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1.
Ann Hematol ; 103(2): 575-582, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37932468

RESUMEN

Autologous stem cell transplantation (ASCT) is a salvage therapy for relapsed or refractory diffuse large B-cell lymphoma (DLBCL). We have developed a novel conditioning regimen called CEAC (oral semustine 250 mg/m2 d-6, etoposide 300 mg/m2 d-5 ~ d-2, cytarabine 500 mg/m2 d-5 ~ d-2, and cyclophosphamide 1200 mg/m2 d-5 ~ d-2) In lymphoma patients in China. Here, we conducted a study to compare the conventional BEAM regimen with the CEAC regimen in 110 DLBCL patients. Propensity-score matching was performed in a 1:4 ratio (22 patients received BEAM and 88 received CEAC). Our results showed no significant difference in the overall response rate (95% vs 97%, P = 1.000) and complete response rate (66% vs 73%, P = 0.580) between the two cohorts. The 5-year progression-free survival (PFS), 5-year overall survival (OS), and 5-year cumulative incidence of relapse (CIR) for all patients were 72% (95% CI 62%-82%), 92% (95% CI 86%-97%), and 29% (95% CI 17%-38%), respectively. There was no significant difference in the 5-year PFS (80% vs 70%, P = 0.637), 5-year OS (95% vs 91%, P = 0.496), and 5-year CIR (20% vs 30%, P = 0.733) between cohorts. In terms of safety, the CEAC cohort had a lower incidence rate of grade 1-2 gastrointestinal hemorrhage (P = 0.023) and severe nausea (P = 0.007) compared with the BEAM cohort. In conclusion, the CEAC regimen seems to be a suitable alternative to the BEAM regimen for ASCT in DLBCL patients.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Linfoma de Células B Grandes Difuso , Humanos , Carmustina/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Melfalán/efectos adversos , Etopósido/efectos adversos , Semustina , Estudios de Cohortes , Puntaje de Propensión , Trasplante Autólogo/métodos , Recurrencia Local de Neoplasia , Ciclofosfamida/efectos adversos , Citarabina/efectos adversos , Linfoma de Células B Grandes Difuso/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos
2.
Br J Haematol ; 202(1): 111-115, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37038274

RESUMEN

As reported, SETD2 is recurrently mutated in acute myeloid leukaemia (AML), but knowledge about the specifics is limited. We enrolled 530 consecutive newly diagnosed AML patients in our study, and we analysed the distribution pattern and prognostic role of SETD2 mutation in AML. SETD2 mutation was found to affect 6.3% of AML patients, and it frequently co-occurred with IDH2, NRAS and CEBPA mutations. SETD2-mutated patients saw excellent therapeutic responses but failed to gain better survival time than other patients. This could be because of the high recurrence and mortality in SETD2-mutated patients who have additional mutations, such as NRAS mutation.


Asunto(s)
Leucemia Mieloide Aguda , Nucleofosmina , Humanos , Pronóstico , Mutación , Leucemia Mieloide Aguda/terapia
3.
Ann Hematol ; 102(2): 329-335, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36633637

RESUMEN

A standard salvage regimen for patients with acute myeloid leukemia (AML) who are not in complete remission (CR) after initial induction therapy does not exist. We retrospectively investigated re-induction therapy for 151 patients with AML who did not achieve CR after the initial course between January 2014 and March 2021. The re-induction regimen did not correlate with the CR rate after the second course, whereas patients had similar 5-year overall survival (OS) and event-free survival (EFS) based on different re-induction regimens. Multivariable analysis revealed that International European Leukaemia Net (ELN) risk stratification independently predicted both OS and EFS among patients not in CR after the first course, although the re-induction regimen did not predict prognosis. Urgent salvage alloHSCT may improve the prognosis of patients with refractory AML. In summary, our study showed that the re-induction regimen did not significantly predict the prognosis of patients with AML not in CR after the first course of treatment. The development and selection of an efficient treatment algorithm for the treatment of AML remains a pressing research challenge.


