RESUMEN

BACKGROUND: Post-transplant lymphoproliferative disorders (PTLD) are rare but severe complications that occur after solid organ or allogeneic hematopoietic stem cell transplantations (allo-HSCT), with rapid progression and high mortality. Primary central nervous system (CNS)-PTLD are rarely recognized histo-pathologically. In addition, the diagnostic value of the Epstein-Barr virus (EBV) DNA copies in CNS-PTLD remains poorly understood. OBJECTIVES: We herein report a case of monomorphic EBV-associated CNS-PTLD (diffuse large B-cell lymphoma, DLBCL) after allo-HSCT and perform a meta-analysis to assess the efficacy of PTLD treatment strategies in recent years. METHODS: We present the case report covering clinical manifestations, diagnosis, treatment, and outcomes of a patient with primary CNS-PTLD. Additionally, we include a systematic review and meta-analysis of the clinical characteristics of 431 patients with PTLD after allo-HSCT. We evaluate the main treatment options and outcomes of PTLD management, including rituximab, chemotherapies, and autologous or human leukocyte antigen (HLA)-matched EBV-specific cytotoxic T lymphocyte infusion (EBV-CTLs)/donor lymphocyte infusion (DLI). RESULTS: The meta-analysis revealed an overall response rate of 69.0% for rituximab alone (95% CI: 0.47-0.84), 45.0% for rituximab plus chemotherapies (95% CI: 0.15-0.80), and 91.0% for rituximab plus EBV-CTLs/DLI (95% CI: 0.83-0.96). The complete response (CR) rate after treatments for PTLD was 67.0% (95% CI: 0.56-0.77). Moreover, the 6-month and 1-year overall survival (OS) rate was 64.0% (95% CI: 0.31-0.87) and 49.0% (95% CI: 0.31-0.68), respectively. CONCLUSIONS: This case highlighted the urgent need for effective, low-toxic treatment regimens for CNS-PTLD. Our meta-analysis suggested that rituximab combined with EBV-CTLs/DLI could be a favorable strategy for the management of PTLD after allo-HSCT.

Asunto(s)

Infecciones por Virus de Epstein-Barr , Trasplante de Células Madre Hematopoyéticas , Trastornos Linfoproliferativos , Humanos , Infecciones por Virus de Epstein-Barr/complicaciones , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Herpesvirus Humano 4/aislamiento & purificación , Herpesvirus Humano 4/genética , Linfoma de Células B Grandes Difuso/virología , Linfoma de Células B Grandes Difuso/terapia , Trastornos Linfoproliferativos/etiología , Trastornos Linfoproliferativos/diagnóstico , Trastornos Linfoproliferativos/terapia , Rituximab/uso terapéutico , Trasplante Homólogo/efectos adversos

RESUMEN

Patients undergoing allogenic hematopoietic stem cell transplantation (allo-HSCT) are highly susceptible to infections. The consequent use of masks on wards for allo-HSCT has been controversial in the past decades and was not common before the COVID-19 pandemic. We retrospectively compared incidence and outcomes of viral respiratory infections during allo-HSCT on our specialized ward between 01/2018 and 09/2020 to the era of FFP2 masking between 10/2020 and 10/2022 covering similar seasons of the year. Each group consisted of 150 matched patients. The usage of FFP2 masks reduced the incidence of viral respiratory infections from 22.1 to 2.1% (p < 0.005). This reduced the time on ward from a median of 26 days to 23.5 days (p = 0.002). It also resulted in less use of CT-scans (p = 0.003) and bronchoalveolar lavage procedures (p = 0.057). Median time to proof of infection was 21 days after admission in both groups. No difference was detected in progression free survival, hospital survival or non-relapse mortality (p = 0.78). Our retrospective results indicate that FFP2 masks worn by patients and hospital staff may help to significantly reduce the incidence of viral respiratory infections, including COVID-19, shorten the in-hospital time, and reduce costs without affecting survival.

Asunto(s)

COVID-19 , Trasplante de Células Madre Hematopoyéticas , Máscaras , Infecciones del Sistema Respiratorio , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , COVID-19/prevención & control , COVID-19/epidemiología , Infecciones del Sistema Respiratorio/prevención & control , Infecciones del Sistema Respiratorio/virología , Infecciones del Sistema Respiratorio/epidemiología , Estudios Retrospectivos , Adulto , Trasplante Homólogo/efectos adversos , Anciano , SARS-CoV-2/aislamiento & purificación , Incidencia

RESUMEN

Pneumatosis cystoides intestinalis (PCI) is a rare condition characterized by air accumulation within the subserosa or submucosa of the gastrointestinal wall. We herein report a case involving a woman in her early 30s who developed PCI after undergoing allogeneic hematopoietic stem cell transplantation (HSCT) for acute lymphoblastic leukemia. The patient had a history of multiple COVID-19 infections. Imaging revealed extensive pneumoperitoneum and mesenteric emphysema; nevertheless, the patient remained clinically stable with a benign abdominal examination. She eventually recovered after 1 month of conservative treatment. We believe the PCI in this case had a multifactorial etiology, potentially involving both HSCT and COVID-19. Raising awareness of PCI may help avoid unnecessary surgical interventions and associated morbidity.

