RESUMO
This retrospective study analysed 106 acute myeloid leukaemia (AML) patients undergoing autologous haematopoietic stem cell transplantation (ASCT) to assess the impact of multiple small-dose infusions of granulocyte-colony-stimulating factor (G-CSF)-mobilized haploidentical lymphocytes as post-ASCT maintenance therapy. Among them, 50 patients received lymphocyte maintenance therapy, 21 received alternative maintenance therapy, and 35 received no maintenance therapy. Patients receiving lymphocyte maintenance therapy demonstrated significantly higher overall survival (OS) and disease-free survival (DFS) compared to those without maintenance therapy, with 4-year OS and DFS rates notably elevated. While there were no significant differences in recurrence rates among the three groups, lymphocyte maintenance therapy showcased particular benefits for intermediate-risk AML patients, yielding significantly higher OS and DFS rates and lower relapse rates compared to alternative maintenance therapy and no maintenance therapy. The study suggests that multiple small-dose infusions of G-CSF-mobilized haploidentical lymphocytes may offer promising outcomes for AML patients after ASCT, particularly for those classified as intermediate-risk. These findings underscore the potential efficacy of lymphocyte maintenance therapy in reducing disease relapse and improving long-term prognosis in this patient population.
Assuntos
Fator Estimulador de Colônias de Granulócitos , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Transfusão de Linfócitos , Humanos , Leucemia Mieloide Aguda/terapia , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Transplante de Células-Tronco Hematopoéticas/métodos , Estudos Retrospectivos , Transplante Autólogo , Adolescente , Mobilização de Células-Tronco Hematopoéticas/métodos , Adulto Jovem , Idoso , Transplante Haploidêntico/métodosRESUMO
To evaluate the co-transplantation efficacy of umbilical cord mesenchymal stem cells (UC-MSCs) and peripheral blood stem cells (PBSCs) as a novel approach for refractory or relapsed severe aplastic anemia (R/R SAA) in children and adolescents, thirty-two children and adolescents diagnosed with R/R SAA underwent a retrospective chart review. The patients were categorized into two groups based on the source of PBSCs: the matched sibling donor (MSD) group and the unrelated donor (UD) group. No adverse events related to UC-MSC infusion occurred in any of the patients. The median time for neutrophil engraftment was 13 days (range: 10-23 days), and for platelets, it was 15 days (range: 11-28 days). Acute GVHD of Grade I-II and moderate chronic GVHD were observed in 21.8 and 12.5% of cases, respectively. No statistically significant differences were found between the MSD and UD groups in terms of engraftment, GVHD, and complications, including infection and hemorrhagic cystitis. The median follow-up time was 38.6 months (range: 1.4-140.8 months). As of October 31, 2021, five patients had succumbed, while 27 (84.4%) survived. The 5-year OS rate showed no statistically significant difference between the MSD and UD groups (84.8 ± 10.0 vs. 82.4 ± 9.2%, p = 0.674). In conclusion, the application of UC-MSCs in the treatment of R/R SAA in PBSC transplantation is reliable and safe, they had no graft rejection, low incidence of severe GVHD which may have been contributed by the co-infusion of MSC.
Assuntos
Anemia Aplástica , Transplante de Células-Tronco Mesenquimais , Humanos , Anemia Aplástica/terapia , Anemia Aplástica/mortalidade , Criança , Adolescente , Masculino , Feminino , Pré-Escolar , Transplante de Células-Tronco Mesenquimais/métodos , Estudos Retrospectivos , Transplante de Células-Tronco de Sangue Periférico/métodos , Recidiva , Doença Enxerto-Hospedeiro , Lactente , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodosRESUMO
Anti-thymocyte globulin (ATG) or post-transplant cyclophosphamide (PTCy)-based regimens are widely used for graft-versus-host disease (GVHD) prophylaxis in haploidentical haematopoietic stem cell transplantation (haplo-HSCT). To improve the effectiveness of GVHD prophylaxis in haploidentical peripheral blood stem cell transplantation (haplo-PBSCT), we conducted a multicentre, randomized clinical trial to determine the efficacy of reduced-dose PTCy (40 mg/kg/d on days 3 and 4) combined with low-dose post-transplant ATG (2.5 mg/kg on day 8)-based GVHD prophylaxis (reduced-dose PTCy/ATG) with fludarabine-busulfan-cytarabine (FBA) conditioning for patients with haematological malignancies. From 2018 to 2022, 122 patients from four institutions were randomly assigned 1:1 to either a reduced-dose PTCy/ATG or a standard-dose ATG group ('Beijing Protocol', ATG: 10 mg/kg). All patients achieved myeloid engraftment. Cumulative incidences of grade II-IV (11.5% vs 39.3%, p = 0.001) and grade III-IV (6.6% vs 24.6%, p = 0.014) acute GVHD at day 100 were significantly reduced in the reduced-dose PTCy/ATG group. Furthermore, two-year overall survival, disease-free survival and GVHD-free/relapse-free survival were significantly improved in the reduced-dose PTCy/ATG group (75.4% vs 54.1%, p = 0.021; 72.7% vs 55.0%, p = 0.044; 61.3% vs 42.3%, p = 0.022 respectively). Our results demonstrate that the addition of low-dose ATG to reduced-dose PTCy with FBA conditioning is a promising strategy in haplo-PBSCT.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Transplante de Células-Tronco de Sangue Periférico , Humanos , Soro Antilinfocitário/uso terapêutico , Bussulfano/uso terapêutico , Citarabina/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Ciclofosfamida/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Doença Enxerto-Hospedeiro/tratamento farmacológico , Condicionamento Pré-Transplante/métodos , Estudos RetrospectivosRESUMO
We retrospectively investigated outcomes of haploidentical donor (HID) transplant for adults with standard-risk acute lymphoblastic leukaemia (ALL) in first complete remission (CR1) compared with human leucocyte antigen (HLA)-matched sibling donor (MSD) and HLA-matched unrelated donor (MUD) transplants. A total of 348 adult patients were enrolled, including 127 HID, 144 MSD and 77 MUD recipients. The cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) was 39·5%, 24·0% and 40·3% for HID, MSD and MUD, respectively (P = 0·020). However, there was no difference in grade III-IV aGVHD (11·4%, 7·7%, 13·5%, respectively, P = 0·468). The 5-year cumulative transplant-related mortality was 16·4%, 11·6% and 19·6% (P = 0·162), the 5-year relapse rate post-transplantation was 14·8%, 21·1% and 16·7% (P = 0·231), the 5-year overall survival was 70·1%, 73·7% and 69·8% (P = 0·525), and the 5-year disease-free survival was 68·7%, 67·3% and 63·7%, respectively (P = 0·606). Furthermore, the 3-year GVHD-free, relapse-free survival was not different (50·8%, 54·9% and 52·2%, respectively, P = 0·847). Our results indicate that the outcomes of HID transplants are equivalent to those of MSD and MUD, and that HID transplantation is a valid alternative for standard-risk adults with ALL in CR1 who lack matched donors.
Assuntos
Haplótipos , Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Irmãos , Doadores não Relacionados , Adolescente , Adulto , Terapia Combinada , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Recidiva , Indução de Remissão , Estudos Retrospectivos , Análise de Sobrevida , Condicionamento Pré-Transplante , Transplante Homólogo , Resultado do Tratamento , Adulto JovemRESUMO
Relapse is the major cause of treatment failure after allogeneic stem-cell transplantation (AHSCT) for patients with myelodysplastic syndrome/myeloproliferative syndrome neoplasms (MDS/MPN). We evaluated the impact of molecular mutations on outcome and the value of molecular monitoring post-transplantation. We screened 45 patients with chronic myelomonocytic leukemia (n = 39 patients, including seven with transformed-acute myeloid leukemia), MDS/MPN unclassifiable (n = 5), and atypical BCR-ABL1-negative CML (n = 1) for mutations in ASXL1, CBL, NRAS, and TET2 genes by molecular genetics including a sensitive next-generation sequencing (NGS) technique. In 36 patients, sufficient DNA was available for molecular analyses. In particular, TET2 and CBL mutations were screened applying amplicon deep sequencing. In 89% of cases, at least one mutation could be detected: ASXL1: n = 18 (50%); CBL: n = 7 (19%); TET2: n = 15 (42%); and NRAS: n = 11 (32%). Survival after AHSCT at 5 yr was 46% (95% CI 28-64%) and was not influenced by any mutation. After a median of 6 months after AHSCT in 33% of the patients, one of the molecular markers was still detectable, resulting in a higher incidence of relapse than in patients with undetectable mutations (50% vs. 15%, P = 0.04). In conclusion, pretransplant molecular mutation analysis can help to detect biomarkers in patients with MPN/MDS, which may be subsequently used as minimal residual disease markers after AHSCT.
