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This prospective clinical study aimed to evaluate the efficacy and safety of the pre-emptive treatment modality of azacitidine in combination with interferon-α (IFN-α) in AML/MDS patients post-transplantation. Forty-seven patients aged 17-62 were enrolled with 14 patients having completed the planned 12 cycles. Following initiation, 72.3% responded positively after the first cycle, peaking at 77.2% by the fifth cycle. Notably, 24 patients maintained sustained responses throughout a median follow-up of 1050 days (range, 866-1234). Overall survival, leukaemia-free survival and event-free survival probabilities at 3 years were 69.5%, 60.4% and 35.7% respectively. Cumulative incidences of relapse and non-relapse mortality were 36.5% and 4.3% respectively. Multivariate analysis identified that receiving pre-emptive treatment for fewer than six cycles and the absence of chronic graft-versus-host disease after intervention was significantly associated with poorer clinical outcomes. The combination of azacitidine with IFN-α was well-tolerated with no observed severe myelotoxicity, and the majority of adverse events were reversible and manageable. In conclusion, the use of azacitidine in conjunction with IFN-α as pre-emptive therapy is a safe and effective treatment to prevent disease progression in AML/MDS patients with MRD positivity post-allo-HSCT.
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The low-dose anti-thymocyte globulin (ATG) plus low-dose post transplantation cyclophosphamide (PTCy) -based (low-dose ATG/PTCy-based) regimen had a promising activity in preventing of graft-versus-host disease (GVHD) in adult patients. However, its efficacy in pediatric patients remain to be defined. Here, we presented the findings from 35 pediatric patients undergoing haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) with the new regimen for GVHD prophylaxis. The cumulative incidences (CIs) of grades II-III and III-IV acute GVHD (aGVHD) were 34% (95% CI, 17-48%) and 11% (95% CI, 0-21%) within 180 days post-transplantation, respectively. The CIs of chronic GVHD (cGVHD) and moderate-to-severe cGVHD within 2 years were 26% (95% CI, 7-41%) and 12% (95% CI, 0-25%), respectively. The 2-year probabilities of overall survival, relapse-free survival, and graft-versus-host disease and relapse-free survival were 89% (95% CI, 78-100%), 82% (95% CI, 68-98%) and 59% (95% CI, 43-80%), respectively. The CIs of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) reactivation by day 180 were 37% (95% CI, 19-51%) and 20% (95% CI, 6-32%) respectively. These results strongly advocate for the efficacy of the low-dose ATG/PTCy-based regimen as a robust strategy for GVHD prevention in haplo-PBSCT for pediatric patients.
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Suero Antilinfocítico , Ciclofosfamida , Enfermedad Injerto contra Huésped , Neoplasias Hematológicas , Trasplante de Células Madre de Sangre Periférica , Humanos , Enfermedad Injerto contra Huésped/prevención & control , Enfermedad Injerto contra Huésped/etiología , Suero Antilinfocítico/administración & dosificación , Ciclofosfamida/administración & dosificación , Ciclofosfamida/uso terapéutico , Niño , Masculino , Femenino , Preescolar , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/mortalidad , Adolescente , Lactante , Trasplante Haploidéntico , Inmunosupresores/uso terapéutico , Inmunosupresores/administración & dosificaciónRESUMEN
Introduction: Cytomegalovirus (CMV) can cause various end-organ diseases in immunocompromised hosts, including allogeneic hematopoietic cell transplant (allo-HSCT) recipients. Interestingly, CMV viremia has been associated with various complications and poor prognosis in allo-HSCT recipients. Complications involving the central nervous system (CNS) occur in 9-14% of patients following allo-HSCT. However, autoimmune encephalitis (AE) secondary to CMV infection after allo-HSCT has rarely been reported. Here we report a case of possible AE following CMV viremia after allo-HSCT, which was successfully treated with high-dose pulsed methylprednisolone and intravenous immunoglobulins (IVIg). Case description: A 53-year-old female underwent allo-HSCT for T-lymphoblastic lymphoma/leukemia. The patient developed CMV viremia on day 36 after transplantation, and serum CMV-DNA remained positive after initiating ganciclovir antiviral therapy, turning negative one month later. Four months later, she started experiencing memory impairment, weakness in the left limbs, cognitive dysfunction, and hallucinations. A magnetic resonance imaging brain scan showed scattered ischemic lesions under the