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1.
Am J Hematol ; 98(9): 1394-1406, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37366294

RESUMEN

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell malignancy, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curable treatment. The outcomes after transplant are influenced by both disease characteristics and patient comorbidities. To develop a novel prognostic model to predict the post-transplant survival of CMML patients, we identified risk factors by applying univariable and multivariable Cox proportional hazards regression to a derivation cohort. In multivariable analysis, advanced age (hazard ratio [HR] 3.583), leukocyte count (HR 3.499), anemia (HR 3.439), bone marrow blast cell count (HR 2.095), and no chronic graft versus host disease (cGVHD; HR 4.799) were independently associated with worse survival. A novel prognostic model termed ABLAG (Age, Blast, Leukocyte, Anemia, cGVHD) was developed and the points were assigned according to the regression equation. The patients were categorized into low risk (0-1), intermediate risk (2, 3), and high risk (4-6) three groups and the 3-year overall survival (OS) were 93.3% (95%CI, 61%-99%), 78.9% (95%CI, 60%-90%), and 51.6% (95%CI, 32%-68%; p < .001), respectively. In internal and external validation cohort, the area under the receiver operating characteristic (ROC) curves of the ABLAG model were 0.829 (95% CI, 0.776-0.902) and 0.749 (95% CI, 0.684-0.854). Compared with existing models designed for the nontransplant setting, calibration plots, and decision curve analysis showed that the ABLAG model revealed a high consistency between predicted and observed outcomes and patients could benefit from this model. In conclusion, combining disease and patient characteristic, the ABLAG model provides better survival stratification for CMML patients receiving allo-HSCT.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mielomonocítica Crónica , Humanos , Pronóstico , Trasplante Homólogo/efectos adversos , Estudios Retrospectivos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Injerto contra Huésped/etiología
2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(4): 1173-1180, 2024 Aug.
Artículo en Zh | MEDLINE | ID: mdl-39192415

RESUMEN

OBJECTIVE: To investigate the clinical characteristics and survival analysis of myelodysplastic syndromes (MDS) with RUNX1 gene mutation. METHODS: Clinical data of 177 newly diagnosed MDS patients admitted to the Department of Hematology, the Second Affiliated Hospital of Air Force Military Medical University from October 1, 2015 to October 31, 2022 were retrospectively analyzed. Gene mutation detection was performed by second-generation sequencing technology, and clinical characteristics and prognosis of patients with RUNX1 gene mutation were analyzed. RESULTS: A total of 30 cases (16.95%) of RUNX1 gene mutations were detected, including 15 missense mutations (50.0%), 9 frameshift deletion mutations (30.0%), 4 splice site mutations (13.3%), 1 insertion mutation (3.3%), and 1 nonsense mutation (3.3%). Patients with RUNX1 mutations had a median age of 68.5 years at diagnosis (range: 62.25-78.50 years old). There were no significantly differences between RUNX1 mutations and wild type patients in age distribution, gender, peripheral blood white blood cell count, hemoglobin level, bone marrow and peripheral blood blasts ratio, IPSS-R cytogenetics, IPSS-R stage, etc. (P >0.05). However, there were statistically significant differences in platelet count and whether complicated karyotype. Compared with patients without RUNX1 gene mutation, patients with RUNX1 gene mutation had lower platelet count (P =0.018), and were less likely to have complicatedkaryotype at initial diagnosis (P =0.01). Cox proportional hazards model analysis showed that when other covariates remained unchanged, the higher the platelet count, the better the survival of patients (HR=0.995, 95%CI : 0.990-0.999, P =0.036); In the IPSS-M prognostic stratification, keeping other covariates unchanged, the risk of progression or death of myelodysplastic syndrome was significantly lower in the medium to high-risk and low-risk groups compared with the high-risk group (HR=0.149, 95%CI : 0.031-0.721, P =0.018; HR=0.026, 95%CI : 0.003-0.234, P =0.001). Survival analysis showed that MDS patients with RUNX1 gene mutation had worse overall survival time (P < 0.001). Patients with RUNX1 mutation had worse OS than non-mutation patients in the early WHO group. RUNX1 mutation and IPSS-M risk stratification mean OS and mean LFS were worse in low-risk patients than in non-mutated patients. CONCLUSION: RUNX1 gene mutation is an adverse prognostic factor in MDS patients, especially in the IPSS-M prognosis stratification group of low-risk, medium-low risk, medium-high risk and WHO classification of early patients.