Asunto(s)
Quimioterapia de Inducción , Leucemia Mieloide Aguda , Humanos , Estudios Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Citarabina , Leucemia Mieloide Aguda/tratamiento farmacológico , Inducción de Remisión , Pronóstico
4.
Ann Hematol ; 102(1): 89-97, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36542104

RESUMEN

Acute myeloid leukemia (AML) patients relapsing after allogeneic hematopoietic stem cell transplantation (allo-HSCT) have a poor prognosis. Cytogenetic evolution (CGE) has been investigated and found to have an important impact on the prognosis of relapsed leukemia, but its impact on AML patients relapsing after transplantation remains controversial. In this study, we analyzed 34 AML patients relapsing after allo-HSCT, among whom 14 developed additional abnormalities in chromosomal karyotype after leukemia recurrence (CGE group) and 20 patients did not (non-CGE group). We found that the cytogenetic characteristics were much more complex at relapse in the CGE group, and the acquisition of aberrations at relapse most commonly involved chromosome 11. The 6-month post-relapse overall survival (PROS) of the CGE group was significantly lower than that of the non-CGE group (21.4% versus 50.0%, P = 0.004). The CGE group also showed a trend of worse 2-year OS (7.1% versus 28.6%, P = 0.096). In the multivariate analyses, the occurrence of chronic graft-versus-host disease (HR 0.27 [95% CI, 0.11-0.68], P = 0.006) and a reduced-intensity FBA conditioning regimen (HR 0.42 [95% CI, 0.18-0.98], P = 0.045) were found to be two independent factors for a better PROS, whereas CGE (HR 3.16 [95% CI, 1.42-7.05], P = 0.005) was associated with a worse PROS. In conclusion, CGE was associated with a poor prognosis in AML patients who relapsed after allo-HSCT, and the importance of monitoring karyotype changes after transplantation should be noted.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Humanos , Estudios Retrospectivos , Trasplante Homólogo , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Enfermedad Crónica , Cariotipificación , Recurrencia , Pronóstico
5.
J Chem Technol Biotechnol ; 98(6): 1356-1364, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38516537

RESUMEN

In this paper we report our kinetic study of an oxidation reaction from valencene to nootkatone using enzyme in an oscillatory baffled reactor. The aims of this work are to elucidate the reaction mechanism and evaluate reaction kinetics. Towards these objectives, a full kinetic model using the Langmuir-Hinshelwood method was established and applied to the experimental data, allowing reactor schemes and orders to be confirmed and reaction rate constants to be extracted. Our full kinetic analysis suggests that most of the reversible reaction steps can be treated as irreversible, simplifying the overall reaction schemes. The effect of mass transfer on the kinetics was also investigated. © 2023 The Authors. Journal of Chemical Technology and Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry (SCI).

6.
Biol Blood Marrow Transplant ; 26(10): 1840-1854, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32534102

RESUMEN

Secondary failure of platelet recovery (SFPR) can occur after allogeneic hematopoietic stem cell transplantation (alloHSCT), and 20% of cases are related to acute graft-versus-host disease (aGVHD). The underlying mechanisms of this association are unclear, however. The aim of the present study was to investigate the potential mechanisms of SFPR secondary to aGVHD, which may provide a new therapeutic strategy for these patients. A total of 468 patients with malignant hematologic disease who underwent alloHSCT were included. Sixty-six patients developed SFPR after alloHSCT, and in 45 of these 66 patients (68.2%), SFPR was secondary to grade II-IV aGVHD (SFPR/aGVHD). Compared with patients with good graft function (GGF), patients with SFPR had poor overall survival (20.72% versus 88.01%; P < .0001). Grade II-IV aGVHD was identified as an independent risk factor for SFPR in multivariate analysis (hazard ratio, 9.512; P < .0001). We observed reduced erythroid and megakaryocyte colony formation in bone marrow (BM) samples isolated from SFPR/aGVHD patients, consistent with the lower frequency of megakaryocyte and erythrocyte progenitors in BM. Levels of the inflammatory cytokines IL-2R and TNF-R1 were significantly higher in the SFPR/aGVHD group compared with the GGF group (P = .002 and .001, respectively), as were the frequencies of proinflammatory T helper subsets. Furthermore, the pathways that regulate hematopoiesis and immune responses were universally underexpressed in CD34+ cells isolated from SFPR/aGVHD patients. Differentially expressed genes were significantly enriched in the hematopoietic cell lineage pathway and other pathways involved in both immune responses and megakaryopoiesis. In summary, we found that both the immune microenvironment and compromised proliferation of hematopoietic primitive cells contribute to the development of SFPR secondary to aGVHD, and our data provide new insight into the mechanisms of SFPR in the context of aGVHD.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Enfermedad Aguda , Plaquetas , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Megacariocitos , Trasplante Homólogo
7.
Pharm Dev Technol ; 25(2): 219-226, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31651201