bilateral frontal cortex. Viral detection in cerebral spinal fluid (CSF) by next-generation gene sequencing technology showed no obvious abnormality. Antibodies specific to AE and paraneoplastic diseases in serum and CSF were absent. The oligoclonal bands in the CSF were detected using isoelectric focusing and immunofixation, and the results were negative. However, after extensive investigation regarding infections, autoimmune disorders, and recurrence of the malignancy, possible AE could not be excluded. The patient was treated with high-dose steroids combined with IVIg therapy; the patient's symptoms were significantly improved. Conclusion: The mechanisms of AE after allo-HSCT and the relationship with CMV infection should be further studied. Therefore, reporting this and similar cases will improve our awareness and understanding of the underlying disease mechanisms.
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Posttransplant lymphoproliferative disorder (PTLD) is a rare lymphoid and/or plasmocytic proliferation that occurs after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aimed to identify the pathologic features and clinical outcomes of T-cell PTLD, an extremely rare subtype of PTLD, after allo-HSCT. In this study, six allo-HSCT recipients with T-cell PTLD from five transplant centers in China were enrolled. All the T-cell PTLD were donor-derived, and three patients were with monomorphic and three with polymorphic types, respectively. All patients received cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based chemotherapy. Five patients achieved complete response (CR), and one experienced progressive disease (PD). The median time from HSCT to onset was 4 (range: 0.6-72) months, analyzed in combination with the other 16 patients with T-cell PTLD identified from previous reports. About 56.3% of the T-cell samples (9/16) were positive for in situ hybridization with an Epstein-Barr virus (EBV)-encoded small nuclear early region (EBER ISH). CHOP-based chemotherapy might be the optimal strategy for patients who showed no response to empiric therapy with a CR rate of 87.5%. In conclusion, our study observed that T-cell PTLD has distinct clinical manifestations and morphological features, which characterized by less relation to EBV, later occurrence, and poorer prognosis when compared with B-cell PTLD.
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Trasplante de Células Madre Hematopoyéticas , Trastornos Linfoproliferativos , Linfocitos T , Trasplante Homólogo , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Trastornos Linfoproliferativos/etiología , Masculino , Femenino , Adulto , Linfocitos T/inmunología , Trasplante Homólogo/métodos , Trasplante Homólogo/efectos adversos , Adolescente , Niño , Persona de Mediana Edad , Adulto Joven , Ciclofosfamida/uso terapéuticoRESUMEN
Acute myeloid leukemia (AML) is a prevalent hematological malignancy among adults. Recent studies suggest that the length of telomeres could significantly affect both the risk of developing AML and the overall survival (OS). Despite the limited focus on the prognostic value of telomere-related genes (TRGs) in AML, our study aims at addressing this gap by compiling a list of TRGs from TelNet, as well as collecting clinical information and TRGs expression data through the Gene Expression Omnibus (GEO) database. The GSE37642 dataset, sourced from GEO and based on the GPL96 platform, was divided into training and validation sets at a 6:4 ratio. Additionally, the GSE71014 dataset (based on the GPL10558 platform), GSE12417 dataset (based on the GPL96 and GPL570 platforms), and another portion of the GSE37642 dataset (based on the GPL570 platform) were designated as external testing sets. Univariate Cox regression analysis identified 96 TRGs significantly associated with OS. Subsequent Lasso-Cox stepwise regression analysis pinpointed eight TRGs (MCPH1, SLC25A6, STK19, PSAT1, KCTD15, DNMT3B, PSMD5, and TAF2) exhibiting robust predictive potential for patient survival. Both univariate and multivariate survival analyses unveiled TRG risk scores and age as independent prognostic variables. To refine the accuracy of survival prognosis, we developed both a nomogram integrating clinical parameters and a predictive risk score model based on TRGs. In subsequent investigations, associations were emphasized not solely regarding the TRG risk score and immune infiltration patterns but also concerning the response to immune-checkpoint inhibitor (ICI) therapy. In summary, the establishment of a telomere-associated genetic risk model offers a valuable tool for prognosticating AML outcomes, thereby facilitating informed treatment decisions.
