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1.
Rinsho Ketsueki ; 60(9): 1331-1336, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31597860

RESUMO

Chronic active EBV infection (CAEBV) is one of the EBV-associated T/NK lymphoproliferative diseases. The prognosis of CAEBV is very poor, and without curative therapy, almost half of patients will die within five years of onset. The results of a 3-step treatment regimen consisting of step 1 (immunochemotherapy), step 2 (multi-drug chemotherapy), and step 3 (hematopoietic cell transplantation, HCT) are excellent. HCT is the only cure for CAEBV, and reduced-intensity conditioning (RIC) is superior to myeloablative conditioning (MAC). The overall survival rate is typically more than 90% following bone marrow transplantation and cord blood transplantation.


Assuntos
Infecções por Vírus Epstein-Barr/terapia , Transplante de Células-Tronco Hematopoéticas , Transtornos Linfoproliferativos/terapia , Tratamento Farmacológico , Humanos , Transtornos Linfoproliferativos/virologia , Prognóstico , Taxa de Sobrevida , Condicionamento Pré-Transplante
2.
J Korean Med Sci ; 34(30): e203, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31373185

RESUMO

BACKGROUND: Post-transplant lymphoproliferative disease (PTLD) is one of the major complications of organ transplantation, especially in children with Epstein-Barr virus (EBV) viremia (EV). We performed a retrospective study to evaluate risk factors for PTLD in children with EV. METHODS: Among 199 pediatric kidney transplantation (KT) recipients at our center from January 2001 to October 2015, records of those with EBV viral loads of > 1,000 copies/mL and/or PTLD were reviewed. RESULTS: Diagnosis of PTLD was made in seven patients (PTLD group), and 39 patients had EV only (EV only group). The median time from KT to EV and PTLD diagnosis was 6.7 (range 0.4-47.8) months and 8.2 (range, 2.8-98.9) months, respectively. There were no significant differences between the groups in terms of sex, age at transplantation, donor type, EBV viral load, or EV-free duration after KT. Higher tacrolimus level before EV (hazard ratio, 44.5; P = 0.003) was an independent risk factor for PTLD in multivariate Cox regression analysis. Six patients with a high EBV load (median 171,639 copies/mL) were treated with preemptive rituximab (RTX) therapy, resulting in transient reduction of EBV load. None of these patients developed PTLD (median follow-up 51.5 months); however, two had neutropenia and two developed infection requiring hospital admission. CONCLUSION: In pediatric KT recipients, higher tacrolimus levels were associated with a higher incidence of PTLD. Conversely, those who received preemptive RTX for EV did not develop PTLD.


Assuntos
Herpesvirus Humano 4/isolamento & purificação , Transplante de Rim/efeitos adversos , Transtornos Linfoproliferativos/terapia , Viremia/etiologia , Antineoplásicos Imunológicos/uso terapêutico , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Neutropenia/etiologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Rituximab/uso terapêutico , Transplante Homólogo , Carga Viral , Viremia/tratamento farmacológico , Viremia/virologia
3.
Eur J Oncol Nurs ; 42: 21-27, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31446260

RESUMO

PURPOSE: Hematopoietic stem cell transplant (HSCT) is an intensive treatment associated with distressing treatment and disease-related symptoms that affect patient outcomes such as functional status and quality of life. Self-efficacy for symptom management (SESM) is a person's belief in their ability to perform behaviors to prevent and relieve symptoms. Presence of SESM can impact symptom distress and functional status. This study describes the changes over time and relationships among SESM, symptom distress, and physical functional status in adults during the acute phase of HSCT. METHODS: Patients (n = 40) completed measures of symptom distress, SESM, and physical function at time points prior to and at days 7, 15 and 30 post-transplant. Clinical outcomes were length of stay and number of readmissions. RESULTS: Symptom distress, physical function, and SESM changed significantly over time. There was a significant negative relationship between symptom distress and physical function and between symptom distress and SESM at all points. The lowest levels of SESM and physical function were at day 7 when symptom distress was highest. Symptom distress was a moderator for the relationship between physical function and SESM at day 15. CONCLUSION: This was the first study to examine SESM in the acute phase of HSCT. Higher SESM was associated with fewer symptoms and increased physical function. Less symptom distress was associated with higher physical function and confidence to manage symptoms. These findings provide the basis for development of patient-centered interventions to enhance SESM when symptoms are at their highest immediately after HSCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia/psicologia , Transtornos Linfoproliferativos/psicologia , Síndromes Mielodisplásicas/psicologia , Cuidados Paliativos , Autoeficácia , Adulto , Idoso , Feminino , Hospitalização , Humanos , Leucemia/terapia , Transtornos Linfoproliferativos/terapia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/terapia , Projetos Piloto , Qualidade de Vida , Autocuidado , Avaliação de Sintomas
4.
Surg Pathol Clin ; 12(3): 733-743, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31352985

