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BACKGROUND: Recipient functional status prior to transplantation has been found to impact post-transplant outcomes in heart, liver and kidney transplants. However, information on how functional status, before and after transplant impacts post-transplant survival outcomes is lacking. AIM: To investigate the impact of recipient functional status on short and long term intestinal transplant outcomes in United States adults. METHODS: We conducted a retrospective cohort study on 1254 adults who underwent first-time intestinal transplantation from 2005 to 2022. The primary outcome was mortality. Using the Karnofsky Performance Status, functional impairment was categorized as severe, moderate and normal. Analyses were conducted using Kaplan-Meier curves and multivariable Cox regression. RESULTS: The median age was 41 years, majority (53.4%) were women. Severe impairment was present in 28.3% of recipients. The median survival time was 906.6 days. The median survival time was 1331 and 560 days for patients with normal and severe functional impairment respectively. Recipients with severe impairment had a 56% higher risk of mortality at one year [Hazard ratio (HR) = 1.56; 95%CI: 1.23-1.98; P < 0.001] and 58% at five years (HR = 1.58; 95%CI: 1.24-2.00; P < 0.001) compared to patients with no functional impairment. Recipients with worse functional status after transplant also had poor survival outcomes. CONCLUSION: Pre- and post-transplant recipient functional status is an important prognostic indicator for short- and long-term intestinal transplant outcomes.

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Posttransplantation complications pose a major challenge to the long-term survival and quality of life of organ transplant recipients. These complications encompass immune-mediated complications, infectious complications, metabolic complications, and malignancies, with each type influenced by various risk factors and pathological mechanisms. The molecular mechanisms underlying posttransplantation complications involve a complex interplay of immunological, metabolic, and oncogenic processes, including innate and adaptive immune activation, immunosuppressant side effects, and viral reactivation. Here, we provide a comprehensive overview of the clinical features, risk factors, and molecular mechanisms of major posttransplantation complications. We systematically summarize the current understanding of the immunological basis of allograft rejection and graft-versus-host disease, the metabolic dysregulation associated with immunosuppressive agents, and the role of oncogenic viruses in posttransplantation malignancies. Furthermore, we discuss potential prevention and intervention strategies based on these mechanistic insights, highlighting the importance of optimizing immunosuppressive regimens, enhancing infection prophylaxis, and implementing targeted therapies. We also emphasize the need for future research to develop individualized complication control strategies under the guidance of precision medicine, ultimately improving the prognosis and quality of life of transplant recipients.

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Introduction: The prognosis of relapsed/refractory acute myeloid leukemia (r/rAML) is dismal, and allogeneic hematopoietic stem cell transplant (allo-HSCT) is a potential cure. Combining anti-PD-1, hypomethylating agent (HMA), and CAG (cytarabine, aclarubicin/idarubicin, granulocyte colony-stimulating factor) regimen has showed primary efficacy in r/rAML. However, pre-transplant exposure to anti-PD-1 may lead to severe graft-versus-host disease (GVHD). This preliminary study aimed to evaluate the safety and efficacy of allo-HSCT in r/rAML patients receiving the anti-PD-1+HMA+CAG regimen. Methods: Fifteen r/rAML patients (12 related haploidentical donors [HIDs], 2 matched siblings, 1 unrelated donor) received this regimen and subsequent peripheral blood HSCT. Results: Four patients with HIDs received a GVHD prophylaxis regimen consisted of Anti-thymocyte globulin and a reduced-dose of post-transplant cyclophosphamide. The median follow-up was 20.9 months (range, 1.2-34.2). The cumulative incidences of acute GVHD grade 2-4 and grade 3-4 were 40% and 13.3%, respectively. The 2-year incidence of moderate-to-severe chronic GVHD, non-relapse mortality, and relapse were 10%, 22.3%, and 22.5%, respectively. The 2-year overall survival and GVHD-free/relapse-free survival rates were 54% and 48.6%, respectively. No death or relapse was observed in the PTCy group. Conclusion: The anti-PD-1+HMA+CAG regimen bridging to allo-HSCT for r/r AML was tolerable with promising efficacy. GVHD prophylaxis with PTCy for HID-HSCT showed preliminary survival advantage.

