RESUMO
Vitamin D sufficiency is associated with a reduced risk of fractures, diabetes mellitus, cardiovascular events, and cancers, which are frequent complications after renal transplantation. The VITALE (VITamin D supplementation in renAL transplant recipients) study is a multicenter double-blind randomized trial, including nondiabetic adult renal transplant recipients with serum 25-hydroxy vitamin D (25(OH) vitamin D) levels of <30 ng/mL, which is randomized 12 to 48 months after transplantation to receive high (100 000 IU) or low doses (12 000 IU) of cholecalciferol every 2 weeks for 2 months and then monthly for 22 months. The primary outcome was a composite endpoint, including diabetes mellitus, major cardiovascular events, cancer, and death. Of 536 inclusions (50.8 [13.7] years, 335 men), 269 and 267 inclusions were in the high-dose and low-dose groups, respectively. The serum 25(OH) vitamin D levels increased by 23 versus 6 ng/mL in the high-dose and low-dose groups, respectively (P < .0001). In the intent-to-treat analysis, 15% versus 16% of the patients in the high-dose and low-dose groups, respectively, experienced a first event of the composite endpoint (hazard ratio, 0.94 [0.60-1.48]; P = .78), whereas 1% and 4% of patients in the high-dose and low-dose groups, respectively, experienced an incident symptomatic fracture (odds ratio, 0.24 [0.07-0.86], P = .03). The incidence of adverse events was similar between the groups. After renal transplantation, high doses of cholecalciferol are safe but do not reduce extraskeletal complications (trial registration: ClinicalTrials.gov; identifier: NCT01431430).
Assuntos
Doenças Cardiovasculares , Transplante de Rim , Deficiência de Vitamina D , Masculino , Adulto , Humanos , Colecalciferol/efeitos adversos , Transplante de Rim/efeitos adversos , Vitamina D/uso terapêutico , Vitaminas/efeitos adversos , Método Duplo-Cego , Suplementos Nutricionais , Doenças Cardiovasculares/etiologia , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/tratamento farmacológicoRESUMO
We report the transmission of acute myeloid leukemia (AML) undetected at donation from a deceased organ donor to two kidneys and one liver recipients. We reviewed the medical records, and performed molecular analyses and whole exome sequencing (WES) to ascertain AML donor origin and its molecular evolution. The liver recipient was diagnosed 11 months after transplantation and died from complications 2 months later. The two kidney recipients (R1 and R2) were diagnosed 19 and 20 months after transplantation and both received treatment for leukemia. R1 died of complications 11 months after diagnosis, while R2 went into complete remission for 44 months, before relapsing. R2 died 10 months later of complications from allogenic bone marrow transplantation. Microsatellite analysis demonstrated donor chimerism in circulating cells from both kidney recipients. Targeted molecular analyses and medical records revealed NPM1 mutation present in the donor and recipients, while FLT3 was mutated only in R1. These findings were confirmed by WES, which revealed additional founder and clonal mutations, and HLA genomic loss in R2. In conclusion, we report the first in-depth genomic analysis of AML transmission following solid organ transplantation, revealing distinct clonal evolution, and providing a potential molecular explanation for tumor escape.
Assuntos
Leucemia Mieloide Aguda , Transplante de Órgãos , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Mutação , Proteínas Nucleares/genética , Nucleofosmina , Transplante de Órgãos/efeitos adversos , Doadores de TecidosRESUMO
Transplant centers have historically been reluctant to proceed with kidney transplantation in individuals with plasma cell dyscrasias (PCDs) due to concern for high rates of PCD recurrence and PCD-related mortality. As novel therapies for PCDs have improved hematologic outcomes, strategies to optimize kidney transplantation in individuals with PCD-mediated kidney disease are needed. In this single-center case series we discuss our protocol for the transplantation of individuals with ESKD attributed to PCD as well as the hematologic and allograft outcomes of 12 kidney transplant recipients with ESKD attributed to PCD. Median follow-up time after kidney transplantation was 44 months (IQR 36, 84). All patients had a functioning allograft 1 year after kidney transplantation. 9/12 patients were alive and had a functioning allograft 5 years after kidney transplantation. Five patients experienced relapse of PCD (of whom three responded well to subsequent therapies) and four patients developed secondary malignancies, including three patients with urologic malignancies. This case series demonstrates that patients with kidney disease attributed to PCD have favorable outcomes with kidney transplantation. Transplant evaluation in patients with PCDs should involve a multidisciplinary team of transplant nephrologists and oncologists to select appropriate candidates. Providers should consider screening for urologic malignancies pre- and post-transplantation.