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Chronic graft-versus-host disease (cGVHD) is a potentially life-threatening complication after allogeneic hematopoietic stem cell transplantation. Standard steroid first-line treatment could not satisfy therapeutic needs due to limited efficacy. As a highly selective Janus kinase (JAK) 1 inhibitor, SHR0302 exhibits a reduced inhibition effect on JAK2 and might have less effect on hematopoiesis. This phase I clinical trial investigated the tolerability and safety of SHR0302 in combination with prednisone, and its early efficacy evidence as a potential first-line treatment to moderate/severe cGVHD. The standard 3 + 3 dose escalation was implemented to find the optimal dose of SHR0302. And prednisone was concurrently administrated with a dose of 1 mg/kg/d and then gradually tapered after 2 weeks. Eighteen patients were enrolled into the study. Grade ≥ 3 treatment-related adverse events were observed in 38.9% of patients. Only one patient developed DLT (grade ≥ 3 hypercholesterolemia) in the highest dose-level group who had pre-existing hypercholesterolemia. The maximum tolerated dose was not reached. No patient discontinued treatment due to AEs. Sixteen out of 18 patients were evaluable for responses, the ORR at week 4 and week 24 were 94.4 and 87.5%, respectively. Overall, the treatment of SHR0302 combined with prednisone was safe and well-tolerated, preliminary clinical results presented a high response for previously untreated cGVHD and a significant reduction in prednisone use in this study. A phase II trial will be conducted to further investigate its therapeutic effects clinically.
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Enfermedad Injerto contra Huésped , Janus Quinasa 1 , Prednisona , Humanos , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Prednisona/uso terapéutico , Masculino , Femenino , Adulto , Persona de Mediana Edad , Janus Quinasa 1/antagonistas & inhibidores , Janus Quinasa 1/metabolismo , Enfermedad Crónica , Adulto Joven , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Anciano , Quimioterapia Combinada , Síndrome de Bronquiolitis ObliteranteRESUMEN
Circular mRNA (cmRNA) is particular useful due to its high resistance to degradation by exonucleases, resulting in greater stability and protein expression compared to linear mRNA. T cell receptor (TCR)-engineered T cells (TCR-T) represent a promising means of treating viral infections and cancer. This study aimed to evaluate the feasibility and efficacy of cmRNA in antigen-specific-TCR discovery and TCR-T therapy. Using human cytomegalovirus (CMV) pp65 antigen as a model, we found that the expansion of pp65-responsive T cells was induced more effectively by monocyte-derived dendritic cells transfected with pp65-encoding cmRNA compared with linear mRNA. Subsequently, we developed cmRNA-transduced pp65-TCR-T (cm-pp65-TCR-T) that specifically targets the CMV-pp65 epitope. Our results showed that pp65-TCR could be expressed on primary T cells for more than 7 days. Moreover, both in vitro killing and in vivo CDX models demonstrated that cm-pp65-TCR-T cells specifically and persistently kill pp65-and HLA-expressing tumor cells, significantly prolonging the survival of mice. Collectively, our results demonstrated that cmRNA can be used as a more effective technical approach for antigen-specific TCR isolation and identification, and cm-pp65-TCR-T may provide a safe, non-viral, non-integrated therapeutic approach for controlling CMV infection, particularly in patients who have undergone allogeneic hematopoietic stem cell transplantation.