RESUMO

The gastrointestinal tract is a common extranodal site of involvement by lymphomas. These may be diagnostically challenging because they can mimic a variety of benign conditions and may be difficult to subclassify when malignant. The classification of gastrointestinal lymphomas is an evolving area with some recent changes. Although some of these entities are rare, they are important to recognize because of the variable clinical presentations, comorbidities, and treatment implications. This article explores new and revised entities in gastrointestinal lymphoproliferative disorders.


Assuntos
Neoplasias Gastrointestinais/diagnóstico , Transtornos Linfoproliferativos/diagnóstico , Doença Celíaca/complicações , Doença Crônica , Diagnóstico Diferencial , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/terapia , Humanos , Transtornos Linfoproliferativos/genética , Transtornos Linfoproliferativos/terapia , Prognóstico
5.
J Clin Exp Hematop ; 59(2): 72-92, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31257348

RESUMO

Other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPD), a category of immunodeficiency-associated LPD according to the World Health Organization classification, is associated with immunosuppressive drugs (ISDs). Several factors, including autoimmune disease (AID) activity, Epstein-Barr virus (EBV) infection, ISD usage, and aging, influence the development of OIIA-LPD, resulting in complicated clinical courses and outcomes. Most OIIA-LPD develops in patients with rheumatoid arthritis using methotrexate (MTX-LPD). The management of MTX-LPD is based on the clinical course, i.e., with/without regression, with/without relapse/regrowth event (RRE), LPD subtype, and ISDs for AIDs after LPD development. There are three clinical courses after ISD withdrawal: regressive LPD without relapse/regrowth (R-G), regressive LPD with RRE (R/R-G), and persistent LPD (P-G). The majority of EBV+ diffuse large B-cell lymphomas are classified in R-G, whereas classic Hodgkin lymphoma is generally classified in R/R-G. Polymorphic LPD (P-LPD) in MTX-LPD develops with heterogeneous pathological features similar to monomorphic LPD. Chemotherapy for MTX-LPD is selected according to that for de novo LPD, although the strategy for aggressive P-LPD and non-specific LPD is not well established. The absolute lymphocyte count in the peripheral blood has been suggested as a candidate marker for MTX-LPD development and RRE. Several clinical issues, including correct diagnosis among overlapping clinicopathological features in MTX-LPD and clinical management of LPD by ISDs other than MTX, require further investigation.


Assuntos
Síndromes de Imunodeficiência/terapia , Transtornos Linfoproliferativos/terapia , Animais , Artrite Reumatoide/tratamento farmacológico , Gerenciamento Clínico , Humanos , Doença Iatrogênica/epidemiologia , Síndromes de Imunodeficiência/induzido quimicamente , Síndromes de Imunodeficiência/patologia , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Transtornos Linfoproliferativos/induzido quimicamente , Transtornos Linfoproliferativos/patologia , Metotrexato/efeitos adversos , Metotrexato/uso terapêutico
6.
Blood ; 134(6): 515-524, 2019 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-31164331

RESUMO

The primary cutaneous CD30+ lymphoproliferative disorders are a family of extranodal lymphoid neoplasms that arise from mature postthymic T cells and localize to the skin. Current classification systems recognize lymphomatoid papulosis (LyP), primary cutaneous anaplastic large cell lymphoma, and borderline cases. In the majority of patients, the prognosis of primary cutaneous CD30+ lymphoproliferative disorders is excellent; however, relapses are common, and complete cures are rare. Skin-directed and systemic therapies are used as monotherapy or in combination to achieve the best disease control and minimize overall toxicity. We discuss 3 distinct presentations of primary cutaneous CD30+ lymphoproliferative disorder and present recommendations for a multidisciplinary team approach to diagnosis, evaluation, and management of these conditions in keeping with existing consensus guidelines.


