RESUMEN
There is an urgent need for an oral, efficient and safe regimen for high-risk APL under the pandemic of COVID-19. We retrospectively analysed 60 high-risk APL patients. For induction therapy (IT), in addition to all-trans retinoic acid (ATRA) and oral arsenic (RIF), 22 patients received oral etoposide (VP16) as cytotoxic chemotherapy (CC), and 38 patients received intravenous CC as historical control group. The median dose of oral VP16 was 1000 mg [interquartile rage (IQR), 650-1250]. One patient died during IT in the control group, 59 evaluable patients (100%) achieved complete haematological remission (CHR) after IT and complete molecular remission (CMR) after consolidation therapy. The median time to CHR and CMR was 36 days (33.8-44) versus 35 days (32-42; p = 0.75) and 3 months (0.8-3.5) versus 3.3 months (2.4-3.7; p = 0.58) in the oral VP16 group and in the control group. Two (9.1%) and 3 (7.9%) patients experienced molecular relapse in different group respectively. The 2-year estimated overall survival and event-free survival were 100% versus 94.7% (p = 0.37) and 90.9% versus 89.5% (p = 0.97) respectively. A completely oral, efficient and safe induction regimen including oral VP16 as cytoreductive chemotherapy combined with ATRA and RIF is more convenient to administer for patients with high-risk APL.
Asunto(s)
Etopósido , Quimioterapia de Inducción , Leucemia Promielocítica Aguda , Humanos , Etopósido/administración & dosificación , Etopósido/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Adulto , Administración Oral , Estudios Retrospectivos , Quimioterapia de Inducción/métodos , Infusiones Intravenosas , Leucemia Promielocítica Aguda/tratamiento farmacológico , Leucemia Promielocítica Aguda/mortalidad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , COVID-19 , Tretinoina/administración & dosificación , Tretinoina/uso terapéutico , SARS-CoV-2 , Inducción de Remisión , Arsénico/administración & dosificación , AncianoRESUMEN
This study aimed to investigate the clinical characteristics and prognosis of Runt-related transcription factor 1 (RUNX1) mutant acute myeloid leukemia (AML) patients by comparing the features of AML patients with or without RUNX1 mutation. We retrospectively analyzed 180 AML patients including 36 AML patients with mutant RUNX1(AML-RUNX1mut ) and 144 AML patients with wild-type RUNX1(AML-RUNX1wt ) were selected using the case-pair method(1:4). Compared to AML-RUNX1wt , AML-RUNX1mut showed higher frequency of ASXL1 (p < 0.001), SRSF2 (p < 0.001), BCORL1 (p < 0.001), RAS (p = 0.010) mutations, and absent NPM1 mutations (p = 0.022). The 3-year overall survival (OS) and disease-free survival (DFS) of AML-RUNX1mut and AML-RUNX1wt were 73.1% versus 68.0% (p = 0.64) and 80.7% versus 71.6% (p = 0.37), respectively. AML-RUNX1mut receiving allogeneic hematopoietic cell transplantation (allo-HSCT) showed better survival than those who did not receive allo-HSCT (3-year OS, 84.3% vs. 52.7%; p = 0.006). Multivariate analysis showed that EZH2 mutation (p = 0.003), white blood cell (WBC) ≥30 × 109 /L (p = 0.036) and age ≥60 years (p = 0.038) were significant independent risk factors for inferior OS of AML-RUNX1mut ; WBC ≥30 × 109 /L (p = 0.013) and DNMT3A mutation (p = 0.045) were significant independent risk factors for shorter DFS of AML-RUNX1mut . In conclusion, AML-RUNX1mut showed unique clinical characteristics, but the survival between AML-RUNX1mut and AML-RUNX1wt were comparable. EZH2 co-mutation, DNMT3A co-mutation, old age and high WBC count were associated with inferior survival of AML-RUNX1mut . Allo-HSCT can significantly improve the prognosis of AML-RUNX1mut .