Asunto(s)

Trasplante de Células Madre Hematopoyéticas , Neumatosis Cistoide Intestinal , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Neumatosis Cistoide Intestinal/etiología , Neumatosis Cistoide Intestinal/diagnóstico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Femenino , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Adulto , COVID-19/complicaciones , Tomografía Computarizada por Rayos X , SARS-CoV-2 , Trasplante Homólogo/efectos adversos

RESUMEN

Backgrounds: Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for hematological malignancies, it can be associated with relevant post-transplant complications. Several reports have shown that polymorphisms in immune system genes are correlated with the development of post-transplant complications. Within this context, this work focuses on identifying novel polymorphisms in cytokine genes and developing predictive models to anticipate the risk of developing graft-versus-host disease (GVHD), transplantation-related mortality (TRM), relapse and overall survival (OS). Methods: Our group developed a 132-cytokine gene panel which was tested in 90 patients who underwent an HLA-identical sibling-donor allo-HSCT. Bayesian logistic regression (BLR) models were used to select the most relevant variables. Based on the cut-off points selected for each model, patients were classified as being at high or low-risk for each of the post-transplant complications (aGVHD II-IV, aGVHD III-IV, cGVHD, mod-sev cGVHD, TRM, relapse and OS). Results: A total of 737 polymorphisms were selected from the custom panel genes. Of these, 41 polymorphisms were included in the predictive models in 30 cytokine genes were selected (17 interleukins and 13 chemokines). Of these polymorphisms, 5 (12.2%) were located in coding regions, and 36 (87.8%) in non-coding regions. All models had a statistical significance of p<0.0001. Conclusion: Overall, genomic polymorphisms in cytokine genes make it possible to anticipate the development all complications studied following allo-HSCT and, consequently, to optimize the clinical management of patients.

Asunto(s)

Citocinas , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Trasplante Homólogo , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Masculino , Femenino , Citocinas/genética , Adulto , Enfermedad Injerto contra Huésped/genética , Enfermedad Injerto contra Huésped/etiología , Persona de Mediana Edad , Trasplante Homólogo/efectos adversos , Adulto Joven , Adolescente , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/mortalidad , Antígenos HLA/genética , Antígenos HLA/inmunología , Polimorfismo Genético , Anciano

RESUMEN

OBJECTIVE: To analyze the risk factors of Epstein-Barr virus (EBV) infection after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and its impact on survival. METHODS: The clinical data of 347 patients who underwent their first allo-HSCT in our hospital from January 2014 to June 2021 were retrospectively analyzed. Patients were divided into EBV (n =114) and Non-EBV (n =233) groups according to whether they were infected with EBV. The incidence of EBV infection after allo-HSCT was calculated, and the risk factors of EBV infection were analyzed. RESULTS: A total of 114(32.8%) patients presented EBV infection (all peripheral blood EBV-DNA were positive). EBV infection occurred in 88 patients within 100 days after transplantation, which accounted for 77.2% of all patients with EBV infection. 5 cases (1.44%) were confirmed as post-transplant lymphoproliferative disorder (PTLD). The median onset time of patients was 57(7-486) days after transplantation. Multivariate analysis showed that the use of ATG/ATG-F, occurrence of CMV viremia, and grade III-IV aGVHD were risk factors for EBV infection. Furthermore, compared to BUCY, the use of intensified preconditioning regimens containing FA/CA was significantly increased the risk of EBV infection. CONCLUSION: EBV infection is a common complication after allo-HSCT. Intensified preconditioning regimens, use of ATG/ATG-F, CMV viremia and grade III to IV aGVHD increase the risk of EBV infection after allo-HSCT.