Assuntos
Antígeno Ki-1/genética , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/terapia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/terapia , Adulto , Idoso , Biomarcadores , Biópsia , Terapia Combinada/métodos , Feminino , Humanos , Antígeno Ki-1/metabolismo , Transtornos Linfoproliferativos/etiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Cutâneas/etiologia , Avaliação de Sintomas , Resultado do Tratamento
7.
Ann Hematol ; 98(9): 2163-2177, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31243569

RESUMO

In allogeneic hematopoietic stem cell transplantation recipients, reactivation of Epstein-Barr virus (EBV) can cause post-transplantation lymphoproliferative disorder (PTLD), which may rapidly progress to multiorgan failure and even death. Development of EBV PTLD correlates very closely with use of anti-thymocyte globulin (ATG) and type of transplant. To assess the incidences and clinical features of EBV DNAemia and PTLD in the setting of stem cell transplantation using unmanipulated G-CSF-primed allogeneic peripheral blood stem cells as graft, we performed a retrospective analysis of stem cell transplantation from HLA-matched sibling donors (MSD-SCT, n = 90) or HLA-haploidentical related donors (HID-SCT, n = 110) in patients with hematological malignancies. All of HID-SCT recipients and 27.8% of MSD-SCT recipients received an ATG-containing conditioning regimen. One-year cumulative incidence of EBV DNAemia was 44.1%, ranging from 4.8% in MSD-SCT recipients not using ATG to 20.0% in MSD-SCT recipients using ATG, and 73.7% in HID-SCT recipients. Risk factors for EBV reactivation included use of ATG (p = 0.008), male donor (p = 0.034), and cytomegalovirus DNAemia (p < 0.001). One-year incidence of EBV PTLD was 11.9%, ranging from 1.8% in recipients of MSD-SCT not using ATG to 4.4% in recipients of MSD-SCT using ATG, and 23.5% in recipients of HID-SCT. Risk factors for PTLD after HID-SCT included in fludarabine-containing conditioning regimen (p = 0.010), cytomegalovirus DNAemia (p = 0.036), and patient's age < 40-yr (p = 0.032). Two-year non-relapse mortality was higher for patients with EBV DNAemia than those without EBV DNAemia (35.8% vs. 15.3%, p = 0.002). One-year relapse-free survival and overall survival among patients with PTLD were 40.2% and 44.9%, respectively, as opposed to 63.4% and 68.4% among patients without PTLD (both p < 0.05). In multivariate analyses, EBV DNAemia predicted a lower risk of relapse (p = 0.025), while PTLD was a marginally significant predictor of relapse (p = 0.092). This study identified patients at risk of EBV reactivation and PTLD after unmanipulated allogeneic peripheral blood stem cell transplantation.


Assuntos
DNA Viral/sangue , Infecções por Vírus Epstein-Barr , Neoplasias Hematológicas , Herpesvirus Humano 4/metabolismo , Transtornos Linfoproliferativos , Transplante de Células-Tronco de Sangue Periférico , Condicionamento Pré-Transplante , Adolescente , Adulto , Aloenxertos , Criança , Intervalo Livre de Doença , Infecções por Vírus Epstein-Barr/sangue , Infecções por Vírus Epstein-Barr/mortalidade , Infecções por Vírus Epstein-Barr/terapia , Feminino , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/virologia , Humanos , Transtornos Linfoproliferativos/sangue , Transtornos Linfoproliferativos/mortalidade , Transtornos Linfoproliferativos/terapia , Transtornos Linfoproliferativos/virologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Irmãos , Taxa de Sobrevida
8.
Pediatr Blood Cancer ; 66(8): e27803, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31062898

