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1.
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
2.
Eur J Haematol ; 102(6): 465-471, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30828868

RESUMO

Post-transplant lymphoproliferative disorder (PTLD) is an infrequent complication of allogeneic stem cell transplant (allo-SCT). AIMS: To estimate the frequency and management of PTLD in Spain and to identify prognostic factors influencing outcomes. METHODS: Multicenter, retrospective analysis of allo-SCT performed in 14 transplant units over a 15-year period. RESULTS: 102 PTLD were diagnosed among 12 641 allo-SCT, leading to an estimated frequency of 0.8%. PTLD was diagnosed at a median of 106 days after SCT. Eighty-seven cases (85%) were diagnosed between 2007 and 2013. At diagnosis, 22% and 17% of the patients had gastrointestinal tract and CNS involvement. Eighty-seven (85%) received rituximab treatment, alone or in combination with immunosuppression reduction, with an ORR of 50.6%. With a median follow-up for survivors of 58 months, the 2-year overall survival (OS) was 33% and the PTLD-related mortality 45%. Age ≥ 40 years, malignant underlying disease, non-response to rituximab, and severe thrombocytopenia or lymphocytopenia at PTLD diagnosis were associated with worse overall survival. CONCLUSIONS: Only a small proportion of allografted patients were diagnosed a PTLD. Its clinical course was highly aggressive, and prognosis poor, especially in those failing rituximab. The prognostic impact found of the platelet, and lymphocyte count at diagnosis requires further confirmation.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transtornos Linfoproliferativos/epidemiologia , Transtornos Linfoproliferativos/etiologia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica , Biomarcadores , Criança , Pré-Escolar , Terapia Combinada/métodos , Ciclofosfamida , Doxorrubicina , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/virologia , Feminino , Humanos , Lactente , Estimativa de Kaplan-Meier , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Avaliação de Resultados da Assistência ao Paciente , Prednisona , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Espanha/epidemiologia , Transplante Homólogo , Vincristina , Adulto Jovem
3.
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
4.
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
5.
Am J Surg Pathol ; 42(12): 1647-1652, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30222603

RESUMO

Nonclonal expansions of immature T cells outside of the thymus, termed indolent T-lymphoblastic proliferation (iT-LBP), have been identified in rare lymphoproliferative disorders. We report that iT-LBP is a frequent finding in cases of follicular dendritic cell sarcoma (FDCS), and shows an association with paraneoplastic autoimmune multiorgan syndrome (PAMS). We studied 31 cases of FDCS by paraffin immunohistochemistry using antibodies to CD21, CD23, CD35, clusterin, CXCL13, podoplanin, CD3, CD4, CD8, CD20, CD1a, and TdT. Chart review was performed to characterize the clinical behavior including evidence of autoimmune disease. FDCS occurred in a wide variety of nodal and extranodal sites. Fourteen of 31 (45%) cases contained immature TdT-positive T cells; in 5 cases these cells were numerous and present throughout the tumor. Four of these 5 patients with numerous immature T cells developed autoimmune disease, clinically categorized as PAMS and/or myasthenia gravis. PAMS persisted after tumor resection, causing severe morbidity and mortality. These findings suggest that the neoplastic follicular dendritic cells can recruit or foster the proliferation of immature T cells and that these cells may play a role in mediating PAMS. Recognition of iT-LBP in FDCS is important to avoid misdiagnosis as thymoma or T-lymphoblastic lymphoma, and may predict serious autoimmune complications in some patients.


Assuntos
Doenças Autoimunes/imunologia , Proliferação de Células , Sarcoma de Células Dendríticas Foliculares/imunologia , Células Dendríticas Foliculares/imunologia , Transtornos Linfoproliferativos/imunologia , Síndromes Paraneoplásicas/imunologia , Linfócitos T/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Autoimunes/mortalidade , Doenças Autoimunes/patologia , Biomarcadores Tumorais/análise , Biópsia , Sarcoma de Células Dendríticas Foliculares/mortalidade , Sarcoma de Células Dendríticas Foliculares/patologia , Sarcoma de Células Dendríticas Foliculares/cirurgia , Células Dendríticas Foliculares/patologia , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Transtornos Linfoproliferativos/mortalidade , Transtornos Linfoproliferativos/patologia , Masculino , Pessoa de Meia-Idade , Síndromes Paraneoplásicas/mortalidade , Síndromes Paraneoplásicas/patologia , Valor Preditivo dos Testes , Prognóstico , Fatores de Risco , Linfócitos T/patologia , Adulto Jovem
6.
Kidney Int ; 94(4): 809-817, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30173897

