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Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a sole viable treatment for acute myeloid leukemia (AML). As the median age of AML is approaching 68 years and the global population is aging, allo-HSCT for is becoming more vital for elderly AML patients (60 years and over). Conditioning regimen is important in determining the clinical outcomes of post-allo-HSCT patients.This review summarized the classic and latest conditioning regimens and evaluated their respective clinical outcomes.Clinicians may appreciate the advantages of each conditioning regimen and formulate optimal options for elderly AML patients.
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Multiple myeloma (MM) is an incurable plasma cell malignancy with a typical course characterized by response to initial treatment and eventual resistance. Despite major advances in the clinical treatment of multiple myeloma driven by the introduction of new drugs (e.g., proteasome inhibitors and immunomodulators), MM remains incurable. Nevertheless, subsequent cycles of remission and relapse continue as long as new treatments are available to patients. With the development of many new treatments, the approval of 12 new drugs over the past 15 years, and the promising trend of clinical trials, the treatment landscape has dramatically changed and patient survival has improved. This article reviews the progress of new treatments for MM.
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Objective:To explore the strategies of reducing relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with high-risk myelodysplastic syndrome (MDS) from the perspectives of optimizing the conditioning regimen and pre-transplant cytoreductive therapy.Methods:A total of 84 patients with high-risk MDS undergoing allo-HSCT between January 2013 and September 2019 were retrospectively analyzed. Based upon preparative regimens, they were divided into two groups of decitabine intensified BUCY2 ( n=49) and BUCY2 regimen ( n=35), based upon whether or not pre-treatment prior to allo-HSCT: cytoredutive treatment ( n=34) and none ( n=50). Two groups were compared with regards to hematopoietic reconstitution, graft-versus-host disease (GVHD), relapse rate, transplant-related mortality (TRM) and survival. Results:No significant inter-group differences existed in hematopoietic reconstitution or acute/chronic GVHD. The relapse rate was significantly lower in decitabine intensified group than that in BUCY2 group (18.7% vs 40.0%, P=0.025). Survival was significantly better in decitabine intensified group than that in BUCY2 group (3-year OS: 71.3% vs 51.2%, P=0.038; 3-year DFS: 65.3% vs 45.2%, P=0.033). Moreover, the incidence of recurrence was markedly lower in pre-transplant treatment group than that in non-treatment group (20.7% vs 38.9%, P=0.035). The inter-group incidence of TRM was not different. Three-year OS/DFS of treatment group were remarkably superior to those of non-treatment group (71.2% vs 50.8%, P=0.024; 64.7% vs 45.9%, P=0.044). Conclusions:As an optimal conditioning regimen for high-risk MDS, decitabine intensified BUCY2 regimen could better eliminate tumor burden, remarkably lower relapse rate and improve OS after allo-HSCT. In addition, pre-transplant treatment significantly reduces relapse and offers benefit for OS after allo-HSCT. Therefore intensified conditioning regimen and pre-transplant treatment may be promising strategies of reducing relapse and improving survival for high-risk MDS. However, it still needs further confirmation from prospective randomized controlled trials.
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Relapse remains the worst life-threatening complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with acute myeloid leukemia (AML), whose prognosis has been historically dismal. Given the rapid development of genomics and immunotherapies, the interference strategies for AML recurrence have been changing these years. More and more novel targeting agents that have received the U.S. Food and Drug Administration (FDA) approval for
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Objective To explore the role of cerebrospinal fluid chimerism in central nervous relapse surveillance for patients of acute leukemia after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods The follow-up data were retrospectively collected and analyzed in 104 patients with acute leukemia after allo-HSCT.Comparisons were made between patients with complete chimerism and mixed chimerism in cerebrospinal fluid.The role of recipient DNA percentage and its changing trend in predicting central nervous relapse were also explored.Analysis was conducted for determining the risk factors of central nervous relapse.And the effectiveness of prophylaxis with intrathecal injection was also examined.Results The incidence of relapse was higher in patients with mixed chimerism (P＜0.001),high percentage of recipient DNA (P＜0.05) and higher mixed chimerism (P＜0.001).Hyperleukocytosis at an initial diagnosis was a risk factor of central nervous relapse.Whether or not intrathecal injection prophylaxis was applied showed no significant difference in relapsing rate.Conclusions Monitoring cerebrospinal fluid chimerism can effectively help predict central nervous relapse among patients of acute leukemia after allo-HSCT.Yet intrathecal injection prophylaxis failed to benefit recipients.