Assuntos
Doenças Mieloproliferativas-Mielodisplásicas/terapia , Transplante de Células-Tronco , Transplante Homólogo , Adulto , Idoso , Biomarcadores Tumorais/genética , Análise Mutacional de DNA , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Valor Preditivo dos Testes , Recidiva , Fatores de Tempo , Adulto JovemRESUMO
OBJECTIVES: This study aims to investigate the risk factors for carbapenem-resistant Pseudomonas aeruginosa bloodstream infection (CRPA-BSI) and identify predictors of outcomes among patients with P. aeruginosa bloodstream infection (PA-BSI). METHODS: A retrospective cohort study was conducted on patients with PA-BSI at Henan Cancer Hospital from 2013 to 2022. RESULTS: Among the 503 incidences analysed, 15.1% of them were CRPA strains. Age, ANC < 100/mmc, receiving antifungal prophylaxis, exposure to carbapenems within the previous 90 days to onset of BSI, and allogeneic HSCT (allo-HSCT) were associated with the development of CRPA-BSI. CRPA-BSI patients experienced significantly higher 28-day mortality rates compared to those with carbapenem-susceptible P. aeruginosa bloodstream infection. Multivariate logistic regression analysis identified age at BSI, active stage of haematological disease, procalcitonin levels, prior corticosteroid treatment, isolation of CRPA, and septic shock as independent predictors of 28-day mortality. CONCLUSIONS: Risk factors for CRPA-BSI include age, ANC < 100/mmc, antifungal prophylaxis, exposure to carbapenems, and allo-HSCT. Additionally, age at BSI, active haematological disease, procalcitonin levels, prior corticosteroid treatment, CRPA isolation, and septic shock contribute to increased mortality rates among patients with PA-BSI.
Assuntos
Antibacterianos , Bacteriemia , Carbapenêmicos , Infecções por Pseudomonas , Pseudomonas aeruginosa , Humanos , Estudos Retrospectivos , Carbapenêmicos/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Infecções por Pseudomonas/mortalidade , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/epidemiologia , Fatores de Risco , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Bacteriemia/mortalidade , Bacteriemia/microbiologia , Bacteriemia/epidemiologia , Idoso , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , China/epidemiologia , Adulto Jovem , HematologiaRESUMO
Objective: To analyze the clinical characteristics and prognostic risk factors of carbapenem-resistant Pseudomonas aeruginosa (CRPA) bloodstream infections in patients with hematologic malignancies. Methods: Medical records and drug susceptibility data of patients with hematologic malignancies complicated by CRPA bloodstream infections admitted to the Cancer Hospital of Zhengzhou University between January 1, 2018, and December 31, 2022, were retrospectively analyzed. Results: A total of 64 patients were included in the study, with a mortality rate of 37.5% (24/64) at 28 days after the occurrence of CRPA bloodstream infection. In Cox regression analysis, an absolute neutrophil count <0.5×109/L at discharge (HR 0.039, 95% CI 0.006 ~ 0.258, p=0.001), admission to the intensive care unit (HR 7.546, 95% CI 1.345 ~ 42.338, p= 0.022), and a higher Pitt bacteremia score (HR 0.207, 95% CI 0.046 ~ 0.939, p = 0.041) were independent risk factors associated with 28-day mortality. Survival analysis showed that patients receiving ceftazidime-avibactam-based (HR 0.368, 95% CI 0.107~ 1.268, p = 0.023) or polymyxin B (HR 2.561, 95% CI 0.721 ~ 9.101, p = 0.015) therapy had a higher survival rate. Conclusion: Patients with hematologic neoplasms had high mortality from CRPA bloodstream infections, and admission to the intensive care unit, higher Pitt bacteremia score (PBS) scores, granulocyte deficiency, and granulocyte deficiency at discharge were independently associated with higher mortality. Early anti-infective treatment with ceftazidime-avibactam or polymyxin B may improve the clinical prognosis of patients.