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Infecciones por Citomegalovirus , Trasplante de Células Madre Hematopoyéticas , Humanos , Animales , Ratones , Infecciones por Citomegalovirus/genética , Infecciones por Citomegalovirus/terapia , Citomegalovirus/genética , Linfocitos T , Receptores de Antígenos de Linfocitos T/genética , Proteínas de la Matriz Viral/genéticaRESUMEN
Introduction: The novel low-dose anti-thymocyte (ATG, 5 mg/kg) plus low-dose post-transplant cyclophosphamide (PTCy, 50 mg/kg) (low-dose ATG/PTCy)-based regimen had promising activity for prevention of graft-versus-host disease (GVHD) in haploidentical-peripheral blood stem cell transplantation (haplo-PBSCT), but its impacts on long-term outcomes remain to be defined. Methods: We performed a large sample, long-term follow-up retrospective study to evaluate its efficacy for GVHD prophylaxis. Results: The study enrolled 260 patients, including 162 with myeloid malignancies and 98 with lymphoid malignancies. The median follow-up time was 27.0 months. For the entire cohort, the cumulative incidences (CIs) of grade II-IV and III-IV acute GVHD (aGVHD) by 180 days were 13.46% (95% CI, 9.64%-17.92%) and 5.77% (95% CI, 3.37%-9.07%); while total and moderate/severe chronic GVHD (cGVHD) by 2 years were 30.97% (95% CI, 25.43%-36.66%) and 18.08% (95% CI, 13.68%-22.98%), respectively. The 2-year overall survival (OS), relapse-free survival (RFS), GVHD-free, relapse-free survival (GRFS), non-relapse mortality (NRM), and CIs of relapse were 60.7% (95% CI, 54.8%-67.10%), 58.1% (95% CI, 52.2%-64.5%), 50.6% (95% CI, 44.8-57.1%), 23.04% (95% CI, 18.06%-28.40%), and 18.09% (95% CI, 14.33%-23.97%, respectively. The 1-year CIs of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) reactivation were 43.46% (95% CI, 37.39%-49.37%) and 18.08% (95% CI, 13.68%-22.98%), respectively. In multivariate analysis, the disease status at transplantation was associated with inferior survivor outcomes for all patients and myeloid and lymphoid malignancies, while cGVHD had superior outcomes for all patients and myeloid malignancies, but not for lymphoid malignancies. Discussion: The results demonstrated that the novel regimen could effectively prevent the occurrence of aGVHD in haplo-PBSCT.
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Infecciones por Virus de Epstein-Barr , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Neoplasias , Trasplante de Células Madre de Sangre Periférica , Células Madre de Sangre Periférica , Humanos , Suero Antilinfocítico/uso terapéutico , Trasplante de Células Madre de Sangre Periférica/efectos adversos , Estudios de Seguimiento , Estudios Retrospectivos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Infecciones por Virus de Epstein-Barr/complicaciones , Células Madre de Sangre Periférica/patología , Herpesvirus Humano 4 , Ciclofosfamida/uso terapéutico , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Enfermedad Injerto contra Huésped/patología , Neoplasias/tratamiento farmacológicoRESUMEN
INTRODUCTION: Unbiased metagenomic next-generation sequencing (mNGS) has been used for infection diagnosis. In this study, we explored the clinical diagnosis value of mNGS for pulmonary complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: From August 2019 to June 2021, a prospective study was performed to comparatively analyze the pathogenic results of mNGS and conventional tests for bronchoalveolar lavage fluid (BALF) from 134 cases involving 101 patients with pulmonary complications after allo-HSCT. RESULTS: More pathogens were identified by mNGS than with conventional tests (226 vs 120). For bacteria, the diagnostic sensitivity (P = 0.144) and specificity (P = 0.687) were similar between the two methods. For fungus except Pneumocystis jirovecii (PJ), conventional tests had a significantly higher sensitivity (P = 0.013) with a similarly high specificity (P = 0.109). The sensitivities for bacteria and fungi could be increased with the combination of the two methods. As for PJ, both the sensitivity (100%) and specificity (99.12%) of mNGS were very high. For viruses, the sensitivity of mNGS was significantly higher (P = 0.021) and the negative predictive value (NPV) was 95.74% (84.27-99.26%). Pulmonary infection complications accounted for 90.30% and bacterium was the most common pathogen whether in single infection (63.43%) or mixed infection (81.08%). The 6-month overall survival (OS) of 88.89% in the early group (mNGS ≤ 7 days) was significantly higher than that of 65.52% (HR 0.287, 95% CI 0.101-0.819, P = 0.006) in the late group (mNGS > 7 days). CONCLUSIONS: mNGS for BALF could facilitate accurate and fast diagnosis for pulmonary complications. Early mNGS could improve the prognosis of patients with pulmonary complications after allo-HSCT. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04051372.