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Objective@#To investigate the risk factors of poor graft function (PGF) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for severe aplastic anemia (SAA) .@*Methods@#Clinical data from 111 SAA patients who received allo-HSCT were analyzed retrospectively. Factors including age, gender, interval to transplantation, the level of serum ferritin before transplantation were analyzed by Cox multivariate regression analysis.@*Results@#Among the 111 patients who underwent allo-HSCT, 16 developed PGF (14.4%) . Multivariate analysis showed donor type (HR=2.656, 95%CI 1.204-5.858, P= 0.016) and the level of serum ferritin before tansplantation (HR=3.170, 95%CI 1.400-7.180, P=0.006) were significant risk factors for PGF.@*Conclusion@#Unrelated donor transplantation and the high level of serum ferritin before transplantation are risk factors for PGF.
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Objective To evaluate the outcome of combination of intensive preconditioning regimen allo-HSCT with imatinib for treatment of Ph chromosome positive acute lymphocyte leukemia (ALL). Methods Between 2009 and 2010, 8 patients diagnosed as Ph+ ALL received allo-HSCT from HLA identical sibling during complete remission. Imatinib was added into the therapies of 5 patients.Seven patients received the intensive preconditioning regimen based on BuCy2, one patient received the regimen of TBI-Cy. A median of 6. 02 × 108/kg mononuclear cells and 3. 14 × 106/kg CD34+ cells were transfused. GVHD prophylaxis included cyclosporine A and methotrexate. Results All patients were well tolerant to the regimen without serious regimen-related toxicity. The median time of ANC≥0. 5 × 109/L was 15. 5 days, and that of PLT≥20 × 109/L was 19 days. Thirty days after allo-HSCT, all patients got donor engraftment successfully. Among 8 cases, 4 cases presented acute GVHD, 2 developed degree Ⅰ , one developed degree Ⅱ , and one developed degree Ⅳ. Seven patients were alive 100 days after allo-HSCT, 3 of whom presented chronic GVHD. At the end of following-up period, 6 patients were alive, among them, 3 patients were alive without relapse; 3 patients relapsed; Two patients died, one from acute GVHD, and one from leukemia relapse. Conclusion Combined intensive preconditioning regimen allo-HSCT with Imatinib was an effective treatment for Ph+ ALL, but the effect of anti-chronic GVHD of imatinib should arouse certain attention.
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Objective To retrospectively analyze and compare the curative outcome of hematopoietic stem cell transplantation (HSCT) from HLA identical siblings vs intensive immunosuppression therapy (IST) for severe aplastic anemia (SAA).Methods From January 2008 to December 2010,41 patients with severe aplastic anemia were treated with related HSCT (n =14) or IST (n =27) which combined antithymocyte globulin (ATG) with cyclosporine-A (CsA) therapy.Results All the patients receiving HSCT reached complete response.Among the patients receiving IST,21 patients could be responsive to the therapy,and 2 patients died.There was significant difference in the response rate between HSCT group and IST group (100 ％ vs 77.8 ％,P＜0.01 ).Conclusion With the improvement of HSCT technology,the curative outcome of HSCT from HLA identical siblings for SAA is much better than IST.