RESUMO

Classic Hodgkin lymphoma post-transplant lymphoproliferative disorder (HL-PTLD) has been rarely reported in children, with limited data available to guide treatment decisions. We report a retrospective review of five children diagnosed with classic HL-PTLD following solid organ transplant between 2007 and 2013 at Stanford University. Patients were treated with Stanford V chemotherapy and involved field radiation therapy. With a median follow-up of 7.2 years (range, 4.7-10.5 years) since diagnosis, all patients remain in remission from HL-PTLD and free from graft failure. In this series, combined modality therapy with risk-adapted chemotherapy and radiation therapy was a successful strategy for the treatment of classic HL-PTLD.


Assuntos
Doença de Hodgkin/terapia , Transtornos Linfoproliferativos/terapia , Transplante de Órgãos/efeitos adversos , Complicações Pós-Operatórias/terapia , Criança , Pré-Escolar , Terapia Combinada , Feminino , Seguimentos , Doença de Hodgkin/etiologia , Doença de Hodgkin/patologia , Humanos , Lactente , Transtornos Linfoproliferativos/etiologia , Transtornos Linfoproliferativos/patologia , Masculino , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/patologia , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
9.
Front Biosci (Landmark Ed) ; 24: 1284-1315, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31136980

RESUMO

Cellular therapies are a rapidly evolving approach to treat cancer in the light of their unique mechanism of action that potentially overcomes drug resistance and induces durable remissions. Modalities of adoptive cell therapy include gene-modified T cells expressing novel T cell receptors or chimeric antigen receptors (CAR) that modify the immune system to recognize tumor cells and carry out potent anti-tumor effector functions. CAR T cells have shown very promising clinical results and several trials are being conducted worldwide to establish their role in cancer treatment. Most successful results have been observed in lymphoproliferative disorders with the use of CD19-directed CAR T cells, which led to their commercial approval by FDA. In this review, we provide a comprehensive overview of the current role of CAR T cell therapies in hematological malignancies and solid tumors, their associated toxicities and potential future developments in the armamentarium for cancer treatment.


Assuntos
Imunoterapia Adotiva/métodos , Neoplasias/terapia , Receptores de Antígenos Quiméricos/imunologia , Linfócitos T/imunologia , Antígenos CD19/imunologia , Antígenos CD19/metabolismo , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/patologia , Neoplasias Hematológicas/terapia , Humanos , Imunoterapia Adotiva/tendências , Transtornos Linfoproliferativos/imunologia , Transtornos Linfoproliferativos/patologia , Transtornos Linfoproliferativos/terapia , Neoplasias/imunologia , Neoplasias/patologia , Medicina de Precisão/métodos , Medicina de Precisão/tendências , Receptores de Antígenos Quiméricos/metabolismo , Linfócitos T/metabolismo , Resultado do Tratamento
10.
Cancer Treat Res ; 176: 249-268, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30596222

RESUMO

Primary cutaneous CD30-positive lymphoproliferative disorders (CD30+ LPD) encompass lymphomatoid papulosis (LyP), primary cutaneous anaplastic large cell lymphoma (pcALCL), and borderline lesions [1]. CD30+ LPD are the second most common cutaneous T-cell lymphomas (CTCL) after mycosis fungoides (MF) and represent approximately 25% of all CTCL cases [2]. Their common phenotypic hallmark is an expression of the CD30 antigen, a cytokine receptor belonging to the tumor necrosis factor (TNF) receptor superfamily. Both LyP and pcALCL show numerous clinical, histological and immunophenotypic variants, and generally have an indolent course with a favorable prognosis. Overlapping features of LyP and pcALCL with other CD30+ T-cell lymphomas, inflammatory, and/or infectious conditions emphasize the importance of careful clinicopathologic correlation and staging.