RESUMO
Clinical outcomes of the transplantation strategy combined with a haploidentical stem cell graft and an unrelated umbilical cord blood unit (haplo-cord HSCT) with low-dose antithymocyte globulin (ATG) as graft-versus-host disease (GVHD) prophylaxis for the treatment of acute leukemia remains unclear. This study aimed to explore the clinical outcomes of haplo-cord HSCT in acute leukemia patients with the GVHD prevention strategy of 8 mg/kg ATG compared with haploidentical transplantation with 10 mg/kg ATG. A total of 130 patients with acute leukemia who underwent allogeneic HSCT between January 2016 and December 2020 were included in this study, including 70 patients who received haploidentical stem cell grafts and unrelated umbilical cord blood units (haplo-cord HSCT) with 8 mg/kg ATG (haplo-cord-ATG8 group) and haploidentical HSCT with 10 mg/kg ATG (haplo-ATG10 group) in 60 patients. Clinical data were collected and analyzed retrospectively. Patients in the haplo-cord-ATG8 group were significantly older compared with the haplo-ATG10 group (P = .000). Haplo-cord HSCT with reduced ATG to 8 mg/kg results in more rapid neutrophil recovery (P = .036). No between-group differences were observed in platelet recovery or the incidences of Epstein-Barr virus viremia, bloodstream infection, or hemorrhagic cystitis. The rate of grade II-IV acute GVHD by day 100 post-transplantation was higher in the haplo-ATG10 group (27.16% versus 11.48%; P = .033), as was the rate of chronic GVHD at 1 year (14.60% versus 3.36%; P = .048). The rate of cytomegalovirus reaction was higher in the haplo-ATG10 group (48.31% versus 26.30%; P = .022). With a median follow-up of 27.4 months for the haplo-cord-ATG8 group and 27.5 months for the haplo-ATG10 group, overall survival (OS) at 2 years was 79.4% versus 62.8% (P = .005), event-free survival (EFS) was 76.3% versus 55.9% (P = .001), the cumulative incidence of relapse was 10.11% versus 25.97% (P = .164), and nonrelapse mortality (NRM) was 14.33% versus 24.43% (P = .0040). Multivariate analysis identified Center for International Blood and Marrow Transplant Research Disease Risk Index was the sole significant predictor of relapse, NRM, OS, and EFS. Haplo-cord HSCT supported by cord blood with 8 mg/kg ATG as GVHD prophylaxis results in better outcomes compared with haplo-HSCT with 10 mg/kg ATG.
Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Infecções por Vírus Epstein-Barr , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Humanos , Soro Antilinfocitário/uso terapêutico , Transplante Haploidêntico , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Infecções por Vírus Epstein-Barr/epidemiologia , Infecções por Vírus Epstein-Barr/etiologia , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Estudos Retrospectivos , Herpesvirus Humano 4 , Doença Enxerto-Hospedeiro/prevenção & controle , Doença Enxerto-Hospedeiro/tratamento farmacológico , Leucemia Mieloide Aguda/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Doença Aguda , Recidiva , Doença CrônicaRESUMO
Graft-versus-host disease (GVHD) is caused by a pathologic and destructive response of the organism as a result of the interaction between donor immunocompetent T lymphocytes and the recipient tisular antigens1. Graft-versus-host disease is considered a serious complication of hematopoietic stem cell transplantation. The skin, oral cavity and lungs are commonly affected organs. Among these complications bronchiolitis obliterans syndrome is a serious complication, which even can be life-threatening. Therefore, this research aims to do a clinical observation on the safety and efficacy of umbilical cord mesenchymal stem cells in the treatment of bronchiolitis obliterans after allogeneic haematopoietic stem cell transplantation. Fifteen patients were included in this study, who received allogeneic hematopoietic stem cell transplantation. Among these patients, both of them were treated with azithromycin, montelukast, glucocorticoid and pirfenidone. Two of them did not receive second line anti-rejection treatment due to economic reasons, and three of them were treated with mesenchymal stem cells. These bronchiolitis obliterans syndrome-related symptoms such as shortness of breath, chest tightness and wheezing have improved. Two of them died due to bronchiolitis obliterans syndrome related complications such as respiratory failure. Two of them not only improve the symptoms but also increased the FEV1/FVC, who were treated with mesenchymal stem cells. The comprehensive treatment regimen containing imatinib and ruxolitinib is safe and effective and mesenchymal stem cell is a promising treatment option to improve the prognosis of post-HSCT BOS.