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Aclarubicina , Protocolos de Quimioterapia Combinada Antineoplásica , Enfermedad Injerto contra Huésped , Factor Estimulante de Colonias de Granulocitos , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Trasplante Homólogo , Humanos , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/mortalidad , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Enfermedad Injerto contra Huésped/prevención & control , Enfermedad Injerto contra Huésped/etiología , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Aclarubicina/uso terapéutico , Aclarubicina/administración & dosificación , Adulto Joven , Citarabina/uso terapéutico , Citarabina/administración & dosificación , Idarrubicina/administración & dosificación , Idarrubicina/uso terapéutico , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Adolescente , Resultado del Tratamiento , Recurrencia , Anciano

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Steroid usage poses a risk of Clostridioides difficile infection (CDI), but high-dose corticosteroid treatment can lead to false-negative CD toxin test results. Moreover, CDI-induced nausea can complicate administration of oral antibiotics, which are typically the primary therapy for CDI. In the present case, a 43-year-old woman diagnosed with EBV-associated T-cell post-transplant lymphoproliferative disorder developed CDI during treatment with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP). Following five cycles of CHOP, the patient presented with nausea and diarrhea. CT scans revealed swelling in the ileocecal to transverse area of the colon. While the glutamate dehydrogenase (GDH) antigen test result was positive, the CD toxin test result was negative. However, the nucleic amplification test (NAAT) result was positive, confirming the diagnosis of CDI. Oral treatment with fidaxomicin was initially impractical due to persistent nausea. Instead, treatment began with intravenous metronidazole, and was later switched to fidaxomicin pills. Symptoms improved notably within 10 days, and the patient ultimately made a complete recovery. This case underscores the significance of exploring alternative approaches to CDI management, particularly in immunosuppressed patients.

Asunto(s)

Infecciones por Clostridium , Infecciones por Virus de Epstein-Barr , Trastornos Linfoproliferativos , Técnicas de Amplificación de Ácido Nucleico , Humanos , Femenino , Adulto , Trastornos Linfoproliferativos/diagnóstico , Trastornos Linfoproliferativos/tratamiento farmacológico , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Clostridium/diagnóstico , Infecciones por Clostridium/tratamiento farmacológico , Clostridioides difficile , Herpesvirus Humano 4 , Linfocitos T

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Introduction: Post-transplant relapse of acute myeloid leukemia and myelodysplastic syndrome faces restricted effective salvage regimens. We retrospectively analyzed the use of Azacitidine-donor lymphocyte infusion (AZA/DLI) in this setting. Furthermore, data on bone marrow Wilms tumor gene 1 (WT1) expression were collected. Methods: A Cox proportional hazards model, an outcome-oriented approach for the lowest smoothed plot of the martingale residuals, was performed for the cut-point determination of the respective WT1 expression levels. Finally, a Cox proportional hazards model investigated the association of overall survival (OS) with predictors. Results: An overall response of 41.4% with a median duration of 11.9 months for stable disease and 19.5 months for complete response (CR) patients was achieved. The disease risk index (DRI) high-/very high-risk patients had a shorter OS of 4.4 months than intermediate-risk patients, with 14.5 months, p = 0.007. At transplant, WT1-overexpressing patients (>150 copies) had a shorter median OS of 5.3 months than low-WT1-expressing ones, with 13.5 months, p = 0.024. Furthermore, patients with ≤1000 WT1 copies at relapse had a significantly longer OS with 15.3 months than patients overexpressing WT1, with 4.4 months, p = 0.0002. Conclusions: DRI and WT1 expression associate significantly with OS after AZA/DLI. Hence, WT1 may represent an MRD marker, especially in CR patients at high risk.