Asunto(s)
Subunidad alfa 2 del Factor de Unión al Sitio Principal , Leucemia Mieloide Aguda , Humanos , Persona de Mediana Edad , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Mutación , Nucleofosmina , Pronóstico , Estudios RetrospectivosRESUMEN
Prolonged isolated thrombocytopenia (PT) is a life-threatening comorbidity associated with allogeneic haematopoietic stem cell transplantation (allo-HSCT). Our previous study indicated that dysfunctional bone marrow mesenchymal stromal cells (BM MSCs) played a role in PT pathogenesis and that reactive oxygen species (ROS) accumulation was related to BM MSC senescence and apoptosis. However, the mechanism of the increase in ROS levels in the BM MSCs of PT patients is unknown. In the current case-control study, we investigated whether nuclear factor erythroid 2-related factor 2 (NRF2), which is a central regulator of the cellular anti-oxidant response that can clear ROS in human BM MSCs, was associated with PT after allo-HSCT. We evaluated whether an NRF2 agonist (tert-butylhydroquinone, TBHQ) could enhance BM MSCs from PT patients in vitro. We found that BM MSCs from PT patients exhibited increased ROS levels and reduced NRF2 expression. Multivariate analysis showed that low NRF2 expression was an independent risk factor for primary PT [p = 0.032, Odds ratio (OR) 0.868, 95% confidence interval (CI) 0.764-0.988]. In-vitro treatment with TBHQ improved the quantity and function of BM MSCs from PT patients by downregulating ROS levels and rescued the impaired BM MSC support of megakaryocytopoiesis. In conclusion, these results suggested that NRF2 downregulation in human BM MSCs might be involved in the pathogenesis of PT after allo-HSCT and that BM MSC impairment could be improved by NRF2 agonist in vitro. Although further validation is needed, our data indicate that NRF2 agonists might be a potential therapeutic approach for PT patients after allo-HSCT.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Trombocitopenia , Humanos , Médula Ósea/patología , Estudios de Casos y Controles , Especies Reactivas de Oxígeno/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Trasplante Homólogo/efectos adversos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Células de la Médula Ósea/patología , Trombocitopenia/etiología , Células Madre Mesenquimatosas/metabolismo , Trasplante de Células Madre Mesenquimatosas/efectos adversosRESUMEN
BACKGROUD: To investigate the effect of Luteinizing hormone (LH) level changes on the outcomes of controlled ovarian hyperstimulation (COH) and embryo transfer (ET) in gonadotropin-releasing hormone antagonist (GnRH-ant) protocol. METHODS: A total of 721 patients undergoing GnRH-ant protocol COH for the first IVF/ICSI cycles were retrospectively analyzed. COH process were divided into 2 stages, before (stage 1) and after (stage 2) the GnRH-ant initiation, and each with 5 groups basing on LH levels: LH decreased more than 50% (groups A1, A2), decreased 25-50% (groups B1, B2), change less than 25% (groups C1, C2), increased 25-50% (groups D1, D2), and increased more than 50% (groups E1, E2). RESULTS: There were no significant differences among groups of stage1 regarding COH and ET outcomes. For stage 2, the more obvious the decrease of LH level, the more the number of oocytes retrieved, mature oocytes, fertilized oocytes, embryos cleavaged and the numbers of embryo available (P < 0.05), but without significant differences regarding ET outcomes. We also found the freeze-all rate in Group A2 was higher (P < 0.001). CONCLUSION: LH level changes before GnRH-ant addition were not related to COH and ET outcomes. LH level changes after the addition of GnRH-ant were related to the outcome of COH, and no significant differences were found relating to ET outcomes.