RESUMO

Better prognostication of graft and patient outcomes among kidney transplant recipients with post-transplant lymphoproliferative disease (PTLD) in the rituximab era is needed to inform treatment decisions. Therefore, we sought to estimate the excess risks of death and graft loss in kidney transplant recipients with PTLD, and to determine risk factors for death. Using the ANZDATA registry, the risks of mortality and graft loss among recipients with and without PTLD were estimated using survival analysis. A group of 367 patients with PTLD (69% male, 85% white, mean age 43 years) were matched 1 to 4 to 1468 controls (69% male, 88% white, mean age 43 years), and followed for a mean of 16 years. Recipients with PTLD experienced poorer 10-year patient survival (41%, 95% confidence intervals 36-47%) than controls (65%, 63-68%). Excess mortality occurred in the first 2 years post-transplant (hazard ratio 8.5, 6.7-11), but not thereafter (1.0, 0.76-1.3). Cerebral lymphoma (2.0, 1.3-3.1), bone marrow disease (2.0, 1.2-3.3) and year of diagnosis prior to 2000 (2.2, 1.4-3.5; after 2000 reference) were risk factors of death. PTLD did not confer an excess risk of graft loss (1.08, 0.69-1.70). Thus, PTLD is a risk factor for death, particularly in the first two years after diagnosis. Cerebral or bone marrow diseases were associated with increased mortality risk, but overall survival in the rituximab era (post 2000) has improved.


Assuntos
Doenças da Medula Óssea/mortalidade , Neoplasias Encefálicas/mortalidade , Sobrevivência de Enxerto , Transplante de Rim/efeitos adversos , Transtornos Linfoproliferativos/etiologia , Transtornos Linfoproliferativos/mortalidade , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Linfoma/mortalidade , Masculino , Sistema de Registros , Fatores de Risco , Taxa de Sobrevida , Adulto Jovem
7.
Br J Haematol ; 183(3): 385-399, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30095154

RESUMO

Lymphoma incidence and survival in adolescent and young adult (AYA, defined as 15-39 years of age) and adult patients (>39 years) were assessed using Surveillance, Epidemiology, and End Results (SEER) data. From 2000 to 2014, 431 721 lymphoma cases were reported to SEER, 9% in AYA patients. In the AYA group, the highest age-adjusted incidence rate was for classical Hodgkin lymphoma [HL; 3·4 per 100 000 person-years; 95% confidence interval (CI), 3·38-3·49] followed by diffuse large B cell lymphoma (DLBCL; 1·56, 95% CI, 1·53-1·60) and for adults, it was plasma cell neoplasms (14·17, 95% CI, 14·07-14·27), DLBCL (13·86, 95% CI, 13·76-13·96) and chronic lymphocytic leukaemia (CLL; 13·19, 95% CI, 13·09-13·29). HL comprised 42% of lymphoma cases for AYAs, but only 4% in adults. The occurrence of DLBCL among AYAs and adults was similar, 18% and 20%, respectively. Twenty-eight percent of AYAs compared with 9% of adults presented with stage II disease, and 21% of AYAs compared with 10% of adults had B-symptoms. Extranodal disease was less common (33%) in AYAs than adults (59%). Overall, AYA patients with lymphoma have better 2- and 5-year relative survival rates (RSRs) compared to adults. When restricted to HL and DLBCL, RSR of AYA patients exceeds adult RSR.