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Since the first published report of experimental kidney transplantation in dogs in 1902, there were many experimental and clinical trials of organ transplantation, with many sacrifices. After the establishment of the surgical technique and the discovery of immunosuppressive drugs, transplantation became the definitive treatment strategy for patients with terminal organ failure. However, this is not a common therapy method due to the difficulty of solving the fundamental issues behind organ transplantation, including the shortage of donor graft, potential risks of transplant surgery and economic capability. The pre- and post-transplant management of recipients is another critical issue that may affect transplant outcome. Most liver transplant recipients experience post-transplant complications, including infection, acute/chronic rejection, metabolic syndrome and the recurrence of hepatocellular carcinoma. Therefore, the early prediction and diagnosis of these complications may improve overall and disease-free survival. Furthermore, how to induce operational tolerance is the key to achieving the ultimate goal of transplantation. In this review, we focus on liver transplantation, which is known to achieve operational tolerance in some circumstances, and the mechanical similarities and differences between liver transplant immunology and fetomaternal tolerance, autoimmunity or tumor immunity are discussed.

Asunto(s)

Autoinmunidad , Trasplante de Hígado , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/métodos , Humanos , Animales , Tolerancia Inmunológica , Rechazo de Injerto/inmunología , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/cirugía , Tolerancia al Trasplante/inmunología

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Background/Objectives: Vesicoureteral reflux (VUR) is considered one of the major causes of post-renal transplant febrile urinary tract infections (UTI), leading to impaired renal function and the premature loss of the renal graft. We aimed to evaluate whether surgical VUR correction, such as open redo ureteric reimplantation, could be an option for treatment and provide better outcomes in post-transplant care for patients with UTI compared to their pre-VUR correction clinical state. Methods: Our study presents a retrospective analysis of 10 kidney transplant recipients with febrile UTI at the Renal Transplant Service of a Brazilian public hospital from 2010 to 2020. We selected patients who primarily underwent a surgical correction of post-transplant VUR, which was corrected by extravesical reimplantation without a stent in all patients by the same professional surgeon. Results: From 710 patients who received kidney transplants, 10 patients (1.4%) suffered from febrile UTI post-transplant and underwent surgical correction for VUR. Despite the study's limitations, such as its retrospective nature and limited sample size, the efficacy of open extravesical ureteral reimplantation in reducing post-operative febrile UTI in renal transplant patients was observed. Conclusions: As febrile UTI can contribute significantly to patient mortality after kidney transplantation and VUR emerges as a major cause of post-transplant febrile UTI, it is essential to treat it and consider the surgical outcome. This study emphasizes the timely detection and effective treatment of VUR via extravesical techniques to reduce febrile UTI occurrences post-transplant and it contributes insights into the role of surgical interventions in addressing VUR-related complications post-kidney transplantation.

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INTRODUCTION: Roxadustat, an oral inhibitor of hypoxia-inducible factor prolyl hydroxylase domain enzymes, has been approved for the treatment of renal anemia. However, there is a lack of study on its pharmacokinetics in kidney transplant recipients (KTRs) with early posttransplant anemia (PTA). Therefore, the aim of this study is to elucidate the pharmacokinetic characteristics of roxadustat in KTRs with early PTA and optimize the dosing regimen. METHODS: A population pharmacokinetic (PopPK) analysis was performed based on 72-hour full concentration-time profiles collected from 52 Chinese KTRs. Covariates influencing exposure were assessed using stepwise covariate modelling. Monte Carlo simulations were conducted to recommend the dosing regimen for patients with different levels of covariates. RESULTS: PopPK analysis showed that the concentration-time data can be fully described by a two-compartment model. Body weight (BW) and direct bilirubin (DBIL) levels significant affected the apparent clearance of roxadustat. Based on the established model and the estimated exposures of roxadustat by Monte Carlo simulations, a recommended dosing regimen for KTRs with early PTA at varying BW and DBIL levels were developed. Roxadustat at 100 mg three times weekly were suitable for the majority of KTRs with a DBIL level around 3 µmol/L and BW between 50 and 75 kg. The required dose may need to be increased with higher BW and lower DBIL levels, while decreased with lower BW and higher DBIL levels. CONCLUSIONS: It was the first PopPK analysis of roxadustat in KTRs with early PTA, which provide a research basis for optimizing the dosing regimen.