Asunto(s)
Hormona Luteinizante , Oocitos , Humanos , Estudios Retrospectivos , Transferencia de Embrión , Antagonistas de Hormonas/uso terapéutico , Hormona Liberadora de GonadotropinaRESUMEN
Haploidentical allogeneic haematopoietic stem cell transplantation (haplo-HSCT) is a significant alternative treatment for severe aplastic anaemia (SAA). To improve this process by modifying the risk stratification system, we conducted a retrospective study using our database. 432 SAA patients who received haplo-HSCT between 2006 and 2020 were enrolled. These patients were divided into a training (n = 288) and a validation (n = 144) subset randomly. In the training cohort, longer time from diagnosis to transplantation, poorer Eastern Cooperative Oncology Group (ECOG) status and higher haematopoietic cell transplantation-specific comorbidity index (HCT-CI) score were independent risk factors for worse treatment-related mortality (TRM) in the final multivariable model. The haplo-HSCT scoring system was developed by these three parameters. Three-year TRM after haplo-HSCT were 6% [95% confidence interval (CI), 1-21%], 21% (95% CI, 7-40%), and 47% (95% CI, 20-70%) for the low-, intermediate-, and high-risk group, respectively (P < 0·0001). In the validation cohort, the haplo-HSCT scoring system also separated patients into three risk groups with increasing risk of TRM: intermediate-risk [hazard ratio (HR) 2·45, 95% CI, 0·92-6·53] and high-risk (HR 11·74, 95% CI, 3·07-44·89) compared with the low-risk group (P = 0·001). In conclusion, the haplo-HSCT scoring system could effectively predict TRM after transplantation.
Asunto(s)
Anemia Aplásica/mortalidad , Anemia Aplásica/terapia , Algoritmos , Anemia Aplásica/diagnóstico , Anemia Aplásica/epidemiología , Causas de Muerte , Toma de Decisiones Clínicas , Estudios de Cohortes , Árboles de Decisión , Manejo de la Enfermedad , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Mortalidad , Pronóstico , Índice de Severidad de la Enfermedad , Trasplante Haploidéntico , Resultado del TratamientoRESUMEN
Despite the high cure probability for acute promyelocytic leukaemia (APL), a minority of patients will relapse and the risk factors for relapse are unclear. We retrospectively analysed 212 patients who were diagnosed with non-high-risk APL and received all-trans retinoic acid (ATRA) plus arsenic as front-line therapy at Peking University Institute of Hematology from February 2014 to December 2018. A total of 176 patients (83%) received oral arsenic (realgar-indigo naturalis formula) plus ATRA, 36 patients (17%) received arsenic trioxide plus ATRA and 203 patients were evaluable for relapse. After a median (range) follow-up of 53·6 (24·3-85·4) months, two patients had molecular relapse and eight had haematological relapse. A promyelocytic leukaemia/retinoic acid receptor alpha (PML-RARA) transcript level of ≥6·5% at the end of induction therapy was associated with relapse (P = 0·031). The 5-year cumulative incidence of relapse, event-free survival and overall survival were 5·5%, 92·3% and 96·3% respectively. In conclusion, the present long-term follow-up study further confirmed the high cure probability of ATRA plus oral arsenic as front-line therapy for non-high-risk APL and showed that the PML-RARA transcript level at the end of induction therapy was associated with relapse.