Asunto(s)

Infecciones por Virus de Epstein-Barr , Trasplante de Células Madre Hematopoyéticas , Herpesvirus Humano 4 , Trasplante Homólogo , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Estudios Retrospectivos , Factores de Riesgo , Trasplante Homólogo/efectos adversos , Acondicionamiento Pretrasplante/efectos adversos , Enfermedad Injerto contra Huésped/etiología , Trastornos Linfoproliferativos/etiología , Incidencia , Femenino , Masculino

RESUMEN

INTRODUCTION: Invasive fungal diseases (IFD) constitute a major cause of morbidity and mortality in hematopoietic stem cell transplantation (HSCT) recipients. AREAS COVERED: We describe epidemiology, causes and risk factors of IFD in allogeneic HSCT discussing prophylaxis and treatment in various HSCT phases. We present the most recent studies on this thematic area, including novel data on currently available antifungals, i.e. formulations, dosing, safety, efficacy and therapeutic drug monitoring. Finally, we present the most recent relevant recommendations published. Literature search included PubMed, Scopus, and clinicaltrials.gov between January 2014 and April 2024. EXPERT OPINION: The antifungal agents employed for prophylaxis and therapy should be predicated on local epidemiology of IFD. Fluconazole prophylaxis remains a first-line choice before engraftment when the main pathogen is Candida spp. After engraftment, prophylaxis should be with mold-active agents (i.e. triazoles). For candidiasis, echinocandins are suggested as first-line treatment, whereas aspergillosis responds well to mold-active azoles and liposomal amphotericin B (L-AmB). For mucormycosis, treatment of choice includes L-AmB and isavuconazole. Choice between fever-driven and diagnostics-driven strategies remains equivocal. Open research topics remain: 1) optimization of tools to ensure prompt and accurate IFD diagnosis to avoid unnecessary exposure to antifungals, drug interactions and cost; 2) refinement of treatment for resistant/refractory strains.

Asunto(s)

Antifúngicos , Trasplante de Células Madre Hematopoyéticas , Infecciones Fúngicas Invasoras , Trasplante Homólogo , Humanos , Antifúngicos/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Infecciones Fúngicas Invasoras/prevención & control , Trasplante Homólogo/efectos adversos , Factores de Riesgo , Monitoreo de Drogas

RESUMEN

Allogeneic hematopoietic cell transplantation (HCT) is a crucial treatment for various diseases, including hematological malignancies, solid tumors, and genetic disorders. Despite its curative potential, HCT is associated with severe complications, notably infections, graft-versus-host disease, and organ damage. Infections, particularly bloodstream infections (BSIs), pose a significant threat in the initial weeks post-HCT, necessitating effective management strategies. This retrospective study aimed to clarify the incidence, pathogens, and risk factors associated with BSI within the first 30 days after allogeneic HCT in children/adolescents and young adults (AYAs). The study included 115 patients aged <31 years who underwent 121 allogeneic HCTs at the Department of Pediatrics, Nagoya University Hospital between January 1, 2018, and March 31, 2022. Data encompassed demographic characteristics, HCT details, and BSI information. Overall, 27 of 121 patients developed BSI with the cumulative incidence of 23.5% (95% confidence intervals [CI]: 17.0%-30.6%) at 30 days after HCT. The median onset time of BSI was 7 (range, 4-26 days) after HCT. Gram-positive bacteria accounted for 89% of pathogens isolated from blood cultures, with Streptococcus mitis/oralis being the most common. In multivariable analysis, tandem HCT (subdistribution hazard ratio [SHR]: 5.67, 95% CI: 2.74-11.7, p < 0.001) and peripherally inserted central catheters (SHR: 2.96, 95% CI: 1.34-6.55, p = 0.007) were identified as independent risk factors for BSI. In patients receiving tandem HCT, the pathogens isolated from blood cultures were all gram-positive bacteria, with Streptococcus mitis/oralis accounting for up to 67% of the isolated pathogens. Tandem HCT and PICCs were identified as independent risk factors for BSI after allogeneic HCT in children/AYAs. The pathogens were commonly gram-positive, and Streptococcus mitis/oralis is important in patients who received tandem HCT. These data can provide valuable information for future studies to consider effective interventions to reduce the risk of BSI in high-risk patients.

Asunto(s)

Trasplante de Células Madre Hematopoyéticas , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Masculino , Femenino , Niño , Adolescente , Factores de Riesgo , Adulto Joven , Adulto , Preescolar , Estudios Retrospectivos , Lactante , Trasplante Homólogo/efectos adversos , Incidencia , Bacteriemia/epidemiología , Bacteriemia/etiología , Bacteriemia/microbiología

RESUMEN

The incidence of herpes zoster (HZ) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients is significantly higher than that of the general public. Although routine antiviral prophylaxis is recommended, late-onset HZ has been highlighted, yet limited information is known about its clinical features and predictors. Here, we conducted a retrospective nested case-control study to identify patients with late-onset HZ, defined as a diagnosis of HZ after 1 year of transplantation, among allo-HSCT recipients between 2012 and 2017 at Peking University People's Hospital. Three controls were matched for each patient. A total of 201 patients developed late-onset HZ. Age over 20 years, absence of neutrophil engraftment by 14 days, mental disorders, immunosuppressant use at 1 year, and a peripheral CD4+/CD8+ ratio ≥0.5 at 1 year were independent risk factors, among which the CD4+/CD8+ ratio demonstrated good discriminative power for predicting late-onset HZ. For patients with a CD4+/CD8+ ratio <0.5, patient age, neutrophil engraftment time, mental disorders, and immunosuppressant use were potential risk factors. A stratification algorithm was accordingly established, classifying the transplant recipients into three risk groups. Whether the algorithm could facilitate the administration of posttransplant antiviral prophylaxis merits further validation.