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BACKGROUND: Although the survival of patients with transfusion-dependent thalassemia (TD-TM) is reportedly inferior after haploidentical transplantation, the heterogeneity of transplantation approaches in studies suggests the need to assess the effect of one given conditioning regimen on matched and haploidentical transplantation outcomes. OBJECTIVE: A novel PTCy-based approach for patients with TD-TM undergoing haploidentical HSCT was reported in our prior study. We aimed to retrospectively evaluate the real-world efficacy and safety of GvHD prophylaxis in patients with TD-TM after HSCT from matched donors and haploidentical donors (HIDs). STUDY DESIGN: This was a retrospective multicenter study. Of 238 patients with TD-TM who underwent HSCT, 160 underwent peripheral blood HSCT, using uniform GvHD prophylaxis with PTCy, methotrexate, and cyclosporine, at member centers of the Bone Marrow Failure Working Group of Hunan Province between 2019 and 2023. RESULTS: The median age of the cohort was 6 years (95% confidence interval [CI], 6-7 years) at transplantation. Of 160 donors, 99 (61.9%) were haploidentical family members, and the others were matched donors (13 matched siblings, 48 matched or mismatched unrelated donors). The engraftment rate was 98.8% (95% CI: 96.1%-97.7%). HSCT from HIDs had a lower risk of mixed chimerism (HR 0·078, p=0.022). Within 100 days after transplantation, 31 patients (19.6%, 95% CI: 14.0%-26.3%) had grade II-IV acute GvHD, 9 of whom had grade III-IV acute GvHD (5.7%, 95% CI: 2.9%-10.1%). HIDs were significantly associated with a higher risk of grade II-IV acute GvHD (HR 3.973, p = 0.009). Nineteen patients (11.9%, 95% CI: 7.6%-17.6%) developed late acute GvHD after a median of 516 days (95% CI: 407-709 days). Twenty-six patients (16.5%, 95% CI: 11.3%-22.8%) exhibited any one of the diagnostic, distinctive, or atypical features of chronic GvHD according to the 2014 NIH criteria after a median of 690 days (95% CI: 496-902 days). Among these, 7 had NIH-defined chronic GvHD, 14 had only one distinctive sign with no histological evidence, and 5 had only atypical chronic GvHD signs. Of the 26 patients, 5 were classified as having overlap syndrome. Of 21 patients who were classified as having NIH-defined and potential chronic GvHD, 3 had moderate chronic GvHD, whereas 1 had severe chronic GvHD. Logistic regression analyses identified that grade II-IV acute GvHD independently predicted subsequent chronic GVHD (HR 3.920, p=0.006). The rates of chronic GvHD were similar between the matched and HID groups. Thalassemia-free survival (TFS) and event-free survival (EFS) were 97.5% (95% CI: 94.2%-99.2%) and 90.6% (95% CI: 85.4%-94.4%), respectively, after a median of 690 days (95% CI: 496-902 days). TFS rates were similar between the matched and HID groups (p = 0.549). The EFS rate was significantly higher in the matched group than in the HID group (p = 0.033). CONCLUSIONS: Our study suggests that when PTCy-based uniform GVHD prophylaxis is administered, HSCT from matched donors and HIDs results in a low incidence of severe GVHD and treatment-related mortality with satisfactory survival.

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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

