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BACKGROUND: Autoreactive T cells are a group of specialized cells that exert a peripheral immunosuppressive effectthrough certain mechanisms ensuring self-tolerance within the adaptive immune system. The discovery of the latestsurface markers for natural CD4+CD25+ regulatory T cells has re-emphasized the concept of peripheral regulation orsuppression of T cells. Several groups have begun to investigate the role of regulatory T cells in animal models ofallogeneic hematopoietic stem cell transplantation.OBJECTIVE: To review the recent results regarding protection from graft-versus-host disease by adoptively transferredCD4+ CD25+ regulatory T cells in mice and to discuss the latest findings from clinical studies on hematopoietic stem celltransplantation.METHODS: We retrieved CNKI, PubMed and Medline databases for articles concerning CD4+CD25+ regulatory T cellsand graft-versus-host disease published from 2000 to 2015. According to inclusion and exclusion criteria, 46 paperswere included in result analysis.RESULTS AND CONCLUSION: CD4+CD25+ regulatory T cells expressing the transcriptional repressor FOXP3 mediateimmunoregulatory functions and are critical for the prevention of autoimmune diseases. As peripheral tolerance inductionis a prerequisite for successful allogeneic hematopoietic stem cell transplantation, the role of CD4+CD25+ regulatory Tcells in transplantation models and clinical trials is now under investigation in many laboratories. CD4+CD25+ regulatoryT cells play an important role in the development of graft-versus-host disease after allogeneic hematopoietic stem celltransplantation. CD4+CD25+ regulatory T cells not only effectively prevent and treat graft-versus-host disease but alsoretain graft-versus-leukemia effect.
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Objective To explore the clinical significance of the relationship between the immune function and the pathogenesis of aplastic anemia in children with aplastic anemia(AA),along with the incidence of graft versus host disease (GVHD)by monitoring the changes of T lymphocyte subsets dynamically in +1 ,+3,+6,+1 2 months for blood disease patients after allogeneic hematopoietic stem cell transplantation.Methods Twelve AA patients re-ceived allogeneic hematopoietic stem cell transplantation in Department of Hematology,the Affiliated General Hospital of Beijing Military Region of Anhui Medical University,from January 201 3 to January 201 4,including 4 male and 8 fe-male,with average age of 7.92 years old(3 -1 4 years old)with 5 cases of human leukocyte antigen(HLA)matched and 7 cases of HLA mismatched.The level of T lymphocyte subsets including CD3 +,CD4 +,CD8 +,CD4 +/CD8 +, CD56 +,CD4 +CD25 high +FOXP3 +were monitored with flow cytometry before transplantation and in +1 ,+3,+6,+1 2 months after transplantation dynamically in the peripheral blood.While in the same period the level of T lymphocyte subsets was monitored in 1 2 cases of healthy children at the same period as the healthy control group.Results Fol-lowed up to March 201 5,1 0 cases had abnormal cellular immunity (CD4 +/CD8 + ratio inversion)in the 1 2 AA pa-tients.Compared with the control group,in the AA group,CD3 + was slightly higher,(66.79 ±7.35)% and (62.74 ± 5.58)% respectively(P =0.043),CD4 + was decreased by (33.73 ±7.26)% and (39.54 ±3.46)% respectively (P =0.037),CD8 + was increased by (35.69 ±6.78)% and (25.34 ±4.36)%,respectively (P =0.000),CD4 +/CD8 + decreased by 1 .23 ±0.56 and 1 .78 ±0.34 respectively(P =0.001 )and CD56 + was decreased by (7.46 ± 2.80)% and (1 6.73 ±3.70)% respectively(P =0.000),CD4 +CD25 high +FOXP3 + was decreased by (3.3 ± 1 .5)% and (8.1 ±1 .3)% respectively (P =0.003),whose difference was statistically significant (P <0.05).The lever of CD3 +,CD4 +,CD8 +,CD4 +/CD8 +,CD56 +,CD4 +CD25 high +FOXP3 + had a different degree of recovery after transplantation for all cases and returned to normal in +1 2 months basically.In +1 ,+3,+6,+1 2 months after transplantation,the levels of CD4 +CD25 high +FOXP3 + in GVHD positive group and negative group were (0.4 ± 0.6)% and (1 .6 ±0.7)% respectively,(0.7 ±0.3)% and (2.7 ±0.4)% respectively,(1 .1 ±0.5 )% and (2.9 ±0.7)% respectively,(1 .4 ±0.3)% and (3.6 ±0.2)% respectively,which had statistical significance (P <0.05).Conclusions There was abnormal cell immune function in some cases with AA.After transplantation,the level of CD4 +CD25 high +FOXP3 + is closely related to the acute GVHD,which can be used to predict the occurrence of GVHD.