Assuntos
Neoplasias Hematológicas/mortalidade , Transtornos Linfoproliferativos/mortalidade , Adolescente , Adulto , Fatores Etários , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Taxa de Sobrevida , Estados Unidos/epidemiologia , Adulto Jovem
8.
Transplantation ; 102(9): e382-e391, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29912047

RESUMO

BACKGROUND: Although risk factors for the long-term mortality of liver transplantation are well described, there is a lack of detailed study regarding these factors for adult living donor liver transplantation (LDLT). METHODS: We retrospectively analyzed 528 adult LDLT recipients in our hospital. The risk factors were analyzed for overall deaths more than 5 years post-LDLT. RESULTS: Over the 20-year follow-up, 137 patients died. Patient survival at 1, 3, 5, and 10 years post-LDLT was 87.8%, 81.8%, 79.4%, and 72.8%, respectively. The independent risk factors for more than 5 years post-LDLT overall death were hepatocellular carcinoma recurrence (hazard ratio [HR], 38.9; P < 0.001), lymphoid de novo malignancy (HR, 47.2; P = 0.001), primary sclerosing cholangitis as primary diagnosis (HR, 11.5; P < 0.001), chronic rejection (HR, 6.93; P = 0.006), acute rejection (HR, 2.96; P = 0.017), and bile duct stenosis (HR, 2.30; P = 0.045). CONCLUSIONS: Not only malignancies and rejection but also bile duct stenosis and primary sclerosing cholangitis had significant impacts on late period post-LDLT mortality.


Assuntos
Carcinoma Hepatocelular/cirurgia , Colangite Esclerosante/cirurgia , Doença Hepática Terminal/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/efeitos adversos , Doadores Vivos , Adolescente , Adulto , Idoso , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Colangite Esclerosante/diagnóstico , Colangite Esclerosante/mortalidade , Colestase/mortalidade , Doença Hepática Terminal/diagnóstico , Doença Hepática Terminal/mortalidade , Feminino , Rejeição de Enxerto/mortalidade , Sobrevivência de Enxerto , Humanos , Japão/epidemiologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Transplante de Fígado/métodos , Transplante de Fígado/mortalidade , Transtornos Linfoproliferativos/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
9.
Clin Transplant ; 32(8): e13313, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29888807

RESUMO

Post-transplant lymphoproliferative disease (PTLD) has the highest incidence following intestinal transplantation (ITx). Our center has seen a recent increase in PTLD. Our aim was to review a single-center PTLD experience with a focus on clinical characteristics and outcomes. We completed a retrospective review of biopsy-proven PTLD cases using a prospectively maintained database of 115 ITx recipients transplanted between 1991 and 2014. Nineteen (17%) ITx recipients developed 25 PTLD cases during a median follow-up time of 6.4 (1.6-14.6) years. The incidence of early PTLD was 6% (n = 7). There was a trend toward increased risk of PTLD in children compared with adults (P = .11) and a significantly increased risk of PTLD in re-ITx compared with primary ITx recipients (P = .03). Most PTLD cases were diagnosed between 2010 and 2014 (n = 14). All early PTLD cases were EBV+ on in situ hybridization. Overall graft and patient survival are 68% and 74%, respectively. Second episodes of PTLD were diagnosed in 43% of surviving pediatric patients. Our program has a low incidence of early PTLD with overall excellent graft and patient survival following diagnosis. However, we have also seen a rising incidence of late PTLD. The cause of the increase is unknown as no major changes in immunosuppression protocols have occurred since 1999.


Assuntos
Intestinos/transplante , Transtornos Linfoproliferativos/mortalidade , Transtornos Linfoproliferativos/patologia , Complicações Pós-Operatórias/mortalidade , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Transtornos Linfoproliferativos/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida
10.
Ann Hematol ; 97(9): 1601-1609, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29717367

RESUMO

The benefit of early admission of allogeneic stem cell transplantation (SCT) recipients to the intensive care unit (ICU) as soon as they develop organ injury is unknown. We performed a retrospective study on 92 patients admitted to the ICU to determine the impact of time from organ injury to ICU admission on outcome. The number of organ injuries prior to ICU admission was associated with an increased in-hospital mortality (OR 1.7, 95% CI 1-2.7, p = 0.04). Time between first organ injury and ICU admission was also associated with an increased in-hospital survival (OR 1.4, 95% CI 1.1-1.8, p = 0.02). A score combining these two covariates-the number of organ injuries/day (sum of days spent with each individual organ injury)-further improved the prediction of hospital survival. Patients with more organ injuries/day had significantly higher in-hospital mortality rate even after adjustment for refractory acute GVHD and the SOFA (OR 1.3, 95% CI 1-1.7, p = 0.02). Early ICU admission of allogeneic SCT recipients to the ICU as soon as they develop organ injury is associated with decreased in-hospital mortality.