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Objective To analyze the outcome of idarubicin-intensified myeloablastive conditioning regimen in allogeneic peripheral blood stem cell transplantation (allo-PBSCT) in patients with myelodysplastic syndromes (MDS). Methods From August 2004 to July 2009, 12 patients with MDS were treated with alIo-PBSCT following the idarubicin-intensified conditioning regimen. The conditioning regimen was idarubicin (15 mg/m~2), continuous intravenous infusion for 20 h, days-12 to-10; busulfan (0.8 mg/kg), intravenous infusion every 6 h, days-6 to-4; cyclophosphamide (1.8 g/m~2), intravenous infusion every 6 h, days-3 to-2; cyclosporine A combined with short-term methotrexate was used for the prophylaxes of acute graft versus host disease (aGVHD). Results All twelve patients achieved Trilineage engraftment, and were well tolerated to this regimen. Eight patients survived, and the overall survival was 66.7%, disease-free survival (DFS) 58.3%. Two patients relapsed. OS for neither WHO subgroups nor IPSS subgroups had statistically significant difference. Conclusion Allo-PBSCT with idarubicin-inteusified conditioning regimen is an effective treatment with reduction of the relapse rate for MDS patients.
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This study examined the expressions of human serum tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in patients with acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and their clinical significance. The serum TF and TFPI levels were detected by ELISA in 28 allo-HSCT recipients before and after the transplantation and the changes of TF and TFPI levels were dynamically monitored at different phases of the disease. No significant differences in the serum TF and TFPI levels were found in allo-HSCT recipients in the absence of aGVHD or with grade I aGVHD before and after the transplantation. The levels of serum TF and TFPI were substantially increased in the patients with gradeII aGVHD at the peak of aGVHD (P0.05) and the TF level was lowered but still higher than the baseline level (P<0.05). It was concluded that the levels of serum TF and TFPI were increased significantly in the patients with grade II-IV aGVHD after allo-HSCT and decreased markedly after the treatment. Monitoring the levels of serum TF and TFPI in the patients with allo-HSCT is important to predict the occurrence, outcome and prognosis of aGVHD.
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BACKGROUND: Allogeneic hematopoietic stem cell transplantation is recognized as the only method of curing chronic myelocytic leukemia (CML). Lmatinib mesylate (STI571) is a competitive inhibitor of the bcr-abl tyrosine kinase, as a represent of synthetic gene-targeting drug in recently, which has been used more and more on the Philadelphia chromosome positive CML patients.OBJECTIVE: To compare the efficacy and safety of STI571 to related allogenic hematopoietic stem cell transplantation in the treatment of CML patients.DESIGN, TIME AND SETTING: A controlled observation between ST1571 treated group and transplantation group was performed in the Department of Hematology, Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology between April 2002 and October 2006. PARTICIPANTS: All 90 patients with CML in the chronic phase were selected from Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, and they were diagnosis based on the examinations of bone marrow morphologic, cytogenetics and/or molecular genetics. METHODS: All 90 patients with CML in the chronic phase were divided into two groups. 67 patients received oral STI571 (400 mg/day) in succession at the beginning time from April 2002 to June 2006, and the observation ended until October 2006, Blood routine will be done weekly, and bone marrow morphologic and cytogenetic examination would be done every three months. Other 23 patients selected from Union Hospital from March 1999 to April 2006 accepted allo-HSCT, with BuCy2 or modified BuCy2 as conditioning regimens. Cyclosporin A combining with short-term MTX were used in all patients for prophylaxis of graft-versus-host disease (GVHD). MAIN OUTCOME MEASURES: Hematology responses, eytogenetic response and two years survival in two groups were observed. RESULTS: Complete cytogenetic response was achieved in 60% and 100% of the patient treated with STI571 and transplantation respectively (P < 0.01). But two years survival of ST1571 and transplantation were 83.33% and 77.03% respectively, and no difference was found between the two groups (P > 0.05). No one died or discontinued therapy for adverse effects, and 4 out of 67 (5.97%) had grade 3 or 4 thrombocytopenia and/or leucopenia in the ST1571 group. Moreover, in transplantation group, 7 patients (30.4%) developed grade 2 to 4 acute GVHD, but 4 died of failed treatment. CONCLUTION: Compared with transplantation, patients treated with ST1571 achieved low complete cytogenetic responses and the treatment-related complications were mild and manageable or no need for treatment.