Asunto(s)
Antineoplásicos/uso terapéutico , Trióxido de Arsénico/uso terapéutico , Leucemia Promielocítica Aguda/tratamiento farmacológico , Proteínas de Fusión Oncogénica/genética , Tretinoina/uso terapéutico , Adolescente , Adulto , Anciano , Femenino , Humanos , Quimioterapia de Inducción , Leucemia Promielocítica Aguda/diagnóstico , Leucemia Promielocítica Aguda/genética , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVES: The aim of our study was to determine possible predictors and clinical course of mixed chimerism (MC) in aplastic anemia after transplantation. METHODS: A total of 207 transplants were obtained from haploidentical donors (HID) using busulfan (Bu), cyclophosphamide (Cy), and anti-thymocyte globulin (ATG) regimens, and 69 transplants from matched related donors (MRD) and 29 transplants from unrelated donors (URD) using Cy/ATG regimens were obtained. RESULTS: Incidences of MC were 1.93 ± 0.01%, 20.29 ± 0.01%, and 35.71 ± 0.01% in HID, MRD, and URD transplantation (p < .001). In multivariate analysis, incidence of MC was significantly higher in patients without adding Bu in conditioning (p < .001) and receiving a lower number of CD3 + cells in graft (p = .042). MC was associated with significantly lower II-IV aGvHD (3.70% vs. 27.7%, p = .007), but higher secondary graft rejection rates (14.8% vs. 0.4%, p < .001) and poorer overall survival (72.7 ± 8.9% vs. 89.6 ± 2.0%, p = .011) than those of donor chimerism cohort. CONCLUSIONS: Mixed chimerism was an unsettling status even in non-malignancy. Haploidentical transplantation with more intense regimen by adding Bu to Cy and ATG was associated with reduced MC following HSCT for SAA. An intensified regimen should be explored in matched related or unrelated donors.
Asunto(s)
Anemia Aplásica , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Anemia Aplásica/terapia , Quimerismo , Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Incidencia , Factores Protectores , Estudios Retrospectivos , Acondicionamiento Pretrasplante , Resultado del TratamientoRESUMEN
Basiliximab has been used successfully as a second-line treatment for steroid-refractory (SR) acute graft-versus-host disease (aGVHD) in adult patients after haploidentical hematopoietic stem cell transplant (haplo-HSCT) but has not been studied separately in the pediatric setting. We retrospectively reviewed 100 pediatric patients after haplo-HSCT receiving basiliximab for grades II (57%), III (27%), and IV (16%) SR aGVHD between January 2015 and December 2017. The median number of basiliximab doses was 4 (range, 2 to 9). The day 28 overall response rate was 85%, with complete response in 74% of patients, partial response in 11% of patients, and no response in 15% of patients. The day 28 overall response rates were 94.6% in skin SR aGVHD, 81.6% in gut SR aGVHD, and 66.7% in liver SR aGVHD. Infectious complications included bacterial infection (11%), presumed or documented fungal infections (7%), cytomegalovirus viremia (53%), Epstein-Barr virus viremia (11%), human herpesvirus-6 viremia (7%), and herpes simplex virus viremia (1%). The 3-year overall survival, disease-free survival, nonrelapse mortality, and relapse rates between responders and nonresponders were 81.3% versus 46.7% (P < .001), 79.0% versus 46.7% (P = .001), 6.1% versus 33.3% (P < .001), and 14.9% versus 20.0% (P = .46), respectively. We conclude that basiliximab is an effective second-line agent for pediatric patients with SR aGVHD after haplo-HSCT, particularly for skin SR aGVHD.
Asunto(s)
Infecciones por Virus de Epstein-Barr , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Enfermedad Aguda , Adulto , Basiliximab , Niño , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Herpesvirus Humano 4 , Humanos , Estudios Retrospectivos , EsteroidesRESUMEN
The aim of this study was to evaluate the incidence, risk factors, and outcomes of primary prolonged isolated thrombocytopenia (PT) after haploidentical hematopoietic stem cell transplant (haplo-HSCT). We retrospectively analyzed patients who received haplo-HSCT for various hematologic malignancies at Peking University Institute of Hematology between January 2015 and December 2016. Of the 918 patients, 93 (10.1%) developed primary PT. We designed a propensity score method-based study. For each primary PT patient control subjects (1:3) were selected using a propensity score-matching method. A total of 372 recipients were enrolled in the study: 93 in the PT group and 279 in the control group. Multivariate analysis showed that age older than 25 years (P = .002), median mononuclear cells (P = .000), median CD34+ counts (P = .003), history of grades II to IV acute graft-versus-host disease (GVHD; P = .000), and Epstein-Barr virus (EBV) infection after haplo-HSCT (P = .016) were independent risk factors for primary PT. Primary PT was significantly associated with higher transplant-related mortality (TRM; P < .001), inferior overall survival (P = .001), and disease-free survival (P = .005). In conclusion, the incidence of primary PT after haplo-HSCT was 10.1%. Primary PT was associated with poorer survival and higher TRM along with older age, grades II to IV acute GVHD, and EBV infection after haplo-HSCT.