Assuntos
Papulose Linfomatoide , Transtornos Linfoproliferativos , Micose Fungoide , Neoplasias Cutâneas , Adulto , Humanos , Imunofenotipagem , Antígeno Ki-1 , Papulose Linfomatoide/diagnóstico , Papulose Linfomatoide/terapia , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/imunologia , Transtornos Linfoproliferativos/terapia , Micose Fungoide/diagnóstico , Micose Fungoide/terapia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/terapia
11.
J Infect Chemother ; 25(6): 463-466, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30679025

RESUMO

Exophiala dermatitidis is a dematiaceous fungus that is increasingly becoming the cause of fungal infection in immunocompromised patients. However, the risk factors and optimal treatment modality for E. dermatitidis infection are unknown to date. Herein, we present a fatal case of E. dermatitidis infection in an adult patient that developed after allogeneic hematopoietic stem cell transplantation for chronic active Epstein-Barr virus infection. The dematiaceous fungus caused a breakthrough fungemia despite prophylactic administration of micafungin. Although the patient was intensively treated with liposomal-amphotericin B and voriconazole, serum level of beta-D-glucan continuously increased, and the patient eventually died because of cerebral hemorrhage. An autopsy found multiple involvements of the fungal infection at the bilateral lungs, thoracic cavities, diaphragm, and thyroid. To the best of our knowledge, this is the first reported case of E. dermatitidis infection involving these tissues as determined via autopsy. This case highlights the importance of attention for Exophiala infection in immunocompromised individuals in those given antifungal therapy with echinocandins.


Assuntos
Antifúngicos/uso terapêutico , Exophiala/isolamento & purificação , Hospedeiro Imunocomprometido , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Feoifomicose/tratamento farmacológico , Adulto , Evolução Fatal , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/imunologia , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Transtornos Linfoproliferativos/terapia , Masculino , Feoifomicose/imunologia , Feoifomicose/microbiologia , Feoifomicose/patologia
12.
Ann Hematol ; 98(3): 625-632, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30680506

RESUMO

Post-transplant lymphoproliferative disease (PTLD) is a serious complication of solid organ transplantation. As early diagnosis remains challenging, we investigated the utility of serum-free light chain (FLC) and heavy chain/light chain pairs (HLC) as diagnostic biomarkers. Pre-treatment serum FLC and HLC levels were measured in 20 patients at their first diagnosis of B cell PTLD and in 14/20 patients during follow-up. Results were compared to serum FLC/HLC levels of 90 matched PTLD-free transplanted controls. Renal dysfunction was common in both cohorts, and combined FLC levels were often elevated above the conventional upper limit of normal (45.7 mg/L). Combined FLC levels were higher in patients with PTLD than in transplant controls (p = 0.013), and levels above the conventional ULN were associated with PTLD (OR 3.2, p = 0.05). Following adjustment to cystatin C as a marker of renal function an even stronger association was found for a (dimensionless) threshold value of 37.8 (OR 8.9, p < 0.001). In addition, monoclonal proliferation (abnormal FLC ratio, using an established renal range cutoff) was more common in PTLD than in controls (3/20 vs. 2/90, p = 0.04). Following therapy, at the time of protocolised restaging, patients experiencing subsequent sustained complete remission displayed lower FLC levels than those not experiencing such remission (p = 0.053). No relationship with HLC results was seen. Elevated polyclonal FLC levels (especially when adjusted for renal function) and monoclonal proliferation are a potential biomarker for PTLD diagnosis and disease surveillance. However, prospective validation is necessary before FLC measurement should be incorporated in follow-up of transplant recipients and PTLD management.