Asunto(s)

Trasplante de Células Madre Hematopoyéticas , Herpes Zóster , Trasplante Homólogo , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Herpes Zóster/virología , Herpes Zóster/epidemiología , Herpes Zóster/diagnóstico , Masculino , Femenino , Adulto , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Estudios de Casos y Controles , Trasplante Homólogo/efectos adversos , Adulto Joven , Medición de Riesgo , Antivirales/uso terapéutico , Incidencia , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Relación CD4-CD8 , Adolescente , Factores de Tiempo , Anciano , Herpesvirus Humano 3/inmunología

RESUMEN

The acquisition or reactivation of Epstein-Barr virus (EBV) after allogeneic Hematopoietic Stem Cell Transplant (HSCT) can be associated with complications including the development of post-transplant lymphoproliferative disorder (PTLD), which is associated with significant morbidity and mortality. A number of risk factors for PTLD have been defined, including T-cell depletion, and approaches to monitoring EBV, especially in high-risk patients, with the use of preemptive therapy upon viral activation have been described. Newer therapies for the preemption or treatment of PTLD, such as EBV-specific cytotoxic T-cells, hold promise. Further studies to help define risks, diagnosis, and treatment of EBV-related complications are needed in this at-risk population.

Asunto(s)

Infecciones por Virus de Epstein-Barr , Trasplante de Células Madre Hematopoyéticas , Herpesvirus Humano 4 , Trastornos Linfoproliferativos , Trasplante Homólogo , Activación Viral , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Infecciones por Virus de Epstein-Barr/virología , Trasplante Homólogo/efectos adversos , Trastornos Linfoproliferativos/etiología , Trastornos Linfoproliferativos/terapia , Factores de Riesgo

RESUMEN

INTRODUCTION: ARDS (acute respiratory distress syndrome) is the most severe form of acute hypoxic respiratory failure. Most studies related to ARDS have excluded patients with hematologic diseases, let alone allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Numerous patients experiencing severe hypoxic respiratory failure do not meet the Berlin definition due to the limitations of diagnosis and treatment. A new definition of ARDS, remove some diagnosis restrictions, was proposed in 2023. Based on the 2023 new definition of ARDS, we investigated the clinical features of ARDS in allo-HSCT recipients and reported risk factors for in-hospital mortality in allo-HSCT recipients defined by the Berlin definition and the new definition of ARDS respectively. METHODS: From Jan 2016 to Dec 2020, 135 allo-HSCT recipients identified with the new definition and 87 identified with the Berlin definition at three teaching hospitals were retrospectively included in this study. Variables (demographic information, characteristics of hematologic disease and ARDS episode, laboratory tests and SOFA score) with P < 0.05 in univariate logistic regression analysis were included in multivariate stepwise logistic regression analysis. Adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) were reported. RESULTS: Under the new definition, SOFA score (OR = 1.351, 95% CI: 1.146-1.593, P < 0.01) were found as an independent risk factor for in-hospital mortality in ARDS after allo-HSCT, while SpO2/FiO2 (OR = 0.984, 95% CI: 0.972-0.996, P < 0.01) was a protective factor. The infusion of peripheral-derived stem cells was found to be a protective factor against in-hospital mortality in post-transplantation ARDS compared with the infusion of bone marrow-derived stem cells (OR = 0.726, 95% CI: 0.164-3.221, P = 0.04). Under the Berlin definition, PaO2/FiO2 (OR = 0.977, 95% CI: 0.961-0.993, P = 0.01, lactate (OR = 7.337, 95% CI: 1.313-40.989, P < 0.01) and AST (OR = 1.165, 95% CI: 1.072-1.265, P < 0.01) were independently associated with in-hospital mortality. CONCLUSION: These prognostic risk factors we found in allo-HSCT recipients may contribute to closer monitoring and ARDS prevention strategies. These findings require confirmation in prospective, large sample size studies.