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Objective To evaluate the relationship between the amount of grafted cells and the incidence of acute graft versus host disease (aGVHD) after haploid hematopoietic stem cell transplantation (haplo-HSCT). Methods Data of 68 patients who underwent haplo-HSCT from Jan 2009 to Dec 2013 were analyzed retrospectively. Influences of different factors on the incidence of Ⅲ-Ⅳ degree of aGVHD after HSCT were evaluated. Results 68 patients including 42 males and 26 females were 5/10-9/10 HLA match with 19 father donors, 24 mother donors, 16 sibling donors and 9 children donors. 51 patients not suffered Ⅲ-Ⅳdegree of aGVHD included 32 males and 19 females with the mean age of 20 years old (5-55 years old). 17 patients sufferedⅢ-Ⅳdegree of aGVHD including 10 males and 7 females with the mean age of 23 years old (5-54 years old). There were no significant differences in the amount of the grafted mononuclear cells (MNC) and CD34+cells, and the white blood cell counts (WBC) and platelet count (Plt) recovered time between two groups (P>0.05). However, MNC number was related to CD34+cell number (P<0.05) and WBC recover time (P<0.05), and the CD34+cells number was related to WBC and Plt recover time (P< 0.05). Conclusion The incidence of Ⅲ-Ⅳ degree of aGVHD is unrelated to the amount of grafted MNC, and CD34+cells.
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Objective To explore the efficacy and feasibility of idarubicin combined with medium-dose arabinoside in intensive chemotherapy for acute myeloid leukemia (AML). Methods Fifty remittent patients with induced chemotherapy who underwent the intensive consolidation therapy with medium-dose arabinoside from January 2010 to January 2015 in hematology department of General Hospital of Beijing Military Area were considered as the treatment group. The single arabinoside (2 g/m 2, 1/12 h, d1-3) treatment for 50 cases in the same period were considered as the control group. Two groups were performed with 6 courses sequential. There were 28 males, 22 females in the treatment group, and average age was 27.6 years (18-52 years), with 3 cases of M 1, 27 cases of M2, 8 cases of M4, 12 cases of M5. In the control group, there were 30 males, 20 females, and average age was 26.8 years (16-50 years), with 2 cases of M1, 30 cases of M2, 8 cases of M4, 10 cases of M5. Then the complications and disease-free survival of two groups were observed respectively. Results Follow-up was done until June 2015. In the treatment group, 1 case died of pulmonary infection, 2 cases died of septic shock and 3 cases died of pulmonary infection, 1 case died of septic shock in the control group. The treatment related mortality of both groups were 6 % (3/50), 8 % (4/50), the related relapse rates were 32 % (16/50), 52 % (26/50), the disease-free survival rates were 62 % (31/50), 40 % (20/50) respectively in two groups. Conclusion Compared with the single arabinoside, the intensive consolidation therapy with medium-dose arabinoside and idarubicin for the treatment of AML has gained lower relapse rate and the related mortality, and the DFS rate has been improved significantly, which need further clinical application.
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BACKGROUND:Alogeneic hematopoietic stem cel transplantation (alo-HSCT) is an effective mean to cure severe aplastic anemia, and especialy haplotype transplantation is regarded as a transplantation system with Chinese characteristics, and rank at the international leading level. OBJECTIVE:To explore the patterns of haplotype alo-HSCT as a new immune tolerance method for severe aplastic anemia and to solve the transplantation rejection and graft-versus-host disease. METHODS:Twelve patients with severe aplastic anemia who underwent haplotype alo-HSCT at the Department of Hematology, General Hospital of Beijing Military Area, China from April 2013 to May 2014 were enroled. Al these patients received the new regimen of inducing immune tolerance through the application of high-dose cyclophosphamide (400 mg/m2, consecutively 3 days before transplantation; 50 mg/kg, consecutively 3 days after haplotype transplantation). RESULTS AND CONCLUSION:The median time of neutrophil recovery was 17 (13-21) days, and the median time of platelet recovery was 21 (15-31) days. After transplantation, there were one case of degree II acute graft-versus-host disease and one case of chronic graft-versus-host disease, both of which were controled. The folow-up time was 6 months at least, and the median time was 11 months. During the folow-up, one case died of rejection reaction and one case died of severe lung infection. These findings indicate that the new method of inducing immune tolerance with high-dose cyclophosphamide after transplantation for severe aplastic anemia has significant effects in reducing graft-versus-host disease and transplantation-related mortality rate.