RESUMO
Background: Whether autologous hematopoietic stem cell transplantation (ASCT) improves the survival of patients with peripheral T-cell lymphoma (PTCL) remains controversial. Some studies have demonstrated that the efficacy of ASCT is superior in patients with complete remission (CR), whereas patients with partial remission (PR) remain vulnerable to relapse after ASCT, resulting in decreased survival rates. Maintenance therapy after chemotherapy may reduce the relapse rate of PTCL and improve survival; however, the role of maintenance therapy after ASCT in PTCL remains unclear. In this study, we aimed to analyze the efficacy of ASCT and post-transplant maintenance therapy in PTCL. Methods: We retrospectively analyzed the clinical data of 69 patients with PTCL who underwent ASCT at our center between November 2001 and November 2021. According to the patients' intention, thirty patients received post-transplant maintenance treatment, whereas 39 did not. The overall survival (OS) and progression-free survival (PFS) between the groups were compared using the log-rank test. Results: At a median follow-up of 36 months, the entire cohort's 3-year OS and PFS were 67.8% and 53.0%, respectively. The 3-year OS and PFS of patients with CR1, CR2, and PR were 85.3% and 65.4%, 80.0% and 60.0%, and 38.4% and 32.0%, respectively (OS: P=0.001; PFS: P=0.003). The relapse rates between the groups with or without maintenance therapy were 26.7% vs. 52.2%, the 3-year OS was 86.0% vs. 54.2% (P=0.004), and the 3-year PFS was 73.3% vs. 37.5% (P=0.004). Further analysis revealed that the efficacy of maintenance therapy was not significant in patients with CR1 and CR2, whereas patients with PR benefited from maintenance therapy. The relapse rate of patients with PR who received or did not receive maintenance therapy was 33.3% vs. 78.7%, 3-year OS was 66.7% vs. 21.9% (P=0.007), and 3-year PFS was 66.7% vs. 12.5% (P=0.004). Conclusions: Patients with CR in PTCL benefit from ASCT, and post-transplant maintenance therapy reduces the relapse rate and significantly improves OS and PFS in patients with PR.
RESUMO
The most widely used regimens of graft-versus-host disease (GVHD) prophylaxis in HLA-matched unrelated donor peripheral blood stem cell transplantation (MUD-PBSCT) are based on anti-thymocyte globulin (ATG) or post-transplant cyclophosphamide (PTCy). To improve the efficiency of GVHD prophylaxis, a novel regimen, composed of low-dose PTCy (20 mg/kg on day +3 and +4) and low-dose ATG (6 mg/kg), was evaluted in patients with hematological malignancies ungoing 10/10 HLA MUD-PBSCT in first remission (CR1). In our prospective, multicenter study, 104 patients were randomly assigned one-to-one to low-dose PTCy-ATG (n = 53) or standard-dose ATG (10 mg/kg, n = 51). Both the cumulative incidences (CIs) of grade II-IV acute GVHD (aGVHD) and chronic GVHD (cGVHD) at 2 years in low-dose PTCy-ATG cohort were significantly reduced (24.5% vs. 47.1%; P = 0.017; 14.1% vs. 33.3%; P = 0.013). The CI of non-relapse-mortality (NRM) was much lower (13.2% vs. 34.5%; P = 0.049) and GVHD-free, relapse-free survival (GRFS) was significantly improved at 2 years in low-dose PTCy-ATG arm (67.3% vs 42.3%; P = 0.032). The low-dose PTCy-ATG based GVHD prophylaxis is a promising strategy for patients in CR1 after 10/10 HLA MUD-PBSCT.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Transplante de Células-Tronco de Sangue Periférico , Células-Tronco de Sangue Periférico , Soro Antilinfocitário/uso terapêutico , Ciclofosfamida/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Estudos Prospectivos , Estudos Retrospectivos , Doadores não RelacionadosRESUMO
Posttransplant cyclophosphamide (PTCy) as graft-versus-host disease (GVHD) prophylaxis is an effective strategie for patients receiving matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) and haploidentical HSCT (haplo-HSCT). We evaluated the effectiveness and safety of reduced-dose cyclophosphamide, 20 mg/kg for 13 patients in MSD-HSCT cohort and 25 mg/kg for 22 patients in haplo-HSCT cohort, on days + 3, + 4 combined with cotransplantation of peripheral blood stem cells (PBSCs) and human umbilical cord-derived mesenchymal stem cells (UC-MSCs) for severe aplastic anemia (SAA). In MSD-PTCy cohort, the times to neutrophil and platelet engraftment were significantly shorter than those in the MSD-control cohort (P < 0.05). The cumulative incidence of acute GVHD (aGVHD) at day + 100 (15.4%) was lower than that in the MSD-control cohort (P = 0.050). No patient developed chronic GVHD (cGVHD). The 1-year overall survival (OS) and event-free survival (EFS) rates were 100% and 92.3%. In haplo-PTCy cohort, the times to neutrophil and platelet engraftment were significantly shorter than those in the haplo-control cohort (P < 0.05). The cumulative incidences of aGVHD at day + 100 and 1-year cGVHD were 31.8% and 18.2%, and the 1-year OS and EFS rates were 81.8% and 66.9%. Reduced-dose PTCy and cotransplantation of PBSCs and UC-MSCs is an acceptable alternative to patients with SAA.