Asunto(s)
Infecciones por Virus de Epstein-Barr , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Trombocitopenia , Adulto , Anciano , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Herpesvirus Humano 4 , Humanos , Incidencia , Estudios Retrospectivos , Factores de Riesgo , Trombocitopenia/epidemiología , Trombocitopenia/etiologíaRESUMEN
The specific description, risk factors, and outcomes of chronic graft-versus-host disease (cGVHD) in pediatric patients with hematologic malignancies after T cell-replete (TCR) myeloablative haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with antithymocyte globulin (ATG)/granulocyte colony-stimulating factor (G-CSF) have not been previously well described. We retrospectively analyzed the incidence, risk factors, and outcomes of cGVHD documented according to the 2014 National Institutes of Health consensus criteria (NIH-CC) in 292 consecutive pediatric patients with hematologic malignancies after TCR myeloablative haplo-HSCT with ATG/G-CSF between January 2015 and December 2017. A total of 170 patients experienced cGVHD. The 3-year cumulative incidence of total cGVHD and mild, moderate, and severe cGVHD was 57.9%, 27.5%, 18.8%, and 11.9%, respectively. Multivariate analysis showed that acute GVHD (aGVHD) grade II-IV (hazard ratio, 1.578; P = .002) was an independent risk factor for cGVHD. Compared to patients without cGVHD, patients with cGVHD demonstrated a lower 3-year relapse (17.6% versus 27.2%; P = .009), a similar 3-year nonrelapse mortality (NRM) (5.9% versus 5.4%; P = .79), and better 3-year disease-free survival (DFS) (77.8% versus 66.9%; P = .007) and overall survival (OS) (81.3% versus 68.6%; P = .001), particularly those with mild or moderate cGVHD; however, no significant impact of severe cGVHD on relapse, NRM, DFS, or OS was seen. In conclusion, the incidence of severe cGVHD in pediatric patients with hematologic malignancies after TCR myeloablative haplo-HSCT with ATG/G-CSF was acceptable. Previous aGVHD grade II-IV was a risk factor for the occurrence of cGVHD. Only mild or moderate cGVHD was associated with a lower risk of relapse, translating into improved DFS and OS in pediatric patients with hematologic malignancies after TCR myeloablative haplo-HSCT with ATG/G-CSF.
Asunto(s)
Enfermedad Injerto contra Huésped , Neoplasias Hematológicas , Trasplante de Células Madre Hematopoyéticas , Suero Antilinfocítico , Niño , Enfermedad Injerto contra Huésped/etiología , Factor Estimulante de Colonias de Granulocitos , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Incidencia , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Factores de Riesgo , Linfocitos T , Acondicionamiento PretrasplanteRESUMEN
The specific description, risk factors, and outcomes of aGVHD in pediatric haplo-HSCT using TCR protocols without PT-Cy have not been well described previously. We evaluated the incidence, risk factors, and outcomes of aGVHD in 350 consecutive pediatric patients receiving TCR haplo-HSCT without PT-Cy according to the Glucksberg and NIH aGVHD classifications between January 2015 and December 2017 at Peking University Institute of Hematology. The cumulative incidences of grade I, II, III, and IV aGVHD were 28%, 29.7%, 8.3%, and 5.1%, respectively. The type of aGVHD onset was classic in 243 patients (97.2%), and persistent/recurrent/late-onset aGVHD was in seven patients (2.8%). None of the considered variables significantly influenced the incidence of grade III-IV aGVHD. The 3-year OS, DFS, cumulative incidence of NRM, and relapse in malignant disease between severe aGVHD (III-IV) group and grade 0-II aGVHD group were 61.5% vs 77.2% (P = .027), 58.6% vs 75.1% (P = .014), 19.8% vs 5.3% (P = .002), and 21.6% vs 19.6% (P = .59), respectively; in non-malignant diseases, the 3-year OS, DFS, and NRM were 81.8% vs 97.4% (P = .05), 81.8% vs 97.4% (P = .05), and 18.2% vs 2.6% (P = .05), respectively. Under the protocol of pediatric TCR haplo-HSCT without PT-Cy, the persistent/recurrent/late-onset aGVHD was rare, and the incidence of severe aGVHD was acceptable and significantly contributed to NRM and lower survival in both malignant disease and non-malignant diseases.
