| Objective To investigate how the hematopoietic function of severe aplastic anemia(SAA) patients recover in sequential intensified immunosuppressive therapy(SIIST) combined with hematopoietic growth factors(HGF).Methods To learn the therapeutic effects and hematopoietic recovery (transfusion-independence,improvement of pancytopenia and bone marrow proliferation) of 56 SAA patients treated with SIIST and HGF was followed up,and compare between the SAA group and VSAA one.Results 1.Treatment effects:Among 56 SAA patients,22(39.3%) were complete responders;13(23.2%) were partial responders;12(21.4%) showed minor recovery,8 patients didn't response;overall response rate was 83.9%.2.Transfusion-independence:The means of blood and platelet transfusion units of SAA cases in each month before SIIST plus HGF were 8.52 and 76.52; those of blood transfusion units in 3 months,3-6 months,6-9 months and 9-12 months after SIIST plus HGF were 13.40,7.66,2.46 and 2.42 and those of platelet transfusion units were 177.57,64.73,24.75 and 14.44.3.Blood cell count and bone marrow proliferation:Before treatment,at 3,6,9 months and 1,2,3,4 years after SIIST,the patients' Ret(×10~9/L) were 6.48,23.52,28.18,46.04,39.23,60.21,65.09 and 75.84;ANC(×10~9/L)were 0.17,2.80,4.10,3.77,2.35,1.94,1.59 and 1.71;myeloid cells in bone marrow(sternum /iliac)(%) were 14.5/15.7,54.8/54.1,53.8/52.2, 52.4/52.4,57.2/52.2,58.3/52.9,45.6/51.4 and 46.5/55.0;erythrocyte (sternum/iliac)(%) were 8.7/6.0,17.5/16.4,22.0/19.3,25.4/17.3, 28.3/26.2,30.2/25.9,34.0/30.3 and 38.7/33.0;megakaryocyte(sternum/ iliac)(%) were 0.26/0.18,2.48/2.48,38.29/7.08,24.22/19.67, 56.80/27.91,59/17,24/54 and 20/8.4.Quality of response:(1) Times for 25%,50%,75%of blood /platelet transfusion-independence were 86/87,140/126,196/183 days after SIIST of the 35 fully transfusion-independence patients. (2) 46(82.1%) patients' WBC fully returned to normal level while 24(42.9%) patients' RBC completely returned to normal level;blood counts of 22(39.3%) patients completely returned to normal levels.The median time for WBC,RBC and PLT recovery was 35 days,11 months and 12.5 months respectively.(3) The observation of 35 patients of fully achieving transfusion-independence showed that myeloid lineage(sternum/iliac) recovered in 3 months;erythroid lineage of sternum in 9 months,of iliac recovered in 12months and megakaryocyte of sternum and iliac recovered in 12 months respectively.5.The morbidity and mortality of infection:there were 41(73.2%) patients infected in 3 months after SIIST,among whom 4(7.1%) died; 6(10.7%) patients infected in 3-6 months after SIIST,among whom 4(7.1%) died;4(7.1%) patients infected in 6-12 months after SIIST and 6(10.7%) patients infected after 1 year after SIIST,among whom 1(1.8%) died.6.Factors affecting efficacy of SAA patients after SIIST plus HGF6.1 Gender 31 of total 37 male patients(83.8%) completely or partially recovered, and so did 17 of total 19 female patients.There was no significant difference between the two groups(p=0.568).6.2 AgeThe age of SAA cases at onset ranged from 6 to 78 years and the median age was 22 years.The mean age of recovered group was 29.42 years,while that of unrecovered group was 23.75 years.There was no significant difference between the two groups(P=0.687).6.3 The analysis of peripheral blood and bone marrow of cases at onset(1) The level of ANC of pre-treatmentThe mean value of ANC in the recovered group was significantly higher than that of unrecovered group[(0.207±0.162)×10~9/Lvs(0.039±0.073)×10~9/L](t=2.666,p=0.012*).There was only significant difference between partially and unrecovered groups(P=0.032*). (2) The level of Ret of pre-treatmentThe mean value of Ret in recovered group was significantly higher than that of unrecovered group[(7.60±4.27)×10~9/L vs(2.78±1.47)×10~9/L] (t=2.914,P=O.0O6**).There was only significant difference between partially and unrecovered group(P=0.029*).