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BACKGROUND:Al ogeneic hematopoietic stem cel transplantation is currently recognized as the first-line therapy for severe aplastic anemia. However, with the popularity of the one-child families, the source of ful y matched hematopoietic stem cel transplantation is limited, so haploidentical hematopoietic stem cel transplantation is favored. OBJECTIVE:To retrospectively compare and analyze the clinical efficacy and safety of haploidentical al ogeneic hematopoietic stem cel transplantation and ful y matched hematopoietic stem cel transplantation for the treatment of severe aplastic anemia. METHODS:Clinical data of 15 patients with severe aplastic anemia (treatment group) who underwent haploidentical al ogeneic hematopoietic stem cel transplantation in the Department of Hematology General Hospital of Beijing Military Region from January 2013 to January 2015 were retrospectively analyzed. Pretreatment regimen was cyclophosphamide, fludarabine, Busulfex, combined with anti-human lymphocyte immune globulin. Donors received granulocyte colony-stimulating factor, and the transplantation method was bone marrow mobilization combined with peripheral blood stem cel transplantation. Combined immunosuppressive agents including cyclosporine A, methotrexate, tacrolimus, were adopted for prevention of graft versus host disease. Another 15 cases of severe aplastic anemia undergoing ful y matched hematopoietic stem cel transplantation served as control group over the same period. Complications and survival of the two groups were statistical y analyzed. RESULTS AND CONCLUSION:By the end of July 2015, the median fol ow-up time of the treatment group was 20.7 months (6-30 months), and hematopoietic reconstruction was achieved in al cases, including four cases of graft versus host disease, five cases of pulmonary infection, three cases of sepsis, and one case died of pulmonary infection, one cases died of sepsis, and two cases died of graft versus host disease. In the control group, the median fol ow-up time was 19.7 months (5-28 months), hematopoietic reconstruction was achieved in al cases. There were three cases of graft versus host disease, four cases of pulmonary infection, one case died of pulmonary infection, and two cases died of graft versus host disease. The total survival rates of the two groups were 73%and 80%respectively, with no significant difference (P=0.67). The haploidentical al ogeneic hematopoietic stem cel transplantation for severe aplastic anemia is safe and effective, and the clinical efficacy is comparable to the ful y matched hematopoietic stem cel transplantation.
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Objective To investigate the therapeutic effects and adverse reactions of decitabine combined with IA or CAG regimen in the treatment of elderly patients with acute myeloid leukemia.Methods A retrospective analysis was made to observe the therapeutic effects and adverse reactions of 47 elderly patients with acute myeloid leukemia,who were divided into DAC+IA group (17 cases) and DAC+CAG group (28 cases) according to the different chemotherapy.Results In DAC+IA group,the rate of complete remission was 29.4 ％ (5/17),the rate of partial remission was 35.3 ％ (6/17),the effective rate was 64.7 ％ (11/17).In DAC+CAG group,the rate of complete remission was 26.7 ％ (8/30),the rate of partial remission was 30.0 ％ (9/30),the effective rate was 56.7 ％ (17/30),the difference between the two groups was not statistically significant (x2 =0.227,P =0.716).In DAC+IA group the median remission time and the median suvival time were 4.0 and 8.1 months,respectively.And they were 4.0 and 8.1 months,respectively,in DAC+CAG group.No significant difference was showed between the two groups (P value was 0.835,0.266,respectively).Conclusions Compared with decitabine combined with CAG regimen,decitabine combined with IA regimen has similar effect and can be well tolerated.Accordingly,decitabine combined with IA regimen can be used as first-line treatment for elderly patients with acute myeloid leukemia.