Asunto(s)
Enfermedad Injerto contra Huésped/epidemiología , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Inmunidad Celular , Linfocitos T/microbiología , Adolescente , Adulto , Biopsia , Niño , China/epidemiología , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/inmunología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Acondicionamiento Pretrasplante , Adulto JovenRESUMEN
This long-term follow-up study evaluated the effects of corticosteroid prophylaxis on graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) based on a controlled open-label randomized trial in which 228 allotransplant recipients were categorized as low risk (nâ¯=â¯83, group A) or high risk; patients at high risk were randomly assigned to receive (nâ¯=â¯72, group B) or not receive (nâ¯=â¯73, group C) low-dose methylprednisolone prophylaxis. The cumulative incidences of chronic GVHD, relapse, nonrelapse mortality, leukemia-free survival, overall survival, and GRFS were 60%, 19%, 16%, 68%, 73%, and 46%, respectively, in all cases. Compared with the patients in group C, the cases in group B experienced a lower cumulative incidence of moderate to severe chronic GVHD (42% versus 20%; P = .010), herpes zoster infection (28% versus 12%; P = .010), pulmonary infections (42% versus 21%; P = .040), and osteonecrosis of the femoral head (ONFH; 16% versus 6%; P = .045) as well as better GRFS (59% versus 33%; P = .017). Factors associated with GRFS included total dose of corticosteroid used in the first 100days after transplantation (hazard ratio, 1.547; Pâ¯=â¯.015) and platelet recovery (hazard ratio, 1.456; Pâ¯=â¯.037). Our results suggest that low-dose glucocorticoid prophylaxis reduces GVHD and thus reduces the total dose of steroids, which might contribute to lower incidence of infections and ONFH and a superior GRFS, indicating that higher steroid doses are harmful. Reducing the total dose is of course beneficial. (ClinicalTrials.gov number, NCT01607580.).
Asunto(s)
Supervivencia sin Enfermedad , Glucocorticoides/uso terapéutico , Enfermedad Injerto contra Huésped/prevención & control , Metilprednisolona/uso terapéutico , Premedicación/métodos , Trasplante Haploidéntico , Adulto , Femenino , Necrosis de la Cabeza Femoral/inducido químicamente , Necrosis de la Cabeza Femoral/etiología , Estudios de Seguimiento , Glucocorticoides/farmacología , Humanos , Infecciones/inducido químicamente , Infecciones/etiología , Masculino , Metilprednisolona/farmacología , Persona de Mediana Edad , Trasplante Haploidéntico/métodos , Trasplante Haploidéntico/mortalidad , Trasplante HomólogoRESUMEN
Hepatitis E virus (HEV) is increasingly found to cause hepatitis in allogeneic haematopoietic stem cell transplantation (HSCT) patients. However, little is known about HEV infection in patients receiving haploidentical HSCT (haplo-HSCT). Here, we retrospectively evaluate the incidence and clinical course of HEV infection in haplo-HSCT patients. From January 2014 to July 2017, 177 patients with unexplained elevated transaminases after receiving haplo-HSCT at Peking University Institute of Haematology were screened for HEV using HEV serology. HEV RNA was assessed in blood samples when HEV-IgG and/or IgM antibodies were positive. Acute HEV infection was identified in 7 patients (3·9%), 1 of whom had developed a chronic HEV infection. The median time from haplo-HSCT to HEV infection was 17·5 (range, 6-55) months. HEV infection was confirmed by the presentation of anti-HEV IgM + anti-HEV IgG (rising) (n = 5) or HEV-RNA + anti-HEV IgM + anti-HEV IgG (n = 2). None of the patients died of HEV infection directly: 2 patients with HEV infection died showing signs of ongoing hepatitis, and 5 patients cleared HEV with a median duration of HEV infection of 1·5 (range, 1·0-5·7) months. In conclusion, HEV infection is a rare but serious complication after haplo-HSCT. We recommend screening of HEV in haplo-HSCT.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Anticuerpos Antihepatitis/sangre , Hepatitis E , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Aloinjertos , Niño , Preescolar , Femenino , Hepatitis E/sangre , Hepatitis E/genética , Humanos , Incidencia , Lactante , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