Assuntos
Transplante de Rim , Paraproteinemias , Humanos , Transplante de Rim/efeitos adversos , Recidiva Local de Neoplasia/etiologia , Paraproteinemias/complicações , Transplantados , Transplante HomólogoRESUMO
Primary central nervous system lymphoma (PCNSL) occurring following organ transplantation (post-transplantation lymphoproliferative disorder [PTLD]) is a highly aggressive non-Hodgkin lymphoma. It is typically treated with high-dose methotrexate-based regimens. Outcomes are dismal and clinical trials are lacking. It is almost always Epstein-Barr virus (EBV) associated. Two patients (CA1-2) presented with EBV-associated PCNSL after renal transplant. CA1 was on hemodialysis and had prior disseminated cryptococcus and pseudomonas bronchiectasis, precluding treatment with methotrexate. CA2 was refractory to methotrexate. Both were treated off-label with the first-generation Bruton's tyrosine kinase inhibitor ibrutinib for 12 months. Cerebrospinal fluid penetration at therapeutic levels was confirmed in CA1 despite hemodialysis. Both patients entered remission by 2 months. Sequencing confirmed absence of genetic aberrations in human leukocyte antigen (HLA) class I/II and antigen-presentation/processing genes, indicating retention of the ability to present EBV-antigens. Between Weeks 10 and 13, they received third-party EBV-specific T cells for consolidation with no adverse effects. They remain in remission ≥34 months since therapy began. The strength of these findings led to an ongoing phase I study (ACTRN12618001541291).
Assuntos
Infecções por Vírus Epstein-Barr , Linfoma não Hodgkin , Transtornos Linfoproliferativos , Adenina/análogos & derivados , Sistema Nervoso Central , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Herpesvirus Humano 4 , Humanos , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/etiologia , Transtornos Linfoproliferativos/tratamento farmacológico , Transtornos Linfoproliferativos/etiologia , Piperidinas , Linfócitos TRESUMO
Chimeric antigen receptor T cells (CAR-T) are genetically modified T cells with a chimeric antigen receptor directed against a specific tumor-associated antigen like CD19 in lymphoma. CAR-T cells have shown encouraging activity against recurrent and refractory diffuse large B cell lymphomas (DLBCL). However concurrent use of immunosuppressive agents was prohibited in most CAR-T trials effectively excluding patients with prior solid organ transplantation (SOT) and posttransplant lymphoproliferative disorders (PTLD). We report the outcomes for three patients with PTLD refractory to immunochemotherapy 10-20 years after SOT who received CAR-T therapy between January 2018 and December 2019. One patient had an orthotopic heart transplant, the second had a deceased donor kidney transplant, and the third had a pancreas after kidney transplant (PAK). All patients developed complications of CAR-T therapy such as cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and acute kidney injury requiring renal replacement therapy in the two out of three patients. All patients expired after withdrawal of care due to lack of response to CAR-T therapy. In addition, the PAK patient developed acute pancreatitis after CAR-T therapy. This case series identifies the challenges of using CAR-T therapy to manage refractory PTLD in SOT recipients and its possible complications.
Assuntos
Transtornos Linfoproliferativos , Transplante de Órgãos , Pancreatite , Receptores de Antígenos Quiméricos , Doença Aguda , Humanos , Transtornos Linfoproliferativos/etiologia , Transtornos Linfoproliferativos/terapia , Transplante de Órgãos/efeitos adversosRESUMO
The number of solid organ transplant recipients (SOTR), and their life expectancy, is increasing, with higher risk for long-term complications from immunosuppression. We carried out a systematic review describing the burden of anal squamous cell carcinoma (SCC), and its surrogates, in SOTR. We conducted mixed effect model-based meta-analyses evaluating incidence of anal SCC (standardized incidence ratio [SIR] vs general population, and absolute incidence rate [IR]), prevalence of anal squamous abnormalities, and human papillomavirus (HPV) 16. Generalized I2 statistics were calculated, quantifying heterogeneity. Anal SCC incidence in SOTR was elevated vs the general population (pooled SIR = 6.8, 95% confidence interval [CI], 4.3-10.9; 6 studies including 241 106 SOTR; I2 = 82.3%), with an absolute IR of 12.3 (95% CI, 10.4-14.7) per 100 000 person-years (5 studies including 1 079 489 person-years; I2 = 0%). Prevalence of abnormal anal cytology was 12.9% (95% CI, 9.2%-17.7%; 6 studies including 328 SOTR; I2 = 17.4%). For histology, the pooled prevalence estimate of anal squamous intraepithelial lesions was 22.4% (95% CI, 17.3%-28.5%; 3 studies including 214 SOTR; I2 = 0%), with 4.7% (95% CI, 2.5%-8.5%; I2 = 0%) high-grade squamous intraepithelial lesions. Pooled anal HPV16 prevalence was 3.6% (95% CI, 1.6%-7.8%; 4 studies including 254 SOTR; I2 = 17.6%). There was substantial and consistent evidence of elevated anal SCC incidence in SOTR.
