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Objective:To investigate the relationship between telomere length of bone marrow mononuclear cells and prognosis of patients with acute myeloid leukemia (AML) who received allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:Telomere length of bone marrow mononuclear cells before transplantation, after transplantation and before donor mobilization as well as information related to follow-up of 33 AML patients who received allo-HSCT in the Affiliated Hospital of Guizhou Medical University between June 2020 and June 2021 were retrospectively analyzed. Telomere length was detected by using telomeric terminal restriction fragment (TRF) method. Telomere length was compared among patients with different prognoses. The recurrence within 1 year was treated as the gold standard and receiver operating characteristic (ROC) curve was used to analyze the effect of telomere length before transplantation or before donor mobilization in the judgement of the recurrence within 1 year after transplantation. The patients were stratified according to the optimal threshold value of telomere length for patients or donors, and Kaplan-Meier method was used to compare the progression-free survival (PFS) of patients with different stratification, and log-rank test was performed.Results:The median age of 33 patients was 34 years (14-61 years), and there were 17 males and 16 females; 31 patients were initially diagnosed with AML, 1 patient transferred from myelodysplastic syndrome (MDS) to AML, and 1 patient transferred from chronic granulocytic leukemia (CML) to AML; 14 received identical sibling transplantation and 19 received haploidentical sibling transplantation. The median age of the donors was 30 years (20-65 years), including 24 males and 9 females. Telomere length of bone marrow mononuclear cells before mobilization in 33 donors was longer than that in patients before transplantation (33 cases) and at +30 d after transplantation (31 cases) [(6.67±0.31) kb, (6.40±0.33) kb, (6.48±0.33) kb, respectively; all P < 0.05], and the difference between patients before and at +30 d after transplantation was not statistically significant ( t = 0.89, P = 0.378), and the telomere length of bone marrow mononuclear cells in 11 patients +180 d after transplantation was (6.66±0.18) kb. The incidence of acute graft-versus-host disease (aGVHD) after transplantation was 45.5% (15/33), the incidence of infection with clear imaging and pathogenic basis was 39.4% (13/33), the mortality rate within 1 year after transplantation was 3.0% (1/33), and the recurrence rate within 1 year after transplantation was 15.2% (5/33). There were no statistically significant differences in telomere length of donor pre-mobilization bone marrow mononuclear cells between the groups with and without aGVHD and between the infected and non-infected groups (all P > 0.05).Compared with patients who had not relapsed within 1 year after transplantation, telomere length of donor pre-mobilization bone marrow mononuclear cells was shorter in patients who relapsed within 1 year after transplantation [(6.39±0.19) kb vs. (6.72±0.30) kb, t = -3.23, P = 0.011], telomere length was longer in patients before transplantation [(6.75±0.16) kb vs. (6.35±0.36) kb, t = 4.17, P = 0.001]. ROC curve analysis showed that the optimal threshold values for telomere length of pre-transplantation and donor pre-mobilization bone marrow mononuclear cells were 6.48 and 6.42 kb, respectively for patients who relapsed within 1 year after transplantation. PFS in patients with pre-transplantation bone marrow mononuclear cells telomere length < 6.48 kb was better than that in patients with telomere length ≥ 6.48 kb ( P = 0.003); PFS in patients with pre-mobilization bone marrow mononuclear cells telomere length>6.42 kb was better than that in patients with telomere length ≤ 6.42 kb ( P < 0.001). Conclusions:In allo-HSCT for AML, patients have an increased risk of relapse within 1 year after transplantation when their pre-transplantation bone marrow mononuclear cells telomere length is long and the donor bone marrow mononuclear cells telomere length is short.