By using the technique of integration within ordered product of operators, we put forward the combinatorial optical complex wavelet-fractional Fourier transform in the context of quantum optics. The unitary operator for this new transform is found and its normally ordered form is deduced. We apply this new transform to the two-mode vacuum state and the two-mode number state and explain that it can be used to analyze and identify various quantum optical states.
RESUMEN
Poor graft function (PGF) is a life-threatening complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is characterized by defective hematopoiesis. Mesenchymal stem cells (MSCs) have been shown to support hematopoiesis, but little is known about the role of MSCs in the pathogenesis of PGF. In the current prospective case-control study, we evaluated whether the number and function of bone marrow (BM) MSCs in PGF patients differed from those in good graft function (GGF) patients. We found that BM MSCs from PGF patients expanded more slowly and appeared flattened and larger, exhibiting more apoptosis and senescence than MSCs from GGF patients. Furthermore, increased intracellular reactive oxygen species, p-p53, and p21 (but not p38) levels were detected in MSCs from PGF patients. Moreover, the ability of MSCs to sustain hematopoiesis was significantly reduced in PGF patients, as evaluated by cell number, apoptosis, and the colony-forming unit-plating efficiency of CD34+ cells. In summary, the biologic characteristics of PGF MSCs are different from those of GGF MSCs, and the in vitro hematopoiesis-supporting ability of PGF MSCs is significantly lower. Although requiring further validation, our study indicates that reduced and dysfunctional BM MSCs may contribute to deficient hematopoiesis in PGF patients. Therefore, improvement of BM MSCs may represent a promising therapeutic approach for PGF patients after allo-HSCT.
Asunto(s)
Células de la Médula Ósea/metabolismo , Hematopoyesis , Trasplante de Células Madre Hematopoyéticas , Células Madre Mesenquimatosas/metabolismo , Adolescente , Adulto , Aloinjertos , Células de la Médula Ósea/patología , Femenino , Humanos , Masculino , Células Madre Mesenquimatosas/patología , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
Prolonged isolated thrombocytopenia (PT) is a serious complication of allogeneic haematopoietic stem cell transplantation (allo-HSCT). Murine studies and in vitro experiments suggest that mesenchymal stem cells (MSCs) can, not only to support haematopoiesis, but also preferentially support megakaryocytopoiesis in bone marrow (BM). However, little is known about the quantity and function of BM MSCs in PT patients. In a case-control study, we found that BM MSCs from PT patients exhibited significantly reduced proliferative capacities, increased reactive oxygen species and senescence. Antioxidant (N-acetyl-L-cysteine, NAC) treatment in vitro not only quantitatively and functionally improved BM MSCs derived from PT patients through down-regulation of the p38 (also termed MAPK14) and p53 (also termed TP53) pathways but also partially rescued the impaired ability of BM MSCs to support megakaryocytopoiesis. Subsequently, a pilot study showed that the overall response of NAC treatment was obtained in 7 of the enrolled PT patients (N = 10) without significant side effects. Taken together, the results indicated that dysfunctional BM MSCs played a role in the pathogenesis of PT and the impaired BM MSCs could be improved by NAC in vitro. Although requiring further validation, our data indicate that NAC might be a potential therapeutic approach for PT patients after allo-HSCT.