Asunto(s)
Subunidad alfa 2 del Factor de Unión al Sitio Principal , Mutación , Síndromes Mielodisplásicos , Humanos , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Síndromes Mielodisplásicos/genética , Síndromes Mielodisplásicos/diagnóstico , Pronóstico , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Masculino , Femenino
3.
Protein Expr Purif ; 85(1): 109-16, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22813925

RESUMEN

Signal regulatory protein (SIRP) α, a transmembrane protein belonging to the immunoglobulin superfamily, is a receptor for CD47. The interaction between SIRPα and CD47 plays an important role in regulating the phagocytosis of leukemia cells and leukemia stem cells (LSCs) by macrophages. Blocking antibodies against CD47 have been shown to promote phagocytosis of LSCs by macrophages. Here, we consider an alternative way to interrupt the interaction between CD47 and SIRPα. We expressed the extracellular domains of the human SIRPα (hSIRP(ext)) and the human CD47 (hCD47(ext)) in Escherichia coli as Trx fusion proteins, and purified them by using affinity chromatography. We show that the purified fusion protein Trx-SIRP(ext) could interact in vitro with Trx-hCD47(ext). Moreover, Trx-SIRP(ext) could effectively bind to Jurkat T-ALL cells, which expressed CD47 at a high level. CD47(ext), on the other hand, bound to human macrophages. In vitro phagocytosis assay showed that these fusion proteins could enhance the phagocytosis of Jurkat cells by macrophage, with Trx-hSIRP(ext) showed a higher efficiency than Trx-CD47(ext). These results indicated that the soluble Trx-hSIRP(ext) and Trx-CD47(ext) polypeptides could be alternative molecules to interrupt CD47-SIRPα interaction between leukemia cells and macrophages, and might be potentially useful for the targeted therapy of leukemia.


Asunto(s)
Antígenos de Diferenciación/genética , Antígenos de Diferenciación/farmacología , Antígeno CD47/genética , Antígeno CD47/farmacología , Escherichia coli/genética , Macrófagos/efectos de los fármacos , Fagocitosis/efectos de los fármacos , Receptores Inmunológicos/genética , Antígenos de Diferenciación/química , Antígenos de Diferenciación/inmunología , Antígeno CD47/química , Antígeno CD47/inmunología , Humanos , Células Jurkat , Leucemia de Células T/tratamiento farmacológico , Leucemia de Células T/inmunología , Macrófagos/inmunología , Replegamiento Proteico , Estructura Terciaria de Proteína , Receptores Inmunológicos/química , Receptores Inmunológicos/inmunología , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/inmunología , Proteínas Recombinantes de Fusión/farmacología
4.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 30(5): 1577-1585, 2022 Oct.
Artículo en Zh | MEDLINE | ID: mdl-36208269

RESUMEN

OBJECTIVE: To investigate the clinical outcomes and prognostic factors of refractory/relapsed acute myeloid leukemia (AML) patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: The clinical data of 80 refractory/relapsed AML patients who received allo-HSCT from December 2013 to June 2020 were retrospectively analyzed, including the overall survival (OS) rate, disease-free survival (DFS) rate, relapse rate, incidence of transplant-related mortality (TRM), and the related risk factors were explored. RESULTS: Hematopoietic reconstitution was obtained in all 80 patients after transplantation, the 3-year OS and DFS rates were (48.8±6.3)% and (40.8±6.7)%, respectively. The 3-year cumulative incidence of relapse and TRM were 33.8% (95%CI: 0.254-0.449) and 15.0%(95%CI: 0.114-0.198), respectively. Univariate analysis showed that non-remission (NR) status before transplantation, DNMT3A R882 mutations and grade II-IV acute graft-versus-host disease (aGVHD) had negative effects on OS and DFS. Multivariate analysis indicated that the DNMT3A R882 mutations and grade II-IV aGVHD were independent risk factors for OS (HR=0.253, 95%CI: 0.092-0.695, P=0.008; HR=5.681, 95%CI: 2.101-15.361, P=0.001) and DFS (HR=0.200, 95%CI: 0.071-0.569, P=0.003; HR=7.117, 95%CI: 2.556-19.818, P<0.001). The 3-year cumulative incidence of relapse was 71.4%(95%CI: 0.610-0.836) in genetic high-risk group, which was higher than 23.3%(95%CI: 0.147-0.370) in intermediate-risk group and 23.5%(95%CI: 0.127-0.437) in favorable-risk group (P=0.006). CONCLUSION: Allo-HSCT is an effective and safe choice for refractory/relapsed AML patients. DNMT3A R882 mutations and grade II-IV aGVHD are negative prognostic factors of allo-HSCT for refractory/relapsed AML patients.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Pronóstico , Recurrencia , Estudios Retrospectivos , Trasplante Homólogo/efectos adversos
5.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(4): 1163-1168, 2021 Aug.
Artículo en Zh | MEDLINE | ID: mdl-34362497