Assuntos
Anemia Aplástica/terapia , Ciclofosfamida/administração & dosagem , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Mesenquimais/métodos , Transplante de Células-Tronco de Sangue Periférico/métodos , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Anemia Aplástica/mortalidade , Criança , Ciclofosfamida/efeitos adversos , Estudos de Viabilidade , Feminino , Doença Enxerto-Hospedeiro/mortalidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Transplante de Células-Tronco Mesenquimais/mortalidade , Uso Off-Label , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Transplante de Células-Tronco de Sangue Periférico/mortalidade , Irmãos , Doadores de Tecidos , Transplante Haploidêntico/métodos , Resultado do Tratamento , Cordão Umbilical/citologia , Adulto JovemAssuntos
Azacitidina , Bussulfano , Ciclofosfamida , Decitabina , Idarubicina , Síndromes Mielodisplásicas , Humanos , Síndromes Mielodisplásicas/tratamento farmacológico , Bussulfano/uso terapêutico , Bussulfano/administração & dosagem , Ciclofosfamida/uso terapêutico , Ciclofosfamida/administração & dosagem , Decitabina/uso terapêutico , Decitabina/administração & dosagem , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Azacitidina/uso terapêutico , Azacitidina/administração & dosagem , Estudos Prospectivos , Idarubicina/uso terapêutico , Idarubicina/administração & dosagem , Adulto Jovem , Idoso , Condicionamento Pré-Transplante/métodos , AdolescenteRESUMO
OBJECTIVE: To analyze the clinical efficacy and possible influencing factors of autologous hematopoietic Stem cell transplantation (auto-HSCT) in the treatment of patients with multiple myeloma (MM). METHODS: Clinical data of 40 MM patients received auto-HSCT in the Department of Hematology of Henan Cancer Hospital from September 2010 to November 2017 were retrospectively analyzed, the clinical curative efficiency was summarized and the related factors were analyzed. RESULTS: The curative efficiency of the patients before transplantation was 9(22.5%) with complete remission(CR), 5(12.5%) with very good partial remission(VGPR), 26(65%) with partial remission(PR), respectively, one of them was PR after 3 recurrences. The curative efficiency after transplantation was 22(55%) with complete remission(CR), 12(30%) with very good partial remission(VGPR), 6(15%) with partial remission(PR), respectively. And 2 cases were CR after double transplantation. Median follow-up time was 28.4 (3.1 to 88) months,15 cases presented disease progression, 7 cases were dead, 3-year estimated progression-free survival(PFS) and overall survival(OS) rate were 45.1% and 82% respectively. Unvariate analysis showed that the OS was affected by ISS stage (P<0.05), CR and VGPR (P<0.05) after transplantation; PFS was affected by ISS stage (P<0.01), before transplantation induction therapy (27 cases with bortezomizomi or thalidomide) (P<0.05), disease risk stratification (6 cases in high risk group) (P<0.05) , CR and VGPR (P<0.05) before transplantation, CR and VGPR (P<0.01) after transplantation. Cox multivariate regression analysis showed that the independent prognostic factors for OS were ISS stage, CR and VGPR after transplantation; the independent prognostic factors for PFS were the CR, VGPR, ISS stage after transplantation and induction therapy before transplant. CONCLUSION: Auto-HSCT can improve the clinical efficacy and survival rate of MM patients; ISS stage, CR and VGPR after transplantation are independent prognostic factors for OS and PFS, and induction therapy before transplantation is also an independent prognostic factor for PFS.
