RESUMEN
Objective: The outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for myelodysplastic syndromes-evolved acute myeloid leukemia (MDS-AML) were explored. Methods: A retrospective review was conducted for 54 patients with MDS-AML treated with allo-HSCT in the Institute of Hematology and Blood Disease Hospital from January 2018 to August 2022. The clinical effects after transplantation were observed, and the related risk factors influencing prognosis were explored. Results: Of the total 54 patients, 26 males, 28 females, and 53 patients achieved hematopoietic reconstruction. After a median follow-up of 597 (15-1 934) days, the 1 year overall survival (OS) rate, disease-free survival (DFS) rate, relapse rate (CIR) and non-relapse mortality (NRM) rate were 75.8%±5.8%, 72.1%±6.1%, 12.7%±4.9%, and 17.1%±5.2%, respectively. The 3 year estimated OS, DFS, CIR, and NRM rates were 57.8%±7.5%, 58.1%±7.2%, 23.2%±6.6%, and 23.7%±6.6%, respectively. The cumulative incidence of acute graft-versus-host disease (aGVHD) was 57.5%±6.9%, and the cumulative incidence of chronic graft-versus-host disease (cGVHD) was 48.4%±7.7%. Hematopoietic cell transplantation comorbidity index (HCT-CI) before transplantation was ≥2, minimal residual disease (MRD) was positive on the day of reconstitution, grade â ¢/â £ aGVHD, bacterial or fungal infection and no cGVHD after transplantation were adverse prognostic factors for OS (P<0.05). COX regression model for multivariate analysis showed that HCT-CI score before transplantation, bone marrow MRD on the day of response, grade â ¢ or â £ aGVHD, and cGVHD after transplantation were the independent adverse factors for OS (P=0.001, HR=6.981, 95%CI 2.186-22.300; P=0.010, HR=6.719, 95%CI 1.572-28.711; P=0.026, HR=3.386, 95%CI 1.158-9.901; P=0.006, HR=0.151, 95%CI 0.039-0.581) . Conclusion: For patients with MDS-AML and high risk of relapse, allogeneic transplantation must be considered as soon as possible. The enhanced management of post-transplantation complications and maintenance treatment should be provided whenever possible after transplantation.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Trasplante Homólogo , Humanos , Trasplante de Células Madre Hematopoyéticas/métodos , Masculino , Femenino , Síndromes Mielodisplásicos/terapia , Estudios Retrospectivos , Leucemia Mieloide Aguda/terapia , Pronóstico , Tasa de Supervivencia , Enfermedad Injerto contra Huésped/etiología , Supervivencia sin Enfermedad , Factores de Riesgo , Persona de Mediana Edad , Resultado del Tratamiento , AdultoRESUMEN
Objective: To evaluate the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with myelodysplastic syndrome accompanied by myelodysplasia (MDS-EB) and to compare the prognosis of different subtypes of patients classified by World Health Organization (WHO) 2022. Methods: A total of 282 patients with MDS-EB who underwent allo-HSCT at the Hematology Hospital of the Chinese Academy of Medical Sciences from October 2006 to December 2022 were included in the study. The WHO 2022 diagnostic criteria reclassified MDS into three groups: myelodysplastic tumors with type 1/2 of primitive cell proliferation (MDS-IB1/IB2, 222 cases), MDS with fibrosis (MDS-f, 41 cases), and MDS with biallelic TP53 mutation (MDS-biTP53, 19 cases). Their clinical data were retrospectively analyzed. Results: â The median age of 282 patients was 46 (15-66) years, with 191 males and 91 females. Among them, 118 (42% ) and 164 (58% ) had MDS-EB1 and MDS-EB2, respectively. â¡Among the 282 patients, 256 (90.8% ) achieved hematopoietic reconstruction after transplantation, with 11 (3.9% ) and 15 (5.3% ) having primary and secondary implantation dysfunctions, respectively. The cumulative incidence of acute graft-versus-host disease (GVHD) 100 days post-transplantation was (42.6±3.0) %, and the cumulative incidence of grade â ¡-â £ acute GVHD was (33.0±2.8) %. The cumulative incidence of chronic GVHD 1 year post-transplantation was (31.0±2.9) %. Post-transplantation, 128 (45.4% ), 63 (22.3% ), 35 (12.4% ), and 17 patients (6.0% ) developed cytomegalovirus infection, bacteremia, pulmonary fungal infection, and Epstein-Barr virus infection. â¢The median follow-up time post-transplantation was 22.1 (19.2-24.7) months, and the 3-year overall survival (OS) and disease-free survival (DFS) rates were 71.9% (95% CI 65.7% -78.6% ) and 63.6% (95% CI 57.2% -70.7% ), respectively. The 3-year non-recurrent mortality rate (NRM) is 17.9% (95% CI 13.9% -22.9% ), and the 3-year cumulative recurrence rate (CIR) is 9.8% (95% CI 6.7% -13.7% ). The independent risk factors affecting OS post-transplantation include monocyte karyotype (P=0.004, HR=3.26, 95% CI 1.46-7.29), hematopoietic stem cell transplantation complication index (HCI-CI) of ≥3 points (P<0.001, HR=2.86, 95% CI 1.72-4.75), and the occurrence of acute gastrointestinal GVHD of grade â ¡-â £ (P<0.001, HR=5.94, 95% CI 3.50-10.10). â£The 3-year OS and DFS rates in the MDS-IB1/IB2 group post-transplantation were better than those in the MDS-biTP53 group [OS: 72.0% (95% CI 63.4% -80.7% ) vs 46.4% (95% CI 26.9% -80.1% ), P=0.020; DFS: 67.4% (95% CI 60.3% -75.3% ) vs 39.7% (95% CI 22.3% -70.8% ), P=0.015]. The 3-year CIR was lower than that of the MDS-biTP53 group [7.3% (95% CI 4.3% -11.4% ) vs 26.9% (95% CI 9.2% -48.5% ), P=0.004]. The NRM at 3 years post-transplantation in the MDS-IB1/IB2, MDS-f, and MDS-biTP53 groups were 16.7% (95% CI 12.1% -22.1% ), 20.5% (95% CI 9.4% -34.6% ), and 26.3% (95% CI 9.1% -47.5% ), respectively (P=0.690) . Conclusion: Allo-HSCT is an effective treatment for MDS-EB, with monomeric karyotype, HCI-CI, and grade â ¡-â £ acute gastrointestinal GVHD as independent risk factors affecting the patient's OS. The WHO 2022 classification helps distinguish the efficacy of allo-HSCT in different subgroups of patients. Allo-HSCT can improve the poor prognosis of patients with MDS-f, but those with MDS-biTP53 have a higher risk of recurrence post-transplantation.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Síndromes Mielodisplásicos , Trasplante Homólogo , Humanos , Trasplante de Células Madre Hematopoyéticas/métodos , Síndromes Mielodisplásicos/terapia , Persona de Mediana Edad , Adulto , Masculino , Femenino , Pronóstico , Estudios Retrospectivos , Adolescente , Adulto Joven , Anciano , Tasa de Supervivencia , Enfermedad Injerto contra Huésped/etiologíaRESUMEN