RESUMEN

The introduction of continuous manufacturing of pharmaceuticals has highlighted the challenging area of continuous dissolution of solids for work ups to flow chemistry systems. In this study, the use of a 16 mm twin screw extruder (TSE) as a platform technology for solid feeds is investigated using four solid pharmaceutical ingredients (PI) in a mixture of water and IPA. In order for comparison, the same experiments were also carried out in a batch traditional stirred tank vessel (STV). The objectives of this work are to gain further scientific understanding on dissolution kinetics and to compare kinetics in both a batch and continuous system. The concentration of each PI during dissolution is monitored using an in-line UV-ATR probe, allowing the extraction of dissolution kinetics. Faster dissolution rates are achieved in the TSE than in the STV due to higher power dissipation generated by the aggressive shear mixing and thermal energy within the TSE. Complete dissolution of paracetamol is obtained within the residence time of the TSE; complete dissolution of benzoic acid and acetylsalicylic acid are achieved at higher barrel temperatures; however full dissolution of nicotinic acid is not achievable in the TSE under the experimental conditions.


Asunto(s)
Acetaminofén/química , Solubilidad/efectos de los fármacos , Sistemas de Liberación de Medicamentos/métodos , Calor , Cinética , Vehículos a Motor , Elastómeros de Silicona/química , Tecnología Farmacéutica/métodos
8.
Clin Psychol Psychother ; 27(3): 384-395, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32415733

RESUMEN

Corona virus disease 2019 (COVID-19) outbreak has attracted worldwide attention. The COVID-19 outbreak is unique in its rapid transmission and results in heavy stress for the front-line health care workers (HCWs). The current study aimed to exam posttraumatic stress symptoms (PTSSs) of HCWs fighting for the COVID-19 and to evaluate their sleep quality after 1-month stressful suffering. Three hundred seventy-seven HCWs working in different provinces of China participated in the survey between February 1 and 5. The demographic information was collected first. Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5) and the Pittsburgh Sleep Quality Index (PSQI) were selected to measure PTSSs and sleep quality. Results showed that 1 month after the outbreak, the prevalence of PTSSs was 3.8% in HCWs. Female HCWs were more vulnerable to PTSSs with hazard ratio of 2.136 (95% CI = 1.388-3.286). HCWs with higher exposure level also significantly rated more hyperarousal symptoms (hazard ratio = 4.026, 95% CI = 1.233-13.140). There was a significant difference of sleep quality between participants with and without PTSSs (z value = 6.014, p < .001) and among different groups with various contact frequencies (chi-square = 7.307, p = .026). Path analysis showed that there was a significant indirect effect from exposure level to PTSSs through sleep quality (coefficient = 1.750, 95% CI of Boostroop test = 0.543-2.998). In summary, targeted interventions on sleep contribute to the mental recovery during the outbreak of COVID-19. Understanding the mental health response after a public health emergency might help HCWs and communities prepare for a population's response to disaster.


Asunto(s)
Infecciones por Coronavirus/psicología , Personal de Salud/psicología , Personal de Salud/estadística & datos numéricos , Neumonía Viral/psicología , Trastornos por Estrés Postraumático/epidemiología , Trastornos por Estrés Postraumático/prevención & control , Adolescente , Adulto , Betacoronavirus , COVID-19 , China/epidemiología , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias , SARS-CoV-2 , Adulto Joven
9.
Ann Hematol ; 98(7): 1765-1773, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-30993416