Assuntos
Cuidados Críticos/estatística & dados numéricos , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hospitalização/estatística & dados numéricos , Tempo para o Tratamento , Adulto , Feminino , Doença Enxerto-Hospedeiro/diagnóstico , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/mortalidade , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Transtornos Linfoproliferativos/mortalidade , Transtornos Linfoproliferativos/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Tempo para o Tratamento/estatística & dados numéricos , Transplante Homólogo/efeitos adversos , Transplante Homólogo/mortalidade
11.
Mod Pathol ; 31(9): 1457-1469, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29765143

RESUMO

Ongoing development of new drugs, as well as novel indications in the treatment of autoimmune diseases leads to the increasing use of immunomodulatory and immunosuppressive drugs. Immunomodulatory agent-related lymphoproliferative disorders are a known and potentially life threatening complication of chronic administration of these drugs, but are less well characterized compared with post-transplant lymphoproliferative disorders. The heterogeneous drug targets, various underlying disease indications, different drug combinations used and relatively low incidence render data collection and interpretation difficult. In this retrospective paper, we describe the clinicopathological characteristics of a larger single-center series of 72 immunomodulatory agent-related lymphoproliferative disorder cases. We divided the cases according to the therapy, administered in the year preceding diagnosis of a lymphoproliferative disorder, in an immunosuppressive drug, an immunomodulatory drug and a combination of immunosuppressive and immunomodulatory drugs group. We observed differences in "time to lymphoproliferative disorder development" with a shorter time for all the immunomodulatory drug-related cases combined (immunomodulatory and immunomodulatory + immunosuppressive = immunomodulatory-all) vs immunosuppressive-only (p = 0.0031). The proportion of malignant cases in patients receiving immunomodulatory therapy was, however, also significantly lower when compared with the immunosuppressive treated cases (43 vs 88%; p = 0.0184). The immunomodulatory/suppressive agent-related lymphoproliferative disorders were less often associated with the Epstein-Barr virus (EBV) (31 vs 66%; p = 1.829e-05) and the lymphoproliferative disorders incidence in the first year after immunomodulatory/immunosuppressive therapy initiation was lower (18 vs 41%; p = 0.04151)-compared with a published series of 140 post-transplant lymphoproliferative disorder cases from the same center. However, a similar histopathological spectrum from nondestructive, to polymorphic and monomorphic lesions as in post-transplant lymphoproliferative disorders is observed. With increasing use of immunosuppressive and especially immunomodulatory therapy, a higher incidence of immunomodulatory/suppressive agent-related lymphoproliferative disorders is to be expected. Life-long awareness for development of immunomodulatory/suppressive agent-related lymphoproliferative disorders with clinical follow-up and timely biopsies of suspicious lesions is required since these lymphoproliferative disorders arise both early after therapy initiation and many years later. Histopathological confirmation and correct classification is necessary to guide therapy and EBV ISH should be a part of routine pathological diagnostics.


Assuntos
Imunossupressores/efeitos adversos , Transtornos Linfoproliferativos/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Transtornos Linfoproliferativos/induzido quimicamente , Transtornos Linfoproliferativos/mortalidade , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Adulto Jovem
12.
J Pediatr Hematol Oncol ; 40(6): 438-444, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29794643