Assuntos
Mieloma Múltiplo , Recidiva Local de Neoplasia , Protocolos de Quimioterapia Combinada Antineoplásica , Intervalo Livre de Doença , Transplante de Células-Tronco Hematopoéticas , Humanos , Mieloma Múltiplo/terapia , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Transplante AutólogoRESUMO
OBJECTIVE: To study T-cell reconstitution by the assessment of T-cell receptor excision circle (TRECs) and T-cell receptor clonal repertoire after HLA-matched sibling bone marrow transplantation (MSD-BMT) in leukemia patients and try to reveal the rule of T-cells repopulation in MSD-BMT. METHODS: Real-time quantitative PCR detection of TRECs was carried out in the DNA of peripheral blood mononuclear cells from 23 leukemia patients who underwent MSD-BMT. The content of TRECs in 70 normal donor individuals was also detected to determine the normal range of TRECs in healthy subjects. Among them, 10 patients received RT-PCR to amplify 24 subfamily genes of T-cell receptor B variable (TCRBV) and five normal donors served as control. The PCR products were further analyzed with genescan to evaluate the clonality of BV subfamily and calculate the usage rate of BV families. RESULTS: The mean value of TRECs in normal donors was (3351.1 +/- 3711.1) copies/10(5) cells. There was an inverse correlation between the value of TRECs and the age of healthy subjects. Before transplantation, all the patients were detected for the number of TRECs, the mean TRECs number was (307.9 +/- 433.3) copies/10(5) cells and it was far lower than that of healthy subjects. From one month to five months after bone marrow transplantative (BMT), the TRECs levels were low and in some patients they even could not be detected. Six months later, TRECs levels increased obviously and maintained that high nearly one year. 24 months after BMT, the number of TRECs increased and reached the pretransplantation status. One patient was detected 2 m and 3 m after transplantation and found that there was a tendency of additional use of BV families and an increase of the expression of CDR3 polymorphism. 2-15 months after transplantation, in ten of the patients, there were 7-16 BV subfamilies expressing and in more than 48% the expression was polyclinic. Monoclones and oligoclones existed in 24 BV subfamilies. CONCLUSIONS: At an early stage after BMT, the number of TRECs was low and remained so for a long time. TCRBV CDR3 repertoire showed certain BV families expressing. 6 months after BMT, thymus produced certain number of naive T cells and TCRBV CDR3 repertoire showed additional use of BV families and increased expression of polymorphism.
Assuntos
Transplante de Medula Óssea/métodos , Leucemia/cirurgia , Complexo Receptor-CD3 de Antígeno de Linfócitos T/genética , Linfócitos T/imunologia , Adolescente , Adulto , Transplante de Medula Óssea/imunologia , Feminino , Teste de Histocompatibilidade , Humanos , Leucemia/genética , Leucemia/imunologia , Doadores Vivos , Depleção Linfocítica , Masculino , Pessoa de Meia-Idade , Complexo Receptor-CD3 de Antígeno de Linfócitos T/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase Reversa , IrmãosRESUMO
OBJECTIVE: To predict T-cell immune reconstitution by investigating T cell receptor excision circles (TREC) and T-cell receptor beta-chain variable region (TCRBV) clonal repertoire in leukemia patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: Real-time quantitative PCR was used to detect the TREC in 43 leukemia patients undergoing matched sibling donor bone marrow transplantation (MSD BMT), matched unrelated donor (MUD) BMT, or haploidentical-stem cell transplantation (HID-SCT), and in 70 normal individuals. RT-PCR was used to amplify 24 subfamily genes of T-cell receptor beta-chain variable region (TCRBV) in 24 of the 43 patients and 5 normal donors as control. The PCR products were further analyzed by genescane to evaluate the clonality of BV subfamily, characteristics of complementarity determining region 3 (CDR3), and the usage rate in BV subfamily. RESULTS: There were (335.1 +/- 782.5) copies/10(5) cells in the 43 patients before transplantation, far lower than the normal value. The TREC values of the patients of the 3 groups all decreased obviously 3 months after transplantation. The TREC value of the MSD-BMT group recovered faster than the other two groups and reached the value before transplantation in 24 months. The recovery of TREC value in the HID-BMT group was delayed. 3 - 19 months after transplantation, the usage of TCRBV subfamilies was still restricted. There were 6 - 16 BV subfamilies expressed and 33% - 48% of them were polyclonals, the others were monoclones and oligoclones and existed in 24 BV subfamilies, no common monoclone BV subfamilies was expressed. CONCLUSION: Investigation of the TREC and TCRBV clonal repertoire showed that the number of naive T cell is lower and the usage of TCRBV subfamilies skewed 3 - 24 months after allo-HSCT. The immune deficiency of the patients undergoing HID-BMT is more prominent and consistent with the clinical process.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Linfócitos T/imunologia , Adolescente , Adulto , Criança , Deleção Clonal/genética , Deleção Clonal/imunologia , Feminino , Regulação Leucêmica da Expressão Gênica , Humanos , Leucemia/genética , Leucemia/cirurgia , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Linfócitos T/metabolismoRESUMO