Twelve DEK-NUP214 fusion gene-positive patients with acute myeloid leukemia and on allo-HSCT treatment at the Hematology Hospital of the Chinese Academy of Medical Sciences from November 2016 to August 2022 were included in the study, and their clinical data were retrospectively analyzed. The patients comprised five men and seven women with a median age of 34 (16-52) years. At the time of diagnosis, all the patients were positive for the DEK-NUP214 fusion gene. Chromosome karyotyping analysis showed t (6;9) (p23;q34) translocation in 10 patients (two patients did not undergo chromosome karyotyping analysis), FLT3-ITD mutation was detected in 11 patients, and high expression of WT1 was observed in 11 patients. Nine patients had their primary disease in the first complete remission state before transplantation, one patient had no disease remission, and two patients were in a recurrent state. All patients received myeloablative pretreatment, five patients received sibling allogeneic hematopoietic stem cell transplantation, and seven patients received haploid hematopoietic stem cell transplantation. The median number of mononuclear cells in the transplant was 10.87 (7.09-17.89) ×10(8)/kg, and the number of CD34(+) cells was 3.29 (2.53-6.10) ×10(6)/kg. All patients achieved blood reconstruction, with a median time of 14 (10-20) days for neutrophil implantation and 15 (9-27) days for platelet implantation. The 1 year transplant-related mortality rate after transplantation was 21.2%. The cumulative recurrence rates 1 and 3 years after transplantation were 25.0% and 50.0%, respectively. The leukemia free survival rates were (65.6±14.0) % and (65.6±14.0) %, respectively. The overall survival rates were (72.2±13.8) % and (72.2±13.8) %, respectively.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Proteínas de Complejo Poro Nuclear , Trasplante Homólogo , Humanos , Masculino , Femenino , Adulto , Trasplante de Células Madre Hematopoyéticas/métodos , Persona de Mediana Edad , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Adolescente , Estudios Retrospectivos , Adulto Joven , Proteínas de Complejo Poro Nuclear/genética , Proteínas Cromosómicas no Histona/genética , Proteínas de Unión a Poli-ADP-Ribosa/genética , Proteínas de Fusión Oncogénica/genética , Proteínas Oncogénicas/genética , Translocación GenéticaRESUMEN
As the backbone force of China's social and economic construction, the health status of workers is closely related to the nation's productivity and social development. Currently, cancers have become one of the major diseases threatening the health of workers. However, there are still many shortcomings in the cancer screening services for the workers. To standardize cancer screening services for workers, ensure the quality of screening services, and improve the overall screening effectiveness, 19 institutions, including Peking Union Medical College Hospital of the Chinese Academy of Medical Sciences, have jointly formulated the Group Standard "Specification for service of cancer screening for workers (T/CHAA 023-2023)". This standard follows the principles of "legality, scientific rigor, advancement, and feasibility" and combines the frontier scientific advances in cancer screening. It clarifies the relevant requirements for service principles, service design, service delivery, service management, service evaluation, and improving worker cancer screening. Implementing this group standard will help connect the common screening needs of workers, employers, and cancer screening service providers, standardize the screening process, improve screening quality, and ultimately increase the early diagnosis rate and survival rate of cancer patients. Consequently, this group standard will help safeguard workers' health rights and interests, ensure the labor force resources, promote the comprehensive coordinated and sustainable development of society, and contribute to realizing the "Healthy China 2030" strategic policy.
Asunto(s)
Detección Precoz del Cáncer , Humanos , China , Neoplasias/diagnóstico , Tamizaje Masivo/métodosRESUMEN
Objective: To evaluate the efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for the treatment of primary myelofibrosis (PMF) patients. Methods: A total of 14 cases of PMF who underwent allo-HSCT from December 2008 to December 2022 were analyzed retrospectively, including 8 males and 6 females with a median age [M(Q1, Q3)]of 36 (24, 42) years. Three-year overall survival (OS), disease free survival (DFS), cumulative incidence of relapse (CIR), transplantation-related mortality (TRM) were analyzed. Meanwhile, the complications were followed up by telephone and outpatient appointments for 49.6 (9.0,93.1) months. Results: All patients received myeloablative conditioning regimens (MAC). All patients had successful engraftment, and the median time of neutrophils and platelet engraftment were 13.5 (11.8, 18.0) days and 19.5 (13.5, 24.5) days, respectively. â ¡-â £ acute graft versus host disease (GVHD) occurred in 3 cases, while chronic GVHD in 8 cases. The rate of 3-year OS,DFS,CIR and TRM were (92.9±6.9)%, (76.0±12.2)%, (38.6±2.7)% and (7.1±0.5)% respectively after a median follow-up time of 1 489.0 (270.3,2 794.8) days. Two patients died from treatment-related complications, one of which died 39 days after transplantation due to heart failure caused by severe anemia, the other patient died 6 years after relapse due to pulmonary infection. Conclusion: Allo-HSCT can be used as a safe and effective approach to treat PMF.
Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Mielofibrosis Primaria , Masculino , Femenino , Humanos , Estudios Retrospectivos , Mielofibrosis Primaria/terapia , Recurrencia , Acondicionamiento PretrasplanteRESUMEN
Objective: To evaluate the efficacy and safety of HLA-haploidentical hematopoietic stem cell transplantation (allo-HSCT) for hepatitis-related aplastic anemia (HRAA) patients. Methods: Retrospective analysis was performed on hepatitis-associated aplastic anemia patients who received haplo-HSCT at our center between January 2012 and June 2022. October 30, 2022 was the final date of follow-up. Results: This study included 28 HRAA patients receiving allo-HSCT, including 18 males (64.3% ) and 10 females (35.7% ), with a median age of 25.5 (9-44) years. About 17 cases of severe aplastic anemia (SAA), 10 cases of very severe aplastic anemia (VSAA), and 1 case of transfusion-dependent aplastic anemia (TD-NSAA) were identified. Among 28 patients, 15 patients received haplo-HSCT, and 13 received MSD-HSCT. The 2-year overall survival (OS) rate, the 2-year failure-free survival (FFS) rate, the 2-year transplant-related mortality (TRM) rate, the 100-day grade â ¡-â £ acute graft-versus-host disease (aGVHD) cumulative incidence rate, and the 2-year chronic graft-versus-host disease (cGVHD) cumulative incidence rate were 81.4%, 81.4% (95% CI 10.5% -20.6% ), 14.6% (95% CI 5.7% -34.3% ), 25.0% (95% CI 12.8% -45.4% ), and 4.2% (95% CI 0.6% -25.4% ), respectively. After transplantation, all patients had no significant liver function damage. Compared with the MSD-HSCT group, only the incidence of cytomegaloviremia was significantly higher in the haplo-HSCT group [60.0% (95% CI 35.2% -84.8% ) vs 7.7% (95% CI 0-22.2% ), P=0.004]. No statistically significant difference in the Epstein-Barr virus was found in the 2-year OS, 2-year FFS, 2-year TRM, and 100-day grade â ¡-â £ aGVHD cumulative incidence rates and 2-year cGVHD cumulative incidence rate. Conclusion: Allo-HSCT is safe and effective for HRAA, and haplo-HSCT can be used as a safe and effective alternative for newly diagnosed HRAA patients who cannot obtain HLA-matched sibling donors.
Asunto(s)
Anemia Aplásica , Síndrome de Bronquiolitis Obliterante , Infecciones por Virus de Epstein-Barr , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Hepatitis , Masculino , Femenino , Humanos , Adulto , Resultado del Tratamiento , Anemia Aplásica/terapia , Estudios Retrospectivos , Herpesvirus Humano 4 , Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Hepatitis/etiología , Acondicionamiento PretrasplanteRESUMEN
Objective: To investigate the early effect and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with a 10-day decitabine-containing conditioning regimen in the treatment of acute myeloid leukemia (AML) /myelodysplastic syndrome (MDS) . Methods: From April 2021 to May 2022, 31 AML/MDS patients who received allo-HSCT with a 10-day decitabine-containing conditioning regimen were analyzed. Results: AML (n=10), MDS-AML (n=6), CMML-AML (n=1), and MDS (n=14) were identified in 31 patients, 16 males, and 15 females, with a median age of 41 (20-55) yr. Neutrophils and platelets were successfully implanted in 31 patients (100%), with a median implantation duration of 12 (9-30) and 14 (9-42) days, respectively. During the preconditioning period, 16 patients (51.6%) developed oral mucositis, with 15 cases of â /â ¡ grade (48.4%) and one case of â ¢ grade (3.2%). After transplantation, 13 patients (41.9%) developed CMV viremia, six patients (19.4%) developed hemorrhagic cystitis, and four patients (12.9%) developed a local infection. The median time of acute graft versus host disease (aGVHD) following transplantation was 33 (12-111) days. The cumulative incidence of aGVHD and â ¢/â £ grade aGVHD was 41.9% (95% CI 26.9%-61.0%) and 22.9% (95% CI 13.5%-47.5%), respectively. There was no severe cGVHD, and mild and moderate chronic GVHD (cGVHD) incidence was 23.5% (95% CI 12.1%-43.6%). As of November 30, 2022, only one of the 31 patients had relapsed, with a 1-yr cumulative relapse rate (CIR) of 3.2% (95% CI 0.5%-20.7%). There was only one relapse patient death and no non-relapse deaths. The 1-yr overall survival (OS) and disease-free survival (DFS) rates were 92.9% (95% CI 80.3%-100%) and 96.8% (95% CI 90.8%-100%), respectively. Conclusions: A 10-day decitabine-containing conditioning regimen for allo-HSCT reduced relapse and was safe and feasible in treating AML/MDS.
Asunto(s)
Síndrome de Bronquiolitis Obliterante , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Masculino , Femenino , Humanos , Decitabina , Síndromes Mielodisplásicos/terapia , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/complicaciones , Supervivencia sin Enfermedad , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Recurrencia , Enfermedad Crónica , Enfermedad Injerto contra Huésped/etiología , Acondicionamiento Pretrasplante/efectos adversos , Estudios RetrospectivosRESUMEN
Objective: The purpose of this study is to determine the efficacy of haploidentical donor hematopoietic stem cell transplantation in the treatment of severe aplastic anemia. Methods: The clinical data of 76 patients with severe aplastic anemia (SAA) patients who underwent haplo-HSCT from December 2014 to October 2020 were selectively analyzed. There were 50 males and 26 females with a median age of 16 (3-52) years old. There were 49 SAA-â patients, 18 SAA-â ¡ patients, and 9 patients with hepatitis-associated aplastic anemia. There were 15 cases of bone marrow put together with peripheral blood stem cell transplantation and 61 cases of peripheral blood stem-cell transplantation. Conditioning regimens were Cyclophosphamide (CY) + Fludarabine (Flu) + ATG for 46 patients and Busulfan (Bu) + CY+Flu+ATG for 30 patients. Results: Three patients died during the myelosuppressive phase following transplantation, and 73 patients had a median time of neutrophil engraftment of 12 (9-21) days; in addition to 3 patients who died early, 8 patients did not obtain platelet reconstruction after transplantation, and 65 patients had platelet engraftment with a medium time of 14 (9-90) d. The incidence of primary graft failure was 10.9% and the incidence of secondary graft failure was 5.5%. The incidence of â ¡-â £ acute graft-versus-host disease (aGVHD) was 38.4%, the incidence of â ¢-â £ aGVHD was 16.4%, the incidence of chronic graft anti-host disease (cGVHD) was 35.8%, and the incidence of extensive cGVHD was 22.4%. The medium follow-up time was 19.5 (1-75) months, the prospective overall survival (OS) for 2 years was (78.6±5.0) %, the failure-free survival (FFS) was (75.9±5.1) %, and the transplant-related mortality was (20.2±4.9) %. Multi-factor analysis revealed that the patient older than 35 years old, â ¢/â £ aGVHD, HCT-CI≥3, the pre-transplant ferritin ≥1 500 µg/L, the number of neutrophils >1×10(9)/L at the time of onset were risk factors affecting OS (P=0.008, 0.008, 0.014, 0.004, 0.027) . Patients with graft failure had lower OS and FFS than other patients (P<0.001) . Conclusion: Haplo-HSCT is an effective method for treating SAA in children, adolescents, and young patients, and the occurrence of severe aGVHD and severe infection, as well as graft failure, are the main causes of survival rate. The prevention and treatment of severe aGVHD and infection are essential to improve efficacy.