Asunto(s)
Acetilcisteína/administración & dosificación , Células de la Médula Ósea/metabolismo , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda/terapia , Células Madre Mesenquimatosas/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Trombocitopenia/tratamiento farmacológico , Células de la Médula Ósea/patología , Estudios de Casos y Controles , Femenino , Humanos , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patología , Masculino , Células Madre Mesenquimatosas/patología , Proyectos Piloto , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Estudios Prospectivos , Trombocitopenia/etiología , Trombocitopenia/metabolismo , Trombocitopenia/patologíaRESUMEN
OBJECTIVES: Pulmonary infiltrates in allogeneic hematopoietic stem cell transplant (allo-HSCT) patients are potentially life-threatening and require early diagnosis and treatment. We aimed to retrospectively explore the clinical efficacy of polymerase chain reaction (PCR) in conjunction with flexible bronchoscopy (FB) in allo-HSCT patients with pulmonary infiltrates. PATIENTS AND METHODS: We retrospectively reviewed all patients undergoing FB after allo-HSCT at the Peking University Institute of Hematology from January 2013 to December 2016. We used PCR to detect various viruses in FB specimens, particularly for 27 viruses. RESULTS: One hundred forty-nine diagnostic FBs were performed in 130 patients. The overall diagnostic yield was 58%. Eighty-nine percent of the patients with a positive FB result were diagnosed with a pulmonary infection. Viruses were the most common infectious diagnosis (70%), followed by fungi (48%), bacteria (38%), and Pneumocystis jirovecii (12%). Multivariate analyses showed that a chest computed tomography (CT) finding of diffuse pulmonary infiltrates (P = .012) and positive results in assisted microbiological and serological analyses (P = .000) predicted a positive FB result. FB results prompted a treatment modification in 61% of cases. CONCLUSIONS: FB in conjunction with PCR is efficient in the rapid diagnosis and management of pulmonary infiltrates in allo-HSCT patients.
Asunto(s)
Antiinfecciosos/uso terapéutico , Broncoscopía/métodos , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Reacción en Cadena de la Polimerasa/métodos , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Adolescente , Adulto , Niño , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Infecciones del Sistema Respiratorio/etiología , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Previous studies reported the relation between MTLRP genetic polymorphism and type 2 diabetes, however, the conclusion were conflicting. In the present study, we performed a meta-analysis to reveal this association. METHODS: Literature retrieval, selection and assessment, data extraction, and meta-analyses were performed according to the RevMan 5.0 guidelines. In the meta-analysis, we utilized random-effect model or fixed-effect model to pool the Odds ratio (OR) according to the test of heterogeneity. RESULTS: A total of nine case-control studies included 4460 type 2 diabetes patients and 4114 healthy control subjects were analyzed. We did not found association between the MTLRP polymorphism and type 2 diabetes risk in the overall population (CC vs CA + AA: OR = 1.02; 95% CI: 0.89-1.17, P = 0.77; A vs C: OR = 1.02; 95% CI: 0.84-0.96, P = 0.62). However, in subgroup analyses stratified by ethnicity, we found significant association of MTLRP polymorphism with type 2 diabetes in Caucasians (CC vs CA + AA: OR = 1.27; 95% CI: 1.02-1.57, P = 0.03; A vs C: OR = 0.74, 95% CI: 0.60-0.91, P = 0.005). CONCLUSION: The MTLRP polymorphism was associated with type 2 diabetes in Caucasians.