RESUMEN

OBJECTIVE: To compare the clinical efficacy of first-line and salvage autologous hematopoietic stem cell transplantation (auto-HSCT) in the treatment of patients with diffuse large B-cell lymphoma (DLBCL). METHODS: The clinical data of 30 patients with DLBCL aged≤60 years old were retrospectively analyzed, and the patients were divided into first-line auto-HSCT group (15 cases) and salvage auto-HSCT group (refractory relapsed patients, 15 cases) according to the timing of transplantation, and the efficacy was analyzed. Anyone of the factors must be followed in patients receiving first-line HSCT: aaIPI score≥2 points, Ann-Arbor stage III-IV, large mass (diameter≥10 cm) or double expression of c-myc/BCL-2. RESULTS: The median follow-up time for all patients after transplantation was 26 (3-103) months. Until the end of follow-up, 23 patients survived and 7 patients died. All the 7 dead patients with multiple organ failure due to the relapse and disease progression. The median survival time of 7 dead patients from transplantation to death was 6 (3-11) months. Among the 15 patients in the first-line auto-HSCT group, there were 2 patients relapsed (13.3%), 1 dead (6.7%), 14 patients survived [overall survival (OS) rate was 93.3%]. Among the 15 patients treated with salvage auto-HSCT, 6 patients died due to disease progression or relapse (40%), 9 cases survived (OS rate was 60%). There was a statistically significant difference in the mortality of patients between the two groups (6.7% vs 40%, P=0.006). The 3-year PFS and OS rates of patients in first-line auto-HSCT group were both 93.3%. The 3-year PFS and OS of patients in salvage auto-HSCT group were 58.7% and 59.2%. The 3-year OS and PFS of patients in the first-line auto-HSCT group were significantly higher than those in the salvage auto-HSCT group (P=0.03, P=0.04). The bone marrow suppression was the most common adverse complication and all patients showed grade III-IV granulocytopenia. Non-hematological adverse reactions were mainly gastrointestinal adverse reactions and oral mucositis. There was no statistically significant difference in adverse reactions between the two groups. CONCLUSION: First-line auto-HSCT can be used as a consolidation treatment for DLBCL patients with poor prognostic factors. Auto-HSCT can further improve the prognosis of salvage chemotherapy-sensitive patients with refractory relapsed DLBCL.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Linfoma de Células B Grandes Difuso , Supervivencia sin Enfermedad , Humanos , Linfoma de Células B Grandes Difuso/terapia , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Trasplante Autólogo , Resultado del Tratamiento
6.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1683-1688, 2020 Oct.
Artículo en Zh | MEDLINE | ID: mdl-33067974

RESUMEN

OBJECTIVE: To compare the clinical efficacy between frontline haplo-identical hematopoietic stem cell transplantation (haplo-HSCT) and salvage haplo-HSCT for patients with severe aplastic anemia (SAA). METHODS: A total of 39 patients with severe aplastic anemia or very severe aplastic anemia from May 1st, 2013 to December 31st, 2018 were analyzed retrospectively. All of them underwent bone marrow + peripheral blood hemopoietic stem cell transplantation. There were 20 cases who accepted frontline haplo-HSCT for a median course of 1 (1-3) month, and 19 cases who accepted salvage haplo-HSCT for a median course of 72 (6-168) months. Conditioning regimen: 22 cases received Flu/Cy+ATG, and 17 cases received Bu/Cy+ATG. RESULTS: The time of hematopoietic reconstitution, infection rate, and grade I-Ⅱ and Ⅲ-Ⅳ acute/chronic graft versus host disease showed no statistically significance between the frontline haplo-HSCT group and the salvage haplo-HSCT group. In the frontline haplo-HSCT group, 1 case (5%) failed in second engraftment, in the salvage haplo-HSCT group 2 cases (10.5%) failed in primary engraftment and 4 cases (21.1%) in second engraftment. The incidence of engraftment failure was higher in the salvage haplo-HSCT group than that in the frontline haplo-HSCT group (P=0.04). The median time of follow-up after allo-HSCT was 45 months (ranging from 3 to 92). The mortality was 10% (2/20) in the frontline haplo-HSCT group, and 42.1% (8/19) in the salvage haplo-HSCT group. The estimated 5-year failure-free survival rate (FFS) of the frontline haplo-HSCT group was higher than that of the salvage haplo-HSCT group (90% vs 57.4%) (P=0.02). CONCLUSION: The frontline haplo-HSCT is an effective and safe approach for the patients with severe aplastic anemia who lack a HLA-matched sibling donor.


Asunto(s)
Anemia Aplásica , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Anemia Aplásica/terapia , Humanos , Estudios Retrospectivos , Acondicionamiento Pretrasplante
7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 24(3): 827-32, 2016 Jun.
Artículo en Zh | MEDLINE | ID: mdl-27342518

RESUMEN

OBJECTIVE: To investigate the microRNA (miRNA) expression in plasma of patients with aGVHD and without aGVHD after allo-hematopoietic stem cell transplantation (allo-HSCT). METHODS: The miRNAs (miR-423, mirR199a-3p, miR93*, miR377) expression levels in peripheral blood plasma of 25 patients before and after allo-HSCT were detected by real-time PCR. RESULTS: miR-423, miR199a-3p and miR-93* in aGVHD group were significantly upregulated (P<0.05); miR-377 expression was not significantly different between aGVHD and non-aGVHD (P>0.05). CONCLUSION: The expression of miR-423, miR-199a-3p, miR-93* are upregulated in aGVHD group, which can be used as biomarkes to monitor and to diagnose aGVHD.


Asunto(s)
Enfermedad Injerto contra Huésped/patología , Trasplante de Células Madre Hematopoyéticas , MicroARNs/sangre , Biomarcadores/sangre , Enfermedad Injerto contra Huésped/sangre , Humanos , Reacción en Cadena en Tiempo Real de la Polimerasa , Regulación hacia Arriba
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