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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 analyze the genetic characteristics of chromosomes and related fusion genes in acute myeloid leukemia (AML) (non-M3), and to evaluate the prognosis of patients with chemotherapy of DA regimen with different doses of daunorubicin. Methods Fifty-six patients with newly diagnosed non-M3 AML from January 2013 to January 2015 were collected. Adopted short-term culture method was used to treat bone marrow, R-binding chromosome karyotyping was used to detect cytogenetic. Thirty-one types of fusion gene were identified by PCR and 10 % agarose gel electrophoresis. All patients treated by DA regimen were divided into group A, group B and group C according to different dosage of daunorubicin. Then, complete remission (CR) rate and survival time in the 3 groups were observed. The effect of cytogenetic and molecular biology abnormality on the chemotherapy, CR rate and overall survival (OS) of the 3 groups were analyzed by the chi-square test. Results Among the 56 patients, 18 cases (32.1%) had abnormal chromosome karyotype, 6 cases (10.7 %) had abnormal number of chromosome, 16 cases (28.6 %) had abnormal structure of chromosome, and 4 cases (7.1 %) had both abnormal number and structure of chromosome. Meanwhile, the most common abnormal structure was t(8;21), and the most common abnormal quantity were+8, -Y. Detective rate of genetic abnormality was raised to 62.00 % through fusion gene and chromosome karyotype analysis. The total CR rate of DA-induced chemotherapeutic regimen was 73.2 %, and the two-year OS rate was 42.9%. The remission rate of chemotherapy in the middle-risk group was significantly lower than that in the low-risk group (χ 2 = 8.976, P = 0.002), but there was no significant difference between the low-dose chemotherapy group and the standard dose chemotherapy group (P>0.05). The standard dose group showed a significant advantage in the OS rate (χ2= 8.045, P= 0.005). Conclusions Adult acute leukemia has its unique cytogenetic characteristics, which can assist in guiding clinical diagnosis, classification and prognosis. The prognosis of middle-risk patients is significantly lower than the low-risk group. Low-risk patients could benefit from a reduced dose of DA regimen, but the standard dose DA regimen has a significant advantage in long-term survival.
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Objective To evaluate the efficacy and safety and to analyze related complications and potential prognostic factors of allogeneic hematopoietic stem cell transplantation(allo-HSCT ) on hematological malignancies .Methods Patients with hemato-logical malignancies who underwent allo-HSCT from June 2010 to June 2015 were investigated in this retrospective study .Accord-ing to the donor types ,it was divided into compatriots sibling-matched transplantation group (n = 52) and haploid transplantation group (n= 98) .The preconditioning regimens were busulfan/cyclophosphamide ,and anti-thymocyte globulin were needed in haploid transplantation group .Short-term methotrexate + cyclosporine A + mycophenolate mofetil were used for prevention of graft-ver-sus-host disease .The efficacy and safety and related complications of allo-HSCT were analyzed .Results All patients achieved full donor type engraftment ,which was identified by blood type ,chromosome test and DNA polymorphism .The mean times of neutro-phil and platelet engraftment were 12 d and 16 d in compatriots sibling-matched transplantation group and 13 d and 16 d in haploid transplantation group ,respectively .59 cases (39 .3% ) patients were oral mucosa ulcer ,47 patients (31 .3% ) were bacteria and/or fungal infection ,41 cases (27 .3% ) patients were CMV infection ,48 cases (32 .0% ) were acute GVHD ,43 patients (28 .7% ) were chronic GVHD .The median follow-up time of 23 months (1 - 60 months) ,115 patients (76 .7% ,115/150) were disease-free sur-vival ,including 38 cases (73 .1% ,38/52) in compatriots sibling-matched transplantation group ,77 cases (78 .6% ,77/98) in haploid transplantation group ;35 cases (23 .3% ,35/150) patients were died ,including 14 cases (26 .9% ,14/52) in compatriots sibling-matched transplantation group ,21 cases (21 .4% ,21/98) in haploid transplantation group .Death cause analysis showed that 12 ca-ses (8 .0% ) complications from transplantation related death ,of which 5 cases (3 .3% ) were severe infection ,7 cases (4 .7% ) caused by acute GVHD ,23 cases (8 .7% ) patients died because of the primary disease recurrence .The survival rate and mortality was similar between the two groups (P> 0 .05) .Conclusion Allo-HSCT is safe and effective treatment in hematological malignan-cies .The curative effect and security with haploid transplantation were similar to compatriots sibling-matched transplantation .It is necessary to prevent prognostic impact factors such as acute GVHD and infection early .