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Objective: To observe the effect of electroacupuncture (EA) of "concurrent treatment of the brain and heart" on angiogenesis and cortical vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF) in rats with focal cerebral ischemia, and to explore the mechanism of EA in cerebral ischemia treatment. Methods: A total of 108 Sprague-Dawley rats, 27 rats were randomly selected as the sham-operation group, and the rest rats received the right middle cerebral artery occlusion operation for model preparation firstly, and then were divided into a model group, a traditional acupoint group, and a concurrent treatment of the brain and heart group, with 27 rats in each group. In the sham-operation group, only the carotid artery was isolated. EA at Shuigou (CV26), Quchi (LI11), Hegu (LI4), and Zusanli (ST36) in the traditional acupoint group, and EA at Fengfu (GV16), Baihui (GV20), Xinshu (BL15), and Neiguan (PC6) in the concurrent treatment of the brain and heart group were performed 4 h after the operation, once a day, for 14 consecutive days. Rats in the sham-operation group and the model group were identically fixed without any treatment. Before and after treatment, the modified neurological severity score (mNSS), regional cerebral blood flow (rCBF), and CD34 positive expression by immunohistochemistry were measured. The positive protein expression levels of VEGF and BDNF were detected by immunofluorescence, and the mRNA expression levels of VEGF and BDNF were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Results: Compared with the sham-operation group, the mNSS, rCBF, and ischemic side cortical micro-vessel density (MVD) decreased, and the protein and mRNA expression levels of VEGF and BDNF increased in the model group (P<0.01). Compared with the model group, the mNSS of the two EA groups decreased, and the mNSS of the concurrent treatment of the brain and heart group was lower than that of the traditional acupoint group on the 14th day (P<0.05). Compared with the model group, the rCBF in the two EA groups increased, and the rCBF reached the highest on the 14th day (P<0.05 or P<0.01), and the rCBF in the concurrent treatment of the brain and heart group was higher than that in the traditional acupoint group (P<0.05); the MVD of the two EA groups was higher than that of the model group, and the MVD of the concurrent treatment of the brain and heart group was higher than that of the traditional acupoint group on the 7th and 14th days (P<0.05 or P<0.01). Compared with the model group, the protein and mRNA expression levels of VEGF and BDNF in the two EA groups increased (P<0.01). The VEGF expression level was the highest on the 7th day in the concurrent treatment of the brain and heart group (P<0.05), and the BDNF expression level was higher on the 7th and 14th days than on the 3rd day (P<0.05). The mRNA expression levels of VEGF and BDNF in both EA groups reached the highest on the 7th day (P<0.05 or P<0.01). Conclusion: EA therapy can up-regulate the VEGF and BDNF expression levels and increase the rCBF in the cortex of rats with focal cerebral ischemia, which may be one mechanism of EA in the cerebral ischemia treatment. The therapeutic effect is accumulated with the effective time, and the concurrent treatment of the brain and heart group is superior to the traditional acupoint group in promoting angiogenesis.
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ObjectiveTo observe the efficiency of hematopoietic stem cell transplantation to the treatment of hematological malignancies and explore prevention and treatment of the complications correlated with HSCT. Methods110 patients with hematological malignancies which were treated by HSCT were recruited. 61 patients were treated with autologous peripheral blood hematopoietic stem cell transplantation (auto-PBSCT), 49 patients were treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT).Among them,there were 28 patients were used by all HLA-identical sibling allo-PBSCT,20 patients were used by haploid allogeneic bone marrow and peripheral blood stem cell transplantation, one case of acute lymphoblastic leukemia in children were treated with cord blood stem cell transplantation.Results109(99.1％) patients acquired hemopoietic reconstruction. The median time of neutrophils≥0.5×109/L, and platelets≥20×109/L were 10 days and 12 days in auto-PBSCT,and were 12 days and 15 days in allo-PBSCT.The incidence of Ⅰ-Ⅲ degree of acute GVHD (aGVHD) in allogeneic transplantation was 28.6 ％(14/49),however,the incidence of chronic GVHD (cGVHD) was 32.6 ％(16/49).The median follow-up time was 36 (1～60) months.84 patients (76.4 ％) were disease-free.Among them,73.8 ％(45/61) were in auto-PBSCT group,(79.6 ％)39/49 were in allo-HSCT group.26 patients (23.6 ％) were died.There were 26.2 ％(16/61) who were in auto-PBSCT group died of disease relapse,3.3 ％(2/61) had disease relapse.There was no transplant-related deaths.18.4 ％(9/49) who were in allo-HSCT group died of disease relapse, 6.1％(3/49)had disease relapse, 2.0 ％(1/49)died of transplant-related deaths. ConclusionHematopoietic stem cell transplantation is a safe and effective way for the treatment of malignant hematopathy patients,also an important mean for treatment of blood diseases.
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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.