Assuntos
Cadeias Leves de Imunoglobulina/sangue , Transtornos Linfoproliferativos/sangue , Transplante de Órgãos/efeitos adversos , Adulto , Idoso , Biomarcadores/sangue , Criança , Cistatina C/sangue , Feminino , Seguimentos , Humanos , Testes de Função Renal , Transtornos Linfoproliferativos/etiologia , Transtornos Linfoproliferativos/genética , Transtornos Linfoproliferativos/terapia , Masculino , Pessoa de Meia-Idade , Indução de Remissão
13.
Orphanet J Rare Dis ; 14(1): 9, 2019 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-30626415

RESUMO

BACKGROUND: Chylothorax is a rare condition which can be associated with malignant lymphoproliferative disorders (LPDs). We retrospectively analyzed the results of the conservative treatment of 10 patients with persistent non-traumatic malignant chylothorax. RESULTS: Conservative treatment lead to a decline of chylothorax after mean of 66 days and consisted of the treatment of the underlying disease and of simultaneous long-term supportive care (drainage of the thoracic cavity, dietary measures and nutrition management). In most cases (80%), chylothorax disappeared only after a successful therapeutic response of the underlying disease. Low-dose radiotherapy had very good effects in two patients. CONCLUSION: Conservative treatment of malignant chylothorax can be considered a suitable method. Based on our results, successful treatment of the lymphoproliferative disorder seems to be a very important factor for the disappearance of chylothorax.


Assuntos
Quilotórax/radioterapia , Quilotórax/terapia , Transtornos Linfoproliferativos/radioterapia , Transtornos Linfoproliferativos/terapia , Idoso , Quilotórax/tratamento farmacológico , Feminino , Humanos , Leucemia Linfoide/tratamento farmacológico , Leucemia Linfoide/radioterapia , Leucemia Linfoide/terapia , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/radioterapia , Linfoma não Hodgkin/terapia , Transtornos Linfoproliferativos/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ducto Torácico/efeitos dos fármacos , Ducto Torácico/efeitos da radiação
14.
Yakugaku Zasshi ; 139(1): 63-67, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-30606931

RESUMO

Epstein-Barr virus (EBV), a human oncogenic virus, is a B cell-tropic herpesvirus and has the ability to immortalize normal B cells during latent infection. The Epstein-Barr nuclear antigen 1 (EBNA1) protein of EBV is expressed in the most EBV latently infected cells and binds to a specific viral genome region termed "oriP" (origin of plasmid replication) to maintain the stability of the approximately 170 kb double-stranded circular virus genomic DNA (episome) in cells. EBV elimination is thought to inhibit progression of EBV-associated malignancies, and the EBNA1-dependent mechanisms for EBV episome replication and maintenance are considered to be novel molecular targets for anti-EBV therapy. We have explored small-molecule compounds that can inhibit the binding between EBNA1 protein and oriP and found one pyrrole imidazole polyamide named DSE3 which can also inhibit EBV-mediated immortalization of normal B cells. These data suggested that an EBNA1-targeting strategy could be useful to combat EBV-associated malignancies.


Assuntos
Linfoma de Burkitt/terapia , Linfoma de Burkitt/virologia , Replicação do DNA , Genoma Viral/genética , Herpesvirus Humano 4/genética , Doença de Hodgkin/terapia , Doença de Hodgkin/virologia , Imidazóis/farmacologia , Imidazóis/uso terapêutico , Transtornos Linfoproliferativos/terapia , Transtornos Linfoproliferativos/virologia , Terapia de Alvo Molecular , Pirróis/farmacologia , Pirróis/uso terapêutico , Linfócitos B/virologia , Antígenos Nucleares do Vírus Epstein-Barr , Humanos , Plasmídeos/genética , Origem de Replicação/genética
15.
J Allergy Clin Immunol ; 143(1): 266-275, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29778502