Asunto(s)

Trasplante de Células Madre Hematopoyéticas , Mortalidad Hospitalaria , Síndrome de Dificultad Respiratoria , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Masculino , Estudios Retrospectivos , Femenino , Síndrome de Dificultad Respiratoria/mortalidad , Síndrome de Dificultad Respiratoria/terapia , Persona de Mediana Edad , Factores de Riesgo , Adulto , Trasplante Homólogo/efectos adversos , Anciano , Modelos Logísticos , Adulto Joven

RESUMEN

INTRODUCTION: Cytomegalovirus (CMV) infection is a major cause of transplantation-related morbidity and mortality. This study assessed the utility of the QuantiFERON monitor (QFM; Qiagen) for the prediction of early CMV infection and viral burden. METHODS: QuantiFERON-CMV (QF-CMV; Qiagen) and QFM were measured at the post-allogeneic hematopoietic stem cell transplantation (HSCT) week 4. CMV DNA was measured at every visit until post-HSCT week 24. The QFM cutoff specific to CMV infection was established. RESULT: At the post-HSCT week 4, the QFM cutoff predicting CMV infection was 86.95 IU/mL. While QF-CMV results at the post-HSCT week 4 were associated with high-level CMV infection (CMV DNA ≥ 5,000 IU/mL) but not with CMV infection (CMV DNA ≥ 500 IU/mL), QFM was associated with both CMV infection and high-level CMV infection. Both indeterminate QF-CMV and nonreactive QFM were associated with increased peak CMV DNA. CONCLUSION: Low QFM is a risk factor for CMV infection and increased CMV viral loads. QFM at post-HSCT week 4 can be utilized as an assay to predict the risk and burden of early CMV infection in HSCT recipients, in conjunction with other risk factors.

Asunto(s)

Infecciones por Citomegalovirus , Citomegalovirus , ADN Viral , Trasplante de Células Madre Hematopoyéticas , Trasplante Homólogo , Carga Viral , Humanos , Infecciones por Citomegalovirus/diagnóstico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Citomegalovirus/aislamiento & purificación , Citomegalovirus/inmunología , ADN Viral/sangre , Trasplante Homólogo/efectos adversos , Adulto Joven , Anciano , Factores de Riesgo , Adolescente

RESUMEN

INTRODUCTION: This study explored the efficacy of repeat blood cultures in bacteremic acute myeloid leukemia (AML) patients following allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: This was a retrospective study of AML patients who experienced febrile neutropenia (FN) and bacteremia following HSCT at the Taussig Cancer Center from January 1, 2019, to December 31, 2022. The primary endpoint was the rate of positive repeat blood cultures following initial positive blood culture. RESULTS: Fifty patients were included in the study. There were 50 occurrences of FN with positive initial blood cultures that were diagnosed following HSCT. Fifty initial sets of blood cultures and 96 sets of repeat blood cultures were drawn between the 50 occurrences of FN. Twelve of 96 (12.5%) repeat blood culture sets were positive for a pathogen, which occurred over nine of 50 (18.0%) episodes of FN. Three of 96 (3.2%) repeat blood culture sets grew a pathogen that differed from the pathogen that grew in the preceding positive blood culture. CONCLUSION: Among bacteremic AML patients in the post-HSCT period, the yield of repeat blood cultures for detecting previously detected and new pathogens was low.

Asunto(s)

Bacteriemia , Cultivo de Sangre , Neutropenia Febril , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Trasplante Homólogo , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Bacteriemia/microbiología , Bacteriemia/diagnóstico , Bacteriemia/etiología , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/terapia , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Neutropenia Febril/microbiología , Neutropenia Febril/sangre , Adulto , Trasplante Homólogo/efectos adversos , Anciano , Adulto Joven

RESUMEN

Graft-versus-host disease (GVHD) is a potentially serious complication ofallogeneic hematopoietic stem cell transplantation (HSCT). Graft-contaminating T cells (donor T cells) arecrucial for the development ofGVHD since they are able to react against the recipient's antigens. In this study we aim toevaluatethepotentialassociation between the IVS3 + 17 T/C gene variation in the CD28 molecule, a T cells costimulatory factor, and the GVHD occurrence in a Tunisian group of recipients of allo-HSCTs. Results show that there is an association between the presence of this polymorphism and the occurrence of grades II-IV acute GVHD (OR: 2.470, I.C: 1.027-5.938, p = 0.043). As for the chronic GVHD, it seems that the studied gene variation has no impact on the occurrence of this complication, which appeared likely to be affected by the HSCT graft source (PBSC: peripheral blood stem cells) (OR: 5.141, I.C: 1.590-16.620, p = 0.006). Based on these data, we believe that the CD28 IVS3 + 17 T/C polymorphism is a significant factor in the pathogenesis of acute GVHD.

