Impact of HLA compatibility on the outcome of allogeneic hematopoietic stem cell transplantation for chronic myeloid leukemia / 南方医科大学学报

<p><b>OBJECTIVE</b>To analyze the influence of HLA compatibility on the outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with chronic myeloid leukemia (CML).</p><p><b>METHODS</b>This retrospective study involved 121 CML patients including 90 in chronic phase, 8 in accelerated phase and 23 with blast crisis. Of these patients, 85 received related and 36 had unrelated donor allo-HSCT. The conditioning regimens included total body irradiation with cyclophosphamide in 37 patients, and modified BUCY protocol in 84 patients. Cyclosporine A (CsA) and methotrexate (MTX) were used for graft-versus-host disease (GVHD) prophylaxis in patients undergoing HLA-matched sibling donor transplants. CsA, MTX, antihuman thymocyte globulin and mycophenolate were used in all the patients undergoing HLA-mismatched related donor and unrelated donor transplants. The prognostic factors of CML were evaluated using Cox regression and the cumulative overall survival and the disease-free survival were estimated using Kaplan and Meier survival analysis model.</p><p><b>RESULTS</b>The incidence of II-IV acute GVHD was 26.1% in HLA-matched and 53.3% in HLA-mismatched cases (P=0.006), with a 5-year cumulative incidence of chronic GVHD of 47.4% and 49.6%, respectively (P=0.947). The 5-year cumulative incidences of disease relapse was 16.7% in the total patients, with a 5-year cumulative overall survival (OS) of 70.5% and disease-free survival (DFS) of 63.4%. The 5-year OS was 78.2% in HLA-matched cases, as compared with 47.6% in HLA-mismatched cases. Multivariate analysis with Cox regression model identified HLA mismatch, II-IV acute GVHD, and advanced phase as the risk factors affecting the OS.</p><p><b>CONCLUSION</b>HLA mismatch can significantly increase the incidence of II-IV acute GVHD following allo-HSCT and decrease the long-term survival rate, which is not related to the donor source.</p>

Effect of granulocyte colony stimulating factor on myeloid-derived suppressor cells in the bone marrow and peripheral blood: a preliminary study / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of granulocyte colony stimulating factor (G-CSF) on myeloid-derived suppressor cells (MDSCs) in the bone marrow and peripheral blood, and explore the relationship between MDSC and graft-versus-host disease (GVHD).</p><p><b>METHODS</b>Bone marrow, peripheral blood and peripheral blood stem cells were obtained from 12 healthy hemopoietic stem cell donors before and on day 5 after G-CSF mobilization. Flow cytometry was employed to examine the number of MDSC, and the relationship between MDSC number and the incidence of GVHD was analyzed.</p><p><b>RESULTS</b>In normal physiological conditions, MDSC could be detected in the peripheral blood and bone marrow with a cell percentages of (1.35±0.35)% and (2.44±1.11)%, respectively, showing a significantly higher cell percentage in the bone marrow (P=0.015). On the 5th day after G-CSF mobilization, the percentage of MDSCs increased to (4.01±1.82)% in the peripheral blood and to (4.38±2.19)% in the bone marrow, showing no significant difference between them (P=0.083). The mobilization caused a significant increase in the number of MDSCs in the peripheral blood (P=0.047) but not in the bone marrow (P=0.761). The number of MDSCs in the collected samples showed a significant inverse correlation to the incidence of GVHD (P=0.048).</p><p><b>CONCLUSIONS</b>MDSCs are present in the peripheral blood and bone marrow of healthy donors, with a greater number in the bone marrow. G-CSF can mobilize the MDSCs from the bone marrow to the peripheral blood to increase number of MDSCs in the peripheral blood, which may contribute to a lowered incidence of GVHD in hematopoietic stem cell transplantation (HSCT).</p>