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Objective To explore the effect and feasibility of haplotype allogeneic hematopoietic stem cell transplantation (allo-HSCT) used in the childhood patients with refractory and relapsed leukemia.Methods Thirty children with refractory and relapsed leukemia received haplotype allo-HSCT from June 2007 to June 2011 in Beijing Military General Hospital,including 14 cases of acute myeloid leukemia (AML) and 16 cases of acute lymphoblastic leukemia (ALL).Of the 30 cases,there were 11 cases of initial recurrence,16 cases of second or more relapse,and 3 cases of primary refractory leukemia.The bone marrow and peripheral blood of donors were used for transplantation.All children were subjected to pretreatment consisting of cytarabine,busulfan,fludarabine and total body irradiation (TBI),etc.Graft-versus-host disease (GVHD) was prevented by combining variety of immunosuppressants including Cyclosporin A (CsA),Methotrexate (MTX),Mycophenolate mofetil (MMF) and anti-thymocyte immunoglobulin (ATG),etc.The regimen-associated side effect incidence of GVHD and disease-free survival probabilities were observed after HSCT.Results The results showed that all of the 30 children acquired hematopoietic reconstitution,and the median time of granulocytes exceeding 0.5 × 109/L and platelets exceeding 20 × 109/L which were transplanted 100％ by donors was 18.5 days and 24.2 days respectively.The mean follow-up period was 22.5 months (3 ～48 months).Twelve children had experience of acute GVHD,and 6 children had experience of chronic GVHD.Four children died of GVHD,3 died of infection and 6 died of relapse,and the rest children were alive in free situation.The 2-year disease-free survival rate was 55％.Conclusion Haplotype allo-HSCT was an safe and feasible therapy for the childhood patients with refractory and relapsed leukemia.
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Objective To improve the diagnosis efficiency of patients with angioimmunoblastic T-cell lymphoma (AILT)by analyzing the clinical characteristics and curative effect of AILT. Methods Retrospective studies were used on clinicopathological features,immunophenotypes,treatment and survival of 20 angioimmunoblastic T-cell lymphoma patients,who were collected between January 2005 and January 2010 of Beijing Military General Hospital. Results In the 20 patients receiving chemotherapy,the median age was 55.9 years old.All of the 20 had lymph nodes and 11 of whom were accompanied with B group of symptoms,which were confirmed by lymph node biopsy and T cell antigen CD3, CD45Ro positive expression in all the patients. ALL of the patients received the CHOP regimen and combining with other treatment such as DICE,ESHAP, Hyper-CVAD or autologous hematopoietic stem cell transplantation. A follow-up by 5 to 69 months showed that median survival was 20.2 (5-69) months and 1,2,and 3-year disease free survival (DFS) were 67 ％,33 ％,and 11％ respectively.8 patients of the group (40 ％) with a sustained remission (CCS) respectively survived 63,47,27,24,24,12,5,1 months so far.Conclusion Most patients were older with many complications during chemotherapy, which resulted in easy relapse, and even the symptoms were alleviated at the early stage of the chemotherapy. IPI prognostic index is more important with long-term survival in AITL.Therefore further studies are required to improve the outcome.
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Objective To explore the preventative effect of donor peripheral blood stem cell (PBSC) infusion mobilized by granulocyte colony-stimulating factor (G-CSF) for the relapsing patients with leukemia after haplotype hematopoietic stem cell transplantation ( HSCT) , as well as its therapeutic effect and safety. Methods G-CSF was given at 5-10 μg · kg-1 · d-1 to donor and PBSCs were obtained on day 5 and frozen and allotted for storing. PBSC infusion was given to all the 20 patients on day 90 after HSCT,and the second treatment was given to 4 patients on day 30 after the first infusion. The occurrence of graftversus-host disease ( GVHD) , relapse rate of high risk leukemia and long-term survival were evaluat after PBSC infusion. Results A total of 19 patients had acute GVHD after PBSC infusion for a median of 25 (12-60) months, 4 of them were ≥ degree Ⅲ. The cumulative incidence rate was 22.9%, and all of them accepted PBSC infusion twice. Thirteen patients had assessable chronic GVHD, 10 of them were restricted,and no one died of it. Nine patients died of relapse of leukemia. The remaining 11 patients survived leukemia free, including 4 with chronic myelogenous leukemia, 4 with acute myeloid leukemia (AML) , 1 with lymphoma-leukemia and 2 with myelodysplastic syndrome-AML (MDS-AML). Kaplan-Meier analysis showed the disease free survival rate of 2-year was 52. 5%. Conclusion The prophylactic donor PBSC infusion mobilizing with G-CSF is effective, safe and feasible for the relapse of leukemia.