Asunto(s)

Antígenos CD28 , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Hermanos , Humanos , Enfermedad Injerto contra Huésped/genética , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/inmunología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Antígenos CD28/genética , Túnez , Masculino , Adulto , Femenino , Persona de Mediana Edad , Adolescente , Adulto Joven , Trasplante Homólogo/efectos adversos , Antígenos HLA/genética , Antígenos HLA/inmunología , Polimorfismo de Nucleótido Simple , Predisposición Genética a la Enfermedad , Genotipo , Polimorfismo Genético , Niño , Frecuencia de los Genes

RESUMEN

OBJECTIVES: Efficacy and safety of letermovir as prophylaxis for clinically significant cytomegalovirus infections (csCVMi) was evaluated in randomised controlled trials while most of the real-world studies are single-centre experiences. METHODS: We performed a retrospective, multi-centre case-control study at six German university hospitals to evaluate clinical experiences in patients receiving CMV prophylaxis with letermovir (n = 200) compared to controls without CMV prophylaxis (n = 200) during a 48-week follow-up period after allogeneic hematopoietic cell transplantation (aHCT). RESULTS: The incidence of csCMVi after aHCT was significantly reduced in the letermovir (34%, n = 68) compared to the control group (56%, n = 112; p < 0.001). Letermovir as CMV prophylaxis (OR 0.362) was found to be the only independent variable associated with the prevention of csCMVi. Patients receiving letermovir showed significantly better survival compared to the control group (HR = 1.735, 95% CI: 1.111-2.712; p = 0.014). Of all csCMVi, 46% (n = 31) occurred after discontinuation of letermovir prophylaxis. Severe neutropenia (<500 neutrophils/µL) on the day of the stem cell infusion was the only independent variable for an increased risk of csCMVi after the end of letermovir prophylaxis. CONCLUSIONS: Our study highlights the preventive effects of letermovir on csCMVi after aHCT. A substantial proportion of patients developed a csCMVi after discontinuation of letermovir. In particular, patients with severe neutropenia require specific attention after drug discontinuation.

Asunto(s)

Acetatos , Antivirales , Infecciones por Citomegalovirus , Trasplante de Células Madre Hematopoyéticas , Quinazolinas , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Masculino , Infecciones por Citomegalovirus/prevención & control , Femenino , Persona de Mediana Edad , Quinazolinas/uso terapéutico , Estudios Retrospectivos , Antivirales/uso terapéutico , Adulto , Acetatos/uso terapéutico , Acetatos/administración & dosificación , Estudios de Casos y Controles , Anciano , Trasplante Homólogo/efectos adversos , Adulto Joven , Citomegalovirus , Adolescente , Alemania/epidemiología , Incidencia

RESUMEN

OBJECTIVES: This study aimed to characterize incidences of CMV reactivations within one year post-allo-SCT and identify risk factors for CMV second reactivation episode in population with high seropositivity where first CMV reactivation episode deemed to be high. METHODS: This retrospective cohort study analyzed data from 359 allo-SCT patients aged 14 and older admitted to a tertiary academic hospital. Data on demographic and clinical factors, CMV serostatus, conditioning regimens, graft-versus-host disease prophylaxis, engraftment time, and CMV reactivations were collected. RESULTS: First and second CMV reactivations occurred in 88.9% and 18.4% of post-allo-SCT patients respectively. Patients were stratified into two groups based on primary disease necessitating allo-SCT, patients with malignant (Group 1) and non-malignant (Group 2) hematological disease. Factors associated with the second reactivation included cord blood as a stem cell source, human leukocyte antigen mismatch, acute graft-versus-host disease, and hematological malignancies. Patients with non-malignant hematological disease displayed better outcomes, including a higher rate of spontaneous clearance of first CMV reactivation (70% versus 49.4%) and lower rates of second CMV reactivation (9.6% versus 31%) than those with malignant hematological disease. The one-year overall survival rate was 87.7% (95.5% in non-malignant hematological disease and 78.13% in malignant hematological disease). CONCLUSION: Our findings are concordant with previous local study in regard to high rate of first CMV reactivation post-allo-SCT. It appears that patients with nonmalignant hematological disease had better outcomes, such as lower second CMV reactivation and higher survival rates compared to patients with malignant hematological disease. Further investigation is needed to identify other factors affecting recurrent CMV reactivations in allo-SCT in patients with malignant hematological disease.

Asunto(s)

Infecciones por Citomegalovirus , Citomegalovirus , Trasplante Homólogo , Activación Viral , Humanos , Masculino , Femenino , Infecciones por Citomegalovirus/virología , Infecciones por Citomegalovirus/epidemiología , Persona de Mediana Edad , Adulto , Estudios Retrospectivos , Adulto Joven , Citomegalovirus/inmunología , Adolescente , Factores de Riesgo , Anciano , Trasplante Homólogo/efectos adversos , Recurrencia , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre/efectos adversos , Incidencia

RESUMEN

The impact of pre-graft COVID-19 vaccinations in donor or recipient as well as pre-graft infection has been studied in 157 adults having received allogeneic stem cell transplantation (Allo-SCT) for various hematological diseases during the delta/omicron waves. We showed here that pre-Allo-SCT COVID-19 vaccination and/or infection do not provide more protection in patients receiving vaccine, immunotherapy or both after transplant. COVID-19 vaccination is and remains of crucial importance after Allo-SCT, reinforcing the recommendation to start COVID-19 vaccination as soon as the third month following the transplant.