RESUMEN

To investigate the effect of chronic graft-versus-host disease (cGVHD) on the outcomes of acute myeloid leukemia (AML) patients who relapsed after allogenic hematopoietic cell transplantation, we performed a retrospective analysis on 218 patients with a median follow-up of 21.4 (3.4-179.6) months. A total of 103 patients developed cGVHD, with a 2-year cumulative incidence of 48.9% (95% CI 42.1-55.7%). The estimated 3-year overall survival was 85.7% (95% CI 75.7-95.7%), 48.8% (95% CI 31.7-66.0%), and 54.1% (95% CI 44.3-63.8%) for patients with limited cGVHD, extensive cGVHD, and without cGVHD (P < 0.001). The 3-year event-free survival were 75.5% (95% CI 63.7-87.4%), 46.0% (95% CI 28.8-63.2%), and 45.0% (95% CI 35.6-54.4%) (P < 0.001), while the 3-year cumulative relapse rates were 22.8% (95% CI 11.0-34.6%), 11.6% (95% CI 5.3-22.6%), and 40.3% (95% CI 31.0-49.6%), respectively (P < 0.001). At the last evaluation, 62 patients relapsed with 17 patients having active cGVHD and 45 without. Compared to patients relapsing without cGVHD, patients who relapsed with cGVHD had a longer duration of remission and a better 2-year post-relapse survival [10.9 months (3.7-42.2) versus 4.4 months (2.2-28.3); P < 0.001]; [32.8% (95% CI 8.2-57.4%) versus 4.5% (95% CI 0-12.8%); P = 0.043]. For patients who relapsed with cGVHD, the remission rates were both 60% after salvage chemotherapy with or without donor lymphocyte infusion (P = 1.000). In conclusion, cGVHD may exert a stronger graft-versus-leukemia effect, which may decrease the post-transplantation relapse rate and may also benefit those patients who eventually relapsed after transplantation in terms of prolong post-relapse survival.


Asunto(s)
Enfermedad Injerto contra Huésped , Efecto Injerto vs Leucemia , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Transfusión de Linfocitos , Adolescente , Adulto , Enfermedad Crónica , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/mortalidad , Enfermedad Injerto contra Huésped/terapia , Humanos , Incidencia , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/terapia , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Tasa de Supervivencia
10.
Blood ; 127(18): 2249-60, 2016 05 05.
Artículo en Inglés | MEDLINE | ID: mdl-26884373

RESUMEN

Cutaneous sclerosis is one of the most common clinical manifestations of chronic graft-versus-host disease (cGVHD). Donor CD4(+) T and B cells play important roles in cGVHD pathogenesis, but the role of antibodies from donor B cells remains unclear. In the current studies, we generated immunoglobulin (Ig)H(µÎ³1) DBA/2 mice whose B cells have normal antigen-presentation and regulatory functions but cannot secrete antibodies. With a murine cGVHD model using DBA/2 donors and BALB/c recipients, we have shown that wild-type (WT) grafts induce persistent cGVHD with damage in the thymus, peripheral lymphoid organs, and skin, as well as cutaneous T helper 17 cell (Th17) infiltration. In contrast, IgH(µÎ³1) grafts induced only transient cGVHD with little damage in the thymus or peripheral lymph organs or with little cutaneous Th17 infiltration. Injections of IgG-containing sera from cGVHD recipients given WT grafts but not IgG-deficient sera from recipients given IgH(µÎ³1) grafts led to deposition of IgG in the thymus and skin, with resulting damage in the thymus and peripheral lymph organs, cutaneous Th17 infiltration, and perpetuation of cGVHD in recipients given IgH(µÎ³1) grafts. These results indicate that donor B-cell antibodies augment cutaneous cGVHD in part by damaging the thymus and increasing tissue infiltration of pathogenic Th17 cells.


Asunto(s)
Subgrupos de Linfocitos B/inmunología , Enfermedad Injerto contra Huésped/inmunología , Isoanticuerpos/inmunología , Animales , Subgrupos de Linfocitos B/metabolismo , Subgrupos de Linfocitos B/trasplante , Quimiocina CCL20/metabolismo , Enfermedad Crónica , Células Dendríticas/metabolismo , Enfermedad Injerto contra Huésped/patología , Inmunoglobulina G/análisis , Cadenas Pesadas de Inmunoglobulina , Cadenas gamma de Inmunoglobulina/genética , Cadenas gamma de Inmunoglobulina/inmunología , Cadenas mu de Inmunoglobulina/genética , Cadenas mu de Inmunoglobulina/inmunología , Interleucina-23/metabolismo , Tejido Linfoide/patología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos DBA , Quimera por Radiación , Piel/patología , Organismos Libres de Patógenos Específicos , Células Th17/inmunología , Timo/patología
12.
J Immunol ; 191(1): 488-99, 2013 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-23709681