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BACKGROUND: BuCy2 composed of large-dose oral busulfanum and cyclophosphamide has been one of the main conditioning regimens before transplantation, but oral busulfanum can result in many side effects.OBJECTIVE: To evaluate the efficacy and safety of the conditioning regimen with intravenous busulfanum (Ⅳ Bu) in hematopoietic stem cell transplantation (HSCT) for malignant hematopathy.DESIGN: Case observation.SETTING: Department of Hematology, Union Hospital,Tongji Medical College, Huazhong University of Science and Technology.PARTICIPANTS: A total of 13 patients with chronic myelogenous leukemia (CML) and 6 patients with acute leukemia,who received allogeneic HSCT with the conditioning therapy of modified BuCy2, were enrolled at Institute of Hematopathy, Union Hospital, Huazhong University of Science and Technology from May to December 2006. There were 12 males and 7 females aged 14-50 years with an average of 33 years, and there were 9 cases of related transplantation and 10 cases of unrelated transplantation. Hematopoietic stem cells (HSCs) were harvested from peripheral blood of 18 subjects and bone marrow of 1 subject. All patients and their family members signed the informed consent.METHODS: All patients were treated with allogeneic HSCT with the conditioning therapy of intravenous BuCy2.All patients received the modified combination of busulfanum and cyclophosphamide that was commonly utilized currently.Hydroxycarbamide 40 mg/kg was orally taken ten days before transplantation. Arabinosylcytosin (Ara-C) 2 g/m2 was injected via vein nine days before transplantation. Busulfanum ampule 0.8 mg/kg (equal to 1 mg/kg oral administration)was given by central venous cannula eight, seven and six days before transplantation. The injection was performed over 2 hours controlled by infusion pump, once every 6 hours, totally 12 times. Busulfanum was diluted by saline or 5% glucose to about 0.5 g/L (about 10 times) before Ⅳ Bu. Cyclophosphamide 1.8 g/m2 was intravenously injected every day from five and four days before transplantation. Methyl-CCNU 250 mg/m2 was taken orally three days before transplantation. Occurrence of hepatic vano-occlusive disease (HVOD) and its side effects were determined. Follow-up was performed at month 6.5 after operation to observe disease recurrence and patient survival.MAIN OUTCOME MEASURES: Occurrence and side effects of HVOD 100 days after transplantation, and results of follow-up.RESULTS: Totally 19 patients were involved in the result analysis. In 13 days after transplantation, blood conversion,chromosome karyotype and DNA polymorphism tests verified that reconstruction of hematopoietic function was obtained and two patients got recurrence, of which one patient got complete remission after receiving fludarabine plus cytarabine plus granulocyte colony-stimulating factor (G-CSF) and HSCs from peripheral blood. DNA polymorhism test verified that re-engraftment was obtained. Another patient received chemotherapy. Other patients lived well.
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To investigate the therapeutic effects and associated complications of allogeneic peripheral blood stem cell transplantation (allo-PBSCT), 40 patients with various malignant hematopoietic diseases received allo-PBSCT. The preparative regimens were based on BUCY2 or modified BUCY2. The acute graft versus host disease (aGVHD) was prevented by cyclosporin A and shortterm MTX regimen in all patients. Two patients from donors with one fully mismatched HLA on DRB1 locus and 4 from unrelated donor also administered Zenapox (CD25 MAb) at dosage of 1 mg/kg every day on the day before transplantation and day 4 after transplantation. These 6 patients were also treated with mycophenolate mofetil (MMF). Transfusion of the donor cells: The median of the transfused nucleated cells was 5.38 × 108/kg and that of the CD34+ cells was 7.8 × 106/kg respectively. All the patients gained hematopoietic reconstruction except one who died of infection before engraftment. Seven patients got Ⅱ°-Ε° aGVHD and the incidence was 17.5 %. Fourteen patients got cGVHD and the incidence was 53.8 % in the patients who survived over 6 months.Twenty-eight patients had fever or other characteristics of infection. The median follow-up time was 13.8 months. The incidence of transplantation related mortality (TRM) was 17.5 % and 2 patients relapsed (5.0 %). It was concluded that allo-PBSCT can reconstruct hematopoiesis quickly and is a favorable therapeutic method for leukemia.