Assuntos
Neoplasias do Ânus , Carcinoma de Células Escamosas , Transplante de Órgãos , Infecções por Papillomavirus , Lesões Intraepiteliais Escamosas , Neoplasias do Ânus/epidemiologia , Neoplasias do Ânus/etiologia , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/etiologia , Papillomavirus Humano 16 , Humanos , Transplante de Órgãos/efeitos adversos , Infecções por Papillomavirus/epidemiologiaRESUMO
Renal transplant recipients have an increased risk of non-melanoma skin cancer (NMSC) compared to in the general population. Here, we show polygenic risk scores (PRS) calculated from genome-wide association studies (GWAS) of NMSC in a general, nontransplant setting, can predict risk of, and time to posttransplant skin cancer. Genetic variants, reaching predefined P-value thresholds were chosen from published squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) nontransplant GWAS. Using these GWAS, BCC and SCC PRS were calculated for each sample across three European ancestry renal transplant cohorts (n = 889) and tested as predictors of case:control status and time to NMSC posttransplant. BCC PRS calculated at P-value threshold 1 × 10-5 was the most significant predictor of case:control status of NMSC posttransplant (OR = 1.61; adjusted P = .0022; AUC [full model adjusted for clinical predictors and PRS] = 0.81). SCC PRS at P-value threshold 1 × 10-5 was the most significant predictor of time to posttransplant NMSC (adjusted P = 9.39 × 10-7 ; HR = 1.41, concordance [full model] = 0.74). PRS of nontransplant NMSC is predictive of case:control status and time to NMSC posttransplant. These results are relevant to how genomics can risk stratify patients to help develop personalized treatment regimens.
Assuntos
Biomarcadores Tumorais/genética , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Polimorfismo de Nucleotídeo Único , Complicações Pós-Operatórias/diagnóstico , Neoplasias Cutâneas/diagnóstico , Carcinoma Basocelular/diagnóstico , Carcinoma Basocelular/epidemiologia , Carcinoma Basocelular/etiologia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/etiologia , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Seguimentos , Estudo de Associação Genômica Ampla , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Prognóstico , Fatores de Risco , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/etiologia , Transplantados , Estados Unidos/epidemiologiaRESUMO
The replication kinetics of nonpathogenic anelloviruses belonging to the Alphatorquevirus genus (such as torque teno virus) might reflect the overall state of posttransplant immunosuppression. We analyzed 221 kidney transplant (KT) recipients in whom plasma alphatorquevirus DNA load was quantified by real-time polymerase chain reaction at baseline and regularly through the first 12 posttransplant months. Study outcomes included posttransplant infection and a composite of opportunistic infection and/or de novo malignancy (immunosuppression-related adverse event [iRAE]). Alphatorquevirus DNA loads at month 1 were higher among patients who subsequently developed posttransplant infection (P = .023) or iRAE (P = .009). Likewise, those with iRAE beyond months 3 and 6 also exhibited higher peak viral loads over the preceding periods. Areas under the curve for log10 alphatorquevirus DNAemia estimated by months 1 or 6 were significantly higher in patients experiencing study outcomes. Alphatorquevirus DNA loads above 3.15 and 4.56 log10 copies/mL at month 1 predicted the occurrence of posttransplant infection (adjusted hazard ratio [aHR]: 2.88; 95% confidence interval [CI]: 1.13-7.36; P = .027) and iRAE (aHR: 5.17; 95% CI: 2.01-13.33; P = .001). In conclusion, posttransplant monitoring of plasma alphatorquevirus DNA kinetics may be useful to identify KT recipients at increased risk of immunosuppression-related complications.