RESUMO

Posttransplant lymphoproliferative disorder (PTLD) is a severe complication of solid organ transplantation. A common site for PTLD development is the gastrointestinal (GI) tract. The purpose of this study was to evaluate the incidence, clinical features, and overall survival of pediatric patients with GI-PTLD, and to assess whether major surgical interventions increased mortality. Records of pediatric transplant patients who developed GI-PTLD between January 2000 and June 2015 were retrospectively reviewed at our institution. Of 814 patients who received solid organ transplants, 34 (4%) developed GI-PTLD. Lung and multiorgan transplants had the highest incidence of GI-PTLD (both 11%). Patients often had multisite GI involvement (47%). Within the first year of transplantation, 38% of the 34 patients developed GI-PTLD. Of the patients with Epstein-Barr Virus-positive disease, 12/22 (55%) presented in the first 12 months of transplantation, compared with only 1/12 (8%) of the patients with Epstein-Barr Virus-negative disease (P=0.002). Major surgical interventions were required in 41% of patients; overall survival rate for these surgical patients was 71%, compared with 60% for patients not requiring major surgical interventions (P=0.49). Despite multimodal treatments, overall survival remains poor for patients with GI-PTLD; however, major surgical intervention did not significantly impact overall survival in this cohort.


Assuntos
Gastroenteropatias , Transtornos Linfoproliferativos , Transplante de Órgãos/efeitos adversos , Adolescente , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Seguimentos , Gastroenteropatias/etiologia , Gastroenteropatias/mortalidade , Gastroenteropatias/patologia , Humanos , Incidência , Lactente , Recém-Nascido , Transtornos Linfoproliferativos/etiologia , Transtornos Linfoproliferativos/mortalidade , Transtornos Linfoproliferativos/patologia , Masculino , Estudos Retrospectivos , Taxa de Sobrevida
13.
Br J Haematol ; 181(6): 752-759, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29676444

RESUMO

Primary cutaneous CD30+ T cell lymphoproliferative disorders (PCLPD), the second most common type of primary cutaneous T cell lymphomas, accounts for approximately 25-30% of cutaneous T-cell lymphoma cases. However, only small retrospective studies have been reported. We aimed to identify prognostic factors and evaluate the overall survival (OS) of patients with PCLPD stratified by ethnicity. We identified 1496 patients diagnosed with PCLPD between 2004 and 2014 in the US National Cancer Database. Chi-square test and anova were used to evaluate differences in demographic and disease characteristics, socioeconomic factors and treatments received. OS was evaluated with the log-rank test, Cox proportional hazard regression analysis, and propensity score matching. The study included 1267 Caucasians, 153 African Americans (AA), 43 Asians, and 33 of other/unknown ethnicity. Older age, higher Charlson-Deyo score, higher clinical stage and receipt of chemotherapy were predictors of shorter OS. Primary disease site on a lower extremity was associated with shorter OS, while a head and neck location was associated with longer OS. AA patients had shorter OS when compared to Caucasian patients on multivariate analysis. This ethnic disparity persisted on propensity-score matched analysis and after matching Caucasian and AA patients on demographic and disease characteristics, socioeconomic factors and treatments received, and age and gender-matched relative survival analyses.


Assuntos
Bases de Dados Factuais , Neoplasias de Cabeça e Pescoço , Transtornos Linfoproliferativos , Neoplasias Cutâneas , Adulto , Fatores Etários , Idoso , Intervalo Livre de Doença , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/etnologia , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Antígeno Ki-1 , Transtornos Linfoproliferativos/etnologia , Transtornos Linfoproliferativos/mortalidade , Transtornos Linfoproliferativos/terapia , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias , Estudos Retrospectivos , Fatores Sexuais , Neoplasias Cutâneas/etnologia , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/terapia , Fatores Socioeconômicos , Taxa de Sobrevida , Linfócitos T , Estados Unidos/epidemiologia , Estados Unidos/etnologia
14.
Cancer ; 124(11): 2327-2336, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29579330

RESUMO

BACKGROUND: Posttransplant lymphoproliferative disorder (PTLD) is a life-threatening complication of solid organ transplantation. Histologic heterogeneity and a lack of treatment standards have made evaluating clinical outcomes in specific patient populations difficult. This systematic literature review investigated the impact of the PTLD histologic subtype on survival in a large data set. METHODS: Case series were identified on PubMed with the search terms post-transplant lymphoproliferative disorder/disease, PTLD, and solid organ transplantation, with additional publications identified through reference lists. The patient characteristics, immunosuppressive regimen, treatment, survival, and follow-up time for 306 cases were extracted from 94 articles, and these cases were combined with 11 cases from Emory University Hospital. Patients with a recorded subtype were included in a Kaplan-Meier survival analysis (n = 234). