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OBJECTIVE@#To explore the relationship between occurrence of acute graft-versus-host disease (aGVHD) and various immune cell composition in patients with acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).@*METHODS@#The clinical data of 104 patients with AML undergoing allo-HSCT in our hospital were retrospectively analyzed, and the hematopoietic reconstitution and occurrence of GVHD were analyzed. Flow cytometry was used to detect the proportion of various types of immune cells in the grafts, the number of graft composition in patients with different degrees of aGVHD was calculated and compared, and to analyze the correlation between the severity of aGVHD in AML patients after allo-HSCT and the immune cell components in the graft.@*RESULTS@#There was no significant difference in the time of hematopoietic reconstitution between the high number group of total number of nucleated cells (TNC) and the low number group, while the time of neutrophil and platelet reconstruction in the high number of CD34 group was significantly faster than that in the low number of CD34 group (P＜0.05), and the total hospital stay also tends to be shorten. Compared with patients in 0-Ι aGVHD group, both HLA-matched and HLA-haploidentical transplantation, the infusion amounts of CD3+ cells, CD3+CD4+ cells, CD3+CD8+ cells, NK cells and CD14+ monocytes were higher in patients of Ⅱ-Ⅳ aGVHD group， but the difference was not statistically significant (P>0.05); In addition, in patients with HLA-haploidentical transplantation, the number of CD4+CD25+ cells in Ⅱ-Ⅳ aGVHD group was significantly lower than that in 0-Ι aGVHD group (P<0.05), and the same trend was also observed in HLA-matched transplanted patients, but the difference was not significant (P=0.078).@*CONCLUSION@#High number of CD34+ cells in the graft is beneficial to hematopoietic reconstitution in AML patients. To a certain degree, high number of CD3+ cells, CD3+CD4+ cells, CD3+CD8+ cells, NK cells and CD14+ cells tend to increase the occurrence of aGVHD, but high number of CD4+CD25+ regulatory T cells is beneficial to reduce the incidence of aGVHD in AML patients.
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Humans , Retrospective Studies , Hematopoietic Stem Cell Transplantation/adverse effects , CD4-Positive T-Lymphocytes , Leukemia, Myeloid, Acute/complications , Graft vs Host DiseaseABSTRACT
OBJECTIVE@#To explore the effect of recombinant human thrombopoietin (rhTPO) on hematopoietic reconstruction in allogeneic hematopoietic stem cell transplantation (allo-HSCT) model.@*METHODS@#The C57BL/6 mice were employed as the donors, and BALB/c mice as recipients. The bone marrow mononuclear cells of the donor mice were extracted and pretreated, which then were injected with 5×106 per mouse through the tail vein of the recipient to establish an allo-HSCT model. The implantation of hematopoietic stem cells in the recipient mice was detected by flow cytometry on the 28th day after transplantation. Next, the successfully modeled recipient mice were randomly divided into experimental group and control group. The rhTPO was injected into mice in the experimental group on the first day after transplantation, while the saline was injected into mice in the control group. Both groups were injected for 14 consecutive days. The peripheral blood and bone marrow hematopoiesis of the two groups were observed on day 1, 3, 7, 14, and 21 after transplantation.@*RESULTS@#The expression rate of H-2Kb in the bone marrow of recipient mice was 43.85% (>20%) on the 28th day after transplantation, which indicated that the recipient mice were successfully chimerized. Meanwhile, counts of PLTs on the day 3, 7, 14, and 21 after transplantation in the experimental group were higher than those in the control group with statistical significances (P<0.05). In addition, hematopoietic function of bone marrow was suppressed in both groups on day 1, 3 and 7 after transplantation, but hematopoietic bone marrow hyperplasia was better in the experimental group than in the control group. On day 14 and 21 after transplantation, the hematopoietic function of bone marrow in the two groups was recovered, and the experimental group showed more obvious than the control group.@*CONCLUSION@#rhTPO can effectively stimulate the production of PLTs and facilitate the recovery of white blood cells and hemoglobin after allo-HSCT, and promote hematopoietic recovery and reconstitution of bone marrow.
Subject(s)
Humans , Animals , Mice , Thrombopoietin , Mice, Inbred C57BL , Hematopoietic Stem Cell Transplantation , Hematopoietic Stem Cells , Bone Marrow , Recombinant Proteins , Mice, Inbred BALB CABSTRACT
Objective:To explore the safety and efficacy of EAC [etoposide+ cytarabine+ cyclophosphamide (CTX)] mobilization scheme for mobilizing stem cells in patients with lymphoma undergoing autologous hematopoietic stem cell transplantation (ASCT).Methods:A total of 36 patients with lymphoma who had collected peripheral blood stem cells through EAC or CTX+ granulocyte colony stimulating factor (G-CSF) mobilization scheme in Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from June 2018 to March 2020 were retrospectively analyzed. Among them, 16 patients used EAC mobilization (EAC group), and 20 patients used CTX (CTX group). When white blood cells≤1.0×10 9/L, G-CSF (10 μg/kg per day) was given subcutaneously in two doses. The changes of hematology indexes, the number of collected cells, adverse reactions during mobilization collection and hematopoietic reconstitution after ASCT were observed. Results:The peripheral blood stem cells were collected on 5 d (3-8 d) after EAC+ G-CSF mobilization and 7 d (4-12 d) after CTX+ G-CSF mobilization. The success rates of collection in the EAC group and CTX group were 100% (16/16) and 75.0% (15/20) respectively, the high-quality collection rates were 87.5% (14/16) and 25.0% (5/20) respectively, and there were statistically significant differences ( P=0.041; P<0.001). The median of CD34 + cells of the two groups was 13.67×10 6/kg and 3.45×10 6/kg respectively, the median of mononuclear cells was 7.16×10 8/kg and 5.09×10 8/kg respectively, the median of CD34 + cells/mononuclear cells was 1.44% and 0.67% respectively, and there were statistically significant differences ( Z=-4.219, P<0.001; Z=-2.118, P=0.034; Z=-3.104, P=0.002). In the EAC group and CTX group, the incidences of grade 3 and above granulocytopenia were 100% (16/16) and 90.0% (18/20) respectively, the incidences of grade 3 and above hemoglobin reduction were 43.8% (7/16) and 25.0% (5/20) respectively, the incidences of grade 3 and above thrombocytopenia were 87.5% (14/16) and 65.0% (13/20) respectively, and there were no statistically significant differences ( P=0.492; P=0.298; P=0.245). There were no significant differences in the incidences of infection, adverse reactions of digestive system or other adverse reactions between the two groups (all P>0.05). All patients accepted improved Bucy scheme before ASCT. The median implantation time of neutrophils and platelets was 9.0 d and 10.5 d in the EAC group, which was 12.0 d and 13.5 d in the CTX group, and there were statistically significant differences ( Z=-4.698, P<0.001; Z=-3.757, P<0.001). Conclusion:EAC mobilization scheme can significantly increase the number of hematopoietic stem cell. This scheme has a high success rate of high-quality collection and the adverse reactions are within the controllable range. It provides a high-quality mobilization scheme for hematopoietic stem cell mobilization and collection, which is worthy of clinical promotion and application.
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Objective To investigate the influences of donor HBV infection on allogeneic hematopoietic stem cell transplantation recipients.Methods We made a retrospective analysis of data of four patients without HBV infection who underwent allogeneic hematopoietic stem cell transplantation from January 2015 to December 2016. Among them donors of these patients all had HBV infection.We then observed the influences of HBV infection on hematopoietic reconstruction,hepatic vein occlusive disease and HBV infection.Results HBV serological conditions of two donors were HbsAb,HbeAb and HbcAb positive,and quantitative of HBV-DNA was negative;the donor and the recipient did not use anti-HBV drugs.One donor was HbsAg,HbeAb and HbcAb positive,and the quantitative of HBV-DNA was also positive.Another donor was HbsAg and HbcAb positive,and the quantitative of HBV-DNA was also positive.These two donors received oral nucleoside therapy one month before stem cell collection and the recipients of these two donors also took nucleoside drugs one week before the conditioning.Hepatitis B immune globulin was given after transfusion of stem cells and the third day and seventh day after transplantation.Quantitative of HbsAb was detected each month and if it was less than 150 IU,hepatitis B immune globulin would be given.All the recipients had hematopoietic reconstruction and no VOD or hepatitis B virus infection occurred.Conclusion Oral administration of nucleoside drugs combined with hepatitis B immunoglobulin can effectively prevent HBV infection in recipients with HBV infection donors.
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Objective To observe the efficacy of autologous hematopoietic stem cell transplantation on the treatment of patients with acute myeloid leukemia (AML) in complete remission stage. Methods Clinical data of 14 AML patients underwent autologous hematopoietic stem cell transplantation were analyzed retrospectively, including 7 low-risk patients, 6 moderate-risk patients and 1 high-risk patient. After pretreatment, pre-cryopreserved autologous peripheral blood stem cells were retransfused. And component blood transfusion, increasing white blood cell (WBC) count and preventing from infection, etc. were given. Hematopoietic reconstitution of autologous stem cells in the patients was observed, and incidence of transplantation related complications was obtained. Furthermore, survival curves were drawn, and postoperative 1- and 3-year overall survival rates and disease-free survival (DFS) rates were calculated. Results Hematopoietic reconstitution was achieved in all 14 patients. The median time of WBC implantation was 12(9-28) d, and that of platelet implantation was 29(8-158) d. Two patients suffered from E. coli septicemia during neutropenia stage, 1 from proteus vulgaris septicemia, 1 from cytomegalovirus viremia within 29 d after transplantation and the remaining from infection or gastrointestinal reaction after pretreated. All patients were cured by anti-infection and other symptomatic relief and supportive treatment. All patients were followed up for 29.8(5.3-61.5) months. In 14 patients, 5 cases recurred. 11 patients survived and 3 died of recurrence. The postoperative 1- and 3-year overall survival rates were 86％ and 79％, and the postoperative 1- and 3-year DFS rates were 64％ and 57％. Conclusions Autologous hematopoietic stem cell transplantation is effective in the treatment of majority patients with low- or moderate-risk AML.
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non-myeloablative BuCy+fludarabine conditioning regimen,and another one was treated with TBI+VP-1 6 +CTX+CCNU conditioning regimen.Only one case received short-term MTX,cyclosporin A and ATG regimen for prevention of graft-versus-host disease (GVHD).The GVHD prevention regimens of the other patients were based on short-term MTX,cyclosporin A,ATG and mycophenolate mofetil regimen.The hematopoietic reconstitution, complications and prognosis were observed.Results One patient died of intracranial hemorrhage,and hematopoi-etic reconstitution was achieved in the other 20 patients.The median time for hematopoietic reconstitution shortened by one day in large-dose group compared with that in low-dose group.Adverse reactions included high fever, shivering,gastrointestinal tract adverse reaction,liver injury,oral mucositis and other rare side effects.GVHD occurred more frequently in patients with HLA mismatched transplantation.Nine patients with aGVHD and 9 patients with cGVHD recovered after effective treatment.Within 100 days after transplantation,18 patients had bacterial or fungal infection,mainly upper respiratory tract infection;7 patients had cytomegalovirus infection;2 had EB viremia,and one had urinary BK virus infection.Only one patient died of VOD.Hemorrhagic cystitis occurred in 5 patients and improved after treatment.The median survival time was 24 months (ranging from 136 days to 9 years).One-year and 3-year overall survival rates were 85.2% and 63.9%,the disease free survival rates were 81% and 23.8%,recurrence free survival rates were 71.4% and 14.3%,respectively.Conclusion URD-HSCT was an effective method to treat leukemia.Conditioning regimen of BuCy and modified BuCy2 were safe and effective,the adverse reactions were reversible and well tolerated.Hematopoietic reconstitution time shortened in large-dose MNC and CD34 + cell number groups compared with that in low-dose group.The occurrence rate of GVHD with HLA mismatched transplantation was more than that of HLA matched transplantation.Low-dose heparin,prostaglandin E1 and Danshen injection can effectively prevent VOD.
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ObjectiveTo evaluate the efficacy of allogeneic stem cell transplantation (allo-HSCT) in treatment of hematologic malignancies and observe hematopoietic reconstitution, graft versus host disease (GVHD) occurrence,transplant-related complications and the outcome of disease.Methods20 patients with hematologic malignancies cured by allo-HSCT were analyzed retrospectively. 15 males and 5 females patients were enrolled, and the median age was 39(8-59)years. Mobilization of donor’ s stem cells using rhG-CSF program 3 days before transplantation.Conditioning regimen:the patients with HLA-matched used modified Bu/Cy programs,the patients with HLA-mismatched (with 1 to 3 loci mismatched) used the modified Bu/Cy+ ATG program;the patient with T-ALL and the patient with MM used Flu+Bu/Cy program. GVHD prevention programs: mycophenolate mofetil + cyclosporine + short course methotrexate. Results20 patients were successfully engrafted,the median time of absolute neutrophil count (ANC) ＞ 0.5×109/L was 13 (12-17) days,the median time of Plt ＞ 20×109/L was 16(12-23)days, and the hematopoietic reconstitution was rapid in those patients who were transplanted by the donors with the collected amount of CDh cells ＞ 2.5× 106/kg (recipient body weigh) or the collected amount of mononuclear cell ＞ 5.0×10s/kg (recipient body weigh).No severe hemolytic reaction occurred in 11 cases of blood group incompatibility between donor and recipient after transplantation,11 cases (55 ％) developed acute GVHD (aGVHD):4 cases Ⅰ degree aGVHD,4 cases Ⅱ degree aGVHD,2 cases Ⅲ degree aGVHD,1 case Ⅳ degree aGVHD,all patients were improved after treatment.All patients attained complete remission (CR) after transplantation.Follow-up 6 (2-14) months,1 patient died in 5 months after transplantation because of leukemia relapse, 1 case died in 4 months after transplantation because of self-disabling autoimmune hemolytic cyclosporine, chronic GVHD(cGVHD)and multiple organ failure,the remaining patients still were in CR state.ConclusionAllo-HSCT is the effective way to treat hematologic malignancies. Engraftment is closely related with the quantity of hematopoietic stem cells from donor.Blood group incompatibility was not an obstacle for transplantion.Relapse,GVHD,infection are the major cause of death after transplantation.
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Objective To explore a proper dose of endothelial progenitor cells (EPCs)administration that can achieve optimal hematopoietic improving effectiveness in a murine allogeneic hernatopoietic stem cell transplantation (allo-HSCT) model.Methods Female Balb/c mice were lethally irradiated with 60Co source,and then were injected intravenously with 5 106 bone marrow cells from C57BL/6 mice (bone marrow transplantation group).In co-transfer experiments,5 × 104,1 ×105,5 × 105 or 1 × 106 donor EPCs (EPCs treated groups) were injected simultaneously with bone marrow cells.The recipients were monitored for survival,peripheral white blood cells,hematopoietic stem cells (HSCs) and bone marrow histology.Results Compared with bone marrow transplantation group,all EPCs treated groups had accelerated recovery of peripheral white blood cells (P＜0.05),platelets (P＜0.05) and HSCs (P＜0.05).When infused with less than 5 × 105 EPCs,these effective hernatopoietic improving phenomena showed a positive correlation with the administrated doses of EPCs.However,when infused with 1 × 106 EPCs,the mice showed lower survival rate (P＜0.05)and slower recovery of peripheral white blood cells (P＜0.05),platelets (P＜0.05) and HSCs (P＜0.05) than 5 × 105 EPCs treated grpup.Bone marrow histopathology analysis confirmed the above findings.Conclusion Co-transfer with donor EPCs can improve survival rate and hematopoietic reconstitution of recipient mice in allo-HSCT,and 5 × 105 EPCs should be a proper dose to achieve the best effectiveness.
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The effect of ligustrazine on the expression of CD31 in syngenic bone marrow transplantation (BMT) mice was studied. Fifty-six Balb/c mice were divided into 3 groups: normal control group, BMT control group, and ligustrazine treated group. Syngenic BMT mouse models were established according to the literatures. In BMT control group and the ligustrazine treated group, the mice were given respectively orally 0.2 mL saline and 2 mg ligustrazine twice a day. On the 7th,14th, and 21st day after BMT, the mice were killed. The expression of CD31 on the surface of bone marrow nuclear cells (BMNC) was detected by flow cytometry. Peripheral blood leukocytes, platelets and BMNC were counted. Histological observation of bone marrow was made. The results showed that in ligustrazine treated group the peripheral blood leukocytes, platelets and BMNC counts, and the expression of CD31 on the day 7, 14, 21 after BMT were higher than in BMT control group (P＜0.01 or P＜0.05). In conclusion, ligustrazine could obviously enhance the CD31expression on the surface of BMNC after syngenic BMT in mice, which may be one of the mechanisms underlying the ligustrazine accelerating hematopoietic reconstitution in syngenic BMT.
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0.05).There was a positive correlation between the tempo of the engraftment and the progressive increase of the doses of MNC in the range of (3～5.99)?108/kg,but which was not found in the range of 6?108/kg.Conclusion These results indicate that MNC taken as an index for the measurement of the hematopoietic stem cell/progenitor content can reliably predict hematopoietic reconstitution after both HLA-matched and-mismatched sibling donor peripheral blood stem cell transplantation,with the rate and tempo of engraftment comparable with that in CD34+ cell group,and however,the target dose was reached with one apheresis in all 83 donors in MNC group(100%),as compared with 14 donors in CD34+ cell group(37.84%),suggesting that MNC may replace CD34+ cell as an independent index for the assessment of the stem cell/progenitor content in clinical practice.
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Abstract We investigated the effects of IL-3, IL-6 and IL-4, alone and in combination with G-CSF and GM-CSF on hematopoietic reconstitution following murine allogenic bone marrow transplantation. The most effective combination for increasing the circulating absolute neutrophil count (ANC) above the control value at day 6 posttransplant was the combination of IL-3 and GM-CSF and showed a significant synergistic effect. When used alone, both IL-6 and G-CSF raised platelet count at day 6 after transplantation (312?10~(9)/L, P=0.02 and 309?10~(9)/L, P=0.01 respectively) compared to control mice(216?109/L). In combination, only IL-3 with G-CSF significantly increased the day 6 platelet count (328?10~(9)/L). We found that neutrophil recovery at day 7 after transplantation was significantly suppressed by IL-4 in a dose-dependent fashion and that the recovery of nentrophils accelerated by IL-3, and G-CSF was also significantly suppressed by IL-4.
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In the present study, the effect of fibroblast-mediated IL-2 gene therapy on immune and hematopoietic reconstitution was observed after syngeneic bone marrow transplantation (BMT) in the mice which had received high-dose chemotherapy. The NK activity , LAK activity and the proliferation of BMT were augmented significantly , while there were no effects on the formation of CFU-GM, CFU-MK and CFU-E of bone marrow after IL-2 gene therapy. The results suggested that fibroblast-mediated IL-2 gene therapy can accelerate and prompt the process of immune reconstitution, then enchance the antitumor effect and reduce the complication such as infection after BMT. The experiment provide basis for the application of IL-2 gene therapy in BMT in the future.