Acute lymphoblastic leukemia (ALL) patients who fail to acquire complete remission (CR) or who relapse after initial response have poor prognosis. At present there is no consensus as to the standard salvage therapy for these patients. In this study, we retrospectively evaluate safety and efficacy of a salvage regimen (CAGLP) consisting of G-CSF, low-dose cytarabine, aclarubicin, l-asparaginase and prednisone. Thirty-six patients were included with primary refractory (n=13) or relapse (n=23). The overall response rate (ORR) and CR rate were 86.1% and 63.9%, respectively. With a median follow-up of 34 months, the probability of overall survival (OS) at 2 years was 30%±10% and the disease-free survival (DFS) rate was 15%±8%. Treatment-related mortality was 5.6%. Our preliminary results indicated that CAGLP was feasible, safe and effective as a salvage reinduction chemotherapy for primary refractory and relapsed ALL patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Terapia de Salvação/métodos , Aclarubicina/administração & dosagem , Aclarubicina/efeitos adversos , Adolescente , Adulto , Criança , Pré-Escolar , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Intervalo Livre de Doença , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: For recipients of allogeneic hematopoietic stem-cell transplantation (alloHSCT), we hypothesized that prophylactic therapy during neutropenia with granulocyte-macrophage colony-stimulating factor (GM-CSF) decreases invasive fungal disease (IFD). PATIENTS AND METHODS: We randomly assigned 206 patients undergoing alloHSCT to receive once-daily subcutaneous GM-CSF (5 to 7 µg/kg per day), granulocyte colony-stimulating factor (G-CSF; 5 to 7 µg/kg per day), or a combination of G-CSF and GM-CSF (2 to 3 µg/kg per day each). Treatment was started on day 5 after transplantation and was continued until the absolute neutrophil count was ≥ 1.5 × 10(9)/L for 2 consecutive days. The primary outcomes were 100-day incidence of proven and probable IFD and response rate of antifungal treatment. RESULTS: For the intent-to-treat population, there was no significant difference in 100-day incidences of proven and probable IFD among the three groups. The antifungal treatment response was better in the GM-CSF group and G-CSF+GM-CSF group than in G-CSF group from day 22 to day 100 (P = .009). The 100-day cumulative mortality after transplantation was lower in the GM-CSF group than in the G-CSF group (10.3% v 24.6%, respectively; P = .037). The GM-CSF and G-CSF+GM-CSF groups had lower 100-day transplantation-related mortality than the G-CSF group (8.8%, 8.7%, and 21.7%, respectively; P = .034). After a median follow-up of 600 days, IFD-related mortality was lower in the groups that received GM-CSF or G-CSF+GM-CSF compared with G-CSF (1.47%, 1.45%, and 11.59%, respectively; P = .016). There were no significant differences in relapse, graft-versus-host disease, or hemorrhage-related mortality among the three groups of patients. CONCLUSION: For recipients of alloHSCT, compared with G-CSF, prophylactic GM-CSF was associated with lower 100-day transplantation-related mortality, lower 100-day cumulative mortality, and lower 600-day IFD-related mortality.
Assuntos
Antifúngicos/uso terapêutico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Fator Estimulador de Colônias de Granulócitos e Macrófagos/administração & dosagem , Doenças Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Micoses/tratamento farmacológico , Adolescente , Adulto , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/mortalidade , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Doenças Hematológicas/mortalidade , Doenças Hematológicas/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Micoses/etiologia , Micoses/mortalidade , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Transplante Homólogo , Adulto JovemRESUMO
OBJECTIVE: To explore the clinical features and survival of patients with CD56 expression in de- novo acute myeloid leukemiaï¼AMLï¼with tï¼8;21). . METHODS: Clinical data of 82 de novo AML with tï¼8;21ï¼who were newly diagnosed from Jan 2008 to Apr 2014 were analyzed retrospectively, 50 expressed CD56 and 32 not. Clinical characteristics and prognoses were compared between patients expressing and nonexpressing CD56. RESULTS: There were no statistically significant differences in terms of age, gender, white blood cell countï¼WBCï¼, percentage of bone marrow blasts, extramedullary infiltration rate, the early mortality or the presence of additional cytogenetic abnormalities between CD56 + and CD56- groupsï¼Pï¼0.05). The expressions of lymphatic antigens CD19 between CD56 + and CD56- groups showed significant difference ï¼30.0% vs 53.1% , P=0.036). The complete remission and 3-year overall survivalï¼OSï¼showed no significant differences between CD56+ and CD56-groups, while 3- year disease- free survivalï¼DFSï¼showed significant differencesï¼25.8% vs 46.9%, P=0.014). Multivariable analysis for DFS identified CD56 positivity as an independent predictor. DFS of who received allogeneic hematopoietic stem cell transplantationï¼HSCTï¼was better than those treated with intermediate- dose cytarabine/high dose cytarabineï¼IDACï¼as postremission therapy. CONCLUSION: The expression of CD56 in de-novo AML with tï¼8;21) appeared to be associated with poorer prognosis.