Asunto(s)

Vacunas contra la COVID-19 , COVID-19 , Trasplante de Células Madre Hematopoyéticas , Trasplante Homólogo , Vacunación , Humanos , COVID-19/prevención & control , COVID-19/inmunología , Masculino , Vacunas contra la COVID-19/administración & dosificación , Vacunas contra la COVID-19/inmunología , Femenino , Persona de Mediana Edad , Adulto , Trasplante Homólogo/efectos adversos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Anciano , Inmunoterapia/métodos , SARS-CoV-2/inmunología , Trasplante de Células Madre/efectos adversos

RESUMEN

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an important therapeutic option for patients with hematologic malignancies. However, the development of graft-versus-host disease (GVHD) after allo-HSCT remains a challenge. Although systemic steroid therapy is the established first-line therapy for acute GVHD (aGVHD) and chronic GVHD (cGVHD), many patients are unresponsive or resistant to corticosteroid therapy, and the response is insufficient. This study aimed to evaluate the clinical characteristics of patients who developed aGVHD and cGVHD after allo-HSCT. This noninterventional, retrospective study used large national registry data from the Transplant Registry Unified Management Program. The study included 29,690 patients with a hematologic disease who underwent their first allo-HSCT between January 2010 and December 2019. The primary study endpoints were the cumulative incidence of aGVHD and cGVHD. The secondary endpoints were overall survival (OS) and nonrelapse mortality (NRM) of patients with aGVHD and cGVHD and OS and NRM of patients who received second-line therapy for aGVHD. Of 29,690 patients who underwent allo-HSCT, the graft source was related bone marrow (RBM) in 2807, related peripheral blood (RPB) in 6167, unrelated bone marrow in 10,556, unrelated peripheral blood (UPB) in 774, and unrelated cord blood in 9339. The cumulative incidence of grade II-IV aGVHD at 100 days was high after the related and unrelated mismatched transplantation. The response rates for first- and second-line therapy for aGVHD were low in the RBM/RPB-mismatched (59.6%/61.6%) and UPB-mismatched subgroups (45.5%), respectively. The 3-year NRM in patients with aGVHD was high in the RPB and UPB mismatched subgroups (37.9% and 31.2%, respectively). Developing a novel treatment for steroid-refractory aGVHD is necessary to improve transplantation outcomes, particularly for patients undergoing HLA-mismatched allo-HSCT.

Asunto(s)

Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Sistema de Registros , Trasplante Homólogo , Enfermedad Injerto contra Huésped/epidemiología , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Estudios Retrospectivos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Japón/epidemiología , Adolescente , Trasplante Homólogo/efectos adversos , Adulto Joven , Niño , Anciano , Preescolar , Resultado del Tratamiento , Lactante

RESUMEN

Background: Children undergoing allo-HCT are at high risk of EBV-related complications. The objective of the study was to analyze the impact of prophylactic post-transplant rituximab on EBV infection and EBV-PTLD in children after allo-HCT, to determine the risk factors for the development of EBV infection and EBV-PTLD and to determine their outcomes. Additionally, the impact of EBV-driven complications on transplant outcomes was analyzed. Methods: Single center retrospective analysis of EBV-related complications in pediatric population undergoing allo-HCT, based on strategy of prophylaxis with rituximab. Overall 276 consecutive children, including 122 on prophylaxis, were analyzed for EBV-driven complications and transplant outcomes. Results: Prophylaxis with rituximab resulted in significant reduction of EBV infection (from 35.1% to 20.5%; HR=2.7; p<0.0001), and EBV-PTLD (from 13.0% to 3.3%; HR=0.23; p=0.0045). A trend for improved survival was also observed (HR=0.66; p=0.068), while non-relapse mortality was comparable in both cohorts. The peak value of viral load was a risk factor in the development of EBV-PTLD: 10-fold higher peak viral load in comparison to the baseline 104 copies/mL, caused a 3-fold (HR=3.36; p<0.001) increase in the risk of EBV-PTLD. Rituximab treatment was effective as a preemptive therapy in 91.1%, and in 70.9% in EBV-PTLD. Patients who developed PTLD had dismal 5-year overall survival (29% vs 60%; p<0.001), and an increased risk of relapse (72% vs 35%; p=0.024). Conclusions: Rituximab for prophylaxis of EBV infection and EBV-PTLD was highly effective in pediatric population. Treatment of EBV-PTLD was successful in 70%, however the occurrence of EBV-PTLD was associated with an increased risk of relapse of primary malignant disease.