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Background: Graft Versus Host Disease (GvHD), which can be observed at a rate of 30-80% after allogeneic stem cell transplantation (ASCT) is an important complication that adversely affects the survival and quality of the life of patients. Posttransplant cyclophosphamide (PTCy) effectively prevents GvHD after HLA-haploidentical ASCT. In our study, the use of PTCy in 1-antigen HLA-mismatched unrelated donor (9/10MMUD) ASCT was compared with standard GvHD prophylaxis in HLA-identical related donor (MRD) ASCT. Materials and Methods: We conducted a retrospective study of the comparison of 42 patients with 9/10 MMUD ASCT receiving PTCy+Methotrexate (MTX)+Calcineurin Inhibitor (CNI) and 37 patients with HLA-identical MRD who received MTX+CNI  in 3 bone marrow transplantation centers.  Results: Cumulative incidences of grade I-II (64.6% vs 45.4%, p=0.187) or grade III to IV acute GvHD (35.4% vs54.6%, p=0.187) and chronic GvHD (11.9% vs 29.7%, p=0.096) were similar in the PTCy group and control group. No statistically significant differences were observed between PTCy and the control group in overall survival rate (52.4% vs 62.2%, p=0.381), progression-free survival (1483.97 vs 1200.70 days, p=0.502), relapsed-related mortality rate (21.4% vs 16.2%, p=0.556) and treatment-related mortality rate (16.7% vs 21.6%, p=0.575). Conclusion: With the addition of PTCy to standard GvHD prophylaxis in 9/10MMUD ASCT, the risk of GvHD due to incompatibility and unrelated transplantation is eliminated, and transplantation success is achieved with MRD ASCT. PTCy-based prophylaxis is an effective and safe strategy to prevent GvHD in 9/10 MMUD ASCT without increasing the risk of relapse and treatment-related mortality.

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Existing on the spectrum of post-transplant lymphoproliferative disorders (PTLD), plasmablastic lymphoma (PBL) is a highly aggressive form of B-cell non-Hodgkin lymphoma. Since its discovery in 1997, fewer than 5 cases of postliver transplantation-associated PBL have been recorded. Despite increased awareness of PTLD and improvement in imaging, PBL often presents with disseminated disease at the time of diagnosis. Treatment usually involves immunosuppression reduction and the use of chemo/immunotherapy, but the prognosis remains poor, with median survival being less than 12 months. We present to you a case of Epstein-Barr virus-negative PBL occurring more than 6 years postliver transplantation.

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Early post-allogeneic hematopoietic stem cell transplantation (allo-HSCT) relapse in patients with acute myeloid leukemia (AML) has an almost invariably dismal prognosis. Recent studies have demonstrated that FLT3 inhibition enhances the graft-versus-leukemia effect in vitro and in vivo. Thus, FLT-3 inhibitors may be viable treatment options in this setting. Here, we report three patients with FLT3 and NPM1 mutated AML who relapsed early after allo-HSCT and were treated with gilteritinib (associated with donor lymphocyte Infusion in two patients) to achieve long-term remission without a second transplantation.

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Background: We present comparative data of children with Fanconi anemia undergoing haploidentical hematopoietic stem cell transplantation (HSCT) with or without the addition of rabbit anti-thymocyte globulin (r-ATG) to the conditioning regimen. Patients and methods: This retrospective study included children with Fanconi anemia aged up to 18 years who underwent haploidentical HSCT between January 2015 and December 2022. The children were included in two cohorts in this study. Cohort 1 included children who received conditioning with fludarabine/cyclophosphamide/single fraction of 2 Gy TBI. The children in cohort 2 received the same conditioning along with r-ATG. Post-transplant cyclophosphamide was administered at a dose of 25 mg/kg on day3 and day4 in both cohorts. Results: A total of 35 children were included in the study, 25 in cohort 1 and 10 in cohort 2. Neutrophil engraftment was documented around day 14-16 post infusion in 21 children (84%) in cohort 1 and in 8 children (80%) in cohort 2. There was a significant difference in the incidence of the severity of graft versus host disease (GVHD) between the two cohorts (p = 0.003). In cohort 1, acute GVHD was documented in 17 children (68%), with grade 1/2 skin GVHD in 10 children, and grade 3/4 skin and gut GVHD in 7 children. Grade 4 gut GVHD was the cause of death in three children in cohort 1. In cohort 2, acute GVHD was documented in one child (10%) who had grade 4 skin and gut GVHD and succumbed to the above. Chronic GVHD was noted in nine (36%) children in cohort 1, and in one child (10%) in cohort 2. Cytomegalovirus reactivation was documented in 11 children (44%) in cohort 1 and three children (30%) in cohort 2. Overall survival was found to be 16/25 (64%) in cohort 1, with a median follow-up of 49 months, and 7/10 (70%) in cohort 2, with a median follow-up of 12 months. Conclusion: Serotherapy with r-ATG significantly reduced the incidence of GVHD from 68% to 10% in children with Fanconi anemia, with an increase in overall survival from 64% to 70%, although it did not affect graft failure. Further studies should focus on decreasing graft failure rates with early HSCT before multiple transfusions.

