Integrative Treatment Of Aplastic Anemia Medication Select A Preliminary Study Of The Prediction System

Purpose To do researches on T lymphocyte cell subgroups, T helper cells (Th), T-bet and GATA-3 gene expression regularity in aplastic anemia (AA) patients' peripheral blood. To evaluate the potential usefulness of a multivariable model in predicting the selection of immunosuppressive therapy (IST) or androgens in patients with AA, which coagulate immunology, microbiology and clinical parameters in all, and its application to the clinical practice.Methods 85 patients were selected and treated in general. There were 4 forms of groups to be made according to symptoms of differenciation in traditional Chinese medicine (TCM), diagnosis in modern medicine, effectiveness and therapeutic methods. Peripheral blood T cell sub-groups and Th were serially analyzed by flow cytometer before and after the treatment. At the same time T-bet and GATA-3 genes were also assessed by real time RT-PCR. Then Logistic formulate and ROC curves were made based on cases responding to IST or Androgens. The multivariable model is set up to predict the selection of drugs (IST or Androgens) in clinical practice.Results 1. After treatments for 2 courses, the total effectiveness ratio in kidney-yin deficiency group and kidney-yang deficiency group were respectively 97.2% and 61.2%. In acute aplastic anemia (AAA) and chronic aplastic anemia (CAA) groups they were 65.3% and 91.7% respectively, AAA and CAA in kidney-yang deficiency group were 100% and 96.4%, AAA and CAA in kidney-yin deficiency group were 57.5% and 75%. The above results showed that curative effect in kidney-yang group was higher than kidney-yin group, and CAA higher than AAA group, which administrated that Chinese and western cooperational dignostic methods were helpful to predict therapeutic effect. 2. The curative patients with androgens (62.5%) were more in CAA (62.5%) and kidney-yang deficiency group (65.6%). The therapeutic patients with IST were more in AAA (59.3%) and kidney-yin deficiency group (63%). So from the above data, we could conclude that CAA in kidney-yang deficiency group was better to use androgens and AAA in kidney-yin group was better with IST. However, the accurative ratio was 50%~60%. 3. The peripheral blood in kidney-yin deficiency group was much lower than kidney-yang deficiency group as white blood cell (WBC), hemoglobin (HB) and platelet (PUT) was discussed (P<0.01). And after treatment, the therapeutic effect in kidney-yang deficiency group was better (P<0.01).4. The symptoms in kidney-yin group were more serious than those of kidney-yang deficiency group (P<0.05). The symptoms in kidney-yang deficiency group dicreased and patients recover more obviously (P<0.05). In all the symptoms observed, lumbar ache and painful heel were more often seen and can be made main symptoms of kidney deficiency syndrome. As curation was concerned, kidney-yang deficiency group was more curable than kidney-yin deficiency group. 5. Compared with controls, before the treatment, there were a series of immunological factors differenciation in AA patients. They returned to normal and had no significent differences in kidney-yang deficiency group as with controls, though in kidney-yin group the immune function was not yet recovered and rather contractory. And in diagnostic groups, immunological terms in AAA were more difficult to ameliorate than those in CAA group. 6.The logarithm of T-bet/β-actin in Kidney-Yang group, chronic AA group, partly cured group decreased obviously (P<0.05). After Bushen Chinese herbs' treatment, The logarithm of T-bet/β-actin changed and lowered in kidney-yin deficiency group, acute AA group and partly cured group (P<0.05). The logarithm of T-bet/GATA-3 in kidney-yin deficiency group, chronic AA group, group of no respondence minimized statistically, which changed to normal level after Chinese herbs' treatment. The results inferred that T-bet/GATA-3 might have predictions of androgens and IST selections. 7.With the discriminant and logistic statistics, lg(T-bet/β-actin), lg(T-bet/GATA-3), Thl/Th2, CD3~+CD8~+(%) and CD3~+HLA-DR~+(%) 5 indexes were screened out to act as predicting factors. Together with clinical symptoms and diagnosis, the logistic formula was made to predict the selection of IST or androgen drugs. 8. A point between the 2 stages was found out through the calculation of the logistic formulate and ROC curve. The point was 0.832. When P≥0.832, it was in the abnormal immunological stage, IST should be used. When P<0.832, then it was in the bone marrow failure stage, androgens should be added. 9.The predictive formula indications of clinical probabilities and evaluations showed that 42.2%(14/33) patients could have benefits from the predictions made by the formula, which could advance the curative ratio and fanal results. All in all, the predictive system could obviously enhance AA curativeness and did well to clinical physicians in selection of androgens or IST properly and accurately.Conclusions 1. Bushen Chinese herbs have effectiveness and accuracy of treating AA with no side effect. The therapeutic effect of Bushen Chinese herbs is more effeictive in kidney-yang group than in that in kidney-yin group. 2. A noval theory is proposed that there are 2 stages that are abnormal immunological stage and bone marrow failure stage in the course of AA. In the former stage, IST should be used. In the later one, androgens are prefered. 3. Immunologicl factors as CD3~+CD8~+, CD3~+CD25~+, CD3~+HLA-DR~+, Thl/Th2 and microbiological factors as T-bet and GATA-3 genes are the characteristics of abnormal state in AA patients. 4. A formula incorporating laboratory terms and clinical evidence is made to predict selections of IST and androgens. A point of P=0.832 is ascertained as the borderline of 2 states in AA, which are abmoral immunological state and bone marrow failure state. 5. Retrospective clinical probability analysis shows that the exactivity of the prodicting system is 88.9%, probably raising the effectiveness of AA.