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To combine the advantages of elastic and nonelastic triboelectric materials, this work proposes a new type of triboelectric nanogenerator (TENG) based on stacking -the stacked FKM/PU TENG. By stacking the elastomer polyurethane (PU) and the nonelastomer fluororubber (FKM), the FKM/PU TENG combines the inherent triboelectric characteristics of both materials and the unique elasticity of PU to achieve an output performance that is much higher than that of the FKM-TENG or the PU-TENG. The maximum instantaneous open-circuit voltage and short-circuit current of the FKM/PU TENG reach 661 V and 71.2 µA, respectively. Under the limiting conditions of 3 Hz and maximum compression, this device can attain a maximum power density of 49.63 W/m3 and light more than 500 LEDs. Therefore, stacking materials with different properties gives the FKM/PU TENG high output performance and great application potential, which can contribute to future development of discrete mechanical energy harvesting.
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The contribution of lymphocyte subset composition of the graft on the outcomes following haploidentical peripheral blood stem cell transplantation (haploPBSCT) is not fully elucidated. We retrospectively analyzed 314 patients with hematological malignancies who underwent haploPBSCT from 2016 to 2020 in our center. We obtained a cutoff value of CD3+ T cell dose (2.96 × 108/kg) that separated the risk of II-IV acute graft-versus-host disease (aGvHD) and divided patients into the low CD3+ T cell dose group (CD3+ low) and the high CD3+ T cell dose (CD3+ high) group. Significantly higher incidences of I-IV aGvHD, II-IV aGvHD, and III-IV aGvHD were identified in the CD3+ high group (50.8%, 19.8%, and 8.1% in the high group, 23.1%, 6.0%, and 0.9% in the low group, P < 0.0001, P = 0.002, and P = 0.02, respectively). We found that CD4+ T cell and its naïve and memory subpopulations of grafts had a significant impact on aGvHD (P = 0.005, P = 0.018, and P = 0.044). Besides, we found an inferior reconstitution of natural killer (NK) cells in the CD3+ high group than in the low group within the first-year posttransplant (239 cells/µL vs 338 cells/µL, P = 0.0003). No differences in engraftment, chronic GvHD (cGvHD), relapse rate, transplant-related mortality (TRM), and overall survival (OS) were identified between the two groups. In conclusion, our study found that a high CD3+ T cell dose led to a high risk of aGvHD and inferior reconstitution of NK cells in the haploPBSCT setting. In the future, carefully manipulating the composition of lymphocyte subsets of grafts might reduce the risk of aGvHD and improve the transplant outcome.
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Enfermedad Injerto contra Huésped , Neoplasias Hematológicas , Trasplante de Células Madre Hematopoyéticas , Trasplante de Células Madre de Sangre Periférica , Humanos , Trasplante de Células Madre de Sangre Periférica/efectos adversos , Estudios Retrospectivos , Recurrencia Local de Neoplasia , Enfermedad Injerto contra Huésped/etiología , Subgrupos Linfocitarios , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Acondicionamiento PretrasplanteAsunto(s)
Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Adulto , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Antígenos CD19 , Linfocitos T , Inmunoterapia Adoptiva , Lectina 2 Similar a Ig de Unión al Ácido SiálicoRESUMEN
Swine manure is usually transmitted by the "collection-storage-transport" mode of the biogas project. However, this particular application pattern results in high volatile fatty acids (VFAs) concentration due to the long transition time in the "collection-storage-transport" process. In this work, acidulated swine manure anaerobic digestion (AD) with bentonite supplementation was firstly investigated with an expectation of acid alleviation, performance enhancement and microbial mechanism. Results indicated that the methane production rate in the 20 g/L bentonite-added digester was 2.87 fold higher than that of the control digester. Chemical oxygen demand (COD) removal rate was elevated by 140.1% via bentonite supplementation. Besides, the rapid decrease of VFAs and ammonia indicated that bentonite supplementation could offer buffering capacity and alleviate acid inhibition. Microbial community analysis revealed that acetoclastic methanogenesis (Methanosaeta and Methanosarcina) was the predominant methanogenesis pathway in this AD system. Syntrophic acetate oxidation (SAO) bacteria were discovered in the bentonite-added digester, and they converted acetate into H2/CO2 to support hydrogenotrophic methanogenesis. This study could offer guidance for acidulated swine manure AD in the practical biogas project.
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Bentonita , Estiércol , Animales , Porcinos , Estiércol/microbiología , Anaerobiosis , Reactores Biológicos , Biocombustibles , Ácidos Grasos Volátiles , Suplementos DietéticosRESUMEN
Though it has been widely accepted that infections of the respiratory tract is associated with aetiology of acute exacerbation of chronic obstructive pulmonary disease (AECOPD), more recent techniques have shown emerging evidence on the importance of alterations of diversity and composition of microbiota itself in the disease process. Specifically, these alterations is widely present in COPD patients from a variety of populations, and is associated with severity of disease, frequency of acute exacerbation, as well as prediction of exacerbation. In addition, the microbiota from respiratory tract contributes to disease mechanisms, and more recently have been shown to interact with gut microbiota in a bidirectional way. Therefore, updating progress in the field is crucial as it not only reveals potential underlying mechanisms of the disease, but also highlights the potential utilisation of microbiota as a biomarker for disease prediction and as a target for treatment. In this narrative review, we summarize current updates on microbiota dysbiosis in COPD, including techniques for sampling and analysis of microbiota, recent findings on the presence of microbiota dysbiosis and its correlation with clinical prediction and prognosis of the disease, as well as its potential roles in disease mechanisms. In addition, how gut-lung axis contributes to COPD progression is also discussed. Finally, we addressed the utilisation of prebiotic and probiotic treatment for COPD. Together, we hope to provide useful information to advocate the use of microbial parameters as important tools for diagnosis, treatment and long-term follow-up for COPD patients.