Assuntos
Anelloviridae/genética , DNA Viral/metabolismo , Imunossupressores/efeitos adversos , Transplante de Rim , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
All 179 reports to the OPTN of potential renal cell carcinoma (RCC) transmission from 1/1/2008 through 12/31/2016 were reviewed. Cases were divided into those with donor tumor known or suspected at time of transplant (N = 147 donors), and those in which tumor was initially found after transplant (N = 32). We sought to understand the risk of transplanting either the affected kidney, the contralateral kidney or non-renal organs from donors with a suspected/confirmed unilateral RCC. In the case of RCC found prior to transplant, transplantation of 21 kidneys following excision of tumor, 47 contralateral kidneys and 198 non-renal organs was performed. No cases of RCC transmission were documented in this population. An additional six cases of live donor kidney transplantation involving resection of RCC were reported, also without transmission. Six of 9 other recipients in whom the diagnosis of RCC became available after implantation underwent allograft nephrectomy and 3 received tumor resection. No recurrent RCC was documented. Given the low rate of transmission and available treatment options, consideration should be given to judicious use of organs from donors with small solitary RCC.
Assuntos
Carcinoma de Células Renais/patologia , Seleção do Doador , Falência Renal Crônica/cirurgia , Transplante de Rim/estatística & dados numéricos , Sistema de Registros/estatística & dados numéricos , Doadores de Tecidos/provisão & distribuição , Obtenção de Tecidos e Órgãos/normas , Adulto , Comitês Consultivos , Idoso , Carcinoma de Células Renais/cirurgia , Feminino , Seguimentos , Humanos , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Nefrectomia/estatística & dados numéricos , Prognóstico , Estudos Retrospectivos , Fatores de RiscoRESUMO
We report 4 cases of breast cancer transmission to transplant recipients from a single organ donor that occurred years after donation. The diagnosis of breast cancer was occult at the time of donation. All of the recipients developed a histologically similar type of breast cancer within 16 months to 6 years after transplantation. Three out of 4 recipients died as a result of widely metastasized disease. One of the recipients survived after transplant nephrectomy followed by cessation of immunosuppression and chemotherapy. This extraordinary case points out the often fatal consequences of donor-derived breast cancer and suggests that removal of the donor organ and restoration of immunity can induce complete remission.
Assuntos
Neoplasias da Mama/etiologia , Transplante de Rim/efeitos adversos , Transplante de Fígado/efeitos adversos , Transplante de Pulmão/efeitos adversos , Doadores de Tecidos , Adulto , Neoplasias da Mama/fisiopatologia , Neoplasias da Mama/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , TransplantadosRESUMO
Immune checkpoint inhibitors are new therapeutic options for metastatic melanoma, but few data are available in organ transplant recipient populations. Six French patients, three men and three women, mean age 66 years (range 44-74), all kidney transplant recipients, received ipilimumab (CTLA-4 inhibitor) for metastatic melanoma. At diagnosis of advanced melanoma, immunosuppressive therapy had been minimized in all but one. Adverse effects included one case of grade 1 diarrhea and one of grade 1 pruritus. One patient had acute T cell-mediated rejection confirmed by histology after the first injection of ipilimumab. After a median follow-up of 4.5 (3-20) months, one patient achieved partial response, one had stable disease, and four had disease progression. All the patients died, five from melanoma, one from another cause. In this series and in the literature, ipilimumab proved to be safe and possibly active. The acute rejection we encountered was probably related to both a rapid, drastic reduction of immunosuppression and the use of ipilimumab. Our safety data on ipilimumab contrast with the organ transplant rejections already reported with PD-1 inhibitors. We consider that immunosuppression should not be minimized, as the impact on metastatic disease control is probably small.
Assuntos
Rejeição de Enxerto/tratamento farmacológico , Sobrevivência de Enxerto/efeitos dos fármacos , Ipilimumab/uso terapêutico , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Idoso , Antineoplásicos Imunológicos/uso terapêutico , Feminino , Seguimentos , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/patologia , Humanos , Masculino , Melanoma/etiologia , Melanoma/patologia , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/patologiaRESUMO
This study evaluated the independent contribution of voriconazole to the development of squamous cell carcinoma (SCC) in lung transplant recipients, by attempting to account for important confounding factors, particularly immunosuppression. This international, multicenter, retrospective, cohort study included adult patients who underwent lung transplantation during 2005-2008. Cox regression analysis was used to assess the effects of voriconazole and other azoles, analyzed as time-dependent variables, on the risk of developing biopsy-confirmed SCC. Nine hundred lung transplant recipients were included. Median follow-up time from transplantation to end of follow-up was 3.51 years. In a Cox regression model, exposure to voriconazole alone (adjusted hazard ratio 2.39, 95% confidence interval 1.31-4.37) and exposure to voriconazole and other azole(s) (adjusted hazard ratio 3.45, 95% confidence interval 1.07-11.06) were associated with SCC compared with those unexposed after controlling for important confounders including immunosuppressants. Exposure to voriconazole was associated with increased risk of SCC of the skin in lung transplant recipients. Residual confounding could not be ruled out because of the use of proxy variables to control for some confounders. Benefits of voriconazole use when prescribed to lung transplant recipients should be carefully weighed versus the potential risk of SCC. EU PAS registration number: EUPAS5269.