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To investigate the therapeutic effects and associated complications of allogeneic peripheral blood stem cell transplantation (allo-PBSCT). 40 patients with various malignant hematopoietic diseases received allo-PBSCT. The preparative regimens were based on BUCY2 or modified BUCY2. The acute graft-versus host disease (aGVHD) was prevented by cyclosporin A and short-term MTX regimen in all patients. Two patients from donors with one fully mismatched HLA on DRB1 locus and 4 from unrelated donor also administered Zenapox (CD25 MAb) at dosage of 1 mg/kg every day on the day before transplantation and day 4 after transplantation. These 6 patients were also treated with mycophenolate mofetil (MMF). Transfusion of the donor cells: The median of the transfused nucleated cells was 5.38 x 10(8)/kg and that of the CD34+ cells was 7.8 x 10(6)/kg respectively. All the patients gained hematopoietic reconstruction except one who died of infection before engraftment. Seven patients got II degrees-IV degrees aGVHI) and the incidence was 17.5%. Fourteen patients got cGVHD and the incidence was 53.8% in the patients who survived over 6 months. Twenty-eight patients had fever or other characteristics of infection. The median follow-up time was 13.8 months. The incidence of transplantation related mortality (TRM) was 17.5% and 2 patients relapsed (5.0%). It was concluded that allo-PBSCT can reconstruct hematopoiesis quickly and is a favorable therapeutic method for leukemia.
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China/epidemiologia , Ciclosporina/uso terapêutico , Seguimentos , Doença Enxerto-Hospedeiro/prevenção & controle , Leucemia/terapia , Leucemia Linfoide/terapia , Leucemia Mieloide Aguda/terapia , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Sepse/epidemiologia , Sepse/etiologiaRESUMO
In order to study the role of annexin II, a recombinant expression vector, pZeoSV2(+) ANN II, containing the annexin II cDNA, was developed. The 1.1-kb-length annexin II cDNA was inserted into a expression vector, PZeoSV(+) and transfected into HL-60 cells which had low baseline expression of Ann- II. pZeoSV(+) ANN II was analyzed by restriction mapping and the Ann- II sequence identified. The ability of the transfected cells, non-transfected and mock-transfected cells to stimulate t-PA-depend plasminogen activation was compared. The results showed that HL-60 with pZeoSV(+) ANN II transfection could significantly increase the plasminogen activation (8.9 +/- 1.2 U) in vitro with the difference being significant as compared with non-transfected (1.5 +/- 0.4 U) and mock-transfected cells (4.2 +/- 0.9 U), respectively. Antiannexin II oligonucleotides significantly inhibited the binding ability of t-PA and plasminogen to annexin II, and obviously reduced the plasminogen activation in vitro. The above findings showed human umbilical vein endothelial cells (HUVECs) treated with sense or missense oligonucleotides indicated no significant change in binding of t-PA and PLG. Treatment of HUVECs with antiannexin II oligonucleotides could significantly reduce the plasminogen activation by 2.4 +/- 0.3 U as compared with sense oligonucleotide group in binding of t-PA and PLG. These results, therefore, suggest that Ann- II can bind plasminogen and participate in the stimulation of t-PA-dependent activation of plasminogen, and that interference with Ann-II mRNA by antisense oligonucleotide may be a new strategy for the therapy of bleeding in patients with hyperfibrinolysis.