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Microbiota , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Disbiosis , Progresión de la Enfermedad , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , PulmónRESUMEN
BACKGROUND: The impact of donor age on the immune reconstitution of patients with hematological malignancies who underwent hematopoietic cell transplantation (HCT) is unclear. METHOD: We retrospectively compared the outcomes of 381 patients who underwent allogeneic peripheral blood stem cell transplantation (PBSCT) from 308 donors under 50 years of age and 73 donors over 50 years of age. IVIG was regularly supplemented for patients in the first 3 months post-HCT. RESULTS: The counts of CD8+CD45RA+ naïve T cells were significantly lower in patients of the older donor group than in the younger donor group in the first year after PBSCT (190.6 cells/µl vs. 239.6 cells/µl, p = .018). Patients in the older donor group had significantly fewer CD19+ B cells on day +270 (123.4 cells/µl vs. 183.5 cells/µl, p = .021) and day +365 (169 cells/µl vs. 271.1 cells/µl, p = .01) after PBSCT. Serum IgA (.76 g/L vs. .97 g/L, p < .001) and IgM levels (.75 g/L vs. 1.04 g/L, p < .001) were significantly lower in patients in the older donor group from day +60 to +365 after PBSCT. The EBV reactivation rate within the first 3 months after PBSCT was significantly higher in patients in the older donor group (48.6% vs. 38.3%, p = .034). However, the incidences of CMV reactivation, II-IV acute graft-versus-host disease (aGvHD), chronic GvHD (cGvHD), 3-year relapse rate, 3-year transplant-related mortality (TRM) and 3-year overall survival (OS) were not significantly different between the two groups. CONCLUSION: In conclusion, donors ≥50 years old were associated with inferior immune reconstitution and higher EBV reactivation in patients after PBSCT, but no change in OS.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Reconstitución Inmune , Trasplante de Células Madre de Sangre Periférica , Anciano , Humanos , Persona de Mediana Edad , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Recurrencia Local de Neoplasia/etiología , Trasplante de Células Madre de Sangre Periférica/efectos adversos , Estudios RetrospectivosRESUMEN
Maternal and collateral donors were associated with a higher incidence of graft-versus-host disease (GvHD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). A more effective regimen for GvHD prophylaxis after haplo-HSCT with maternal/collateral donors needed to be explored. A retrospective study was performed on 62 patients after haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) with maternal/collateral donors, which included 35 patients with low-dose antithymocyte globulin (ATG) plus low-dose posttransplant cyclophosphamide-based (low-dose ATG/PTCy-based) and 27 with ATG-based regimens for GvHD prophylaxis. The 180-day cumulative incidences (CIs) of grades II-IV and III-IV acute GvHD (aGvHD) were 17.7% and 6.8% in low-dose ATG/PTCy-based group, which were significantly lower than that in ATG-based group (55.4% and 31.9%) (P = 0.003 for grade II-IV and P = 0.007 for III-IV aGvHD). In low-dose ATG/PTCy-based group, the 1-year overall survival (OS) and relapse-free survival (RFS) were 80.0%and 80.4%, which were higher than that in ATG-based group with OS of 59.4% and RFS of 62.0%. In multivariate analysis, the low-dose ATG/PTCy-based regimen significantly reduced the risk of grade II-IV (HR = 0.357; P = 0.049) and grade III-IV aGvHD (HR = 0.190; P = 0.046) as an independent risk factor. The results suggested that the low-dose ATG/PTCy-based regimen could effectively prevent the occurrence of aGvHD after haplo-PBSCT with maternal/collateral donors compared with the ATG-based regimen.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre de Sangre Periférica , Humanos , Enfermedad Injerto contra Huésped/prevención & control , Enfermedad Injerto contra Huésped/etiología , Suero Antilinfocítico/uso terapéutico , Trasplante de Células Madre de Sangre Periférica/efectos adversos , Acondicionamiento Pretrasplante/métodos , Estudios Retrospectivos , Ciclofosfamida/uso terapéuticoRESUMEN
