 monoclonal antibody were particularly used in HLA-mismatched HSCT. During the time of following-up (above 6 months), All patients achieved full engraftment.1 patient who received the HLA-mismatched transplantation failed to engraft. The rejection of patient was reversed by second HSCT from different donor. The days of ANC>0.5×10⁹ and Platelets>20×10⁹ were 15 (range, 10–25) and 17 day (range, 11–30), respectively, and the accumulative percent of Platelets>50×10⁹ until 100 days were 77%. The cumulative incidences of grades II to IV acute graft-versus-host disease (aGVHD) in the matched and mismatched cohorts were 22% versus 29%(P>0.05). The cumulative incidence of cGVHD in matched and mismatched transplantation was 45% versus 51%, respectively. The recovery time to 200/ul and 400/ul of CD4 cells were 6 and 12 months, which were all no significant difference between HLA mismatched and matched groups. The median follow-up period was 47 months (range 6–112 months). The transplant related mortality was 11 cases (5 died of aGVHD, 6 died of infection), and 12 cases were relapse (11 cases died, 1 cased were controlled by donor lymphocyte infusion) in HLA mismatched patients. The DFS of 2 years were 58.2% and 71.5% in HLA mismatched and matched groups by Kaplan-Meier survival analysis, which wsa no significant difference between two groups. Actual two-year disease-free survival in HLA mismatched groups was 56.5%, the patients in chronic phase or accelerated phase and in blast crisis were 70.8% and 36.5% , respectively, with the statistical significance. In summary, HCT performed with related HLA-mismatched donors is a feasible approach with acceptable outcomes for treatment of CML .but the status of pro-transplantation affected patient’s prognosis.