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Objective To investigate the effect of donor lymphocyte infusion (DLI) for preventing relapse of leukemia after haplotype hematopoietic stem cell transplantation (HSCT), and evaluate the therapeutic effect and the safety of DLI. Methods The 20 haplotype HSCT patients who received DLI were studied for the occurrence of graft-versus-host disease (GVHD) and long-term survival. Results Eleven of twenty patients survived leukemia-free for a median of 25(4-60) months, and leukemia-free survival rate was 55 %. 9 cases died of relapse. 19 patients occurred acute GEHD (aGVHD) after received DLI, 4 of them were severe.Conclusion The prophylactic DLI is effective for preventing from relapse of leukemia. It might be feasible option.
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Objective To improve the diagnosis level of solitary bone plasmacytoma (SBP) through analysing the clinical characteristics and therapy of this disease. Methods The clinical data of 18 cases were retrospectively analysis since 1999 in five hospitals, the clinical characteristics and therapeutic effect was summarized. Results The average age of 18 cases is 54.2 year (35-78), male were 1.6 times than female. 8 of 10 patients survived for 1-10 year after chemoradiotherapy, 2 of them progressed to multiple myeloma (MM)and died. 5 of 8 patients survived after only chemotherapy or radiotherapy. There were 11 cases of all patients in continue complete remission (CCS), the average CCS time was 47.3 months. Conclusion SBP is a type low-grade malignant tumor. Chemotherapy and radiotherapy is the main therapy. The patients can gain satisfactory prognosis with chemoradiotherapy, part of them can progress to MM.
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Objective To investigate the effects of Basiliximab on alloreactive T lymphocytes precursors, hematopoietic progenitor cells by ex vivo assay and prophylaxis of graft-versus-host disease (GVHD) in mismatched bone marrow transplantation.Methods Two groups were set up: (1) Basiliximab group including 72 leukemia patients subject to haploidentical bone marrow transplantation (BMT) with Basiliximab for prophylaxis of GVHD without ex vivo T-cell depletion. (2) Control group having 15 patients receiving the same regimen before Nov. 2000, without Basiliximab for GVHD prophylaxis. Limiting-dilution method was used to determine the effect of Basiliximab on reactivity of cytotoxic T lymphocyte precursors (CTLP). In the semi-solid hematopoietic culture system, the effect of Basiliximab on the colony proliferation of CFU-GM, BFU-E and CFU-Meg was measured. Results In Basiliximab group, 72 patients established trilineage with full donor hematopoietic reconstitution. Engraftment rate showed no statistical difference between the two groups. The incidence of grade Ⅱ-Ⅳ GVHD was 12.5 % (9 cases) in Basiliximab group and 33.3 % (5 cases) in control group respectively (P
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Objective To explore the effects of Basiliximab (Simulect) on reducing the incidence of severe acute GVHD in haploidentical bone marrow transplantation (BMT). Methods Nine patients with leukemia received haplotype Allo-BMT from HLA two or three loci mismatched related donor. Most patients were classified as high risk category. The donors of patients were administrated with G-CSF 250 ?g/day for 7 doses prior to marrow harvest. In addition to combination of CsA, MTX, ATG and Mycophenolate mofetil for GVHD prophylaxis, Simulect was administered to prevent severe GVHD. A total 40 mg Simulect was given in two doses of 20 mg each by 30 min intravenous infusion on 2 h before transplantation and day 4 after transplantation.Results All patients were engrafted. 100 % donors hematopoietic cells after transplantation was determined by cytogenetic evidence analysis. None developed the Ⅱ-Ⅳ acute GVHD. Eight patients could be evaluated for chronic GVHD. All experienced chronic GVHD confined to the skin. The median follow-up duration was 14 months (range 12～20 months). One patient died from CMV infection on 3 months and one patient died from disease relapse on 14 months. The remaining 7 patients were survived in disease free situation.Conclusion The use of Simulect in haploidentical bone marrow transplantation is effective on preventing acute severe GVHD and improving disease-free survival.
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OBJECTIVE To assess the clinical effectiveness of antibiotic combined therapy for febrile neutropenia as an empirical treatment.METHODS We analyzed bacterial epidemiology form Jan 2001 to Feb 2003 and performed a study in 202 neutropenic febrile patients after chemotherapy or(HSCT).Three groups were divided.In first group(84 cases) carbapenems and vancomycin were used.In second group(78 cases)and in third group(40(cases)) used cephalosporin or quinolone.RESULTS Carbapenems plus vancomycin were with response rate of 93%,and(without) vancomycin were only 66%.Cephalosporin or quinolone was with response rate only of 30%.(CONCLUSIONS) Strong antibiotic with vancomycin is effective for treating patients with neutropenia and fever(under) limited bacterial epidemiology.