Asunto(s)
Anemia Aplásica , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Niño , Masculino , Adolescente , Femenino , Humanos , Adulto Joven , Adulto , Persona de Mediana Edad , Anemia Aplásica/terapia , Haploidia , Estudios Prospectivos , Acondicionamiento Pretrasplante , Estudios Retrospectivos , Ciclofosfamida , BusulfanoRESUMEN
Objective: TP53-abnormal MDS/acute myeloid leukemia (AML) patients' allogeneic hematopoietic stem cell transplantation (allo-HSCT) treatment's effectiveness and influencing factors should be studied. Methods: 42 patients with TP53 gene status change MDS/AML who underwent allo-HSCT from 2014.8.1 to 2021.7.31 at the Hematology Hospital of the Chinese Academy of Medical Sciences were the subject of a retrospective analysis. The 42 patients were divided into three groups: the TP53 deletion group (group A) , TP53 mono-alle mutation group (group B) , and TP53 multi-hit group (group C) . The differences in clinical features and prognostic factors after transplantation were analyzed. Results: There were 42 MDS/AML patients, including 21 patients with MDS, and 21 patients with AML. The median follow-up period was 34.0 (7.5-75.0) months and the median patient age at the time of transplantation was 41.5 (18-63) years old. The total OS was 66.3% (95% CI 53.4%-82.4%) in 3 years after transplantation, and EFS was 61.0% (95% CI 47.7%-78.0%) in 3 years. For 3 years after receiving hematopoietic stem cell transplantation, there were no statistically significant differences in 3-year OS and EFS in groups A, B, and C (P≥0.05) . The 3 years OS was 82.5% (95% CI 63.1%-100.0%) in group A, 60.6% (95% CI 43.5%-84.4%) in group B, and 57.1% (95% CI 30.1%-100.0%) in group C. Univariate analysis revealed that the number of co-mutant genes, pre-HSCT treatment, and disease type did not affect prognosis, while age, karyotype, co-mutation, positive blast cell before transplantation, and positive blast cell after transplantation were common prognostic factors for OS and EFS (P<0.1) . MRD levels before transplantation were found to be independent risk factors for OS (P=0.037, HR=33.40, 95% CI 1.24-901.17) in a multivariate analysis. Conclusion: Patients with MDS/AML who have TP53 mutations can benefit from allo-HSCT, but patients with complex karyotypes have a worse prognosis. Meanwhile, the final flow cytometry (FCM) monitoring blast cell test before HSCT has a certain guiding significance for prognostic assessment.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Adulto , Humanos , Persona de Mediana Edad , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Pronóstico , Estudios Retrospectivos , Trasplante Homólogo , Proteína p53 Supresora de Tumor/genética , Adolescente , Adulto JovenRESUMEN
Objective: To explore the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acute myeloid leukemia (AML) patients with BCR::ABL1 fusion. Methods: The clinical data of seven AML patients with BCR::ABL1 fusion from November 2012 to January 2022 were retrospectively analyzed, and their survival status was followed up. Results: The median age of patients at the time of diagnosis was 35 years. Four cases (57.1%) were diagnosed with high leukocyte counts. All cases were assayed as BCR::ABL1 positive and accompanied by four types of gene mutations (NPM1, RUNX1, ASXL1, PHF6) . Seven patients received tyrosine kinase inhibitor (TKI) combined with induction chemotherapy and bridged to allo-HSCT, and six patients received maintenance therapy with TKI. Before allo-HSCT, six patients achieved complete remission, and four patients achieved complete molecular remission (CMR) . After allo-HSCT, the three remaining cases also achieved CMR. All patients were in remission post-allo-HSCT. One case died of infection, and the remaining cases survived without relapse. The 3-year cumulative overall survival rate was (80.0±17.9) %. Conclusions: TKI combined with traditional chemotherapy could achieve a high response rate in AML patients with BCR::ABL1 fusion. In addition, allo-HSCT could enhance the molecular response rate. Maintenance therapy post-HSCT with TKI could improve prognosis.
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Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Humanos , Adulto , Estudios Retrospectivos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Inhibidores de Proteínas Quinasas/uso terapéutico , PronósticoRESUMEN
Objective: To evaluate the efficacy and prognosis of basiliximab in the treatment of steroid-refractory or steroid-dependent acute graft-versus-host disease (SR/SD-aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Clinical data of 87 patients with SR/SD-aGVHD in the skin, intestine, and liver after allo-HSCT at the Institute of Hematology & Blood Diseases Hospital Transplantation Center from January 2015 to December 2018 were retrospectively analyzed. The administration plan of basiliximab was as follows: 20 mg for adults and children weighing ≥35 kg and 10 mg for children weighing<35 kg. The drug was administered once on the 1st, 4th, and 8th days, respectively, and then once weekly. The efficacy was evaluated on the 7th, 14th, 21st, and 28th days after basiliximab treatment. Results: â There were 51 males (58.6%) and 36 females (41.4%) , with a median (range) age of 34 (4-63) years. There were 54 cases of classic aGVHD, 33 of late aGVHD, 49 of steroid-refractory aGVHD, and 38 of steroid-dependent aGVHD. â¡Thirty-five patients (40.2%) achieved complete remission (CR) , 23 (26.4%) achieved partial remission (PR) , and 29 had no remission (NR) . The total effective rate[overall response rate (ORR) ] was 66.7% (58/87) . â¢The ORR of the classic and late aGVHD groups was 77.8% (42/54) and 48.5% (16/33) , respectively. â£The median (range) follow-up time was 154 (4-1813) days, the 6-month overall survival (OS) rate of the 87 patients was 44.8% (95% CI 39.5%-50.1%) and the 1-year OS was 39.4% (95%CI 34.2%-44.3%) . â¤After treatment with basiliximab, the 6-month OS in the CR (35 cases) , PR (23 cases) , and NR (29 cases) groups was 80.0% (95%CI 73.2%-86.8%) , 39.1% (95%CI 28.9%-49.3%) , and 6.9% (95%CI 2.2%-11.6%) , respectively (χ(2)=34.679, P<0.001) , and the 1-year OS was 74.3% (95%CI 66.9%-81.7%) , 30.4% (95%CI 20.8%-40.0%) , and 3.4% (95%CI 0%-6.8%) , respectively (χ(2)=43.339, P<0.001) . The OS of the classic and late aGVHD groups was 57.4% (95%CI 50.7%-64.1%) and 24.2% (95%CI 16.7%-31.7%) , respectively (χ(2)=9.109, P=0.004) , and the 1-year OS was 51.9% (95%CI 45.1%-58.7%) and 18.2% (95%CI 11.5%-24.9%) , respectively (χ(2)=9.753, P=0.003) . â¥Univariate and multivariate analyses showed that late aGVHD (OR=3.121, 95%CI 1.770-5.503, P<0.001) , Minnesota score high-risk group before medication (OR=3.591, 95%CI 1.931-6.679, P<0.001) , active infection before medication (OR=1.881, 95%CI 1.029-3.438, P=0.040) , and impairment of important organ function caused by non-GVHD (OR=3.100, 95%CI 1.570-6.121, P=0.001) were independent risk factors affecting the efficacy of basiliximab. Conclusion: Basiliximab has good efficacy and safety for SR/SD-aGVHD, but not in patients with late aGVHD, high-risk group of Minnesota score, and infection or impaired function of important organs.
Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Enfermedad Aguda , Adulto , Basiliximab/uso terapéutico , Niño , Femenino , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Esteroides/uso terapéuticoRESUMEN
Objegtive: To investigate the efficacy and safety of preemptive/salvage therapy with venetoclax (VEN) in patients with recurrence after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Retrospective analysis the clinical data of 25 patients with minimal residual disease (MRD) positive or morphological recurrence after allo-HSCT treated with VEN in the hematological Hospital of Chinese Academy of Medical Sciences from 2021.2 to 2021.11, there were 15 MRD positive patients (preemptive treatment group) and 10 morphological recurrence patients (salvage treatment group) . The dose of VEN in both groups was 400 mg/d, which was reduced to 100 mg/d when combined with azole antifungal drugs. Results: â In the preemptive group, there were 7 males and 8 females, with a median age of 32 (18-52) years; There were 13 cases of acute myeloid leukemia (AML) , 1 case of acute lymphoblastic leukemia (ALL) and 1 case of primary myelofibrosis (PMF) ; the median time from MRD positive to the application of VEN was 2.5 (0-12.5) months. The median course of treatment was 2 (1-4) . On the 7th day of the first course of treatment, the median concentration of VEN was 1945 (688-5383) µg/L. After one course of VEN treatment, MRD in 8 patients turned negative (major responses) , MRD in 4 patients decreased by 50% compared with that before treatment, 3 cases were ineffective, and the overall response rate (ORR) was 80% (12/15) . On the 7th day of treatment, 3 of the 9 patients with VEN blood concentration <1 000 µg/L or >3 000 µg/L turned negative for MRD (33.3%) , and 5 of the 6 patients with VEN blood concentration between 1000 and 3000 µg/L turned negative for MRD (83.3%) . Grade 3/4 neutropenia occurred in 5 patients (33%) and grade 3/4 thrombocytopenia occurred in 5 patients (33%) , there were no new cases of severe infection and death. â¡In the salvage group, there were 7 males and 3 females, with a median age of 44 (28-59) years; there were 6 cases of AML, 2 cases of ALL, 1 case of atypical chronic myeloid leukemia (aCML) , 1 case of refractory hemopenia with multiline dysplasia (MDS-RCMD) ; the median time from relapse to application of VEN was 0 (0-1) months. The median treatment was 1 (1-2) course. The median concentration of VEN on the 7th day of the first course of treatment was 2 419 (1 200-6 155) µg/L. After one course of VEN treatment, 3 cases achieved complete remission (CR) (major responses) and 3 cases achieved partial remission (PR) , 4 cases were ineffective and the ORR was 60% (6/10) . On the 7th day of treatment, 1 of the 4 patients with VEN blood concentration >3 000 µg/L achieved CR (25%) , and 2 of the 6 patients with VEN blood concentration between 1 000 and 3 000 µg/L achieved CR (33.3%) . Grade 3/4 neutropenia and grade 3/4 thrombocytopenia occurred in 10 patients (100%) . One patient died of severe pulmonary infection. â¢The median follow-up was 4.5 (1-8.5) months. The overall survival rate (OS) of the preemptive group and the salvage group were (70.2±12.7) % and (50.0± 15.8) %, respectively (χ(2)=1.873, P=0.171) . The OS of patients with and without primary response to one course of VEN were (90.9±8.7) % and (36.2±14.7) % respectively (χ(2)=6.843, P=0.009) . Three patients with TP53 mutation achieved the major responses after VEN treatment. Conclusion: Preemptive/salvage therapy with VEN after allo-HSCT in patients with hematological malignancies is effective and well tolerated, monitoring the concentration of VEN is expected to improve the curative effect. The prognosis of patients who fail to reach the major responses after one course of preemptive/salvage treatment with VEN is poor, so they need to switch to other treatment schemes as soon as possible.