RESUMEN

Prevention of chronic graft-versus-host disease (cGVHD) remains a major challenge in allogeneic hematopoietic cell transplantation (HCT) owing to limited understanding of cGVHD pathogenesis and lack of appropriate animal models. In this study, we report that, in classical acute GVHD models with C57BL/6 donors and MHC-mismatched BALB/c recipients and with C3H.SW donors and MHC-matched C57BL/6 recipients, GVHD recipients surviving for >60 d after HCT developed cGVHD characterized by cutaneous fibrosis, tissue damage in the salivary gland, and the presence of serum autoantibodies. Donor CD8(+) T cells were more potent than CD4(+) T cells for inducing cGVHD. The recipient thymus and de novo-generated, donor-derived CD4(+) T cells were required for induction of cGVHD by donor CD8(+) T cells but not by donor CD4(+) T cells. Donor CD8(+) T cells preferentially damaged recipient medullary thymic epithelial cells and impaired negative selection, resulting in production of autoreactive CD4(+) T cells that perpetuated damage to the thymus and augmented the development of cGVHD. Short-term anti-CD4 mAb treatment early after HCT enabled recovery from thymic damage and prevented cGVHD. These results demonstrate that donor CD8(+) T cells cause cGVHD solely through thymic-dependent mechanisms, whereas CD4(+) T cells can cause cGVHD through either thymic-dependent or independent mechanisms.


Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/trasplante , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/trasplante , Enfermedad Injerto contra Huésped/inmunología , Enfermedad Injerto contra Huésped/patología , Timo/inmunología , Timo/patología , Enfermedad Aguda , Animales , Linfocitos T CD4-Positivos/patología , Linfocitos T CD8-positivos/patología , Enfermedad Crónica , Trasplante de Células Madre Hematopoyéticas , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C3H , Ratones Endogámicos C57BL , Ratones Noqueados , Timo/trasplante
13.
Biol Blood Marrow Transplant ; 20(8): 1089-103, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24796279

RESUMEN

Chronic graft-versus-host disease (cGVHD) is an autoimmune-like syndrome, and donor B cells play important roles in augmenting its pathogenesis. B cell-depleting anti-CD20 mAb has been administered before or after cGVHD onset for preventing or treating cGVHD in the clinic. Although administration before onset appeared to be more effective, the effect is variable and sometimes minimal. Here, we used 2 mouse cGVHD models to evaluate the preventive and therapeutic effect of anti-CD20 mAb. With the model of DBA/2 donor to MHC-matched BALB/c recipient, 1 intravenous injection of anti-CD20 mAb (40 mg/kg) the following day or on day 7 after hematopoietic cell transplantation when serum autoantibodies were undetectable effectively prevented induction of cGVHD and preserved a strong graft-versus-leukemia (GVL) effect. The separation of GVL effect from GVHD was associated with a significant reduction of donor CD4(+) T cell proliferation and expansion and protection of host thymic medullary epithelial cells. Anti-CD20 mAb administration also prevented expansion of donor T cells and induction of cGVHD in another mouse model of C57BL/6 donor to MHC-mismatched BALB/c recipients. In contrast, administration of anti-CD20 mAb after GVHD onset was not able to effectively deplete donor B cells or ameliorate cGVHD in either model. These results indicate that administration of anti-CD20 mAb before signs of cGVHD can prevent induction of autoimmune-like cGVHD while preserving a GVL effect; there is little effect if administered after cGVHD onset. This provides new insights into clinical prevention and therapy of cGVHD with B cell-depleting reagents.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Enfermedad Injerto contra Huésped/prevención & control , Efecto Injerto vs Leucemia/fisiología , Animales , Anticuerpos Monoclonales Humanizados/administración & dosificación , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL
14.
Ann Hematol ; 93(10): 1685-94, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24844781