RESUMO

BACKGROUND: Activated phosphatidylinositol-3-OH kinase δ syndrome type 1 (APDS1) is a recently described primary immunodeficiency syndrome characterized by recurrent respiratory tract infections, lymphoid hyperplasia, and Herpesviridae infections caused by germline gain-of-function mutations of PIK3CD. Hematopoietic stem cell transplantation (HSCT) can be considered to ameliorate progressive immunodeficiency and associated malignancy, but appropriate indications, methods, and outcomes of HSCT for APDS1 remain undefined. OBJECTIVE: Our objective was to analyze the clinical manifestations, laboratory findings, prognosis, and treatment of APDS1 and explore appropriate indications and methods of HSCT. METHODS: We reviewed retrospectively the medical records of cohorts undergoing HSCT at collaborating facilities. RESULTS: Thirty-year overall survival was 86.1%, but event-free survival was 39.6%. Life-threatening events, such as severe infections or lymphoproliferation, were frequent in childhood and adolescence and were common indications for HSCT. Nine patients underwent HSCT with fludarabine-based reduced-intensity conditioning. Seven patients survived after frequent adverse complications and engraftment failure. Most symptoms improved after HSCT. CONCLUSION: Patients with APDS1 showed variable clinical manifestations. Life-threatening progressive combined immunodeficiency and massive lymphoproliferation were common indications for HSCT. Fludarabine-based reduced-intensity conditioning-HSCT ameliorated clinical symptoms, but transplantation-related complications were frequent, including graft failure.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Síndromes de Imunodeficiência , Transtornos Linfoproliferativos , Adolescente , Adulto , Aloenxertos , Criança , Pré-Escolar , Classe I de Fosfatidilinositol 3-Quinases/imunologia , Intervalo Livre de Doença , Feminino , Humanos , Síndromes de Imunodeficiência/imunologia , Síndromes de Imunodeficiência/mortalidade , Síndromes de Imunodeficiência/patologia , Síndromes de Imunodeficiência/terapia , Transtornos Linfoproliferativos/imunologia , Transtornos Linfoproliferativos/mortalidade , Transtornos Linfoproliferativos/patologia , Transtornos Linfoproliferativos/terapia , Masculino , Taxa de Sobrevida
17.
Leuk Lymphoma ; 60(1): 110-117, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29979906

RESUMO

Epstein-Barr virus (EBV) reactivation is an unresolved medical issue after allogeneic hematopoietic stem cell transplantation (HSCT). Rituximab treatment is recommended for EBV reactivation after HSCT but the number of doses of rituximab to use is unclear. In this study, risk factors and outcomes of patients who needed 1 dose vs >1 doses of preemptive rituximab to clear EBV viremia were compared. A higher viral load was more likely to be associated with higher doses of rituximab. Patients whose EBV viremia cleared with 1 dose of rituximab were more likely to have a preceding reduction of immunosuppression. Overall survival (OS) in these 2 cohorts was not different (18.7 vs 26.6 months, respectively, p = .96). Since rituximab can have side effects and is fairly costly, a predictive model to determine the number of rituximab doses using viral load would be a useful and cost-effective manner to utilize rituximab for this indication.


Assuntos
Infecções por Vírus Epstein-Barr/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transtornos Linfoproliferativos/terapia , Rituximab/administração & dosagem , Viremia/prevenção & controle , Adolescente , Adulto , Idoso , Tomada de Decisão Clínica/métodos , Esquema de Medicação , Infecções por Vírus Epstein-Barr/epidemiologia , Infecções por Vírus Epstein-Barr/etiologia , Feminino , Seguimentos , Herpesvirus Humano 4/efeitos dos fármacos , Herpesvirus Humano 4/isolamento & purificação , Herpesvirus Humano 4/fisiologia , Humanos , Transtornos Linfoproliferativos/mortalidade , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Seleção de Pacientes , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Transplante Homólogo/efeitos adversos , Resultado do Tratamento , Carga Viral/efeitos dos fármacos , Viremia/epidemiologia , Viremia/etiologia , Ativação Viral/efeitos dos fármacos , Adulto Jovem
18.
Clin Immunol ; 198: 39-45, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30572125

RESUMO

The incorporation of next generation sequencing into routine immunological practice has enabled the identification of novel inborn errors of disease, helped define new categories of immune deficiency and extended the clinical spectrum associated with many long-recognised diseases. The family of EBV (Epstein Barr Virus)-sensitive primary immune deficiencies is one such group and in this paper we describe three families: two with X-linked lymphoproliferative disease type-1 (XLP-1) and one with deficiency of Interleukin-2 Inducible T-cell Kinase (ITK). Both diseases have a wide range of clinical manifestations and are united by an exquisite predisposition to EBV, dysgammaglobulinemia, hemophagocytic lymphohistiocytosis, and lymphoma. We detail our approach to diagnosis, treatment, and risk stratification in these diseases where both clinicians and patients must grapple with constant uncertainty.