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Living donation (LD) transplantation is the preferred treatment for kidney failure as compared to donation after brain death (DBD), but age may play a role. We compared the 1-year estimated glomerular filtration rate (eGFR) after kidney transplantation for recipients of LD and DBD stratified by recipient and donor age between 2015 and 2018 in a matched cohort. The strength of the association between donation type and 1-year eGFR differed by recipient age (P interaction < 0.0001). For LD recipients aged 40-54 years versus same-aged DBD recipients, the adjusted odds ratio (aOR) for eGFR ≥60 mL/min/1.73 m2 was 1.48 (95% CI: 1.16-1.90). For DBD recipients aged ≥ 60 years, the aOR was 0.18 (95% CI: 0.12-0.29) versus DBD recipients aged 40-54 years but was 0.91 (95% CI: 0.67-1.24) versus LD recipients aged ≥60 years. In the matched cohort, 4-year graft and patient survival differed by donor age and type. As compared with DBD grafts, LD grafts increased the proportion of recipients with 1-year eGFR ≥60 mL/min/1.73 m2. Recipients aged ≥60 years benefited most from LD transplantation, even if the donor was aged ≥60 years. For younger recipients, large age differences between donor and recipient could also be addressed with a paired exchange program.

Asunto(s)

Muerte Encefálica , Tasa de Filtración Glomerular , Supervivencia de Injerto , Trasplante de Riñón , Donadores Vivos , Humanos , Persona de Mediana Edad , Adulto , Masculino , Femenino , Factores de Edad , Anciano , Donantes de Tejidos , Estudios Retrospectivos

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Post-transplantation primary central nervous system lymphoma (PT-PCNSL) is a rare neoplasm that occurs in immunocompromised patients. It can manifest months or years after transplantation, presenting with various neurological symptoms. A 64-year-old woman, who had received a liver transplant due to autoimmune hepatitis, presented with generalized weakness, headache, and confusion. Further investigation revealed multiple ring-enhancing lesions in the right frontal and temporoparietal regions on brain MRI. A brain biopsy confirmed the diagnosis of PT-PCNSL. This case underscores the importance of considering PT-PCNSL in the differential diagnosis of contrast-enhancing brain lesions in post-transplant patients. Timely recognition of PT-PCNSL is crucial for appropriate management and improved outcomes. To the best of our knowledge, this report describes the first instance of isolated CNS lymphoma in a liver transplant recipient, due to autoimmune hepatitis, successfully brought to complete remission with a rituximab-methotrexate regimen.

Asunto(s)

Hepatitis Autoinmune , Trasplante de Hígado , Linfoma , Humanos , Persona de Mediana Edad , Femenino , Hepatitis Autoinmune/tratamiento farmacológico , Hepatitis Autoinmune/cirugía , Neoplasias del Sistema Nervioso Central/cirugía , Imagen por Resonancia Magnética

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Kidney transplantation is the most effective treatment for end-stage renal failure but is associated with complications, including post-transplant diabetes mellitus (PTDM). It affects the quality of life and survival of patients and the transplanted organ. It can cause complications, including infections and episodes of acute rejection, further threatening graft survival. The prevalence of PTDM, depending on the source, can range from 4 to 30% in transplant patients. This article aims to discuss issues related to diabetes in kidney transplant patients and the latest treatments. Knowledge of the mechanisms of action of immunosuppressive drugs used after transplantation and their effect on carbohydrate metabolism is key to the rapid and effective detection of PTDM. Patient therapy should not only include standard management such as lifestyle modification, insulin therapy or pharmacotherapy based on well-known oral and injection drugs. New opportunities are offered by hypoglycemic drugs still in clinical trials, including glucokinase activators, such as dorzagliatin, ADV-1002401, LY2608204, TMG-123, imeglimine, amycretin and pramlintide. Although many therapeutic options are currently available, PTDM often creates uncertainty about the most appropriate treatment strategy. Therefore, more research is needed to individualize therapeutic plans and monitor these patients.