Assuntos
Antifúngicos/efeitos adversos , Carcinoma de Células Escamosas/etiologia , Pneumopatias/cirurgia , Transplante de Pulmão/efeitos adversos , Neoplasias Cutâneas/etiologia , Voriconazol/efeitos adversos , Adolescente , Adulto , Idoso , Carcinoma de Células Escamosas/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Neoplasias Cutâneas/patologia , Transplantados , Adulto JovemRESUMO
With advances in immunosuppression, graft and patient outcomes after kidney transplantation have improved considerably. As a result, long-term complications of transplantation, such as urologic malignancies, have become increasingly important. Kidney transplant recipients, for example, have a 7-fold risk of renal cell carcinoma (RCC) and 3-fold risk of urothelial carcinoma (UC) compared with the general population. While extrapolation of data from the general population suggest that routine cancer screening in transplant recipients would allow for earlier diagnosis and management of these potentially lethal malignancies, currently there is no consensus for posttransplantation RCC or UC screening as supporting data are limited. Further understanding of risk factors, presentation, optimal management of, and screening for urologic malignancies in kidney transplant patients is warranted, and as such, this review will focus on the incidence, surveillance, and treatment of urologic malignancies in kidney transplant recipients.
Assuntos
Transplante de Rim/efeitos adversos , Neoplasias Urológicas/etiologia , Animais , Humanos , Fatores de Risco , Neoplasias Urológicas/patologiaRESUMO
Kidney transplant recipients require specialized medical care and may be at risk for adverse health outcomes when their care is transferred. This document provides opinion-based recommendations to facilitate safe and efficient transfers of care for kidney transplant recipients including minimizing the risk of rejection, avoidance of medication errors, ensuring patient access to immunosuppressant medications, avoidance of lapses in health insurance coverage, and communication of risks of donor disease transmission. The document summarizes information to be included in a medical transfer document and includes suggestions to help the patient establish an optimal therapeutic relationship with their new transplant care team. The document is intended as a starting point towards standardization of transfers of care involving kidney transplant recipients.
Assuntos
Falência Renal Crônica/cirurgia , Transplante de Rim , Transferência de Pacientes/normas , Guias de Prática Clínica como Assunto/normas , Melhoria de Qualidade , Transplantados , Comunicação , Humanos , Imunossupressores/uso terapêutico , Adesão à MedicaçãoRESUMO
Colorectal cancer (CRC) is a common malignancy worldwide. Some studies suggest that organ recipients are at a higher risk for CRC than the general population. The underlying transplant indications and their inherent risk factors for CRC may drive the variation in incidence rates that are seen in patients receiving different allografts. Recipients with cystic fibrosis are now recognized as a population at high risk for CRC at a young age. Transplant recipients have high mortality following a CRC diagnosis, even if it is detected at an early stage. Certain types of immunosuppression have been shown to accelerate cancer transformation and may contribute to the more aggressive phenotype seen in organ recipients. Given the high incidence and progressive nature of posttransplant CRC, shorter screening intervals with a modality that can detect early-stage polyps may be essential to prevent mortality. Future research is needed to better elucidate the role of immunosuppression in carcinogenesis. This comprehensive review examines CRC risk, screening, and management specific to organ transplant candidates and recipients.
Assuntos
Neoplasias Colorretais/etiologia , Transplante de Órgãos/efeitos adversos , Neoplasias Colorretais/epidemiologia , Humanos , Fatores de RiscoRESUMO
Solid organ transplant recipients (SOTRs) are at increased risk of developing and dying from cancer. However, controversies exist around cancer screening in this population owing to reduced life expectancy and competing causes of death. This systematic review assesses the availability, quality and consistency of cancer screening recommendations in clinical practice guidelines (CPGs). We systematically searched bibliographic databases and gray literature to identify CPGs and assessed their quality using AGREE II. Recommendations were extracted along with their supporting evidence. Thirteen guidelines were included in the review. CPGs for kidney recipients were the most frequent source of screening recommendations, and recommendations for skin cancer screening were most frequently presented. Some screening recommendations differed from those for the general population, based on literature demonstrating higher cancer incidence among SOTRs versus direct evidence of screening effectiveness. Relevant stakeholders such as oncology specialists, primary care providers and public health experts were not involved in the formulation of the screening recommendations. In conclusion, although several guidelines make recommendations for cancer screening in SOTRs, the availability of cancer screening recommendations varied considerably by transplanted organ. More studies are required to inform cancer screening recommendations in SOTRs, and guideline development should involve transplant patients, oncologists and cancer screening specialists.