(3) The level of bone marrow proliferation of pre-treatmentThe percent of myeloid cells in bone marrow of sternum in recovered group was significantly higher than that of unrecovered group[(16.3±12.3)%vs(6.5±7.7)%](t=2.669,p=0.013*).When analyzing the percent of myeloid cells,erythrocyte and megakaryocyte of bone marrow in the totally,partially,slightly and unrecovered group with one way ANOVA,we found that there was significant difference only in erythrocyte between the totally one and slightly one P=0.004**).6.4 The comparison between the SAA group and VSAA oneWe analyzed 27 SAA patients and 29 VSAA ones,and found that:(1) Before treatment,the ANC[(0.38±0.08) vs(0.08±0.08)](t=11.245, p=0.OOO**);and the Ret of SAA group was significantly higher than VSAA one[(9.87±3.41) vs(5.05±3.85)](t=3.696,P=0.001**);(2) Before treatment,the percent of erythrocyte in sternum[(15.5±11.8) vs(5.5±7.5)](t=2.458,p=0.O3O*);and megakaryocyte in iliac[(0.5±1.0)vs 0](t=2.486,P=0.018*) of SAA group was significantly higher than VSAA one.(3) The total effective rate of SAA group significantly higher than VSAA one(100%va 72.4%)(p=0.003**).(4) Before treatment,the units of platelet in SAA group significantly lower than VSAA one[(56.40±21.29)u vs(86.10±29.00)u](t=-2.879,P=0.007**).After treatment the units of blood transfusion of SAA group from 3 to 6 months(Z=2.04,P=0.0207*),from 6 to 9 months(Z=4.10,p＜0.01**),from 9 to 12 rnonths(Z=1.88,p=0.0301*) significantly lower than VSAA one.All units of platelet transfusion of SAA group from 3 to 6 months(Z=2.98, p=0.0014**),from 6 to 9 months(Z=2.21,P=0136**),and from 9 to 12 months(Z=1.71,P=0.0436*) significantly lower than VSAA one. (5) 3 months after treatment,the ANC of SAA group was significantly higher than VSAA one[(4.51±3.44) vs(1.94±2.59)](t=2.295,P=0.029*).(6) After treatment,the percent of transfusion-independence in SAA patients significantly higher than in VSAA one(92.6%vs 34.5%) (P=0.000**).All SAA patients were totally free from blood products infusion after 9 months treatment.Times for 25%,50%,75%of blood transfusion-independence of SAA group was 75,110,150 days;of VSAA group was 122,196,240 days after SIIST.Times for 25%,50%,75%of platelet transfusion-independence of SAA group was 70,110,150 days;of VSAA group was 122,203,250 days after SIIST.(7) The percent of WBC fully returned to normal level(100%vs 65.5%) (p=0.001**),' RBC completely returned to normal level(63%vs 24.1%) (P=0.004**) and blood counts completely returned to normal levels (59.3%vs 20.7%)(P=0.003**) in SAA group all significantly higher than in VSAA one.(8) The morbidity of infection in SAA group before treatment(14.8%vs 93.1%)(p=0.000**) and after treatment(70.4%vs 100%)(p=0.002**) all significantly lower than in VSAA one.Conclusion The overall response rate of SAA patients in sequential intensified immunosuppressive therapy(SIIST) combined with hematopoietic growth factors(HGF) was 85.7%,complete respond rate was 39.3%,partial respond rate was 23.2%and minor respond rate was 23.2%. The diference of the count of ANC,Ret,transfusion units of platelet, percentage of erythroid lineage in sternum bone marrow,megakaryocyte in iliac bone marrow between SAA and VSAA patients were statistically significant.The response rate was obviously higher in SAA group than that in VSAA one after treatment.The patients in SAA group totally recover to transfusion-independence.And the interval between treatment and the latest transfusion of red blood cell or platelets,the 25th,50th,and 75th percentiles time of VSAA group was later than that of-SAA one.We should differently treat SAA patient and VSAA one with the method of SIIS. Generally,we began to judge the effectiveness after 6 months treatment in SAA group,while after 9 months treatment in VSAA group.The response rate and mortality before and after treatment in VSAA group were higher than that in SAA group.The absolute value of neutrophilic granulocyte and reticulocyte,myeloid ratio of bone marrow in sternum,and whether having infective disease before treatment should affect the prognosis.
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