RESUMEN

Acute myeloid leukemia (AML) is generally regarded as a disorder of stem cells, known as leukemic initiating cells (LICs), which initiate the disease and contribute to relapses. Although the phenotype of these cells remains unclear in most patients, they are enriched within the CD34(+)CD38(-) population. In core-binding factor (CBF) AML, the cytogenetic abnormalities also exist in LIC. The aim of this study was to determine the prognostic power of minimal residual disease (MRD) measured by fluorescence in situ hybridization (FISH) in CD34(+)CD38(-) cells sorted by flow cytometry at different periods during therapy. Thirty-six patients under 65 years of age with de novo CBF-AML treated with intensive chemotherapy were retrospectively included in this study. Correlations with relapse-free survival (RFS) and overall survival were evaluated with univariate and multivariate analyses. FISH efficiently identified LICs in the CD34(+)CD38(-) population. The presence of FISH(+)CD34(+)CD38(-) cells before consolidation was negatively associated with cumulative incidence of relapse (64 vs 18 %, P = .012), which showed prognostic value for RFS (12 vs 68 %, P = .008) and OS (11 vs 75 %, P = .0005), and retained prognostic significance for RFS in multivariate analysis. The detection of FISH(+)CD34(+)CD38(-) cells before consolidation therapy significantly correlated with long-term survival. Fluorescence-activated cell sorting (FACS)-FISH could be potentially adopted as a MRD monitor approach in clinical practice to identify CBF-AML patients at risk of treatment failure during therapy.


Asunto(s)
Aberraciones Cromosómicas , Citometría de Flujo/métodos , Hibridación Fluorescente in Situ , Leucemia Mieloide Aguda/patología , Células Madre Neoplásicas/química , ADP-Ribosil Ciclasa 1 , Adolescente , Adulto , Antígenos CD34/análisis , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Separación Celular/métodos , Quimioterapia de Consolidación , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Citarabina/administración & dosificación , Daunorrubicina/administración & dosificación , Femenino , Humanos , Estimación de Kaplan-Meier , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidad , Masculino , Persona de Mediana Edad , Neoplasia Residual , Células Madre Neoplásicas/patología , Proteínas de Fusión Oncogénica/genética , Pronóstico , Proteína 1 Compañera de Translocación de RUNX1 , Adulto Joven
15.
Am J Hematol ; 89(9): 874-81, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24861848

RESUMEN

We retrospectively analyzed 449 patients with AML under the WHO classification of AML 2008 and probed implications of this classification in diagnosis and treatment of acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) among them. The clinical presentations, biological features, treatments, and prognosis of patients diagnosed with AML-MRC were analyzed and compared with those of AML not otherwise specified (AML-NOS). In all patients, 115 (25.6%) were diagnosed as AML-MRC including 64 males and 51 females with median onset age of 48 years (range from 17 to 78). Their complete remission (CR) rate was 60.9% and relapse rate was 57.1%. The observed median overall survival (OS) and disease-free survival (DFS) were 10 and 5 months, respectively, which was significantly shorter than those of AML-NOS patients (P < 0.05). The prognosis of AML-MRC patients with myelodysplastic syndrome (MDS)-related cytogenetics sole was similar to those with history of MDS or myelodysplastic/myeloproliferative neoplasm (MDS/MPN). Patients with MDS-related cytogenetic abnormalities and/or history of MDS or MDS/MPN predisposed significantly shortened CR, OS, and DFS than AML-MRC patients with only multilineage dysplasia (MLD) and AML-NOS patients (P < 0.05). Multivariate analysis showed that age, cytogenetics, and history of MDS or MDS/MPN were independent prognostic factors. Patient diagnosed as AML-MRC presented distinctive clinical and biological features. Presence of MLD does not change the prognosis.