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Background and Objectives: Post-transplant diabetes mellitus (PTDM) is a significant risk factor for the survival of graft recipients and occurs in 10-30% of patients after kidney transplant (KT). PTDM is associated with premature cardiovascular morbidity and mortality. Weight gain, obesity, and dyslipidemia are strong predictors of PTDM, and by modifying them with an active lifestyle it is possible to reduce the incidence of PTDM and affect the long-term survival of patients and grafts. The aim of our study was to determine the effect of regular physical activity on the development of PTDM and its risk factors in patients after KT. Materials and Methods: Participants in the study had to achieve at least 150 min of moderate-intensity physical exertion per week. The study group (n = 22) performed aerobic or combined (aerobic + strength) types of sports activities. Monitoring was provided by the sports tracker (Xiaomi Mi Band 4 compatible with the Mi Fit mobile application). The control group consisted of 22 stable patients after KT. Each patient underwent an oral glucose tolerance test (oGTT) at the end of the follow-up. The patients in both groups have the same immunosuppressive protocol. The total duration of the study was 6 months. Results: The patients in the study group had significantly more normal oGTT results at 6 months compared to the control group (p < 0.0001). In the control group, there were significantly more patients diagnosed with PTDM (p = 0.0212) and with pre-diabetic conditions (impaired plasma glucose and impaired glucose tolerance) at 6 months (p = 0.0078). Conclusions: Regular physical activity after KT provides significant prevention against the development of pre-diabetic conditions and PTDM.

Asunto(s)

Diabetes Mellitus , Ejercicio Físico , Trasplante de Riñón , Humanos , Trasplante de Riñón/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Ejercicio Físico/fisiología , Diabetes Mellitus/prevención & control , Adulto , Factores de Riesgo , Prueba de Tolerancia a la Glucosa

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Mycophenolate mofetil (MMF) is commonly included in post-transplant cyclophosphamide (PTCy) based graft-versus-host disease (GVHD) prophylaxis after haploidentical (haplo) hematopoietic cell transplant (HCT). In the non-PTCy setting, higher MMF dose/kg has been shown to reduce rates of acute graft-versus-host disease (GVHD). When used in conjunction with PTCy, MMF is dosed at 15 mg/kg three times daily up to a maximum dose of 3 g/day. Thus, patients who weigh ≥67 kg receive 3 g/day and a variable dose/kg of MMF. We investigated the impact of MMF dose/kg on clinical outcomes following haploidentical PBSCT with PTCy-based GVHD prophylaxis. All consecutive adult patients with hematologic malignancies receiving haploidentical T cell replete peripheral blood stem cell transplant (PBSCT) with PTCy/MMF and either tacrolimus or sirolimus at the Moffitt Cancer Center or City of Hope between April 2014-August 2020 were included. For analyses, MMF dose relative to patient actual body weight (mg/kg/day), was stratified into categories of low (<29 mg/kg/day), low intermediate (29-34 mg/kg/day), high intermediate (35-41 mg/kg/day), and high (>41 mg/kg/day). Three hundred eighty-six patients were included. Of these, 54 patients received low dose, 73 low intermediate, 137 high intermediate and 122 high dose MMF by relative weight exposure. In multivariate analysis, low MMF dose exposure was associated with reduced rates of relapse in comparison to the high dose group (HR = 0.45, 95% CI: 0.21 to 0.94, P = .03). This led to superior PFS among patients with low compared to high MMF dose exposure (HR = 0.58, 95% CI: 0.34 to 0.99, P = .045). MMF relative dose exposure was not associated with engraftment, GVHD, nonrelapse mortality, or OS. In this study of patients receiving haploidentical PBSCT with PTCy based GVHD prophylaxis, low MMF dose/kg was associated with improved rates of relapse and PFS. Future prospective studies should investigate optimal dosing strategies of MMF when given with the PTCy regimen.