Asunto(s)

Infecciones por Virus de Epstein-Barr , Trasplante de Células Madre Hematopoyéticas , Herpesvirus Humano 4 , Rituximab , Trasplante Homólogo , Humanos , Rituximab/uso terapéutico , Rituximab/efectos adversos , Rituximab/administración & dosificación , Infecciones por Virus de Epstein-Barr/prevención & control , Infecciones por Virus de Epstein-Barr/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Niño , Femenino , Masculino , Preescolar , Estudios Retrospectivos , Adolescente , Herpesvirus Humano 4/inmunología , Lactante , Trasplante Homólogo/efectos adversos , Factores de Riesgo , Trastornos Linfoproliferativos/prevención & control , Trastornos Linfoproliferativos/etiología , Carga Viral , Resultado del Tratamiento

RESUMEN

Introduction: Our study investigated the potential of peripheral blood T cell CD25, CD28, and CTLA-4 gene transcription levels as predictive biomarkers for acute graft-versus-host disease (aGVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Real-time reverse transcription fluorescent quantitative PCR (RT-qPCR) analysis was conducted on day +7, +14, and +21 post-transplantation in patients undergoing allo-HSCT. Results: Elevated levels of CD25 and CTLA-4 mRNA were found to be associated with the occurrence of aGVHD, as well as severe and gastrointestinal aGVHD. Receiver operating characteristic (ROC) curve analysis was utilized to assess the predictive value of each biomarker. Combined analysis of CD25 and CTLA-4 mRNA levels demonstrated promising predictive potential for aGVHD. Conclusion: Our results confirmed that the transcription levels of CD25 and CTLA-4 genes could be used as early predictive biomarkers for aGVHD post-allo-HSCT.

Asunto(s)

Biomarcadores , Antígeno CTLA-4 , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Subunidad alfa del Receptor de Interleucina-2 , Transcripción Genética , Enfermedad Injerto contra Huésped/genética , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/inmunología , Humanos , Antígeno CTLA-4/genética , Masculino , Subunidad alfa del Receptor de Interleucina-2/genética , Femenino , Adulto , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Persona de Mediana Edad , Enfermedad Aguda , Adulto Joven , Adolescente , Trasplante Homólogo/efectos adversos , Pronóstico

RESUMEN

Changes in the gut microbiome have pivotal roles in the pathogenesis of acute graft-versus-host disease (aGVHD) after allogenic haematopoietic cell transplantation (allo-HCT)1-6. However, effective methods for safely resolving gut dysbiosis have not yet been established. An expansion of the pathogen Enterococcus faecalis in the intestine, associated with dysbiosis, has been shown to be a risk factor for aGVHD7-10. Here we analyse the intestinal microbiome of patients with allo-HCT, and find that E. faecalis escapes elimination and proliferates in the intestine by forming biofilms, rather than by acquiring drug-resistance genes. We isolated cytolysin-positive highly pathogenic E. faecalis from faecal samples and identified an anti-E. faecalis enzyme derived from E. faecalis-specific bacteriophages by analysing bacterial whole-genome sequencing data. The antibacterial enzyme had lytic activity against the biofilm of E. faecalis in vitro and in vivo. Furthermore, in aGVHD-induced gnotobiotic mice that were colonized with E. faecalis or with patient faecal samples characterized by the domination of Enterococcus, levels of intestinal cytolysin-positive E. faecalis were decreased and survival was significantly increased in the group that was treated with the E. faecalis-specific enzyme, compared with controls. Thus, administration of a phage-derived antibacterial enzyme that is specific to biofilm-forming pathogenic E. faecalis-which is difficult to eliminate with existing antibiotics-might provide an approach to protect against aGVHD.

Asunto(s)

Bacteriófagos , Enterococcus faecalis , Microbioma Gastrointestinal , Enfermedad Injerto contra Huésped , Adulto , Anciano , Animales , Femenino , Humanos , Masculino , Ratones , Persona de Mediana Edad , Adulto Joven , Bacteriófagos/enzimología , Bacteriófagos/genética , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Disbiosis/complicaciones , Disbiosis/microbiología , Enterococcus faecalis/efectos de los fármacos , Enterococcus faecalis/genética , Enterococcus faecalis/crecimiento & desarrollo , Enterococcus faecalis/metabolismo , Enterococcus faecalis/virología , Heces/microbiología , Vida Libre de Gérmenes , Enfermedad Injerto contra Huésped/complicaciones , Enfermedad Injerto contra Huésped/microbiología , Enfermedad Injerto contra Huésped/prevención & control , Enfermedad Injerto contra Huésped/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Técnicas In Vitro , Intestinos/efectos de los fármacos , Intestinos/microbiología , Perforina/metabolismo , Factores de Riesgo , Trasplante Homólogo/efectos adversos , Secuenciación Completa del Genoma , Farmacorresistencia Bacteriana/efectos de los fármacos , Antibacterianos/farmacología