Asunto(s)
Leucemia Mieloide Aguda/diagnóstico , Síndromes Mielodisplásicos/diagnóstico , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Médula Ósea/patología , Proteínas Potenciadoras de Unión a CCAAT/genética , China , Estudios de Cohortes , Análisis Citogenético , Supervivencia sin Enfermedad , Femenino , Humanos , Cariotipo , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/mortalidad , Masculino , Persona de Mediana Edad , Análisis Multivariante , Mutación , Síndromes Mielodisplásicos/complicaciones , Síndromes Mielodisplásicos/tratamiento farmacológico , Síndromes Mielodisplásicos/mortalidad , Proteínas Nucleares/genética , Nucleofosmina , Estudios Retrospectivos , Adulto Joven , Tirosina Quinasa 3 Similar a fms/genética
16.
Cancer Med ; 13(10): e7310, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38785213

RESUMEN

BACKGROUND: To explore the effects of monitoring measurable residual disease and post-remission treatment selection on the clinical outcomes of B-cell acute lymphoblastic leukemia (B-ALL) in adults. METHODS: Between September 2010 and January 2022, adult patients with B-ALL who received combination chemotherapy, with or without allogeneic hematopoietic stem cell transplantation (allo-HSCT), were included in the retrospective study, which was approved by the Ethics Committee and the observation of Declaration of Helsinki conditions. RESULTS: One hundred and forty-three B-ALL patients achieved complete remission (CR) were included in the study, of whom 94 patients (65.7%) received allo-HSCT in first complete remission (CR1). Multivariate analysis showed that the most powerful factors affecting OS were transplantation (hazard ratio [HR] = 0.540, p = 0.037) and sustained measurable residue disease (MRD) negativity (HR = 0.508, p = 0.037). The subgroup analysis showed that the prognosis of the allo-HSCT group was better than that of the chemotherapy group, regardless of whether MRD was negative or positive after two courses of consolidation therapy. After consolidation therapy, the prognosis of patients with positive MRD remained significantly better in the allo-HSCT group than in the chemotherapy group. However, no significant difference was observed in the prognosis between the allo-HSCT and chemotherapy groups with negative MRD after consolidation therapy. CONCLUSIONS: B-ALL patients who achieve sustained MRD negativity during consolidation therapy have excellent long-term outcomes even without allo-HSCT. Allo-HSCT is associated with a significant benefit in terms of OS and DFS for patients who were with positive MRD during consolidation therapy.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Trasplante de Células Madre Hematopoyéticas , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras , Inducción de Remisión , Humanos , Masculino , Adulto , Femenino , Estudios Retrospectivos , Pronóstico , Persona de Mediana Edad , Adulto Joven , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Adolescente , Resultado del Tratamiento , Trasplante Homólogo
17.
Psychol Trauma ; 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38421756

RESUMEN

OBJECTIVE: The outbreak of COVID-19 not only raised public health concerns but also caused tremendous psychological distress. Deficits in fear played a role in the development and maintenance of posttraumatic stress symptoms (PTSS). We aimed to investigate the relationship between fear and PTSS during COVID-19 at two points. METHOD: The questionnaire at the first time of investigation (T1) was conducted through WeChat or phone from January 30, 2020 to February 25, 2020 as part of the psychological trauma recover project-5-6 in China. And the questionnaire at the second time of investigation (T2) was collected from March 17, 2021 to June 17, 2021. After 12 months, data from 150 participants were included in the final analysis. Fear was measured by a self-reported question. Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5) was designed to assess PTSS. Pearson correlation, multivariate regression analysis, and multiple mediator model were used as statistical analyses. RESULTS: Fear reduced significantly over time. Participants with higher fear presented worse PTSS in both T1 and T2. Positive correlations between fear and PTSS of participants were found over time. Occupation and change of fear are significant predictors in the severity of PTSS over time. Change of fear partially mediated the relationship between the PCL-5 total score in T1 and the development of PTSS. CONCLUSION: Fear reduction was beneficial to trauma resilience. Future interventions could be developed to reduce excessive fear in facing natural disasters or following epidemics. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