Assuntos
Síndromes de Imunodeficiência/complicações , Transtornos Linfoproliferativos/terapia , Proteínas Tirosina Quinases/deficiência , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Linfo-Histiocitose Hemofagocítica/etiologia , Transtornos Linfoproliferativos/genética , Masculino , Pessoa de Meia-Idade , Proteínas Tirosina Quinases/genética , Estudos Retrospectivos
19.
BMJ Case Rep ; 11(1)2018 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-30567235

RESUMO

We present two cases of patient's with long-standing autoimmune diseases being treated with immunosuppressants that developed aggressive lymphoproliferative disorders. Immunosuppressants have a well-known association with disorders. Sustained regression of these lymphoproliferative disorders occurred with simple discontinuation of these immunosuppressive agents.


Assuntos
Doenças Autoimunes/tratamento farmacológico , Imunossupressores/efeitos adversos , Transtornos Linfoproliferativos/induzido quimicamente , Metotrexato/efeitos adversos , Artrite Psoriásica/tratamento farmacológico , Dermatomiosite/tratamento farmacológico , Humanos , Transtornos Linfoproliferativos/terapia , Masculino , Pessoa de Meia-Idade , Suspensão de Tratamento
20.
Crit Rev Oncol Hematol ; 132: 27-38, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30447925

RESUMO

INTRODUCTION AND AIM: Post-transplant lymphoproliferative disorder (PTLD) is a serious complication after solid organ and hematopoietic stem cell transplantation, associated with significant morbidity and mortality. In this systematic review we evaluated the clinical performance of advanced imaging modalities at diagnosis and treatment response evaluation of PTLD patients after solid organ and hematopoietic stem cell transplantation. METHODS: We have carried out a literature search until December 15, 2017 using PubMed/Medline, Embase, "Web of Science" and Cochrane Library databases concerning the performance of computed tomography (CT), magnetic resonance imaging (MRI) and 18F-flurodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) at diagnosis or treatment response evaluation of PTLD patients. RESULTS: A total of 11 studies were included comprising 368 patients, from which FDG-PET(/CT) was the primary imaging modality investigated. The methodological quality according to QUADAS-2 of the reviewed studies was moderate-poor. Subgroup analysis of imaging results for detection and staging in patients with PTLD indicated that FDG-PET/(CT) identified additional lesions not detected by CT and/or MRI in 27.8%, (95% confidence interval [95%CI]) 17.0%-42.0% (I2 = 51.1%), from which extra-nodal sites in 23.6% (95%CI: 7.9%-52.4%) (I2 = 76.6%). False negative results occurred in 11.5% (95%CI: 4.9%-24.5%) (I2 = 73.4%), predominantly in physiological high background activity regions and in early PTLD lesions. False positive results occurred in 4.8% (95%CI: 2.6%-8.6%) (I2 = 0%) predominantly due to inflammatory conditions. Subgroup analysis of imaging results at treatment response evaluation indicated that FDG-PET(/CT) findings altered or guided treatment in 29.0% (95%CI: 14.0%-50.5%) (I2 = 40.1%). False positive results during treatment response evaluation were reported in 20.0% (95%CI: 10.7%-34.2%) (I2 = 0%), predominantly due to inflammatory conditions. CONCLUSION: FDG-PET(/CT) is currently the most frequently investigated imaging modality in PTLD patients. Available studies report promising results in detection, staging and therapy evaluation but suffer from methodological shortcomings. Concerns remain with regard to occurrence of false negatives due to physiological high background activity and early PTLD lesions as well as false positives due to inflammatory conditions.


Assuntos
Transtornos Linfoproliferativos/diagnóstico por imagem , Imagem Multimodal/métodos , Transplante/efeitos adversos , Estudos de Avaliação como Assunto , Humanos , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/etiologia , Transtornos Linfoproliferativos/terapia
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