Asunto(s)
Neoplasias Hematológicas , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad Crónica , Neoplasias Hematológicas/terapia , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/patología , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Pronóstico , Recurrencia , Estudios Retrospectivos , Trasplante Homólogo , Adolescente , Adulto JovenRESUMEN
Objective: To evaluate the outcomes and prognostic factors of adults with acute myeloid leukemia with myelodysplastic-related changes (AML-MRC) who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) . The genetic mutation lineage of patients with AML-MRC and the molecular mutation affecting the transplantation prognosis was discussed. Methods: The clinical data of 75 patients with AML-MRC who underwent allo-HACT from 2006 to 2020 were retrospectively analyzed for clinical characteristics, survival, relapse-related indicators, and risk factors affecting transplantation prognosis. Additionally, the clinical characteristics and prognosis of multilineage dysplasia (M) group, history of myelodysplastic syndrome (MDS) or myelodysplastic syndrome/myelodysplastic proliferative tumor (MDS/MPN) (H) group, and MDS related cytogenetic abnormalities (C) group were compared. The bone marrow of 43 patients underwent targeting second-generation sequencing (137 genes) . Results: â There were 41 males and 34 females with a median age of 41 (18-56) years, a median follow-up time of 35 (95%CI 30-49) months, and a median survival time (OS) of 78 (95%CI 23-) months. Three-year OS and event-free survival (EFS) were 57.1% (95%CI 45.6%-71.4%) and 52.0% (95%CI 40.8%-66.1%) . Also, the three-year cumulative recurrence rate (CIR) and transplant-related mortality rate (TRM) were 26.8% (95%CI 16.6%-30.0%) and 22.7% (95%CI 13.2%-33.8%) , respectively. Furthermore, multivariate analysis revealed that pre-transplant non-CR1 status was an independent risk factor for OS and EFS. Other independent risk factors for OS included abnormal karyotype of -5/5q- chromosome and the absence of chronic graft-versus-host disease (cGVHD) after transplantation. â¡Among the 75 patients, 59 (78.7%) were in group H, 20 had received demethylation drugs before turning to AML and nine cases (12.0%) in group C and seven cases (9.3%) in group M. There was no significant difference in the three-year OS and EFS among the three groups[group M vs H vs C: OS: 71.4% (95%CI 44.7%-100.0%) vs 55.0% (95%CI 41.8%-72.5%) vs 55.6% (95%CI 31.0%-99.7%) , P=0.700; EFS: 71.4% (95%CI 44.7%-100.0%) vs 46.5% (95%CI 34.0%-63.8%) vs 55.6% (95%CI 31.0%-99.7%) , P=0.600]. Compared with primary and secondary AML-MRC, there was no statistically significant difference in the three-year OS and EFS[61.9% (95%CI 41.9%-91.4%) vs 55.0% (95%CI 41.8%-72.5%) , P=0.600; 61.9% (95%CI 41.9%-91.4%) vs 46.5% (95%CI 34.0%-63.8%) , P=0.400]. Furthermore, there was no significant difference in the time to AML between patients who received demethylation treatment before (20 cases) and those who did not (39 cases) [195 (16-937) d vs 162 (9-3167) d, P=0.804]. Moreover, there were no statistically significant differences in the three-year OS and EFS between the two groups (P=0.400, P=0.700) . ⢠NGS test was performed on bone marrow samples of 43 patients (57.3%) , and 73 mutation types were found. Additionally, U2AF1 had the highest mutation incidence (11 cases, 25.6%) , and more than 10% were found: RUNX1 (ten cases, 23.3%) , NRAS (ten cases, 23.3%) , ASXL1 (six cases, 14.0%) , PTPN11 (five cases, 11.6%) , TET2 (five cases, 11.6%) . Univariate analysis showed U2AF1[P=0.875, HR=1.110 (95%CI 0.295-4.195) ], RUNX1[P=0.685, HR=0.728 (95%CI 0.157-3.375) ], NRAS[P=0.919, HR=0.923 (95%CI 0.196-4.334) ] mutation did not affect OS. Conclusion: Chromosome abnormality of -5/5q-, cGVHD, and non-CR1 status before transplantation were independent risk factors for OS in patients with allo-HSCT and AML-MRC. Additionally, the MHC subgroup classification was not a factor affecting the prognosis of transplantation. Treatment with demethylated drugs may not delay MDS turning to AML and prolong the OS after transplantation.
Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios RetrospectivosRESUMEN
Objective: To investigates the relationship between CYP3A5 gene polymorphism, tacrolimus concentration, and acute graft versus host disease (GVHD) in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: A retrospective analysis of the clinical data of 35 Chinese adult patients who received allo-HSCT from July 2019 to February 2020 was conducted. Also, bone marrow samples were collected before transplantation for CYP3A5 genotyping, and intravenous infusion of tacrolimus and a short course of methotrexate (MTX) ± mycophenolate were used to prevent GVHD. The initial concentration was monitored on the second or third day of tacrolimus administration, followed by 2-3 times a week. The drug dose was adjusted according to the target blood concentration (10-15 ng/ml) . Results: In 16 allo-HSCT patients with CYP3A5 *3/*3 gene, the initial concentration of tacrolimus (9.82 ng/ml vs 8.53 ng/ml) , the initial concentration/dose (C/D) ratio (5.72 ng·ml(-1)·mg(-1) vs 4.26 ng·ml(-1)·mg(-1)) , and the median C/D ratio in the first two weeks after HSCT (5.29 ng·ml(-1)·mg(-1) vs 4.61 ng·ml(-1)·mg(-1), 5.65 ng·ml(-1)·mg(-1) vs 4.56 ng·ml(-1)·mg(-1)) were significantly higher than in 19 patients with at least one CYP3A5 * 1 allele (P=0.028, 0.001, 0.037, 0.045) . The incidence of â ¢-â £ aGVHD in patients with CYP3A5*1 alleles was higher than in patients with CYP3A5*3/*3 gene[ (26.3±10.1) %vs (6.2±6.1) %, P=0.187]. Conclusion: CYP3A5 genotype-directed administration may help achieve the target blood concentration of tacrolimus after HSCT more quickly, reduce the incidence of severe aGVHD, and improve the efficacy of transplantation.
Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Citocromo P-450 CYP3A/genética , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Inmunosupresores , Polimorfismo Genético , Estudios Retrospectivos , TacrolimusRESUMEN
Objective: To investigate the long term efficacy and side effects of a donor-derived CD19 chimeric antigen receptor (CAR) T-cell (HI19α-4-1BB-ζ CAR-T) therapy in the treatment of patients with relapsed B-cell acute lymphoblastic leukemia (B-ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: A total of 9 subjects with relapsed B-ALL post allo-HSCT received donor-derived CD19 CAR-T therapy from July 2017 to May 2020. All subjects were infused with donor CD3-positive T cells after lymphodepletion chemotherapy, and a median dose of CAR-T cells was 1.79 (range, 0.86-3.53) ×10(6)/kg. Results: â All subjects achieved complete remission and MRD-negative at 28-42 d post CAR-T cells infusion. â¡Cytokine releasing syndrome (CRS) occurrd in all subjects and was grade 3 in 2, grade 2 in 4, grade 1 in 3 cases respectively. Four subjects developed immune effector cell-associated neurotoxicity syndrome (ICANS) , which was grade 2 in 1, grade 1 in 3. One subject developed grade IV acute graft-versus-host disease (GVHD) , and side effects were all controllable. â¢Four subjects relapsed at a median period of 8.6 (4.6-19.3) months, 2 subjects died of disease progression after receiving chemotherapy and another one also died of disease progression 14 months after a second transplant, only 1 subject achieved complete remission after CD22 CAR-T cell therapy. Until last follow-up date, 6 subjects were leukemia-free and achieved complete donor chimerism. The estimated 1-year and 2-year leukemia-free survival (LFS) rate was 63.5% and 50.8%, with a median LFS of 18.1 months. â£After a median follow-up of 25.1 (range, 6.9-36.7) months, the estimated 2-year and 2.5-year OS rate were 87.5% and 52.5%, respectively. Conclusion: The donor-derived CD19 CAR-T cell therapy obtain a high remission rate in relapsed B-ALL patients post allo-HSCT with tolerable side effects, half subjects survived more than 2 years without disease recurrence, though long-term efficacy requires further observation. Chinese Clinical Trial Registry: ChiCTR1900025419.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Receptores Quiméricos de Antígenos , Antígenos CD19 , Linfocitos B , Humanos , Inmunoterapia AdoptivaRESUMEN
Objective: To explore the clinical characteristics, related factors, and prognostic effect of patients with T cell large granular lymphocytosis following allo-HSCT. Methods: Consecutive patients with T-LGL following allo-HSCT who visited our center from June 2013 to February 2020 were studied retrospectively. We compared patients undergoing allo-HSCT during this period. The clinical characteristics, related factors, cumulative incidence of patients with T-LGL and rates of overall survival (OS) , disease free survival (DFS) , relapse, and non-relapse mortality (NRM) were analyzed. Results: Total 359 patients were enrolled, including 17 with T-LGL and 342 without T-LGL following allo-HSCT. The median follow-up duration was 38 (3-92) month. The cumulative incidence at 1-, 2- and 3-years of T-LGL was 3.64% (95%CI 1.09%-6.19%) , 4.50% (95%CI 1.36%-7.64%) , and 4.84% (95%CI 1.10%-8.76%) , respectively. CMV reactivation (P=0.013) , EB viremia (P=0.034) , and aGVHD (P=0.027) were associated with the development of T-LGL following allo-HSCT. Multivariate analysis showed that benign hematologic diseases[P=0.027, OR=3.36 (95%CI 1.15-9.89) ] and haploidentical hematopoietic stem cell transplantation[P=0.030, OR=4.67 (95%CI 1.16-18.75) ], unrelated donor transplantation[P=0.041, OR=5.49 (95%CI 1.10-28.16) ] were independent predictive factors of T-LGL following allo-HSCT. There was a significant difference in the 3-year OS (100.0% vs. 78.6%, P=0.04) , DFS (100.0% vs. 70.0%, P=0.01) , and NRM (0 vs. 12.6%, P=0.02) between the 2 cohorts. Subgroup analysis showed that malignant diseases recipients who developed T-LGL had better outcomes after allo-HSCT, and there was a significant difference in the NRM (P=0.042) , DFS (P=0.013) , and cumulative relapse rate (P=0.028) between the 2 cohorts. In contrast, the appearance of T-LGL after allo-HSCT in patients with benign diseases had no significant effect on the prognosis. Conclusions: T-LGL was a durable and clinically benign phenomenon occurring in allo-HSCT recipients with malignant diseases. Factors associated with immune reconstitution and T-cell regulatory mechanisms might be major predictors of T-LGL following allo-HSCT.
Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Linfocítica Granular Grande , Humanos , Leucemia Linfocítica Granular Grande/terapia , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Factores de Riesgo , Linfocitos T , Trasplante HomólogoRESUMEN
Objective: To compare differences of autologous and unrelated donor stem cell transplantation (auto-HSCT and URD-HSCT) for adults with primary acute myeloid leukemia (AML) in first complete remission (CR(1)) from a single center and to investigate the appropriate patients for the 2 types of transplant. Methods: In this retrospective investigation, we studied adults with primary AML who received auto-HSCT and URD-HSCT from March 2008 to November 2018. Overall survival (OS) , leukemia-free survival (LFS) , relapse, transplant-related mortality (TRM) , and hematopoietic reconstitution were compared along with the prognostic value of cytogenetics. Results: A total of 147 adult patients were enrolled in this study (n=87 for auto-HSCT and n=60 for URD-HSCT) . Baseline characteristics were comparable between the 2 groups. The accumulative neutrophil engraftment rate at +30 days was not statistically different between the 2 groups[92.6% (95% CI 86.9%-98.3%) vs 98.3% (95% CI 95.0%-100.0%) , P=0.270], whereas the accumulative platelet engraftment rate at +60 days was significantly lower in the auto-HSCT group[83.6% (95% CI 75.8%-91.4%) vs 93.3% (95% CI 87.0%-99.6%) , P<0.001]. In patients undergoing URD-HSCT, the accumulative incidences of acute GVHD (aGVHD) and grade â ¡-â £ aGVHD were 56.7% (95% CI 43.0%-68.2%) and 16.7% (95% CI 8.5%-27.2%) , and the incidences of chronic GVHD (cGVHD) and extensive cGVHD were 33.3% (95% CI 21.7%-45.4%) and 15.0% (95% CI 7.3%-25.2%) , respectively. After a median follow-up of 53.8 (0.8-127.8) months, patients in the 2 groups demonstrated comparable OS and LFS at 5 years after transplant[71.7% (95% CI 61.7%-81.7%) vs 67.8% (95% CI 55.8%-79.8%) , P=0.556; 64.6% (95% CI 54.4%-74.8%) vs 68.1% (95% CI 56.3%-79.9%) , P=0.642]. Patients in the auto-HSCT group showed significantly higher incidence of relapse at 5 years after transplant[31.9% (95% CI 22.2%-42.1%) vs 15.1% (95% CI 7.4%-25.6%) , P=0.015] and significantly lower incidence of TRM[3.4% (95% CI 0.9%-8.9%) vs 16.7% (95% CI 8.5%-27.2%) , P=0.006] compared with the URD group. HLA mismatching had no effects on the incidences of hematopoietic reconstitution, GVHD, OS, LFS, relapse, and TRM. Patients of cytogenetically favorable and intermediate risk demonstrated comparable OS and LFS after auto-HSCT and URD-HSCT, while patients of poor risk had significantly higher relapse and lower LFS after auto-HSCT. Conclusions: In this study, adults with primary AML in CR(1) demonstrated relatively higher relapse but lower TRM after auto-HSCT, resulting in comparable survival to that of URD-HSCT. In the absence of matched sibling donors, patients of cytogenetically poor risk should receive URD-HSCT in order to achieve lower relapse and better survival.
Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Adulto , Humanos , Leucemia Mieloide Aguda/terapia , Estudios Retrospectivos , Trasplante Autólogo , Donante no EmparentadoRESUMEN
Objective: To compare the efficacy of autologous HSCT (auto-HSCT) with matched sibling donor (MSD) HSCT in Ph(+) ALL and provide a basis for the choice of transplantation method. Methods: We retrospectively investigated the outcomes of 78 adult patients with Ph(+) ALL who underwent auto-HSCT (n=31) and MSD-HSCT (n=47) in Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC, from January 2008 to December 2017. The overall survival (OS) rate, leukemia-free survival (LFS) rate, cumulative incidence of relapse (CIR) rate, nonrelapse mortality (NRM) rate, and the impact of achievement of complete molecular response (CMR) within 3 months and sustaining CMR up to transplantation (s3CMR) on transplantation method were explored. Results: The median time of neutrophil and platelet reconstitution in auto-HSCT and MSD-HSCT groups were 12 (10-29) days vs14 (11-24) days (P=0.006) and 17.5 (10-62) days vs 7 (10-33) days (P=0.794) , respectively. In the MSD-HSCT group, the incidence of â ¡-â £ and â ¢-â £ acute graft-versus-host disease (GVHD) was 27.7% (13/47) and 8.5% (4/47) , respectively. The incidence of limited and extensive chronic GVHD was 17.0% (8/47) and 12.8% (6/47) , respectively. The estimated CIR, NRM, LFS, and OS at 3 years were not significantly different between auto-HSCT and MSD-HSCT groups (P>0.05) . For 44 patients who achieved s3CMR, 3-year OS[ (84.0±8.6) % vs (78.0±8.7) %, P=0.612], LFS[ (70.3±10.3) % vs (68.2±10.1) %, P=0.970], CIR[ (24.9±10.0) % vs (14.4±8.0) %, P=0.286], and NRM[ (4.7±4.7) % vs (17.4±8.1) %, P=0.209] of the auto-HSCT and MSD-HSCT groups were not significantly different. However, for 34 patients who did not reach s3CMR, 3-year cumulative relapse rate of patients in the auto-HSCT group was significantly higher than MSD-HSCT group[ (80.0±14.7) % vs (39.6±10.9) %, P=0.057]. Conclusions: auto-HSCT with maintenance therapy after HSCT appears to be an attractive treatment option for patients with Ph(+) ALL especially for those with s3CMR maintained up to transplantation. For non-s3CMR patients, allogeneic transplantation may be more effective from lower relapse.
Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Cromosoma Filadelfia , Estudios Retrospectivos , Hermanos , Acondicionamiento Pretrasplante , Trasplante AutólogoRESUMEN
OBJECTIVE: To clarify the role of LINC00675 in affecting the progression of clear cell renal cell carcinoma (ccRCC) and its potential mechanism, thus providing effective hallmarks and therapeutic targets for the clinical treatment of ccRCC. MATERIALS AND METHODS: Differentially expressed long non-coding RNAs (lncRNAs) in renal epithelial tissues and ccRCC tissues were searched by analyzing the dataset downloaded from The Cancer Genome Atlas (TCGA) and LINC00675 was selected. LINC00675 level in ccRCC cell lines was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Overexpression model of LINC00675 model in 786-O and 769-P cells was constructed by the transfection of pcDNA3.1(+)-LINC00675 (LV-LINC00675). Changes in proliferative, migratory, and invasive capacities of 786-O and 769-P cells overexpressing LINC00675 were assessed. At last, relative levels of ß-catenin, Vimentin, and N-cadherin in ccRCC cells overexpressing LINC00675 were detected by qRT-PCR and Western blot. RESULTS: LINC00675 was downregulated in ccRCC tissues and cell lines. Overexpression of LINC00675 attenuated proliferative, migratory, and invasive capacities of 786-O and 769-P cells. Downregulation in ß-catenin after overexpression of LINC00675, while Vimentin and N-cadherin levels did not change. CONCLUSIONS: LINC00675 is downregulated in ccRCC. Overexpression of LINC00675 attenuates ccRCC to proliferate, migrate, and invade by activating the Wnt/ß-catenin pathway.
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Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/patología , Movimiento Celular , Neoplasias Renales/metabolismo , Neoplasias Renales/patología , ARN Largo no Codificante/metabolismo , Vía de Señalización Wnt , beta Catenina/metabolismo , Proliferación Celular , Células Cultivadas , Regulación hacia Abajo , Humanos , ARN Largo no Codificante/genéticaRESUMEN
Objective: To evaluate the outcomes of myelodysplastic syndromes (MDS) patients who received HLA-matched sibling donor allogeneic peripheral blood stem cell transplantation (MSD-PBSCT) . Methods: The clinical data of 138 MDS patients received MSD-PBSCT from Sep. 2005 to Dec. 2017 were retrospectively analyzed, and the overall survival (OS) rate, disease-free survival (DFS) rate, relapse rate (RR) , non-relapse mortality (NRM) rate and the related risk factors were explored. Results: â After a median follow-up of 1 050 (range 4 to 4 988) days, the 3-year OS and DFS rates were (66.6±4.1) % and (63.3±4.1) %, respectively. The 3-year cumulative incidence of RR and NRM rates were (13.9±0.1) % and (22.2±0.1) %, respectively. â¡Univariate analysis showed that patients with grade â ¢-â £ acute graft-versus-host disease (aGVHD) or hematopoietic cell transplantation comorbidity index (HCT-CI) ≥2 points or patients in very high-risk group of the Revised International Prognostic Scoring System (IPSS-R) had significantly decreased OS[ (42.9±13.2) %vs (72.9±4.2) %, χ(2)=8.620, P=0.003; (53.3±7.6) %vs (72.6±4.7) %, χ(2)=6.681, P=0.010; (53.8±6.8) %vs (76.6±6.2) %vs (73.3±7.7) %, χ(2)=6.337, P=0.042]. For MDS patients with excess blasts-2 (MDS-EB2) and acute myeloid leukemia patients derived from MDS (MDS-AML) , pre-transplant chemotherapy or hypomethylating agents (HMA) therapy could not improve the OS rate[ (60.4±7.8) %vs (59.2±9.6) %, χ(2)=0.042, P=0.838]. â¢Multivariate analysis indicated that the HCT-CI was an independent risk factor for OS and DFS (P=0.012, HR=2.108, 95%CI 1.174-3.785; P=0.008, HR=2.128, 95%CI 1.219-3.712) . Conclusions: HCT-CI was better than the IPSS-R in predicting the outcomes after transplantation. The occurrence of grade â ¢-â £ aGVHD is a poor prognostic factor for OS. For patients of MDS-EB2 and MDS-AML, immediate transplantation was recommended instead of receiving pre-transplant chemotherapy or HMA therapy.