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<p><b>BACKGROUND</b>There are limited eligible clinical markers at present to monitor the progress of chronic myeloid leukemia (CML). Heme oxygenase-1 (HO-1), as one of the most important oxidation-regulating enzymes in vivo, suggests the onset and progression of cancer when highly expressed. Furthermore, HO-1 level is related with the occurrence and development of hematological diseases. But the relationship between HO-1 expression and progression/relapse of CML has seldom been studied hitherto. This study aimed to investigate the relationship between them to find out a new molecular marker for prediction.</p><p><b>METHODS</b>A total of 60 peripheral blood and bone marrow (BM) samples from 25 CML patients in different phases were collected respectively to detect the expressions of HO-1 and bcr/abl using real-time PCR. Routine blood test was performed to detect the changes of leukocyte and platelet counts. The proportion of primitive cells in BM was detected by flow cytometry. The relationship between high HO-1 expression and CML progression and relapse was explored by the analysis of variance by Wilcoxon test and linear regression analysis. The diagnostic accuracy and cutoff values were determined by receiver operating characteristic curve.</p><p><b>RESULTS</b>Relative expression of HO-1 mRNA in CML patients peripheral blood was significantly higher than that of donors (P < 0.0001), which were 0.57±3.78 and (1.417±1.125)×10(-6), respectively. HO-1 expression level in CML patients was 0.061 5±0.062 4, which decreased to 0.009 4±0.006 7 upon CMoR, and remained remarkably higher 0.016 3±0.017 5 than that of normal donors (1.417±1.125)×10(-6), P < 0.001. When relapse occurred, HO-1 expression significantly increased from 0.020 6±0.021 0 to 3.852±10.285 in CMoR stage and undergoing relapse. According to progression of CML, HO-1 expression level in CML patients increased from CP (0.009 5±0.017 6) to AP (0.028 0±0.055 7) and then to BP (0.276 7 ± 0.447 0). And there was a linear correlation between HO-1 expression and proportion of primitive CML cells. The diagnostic accuracies and cutoff values of HO-1 expression for CML-CP, CML-AP, and CML-BP were 1.0, 0.748, and 0.965, respectively, as well as 0.000 070, 0.001 917, and 0.020 696, respectively.</p><p><b>CONCLUSION</b>HO-1 may be a potential molecular indicator for the progression and relapse of CML.</p>
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Female , Humans , Male , Bone Marrow , Metabolism , Flow Cytometry , Gene Expression , Heme Oxygenase-1 , Blood , Genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Diagnosis , Pathology , Predictive Value of Tests , Real-Time Polymerase Chain ReactionABSTRACT
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.
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BACKGROUND: Rituximab single or in combination with CHOP regimen for treatment of CD20-positive non-Hodgkin lymphoma has achieved good curative effects. Autologous hematopoietic stem cell transplantation (AHSCT) has been shown to improve the curative effects and increase survival rate of patients with non-Hodgkin lymphoma. However, the curative effects of these two methods remain disputed. OBJECTIVE: To investigate the efficiency of rituximab in combination with AHSCT on CD 20-positive non-Hodgkin lymphoma. METHODS: Six patients with CD 20-positive non-Hodgkin lymphoma (stage IV) underwent AHSCT and rituximab administration. 375 mg/m~2 rituximab was intravenously administered 2-4 times prior to AHSCT, twice prior to and after peripheral blood stem cells mobilization and preprocessing, respectively, as well as once every 3 months after AHSCT. RESULTS AND CONCLUSION: The mean number of mononuclear cells and CD 34-positive cells was 5.13×10~(-8)/kg and 4.75×10~(-6)/kg, respectively. Following AHSCT, all 6 patients presented normal hematopoietic functions, neutrophils exceeded 0.5×10~(-9)/L at 9-15 days and blood platelet counts exceeded 20×10~(-9)/L at 12-19 days. Hemorrhagic cystitis, interstitial pneumonia, cytomegalovirus infection, or hepatic venous obstruction was not observed during the whole process of AHSCT in each patient. At 6-32 months, patients completely recovered. These results indicate that rituximab in combination with AHSCT is a good method for treatment of CD20-positive non-Hodgkin lymphoma and rituximab maintenance therapy could prevent disease recurrence.
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BACKGROUND:Autologous peripheral blood hemopoietic stem cell transplantation(HSCT)in combination with high-dose chemotherapy significantly improves complete remission and survival rate of multiple myeloma patients.However,the relapse rate is high.Bortezomib is 26S proteasomes inhibitor,and effective on the primary treatment of multiple myeloma.OBJECTIVE:To evaluate the curative effect of HSCT in combination with bortezomib and high dose-melphalan for multiple myeloma.METHODS:A retrospective analysis of 3 patients with a stage-ITT multiple myeloma admitted to Department of Hematology,Affiliated Hospital of Guiyang Medical College from October 2006 to May 2007,was conducted.Chemotherapy and granulocyte colony-stimulating factor were used to mobilize autologous peripheral blood hemopoietic stem cells.All patients were pretreated with 200 mg/m2 melphalan via intravenous drip 3 days before transplantation,followed by HSCT 48 hours after drug termination.RESULTS AND CONCLUSION:All patients obtained prompt and sustained hematopoietic reconstitution,and bone marrow depression restored 30 days following HSCT.Case 1 and 2 obtained complete remission,and case 3 obtained partial remission.Results show that HSCT in combination with bortezomib and high-dose melphalan is a safe and feasible treatment on multiple myeloma.The patients have good tolerance to pretreatment.
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It is difficult for the patients of refractory leukemia to complete remission (CR) and long-term disease-free survival (DFS), and it was always been the hot spots of research in the field of hematologic malignancies. The diagnostic criteria of refractory leukemia were adjusted constantly at domestic and foreign, the high-risk factors about refractory leukemia were found constantly too. New molecular markers that represent mutations or gene overexpression have been identified such as FMS-like tyrosine kinase-3 and nucleophosmin,which will enhance the ability to more accurately prognosticate for patients with acute myeloid leukemia. The treatment of patients with refractory or relapsed acute myeloid leukemia remains challenging. Multiple new agents with tremendous potential were in development and clinical trials. Such as applying resistance reversal agents,enhancing molecular targeted therapy, improving the technology of hematopoietic stem cell transplantation,empoldering the new drugs, and forming a new chemotherapy program etc. Monoclonal antibodies and peptide vaccination with leukemia-associated antigens also brought the hopes of increasing the remission and cure rates for patients with acute myeloid leukemia.