Assuntos
Neoplasias/diagnóstico , Transplante de Órgãos/efeitos adversos , Guias de Prática Clínica como Assunto/normas , Detecção Precoce de Câncer , Humanos , Neoplasias/etiologia , Neoplasias/prevenção & controle , Prognóstico , TransplantadosRESUMO
Several viruses, such as Epstein-Barr virus, are now known to be associated with several human cancers, but not all patients with these viral infections develop cancer. In transplantation, such viruses often have a prolonged time gap from infection to cancer development, and many are preceded by a period of circulating and detectable nucleic acids in the peripheral blood compartment. The interpretation of a viral load as a measure of posttransplant risk of developing cancer depends on the virus, the cancer and associated pathogenic factors. This review describes the current state of knowledge regarding the utility and limitations of peripheral blood nucleic acid testing for Epstein-Barr virus in surveillance and risk prediction for posttransplant lymphoproliferative disorders.
Assuntos
Biomarcadores/sangue , DNA Viral/genética , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4/genética , Neoplasias/diagnóstico , Complicações Pós-Operatórias , DNA Viral/sangue , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/virologia , Humanos , Neoplasias/sangue , Neoplasias/genética , Neoplasias/virologia , Fatores de RiscoRESUMO
Posttransplantation lymphoproliferative disorders (PTLDs) are life-threatening complications after solid organ and hematopoietic stem cell transplantation. Only half of CD20-positive PTLDs respond to rituximab monotherapy, and outcomes remain poor for patients with relapsed/refractory disease, especially those who do not qualify for an anthracycline containing regimen due to frailty or comorbidities. Radioimmunotherapy (RIT) might be an option in this particular setting. We report a panel of eight patients with rituximab refractory/relapsed CD20-positive PTLDs including three ineligible for subsequent CHOP-like chemotherapy who received (90) Y-Ibritumomab tiuxetan as a single agent (n = 7) or combined to chemotherapy (n = 1). Five out of eight patients were kidney transplant recipients, while 2/8 had a liver transplant and 1/8 had a heart transplant. Patients received a median of two previous therapies. Overall response rate was 62.5%. Importantly, all responders achieved complete response. At a median follow-up of 37 months [5; 84], complete response was ongoing in four patients. Toxicity was predominantly hematological and easily manageable. No graft rejection was noticed concomitantly or following RIT administration despite immunosuppression reduction after diagnosis of PTLDs. This report emphasizes the potential efficiency of salvage RIT for early rituximab refractory PTLDs without any unexpected toxicity.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Rejeição de Enxerto/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transtornos Linfoproliferativos/terapia , Transplante de Órgãos/efeitos adversos , Radioimunoterapia , Rituximab/farmacologia , Adulto , Idoso , Resistência a Medicamentos , Feminino , Seguimentos , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto , Humanos , Imunossupressores/uso terapêutico , Transtornos Linfoproliferativos/etiologia , Transtornos Linfoproliferativos/patologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Terapia de Salvação , TransplantadosRESUMO
Primary effusion lymphoma is a rare subclass of non-Hodgkin lymphoma associated with human herpesvirus 8 infection and principally seen in human immunodeficiency virus-positive patients. We report on the case of a 72-year-old human immunodeficiency virus-negative male with a hepatic transplant 10 years prior, who presented with a symptomatic right-sided pleural effusion and was found to have primary effusion lymphoma by flow cytometric and cytopathologic examination. Immunohistochemistry of his lymphoma cells was positive for human herpesvirus 8. Both he and his donor had no identifiable risk factors for human herpesvirus 8 infection. The patient was intolerant of antiviral therapy and chemotherapy, dying 7 months after diagnosis. Posttransplant primary effusion lymphoma is exceedingly rare and carries a very poor prognosis. Individualized treatment strategies are necessary given the scant body of published literature with guidance based solely on case reports.