18.
Transplant Cell Ther ; 30(2): 245.e1-245.e8, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37977336

RESUMEN

The preferred donor (haploidentical donor [HID] versus matched unrelated donor [URD]) choice in patients with acquired severe aplastic anemia (SAA) who lack an HLA-matched sibling donor (MSD) and fail upfront immunosuppressive treatment (IST) therapy is unknown. We retrospectively investigated SAA patients (n = 58) who underwent allogeneic stem cell transplantation (allo-SCT) between January 2012 and October 2022. The 5-year overall survival (OS) and 5-year failure-free survival (FFS) were comparable among the URD (n = 8), HID (n = 25), and MSD (n = 25) cohorts (OS: mean, 87.5 ± 11.7% versus 98.0 ± 6.5% versus 83.3 ± 7.6% [P = .926]; FFS: mean, 60.0 ± 18.2% versus 87.0 ± 7.0% versus 78.3 ± 8.6% [P = .222]). Multivariate analysis revealed that primary engraftment failure independently predicted OS and secondary graft failure predicted FFS among SAA patients who underwent allo-SCT, but donor type and age were not predictive of these outcomes. An urgent second SCT for patients with engraftment failure may be an effective salvage treatment. Our findings show that an alternative donor SCT is indicated for eligible SAA patients without an MSD even if age ≥40 years.


Asunto(s)
Anemia Aplásica , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Humanos , Adulto , Anemia Aplásica/terapia , Estudios Retrospectivos , Hermanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre
19.
Biol Blood Marrow Transplant ; 19(4): 653-60, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23353118

RESUMEN

The prognosis of patients with refractory/relapsed acute myelogenous leukemia (rAML) is poor. Recent studies have shown that more transplant centers are choosing allogeneic peripheral blood stem cell transplantation (allo-PBSCT) for recipients, even with a higher leukemia burden. The purpose of the present study is to evaluate the outcome of rAML patients undergoing allo-PBSCT and to determine whether the disease status can predict the post-transplantation survival. The outcome of 58 patients (median age, 34 years; range, 14 to 52) with rAML who underwent allo-PBSCT in our institution from January 2000 until September 2011 was retrospectively studied. Thirty-three patients had complete remission (CR) before PBSCT, whereas 25 patients had no remission. Donors were matched related (31 patients) and unrelated (27 patients). Reduced-intensity conditioning was used for 18 patients with rAML, and myeloablative conditioning was used for others. Sixty-six consecutive non-rAML patients (median age, 33 years; range, 15 to 51) who received an allo-PBSCT at the same period were used as a control. Full donor-type engraftment was achieved in all patients. After a median follow-up of 61 months, the 5-year overall survival of rAML patients was 54.21% ± 7.06%, which was lower than non-rAML patients (71.82% ± 6.4%, P = .0386). However, the 5-year event-free survival for rAML and non-rAML patients had no statistical significance (53.54% ± 6.87% versus 62.07% ± 6.78%, P = .2626). The 5-year overall survival between rAML patients who had CR and no remission before PBSCT was 56.06% ± 9.2% and 51.85% ± 10.83%, respectively (P = .6408). These data demonstrate that allo-PBSCT is a promising and safe choice for the treatment of rAML, and the results were partially due to the rapid tapering of immunosuppressants in the early stage after PBSCT and prophylactic donor lymphocyte infusion. Meanwhile, the patients who did not achieve CR before PBSCT could also benefit from allo-PBSCT.


Asunto(s)
Leucemia Mieloide Aguda/terapia , Agonistas Mieloablativos/uso terapéutico , Trasplante de Células Madre de Sangre Periférica , Acondicionamiento Pretrasplante/métodos , Adolescente , Adulto , Femenino , Prueba de Histocompatibilidad , Humanos , Leucemia Mieloide Aguda/inmunología , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/patología , Masculino , Persona de Mediana Edad , Pronóstico , Recurrencia , Inducción de Remisión , Estudios Retrospectivos , Análisis de Supervivencia , Trasplante Homólogo
20.
Mol Clin Oncol ; 19(3): 75, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37614372

RESUMEN

Primary plasma cell leukemia (pPCL) is a rare and aggressive form of plasma cell disorder, which accounts for ~70% of all PCL. Survival of pPCL remains poor, and is related with early mortality. There is no standard therapy for patients with pPCL. In the present study, a 26-year-old man who was diagnosed with pPCL was reported. The patient achieved stringent complete remission to the successful treatment of intensive chemotherapy combined with sequential autologous and allogeneic stem cell transplantation (SCT) followed by maintenance therapy with oral administration of ixazomib, thalidomide and dexamethasone (IRD regimen). Development of complex treatment algorithms that combine novel agents, SCT and post-transplantation remission strategies may translate into survival in patients with pPCL.

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