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the consolidation modalities for adult patients with T-cell lymphoblastic lymphoma (T-LBL). However, the optimal conditioning regimen needs to be explored. In the present study, 40 patients with T-LBL undergoing allo-HSCT were retrospectively analyzed, including 23/40 (57.5%) with total body irradiation (TBI)-based conditioning regimen and 17/40 (42.5%) with busulfan (BU)-based regimen. TBI-based regimen significantly increased the cumulative incidence (CI) of grade II to IV acute graft-versus-host disease (aGvHD) as compared with BU-based regimen (13.0% vs 0%, P = 0.000). The relapse risk was significantly lowered in TBI-based group with a 2-year CI of relapse (CIR) of 9.1% as compared with that of 49.6% in BU-based group (P = 0.008). The 1-year and 2-year non-relapse mortalities (NRMs) for all patients were 5.0% and 10.3%, respectively. The 1-year and 2-year NRMs were 8.9% and 16.0% in TBI-based group, and 0.00% and 0.00% in BU-based group (P = 0.140). The 2-year probabilities of overall survival (OS) and relapse-free survival (RFS) were 83.0% [95% confidence interval, 63.4%-100%] and 74.0% (95% confidence interval, 54.4%-93.6%) in TBI-based group, which were higher than that of 35.0% (95% confidence interval, 0.0%-72.2%) and 50.0% (95% confidence interval, 24.5%-75.4%) in BU-based group, respectively (P = 0.020 for OS and P = 0.081 for RFS). In multivariate analysis, TBI-based regimen significantly reduced the risk of relapse [subdistribution hazard ratio (SHR) = 0.030, 95% CI, 0.002-0.040, P = 0.000] and improved the OS [hazard ratio (HR) 0.121, 95% CI, 0.021-0.683, P = 0.017] as an independent prognostic factor. These results suggested that TBI-based regimen might be an optimal choice for adult patients with T-LBL undergoing allo-HSCT.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Trasplante de Células Madre de Sangre Periférica , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Busulfano/uso terapéutico , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Trasplante de Células Madre de Sangre Periférica/efectos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Recurrencia , Estudios Retrospectivos , Linfocitos T , Acondicionamiento Pretrasplante/métodos , Irradiación Corporal Total/efectos adversosRESUMEN
Viral reactivation or infections are common complications after allogeneic hematopoietic stem cell transplantation, especially in haploidentical transplantation. Here, we presented a young patient with Ph-like acute lymphoblastic leukemia who suffered Epstein-Barr virus (EBV) encephalitis and disseminated adenovirus (ADV) infection after haploidentical peripheral blood (PB) stem cell transplantation. The patient was a 16-year-old boy and received PB stem cells from his HLA-haploidentical matched father. On day +44 after transplantation, he had viremia with cytomegalovirus, and EBV was diagnosed as EBV encephalitis after 2 weeks. On day +117, he had disseminated ADV infection and fulminant ADV hepatitis. It is very rare that successive EBV encephalitis and fulminant ADV hepatitis are present in the same patient. We summarized risk factors, clinical manifestations, diagnostic criteria, and effective treatments about EBV encephalitis and disseminated ADV infection. We try to enhance our understanding of the prevention, diagnosis, and potential treatment of EBV and ADV disease by reviewing the entire procedure.
RESUMEN
Parvovirus B19 (PvB19) infection and PvB19 related pure red cell aplasia (PRCA) in recipients with allogeneic hematopoietic stem cell transplantation have been reported sporadically. However, clinical studies with large sample sizes are lacking, especially in patients undergoing HLA-haploidentical peripheral blood stem cell transplantation (haplo-PBSCT). In addition, clinical features, immune reconstitution, and outcomes of these patients are not clear. We conducted a retrospective analysis of 164 patients who received haplo-PBSCT with low-dose anti-thymocyte globulin (ATG) plus low-dose posttransplant cyclophosphamide (PTCy)-based regimen as graft-versus-host disease (GVHD) prophylaxis. We analyzed the incidence of PvB19 related PRCA and compared the clinical characteristics, immune reconstitution, incidence of GVHD, relapse rate, and survival between patients with and without PvB19 related PRCA. A total of 14 (8.5%) recipients developed PvB19 related PRCA after a median of 5.3 months after haplo-PBSCT. These patients with PvB19 related PRCA had slower immune reconstitution, but similar incidences of GVHD, relapse rate, and overall survival compared with recipients without PvB19 related PRCA. PvB19 related PRCA indicated relative delayed and poor immune reconstitution of the recipients early after haplo-PBSCT. PvB19 related PRCA had no effects on GVHD, relapse, and survival.