Effects Of Improved Non-myeloablative Hematopoietic Stem Cell Transplantation For Severe Aplastic Anemia

Objective:1.To explore the clinic effect,survival rates and long-term complications of severe aplastic anemia(SAA) after Non-myeloablative hematopoietic stem cell transplantation (NSCT)2.To investigate whether the Fas/FasL system,the ratio of T cell subsets and the level of proinflammatory lytokine (IFN-r,IL-2) of SAA would be changed before and after NSCT which may be valuable factors in monitoring the disease progress and evaluating the curative effect and prognosis of SAA.Material and Methods:1.We collected 30 SAA patients who received NSCT between 2001 and 2005 in Jinan military hospital Hematology department in which ten SAA patients received HLA-matched NSCT from related donors, two SAA patients received HLA HLA-mismatched NSCT from related donors, eighteen SAA patients received HLA-matched and HLA-mismatched cord blood stem cell transplantation(CBSCT) from unrelated donors, we sum up and makes the statistics. Moreover we comparing the results between SAA-Ⅰand SAA-Ⅱ.2.We collected 30 SAA examples'peripheral blood and bone marrow sample who received NSCT between 2001 and 2005 in Jinan military hospital Hematology department. The level of soluble Fas(sFas) in plasma arid the expression of Fas antigen on monocular cell(MNC) membrane, T cell subsets were detected by flow cytometry(FACS).The expressions of hematopoietic relative factors were assayed by ELISA. And sixteen case of healthy volunteers as control.Results:1.Twenty-four SAA patients have been cured and survived for one year after their transplantations.The ten SAA patients who received HLA-matched NSCT from related donors have obtained the good clinical curative effect.2.One of the two SAA patients who received HLA-mismatched NSCT from related donors has obtained the good clinical curative effect and long term survival.3.The SAA patients who received HLA-matched and HLA-mismatched cord blood stem cell transplantation(CBSCT) from unrelated donors also obtained the good clinical curative effect though whose haematopoiesis reconstruction were slower than PBSCT.4. Compared with SAA-Ⅱ,the haematopoiesis reconstruction of SAA-Ⅰseem more quickly, the clinic effectiveness and survival rates are much higher. The general state was bad, been transfused blood many times and had produced the platelet antibody may be the reason.5.The percents of CD34+Fas+cells were increased significantly(P<0.05) in SAA patients than the normal controls, and the percents of CD34+Fas+cells in SAA-Ⅰwere much higher than that in SAA-Ⅱ(P<0.05).The level of sFas was decreased significantly(P<0.05) in SAA patients than that in normal controls, and the sFas level in SAA-Ⅰwas lower than that in SAA-Ⅱ(P<0.05). The CD34+Fas+cell percentage of Bone marrow gradually decreased with aggravation of the disease, which was negatively correlated with the course. Plasma levels of sFas gradually increased with the extension of the course, which was positively correlated with disease.6.Celluar immune dysfunction existed in most SAA patients, especially the SAA-Ⅰwhich is characterized by T lymphocyte subgroups and the abnormal increase in many hematopoietic negative factoes. The level of IFN-r and IL-2 was increased significantly(P <0.05) in SAA patients than the normal, and the levels in SAA-Ⅰwere higher than those in SAA-Ⅱ(P<0.05).Moreover T lymphocyte subgroups, IFN-r and IL-2 are predictive factors for responsiveness toNSCT, and a high value was associated with a good response.7.If the patient's clinic effectiveness is fine after NSCT,whose dysimmunity can be corrected by NSCT. The recover time in SAA-Ⅰpatients was much slowly than in SAA-II.Conclusions:1.The improved NSCT is an important treatment of SAA,regardless of the donor's HLA is matched or mismatched.2.When the patient were child or those body weight is light, CBSCT may be the available selection.3.NSCT is not the chief selection of SAA-Ⅱ.However when the many kinds of standard treatments can't obtain good clinic effectiveness or this kind of patients'general state of health is good, the times of blood infusion are few and the donor's HLA is matched may consider NSCT as the treatment.4.Fas aberration is involved in the pathogenesis of SAA. The CD34+Fas+cell percentage of Bone marrow and The plasma levels of sFas are related with the aggravation of the disease.5.Most SAA patients may have celluar dysimmunity, characteristicly with the imbalance in T cell subgroups and the abnormal increase in many hematopoietic negative factoes. SAA-Ⅰis more obviously than SAA-Ⅱ. All these results proved that abnormal of T lymphocytes subsets and increases in quantity and producing function of Thl cells might be involved in the destruction of marrow hematopoietic cells and important for the development of bone marrow failure in SAA. Simultaneously the level of T lymphocytes subsets, IFN-r and IL-2 of SAA patients before treatment are best predictive factors for responsiveness to NSCT.6.The dysimmunity of SAA can be corrected by NSCT, especially the SAA-Ⅰpatients:the recover time is more slowly and the clinic effectiveness is much higher than SAA-Ⅱpatients'.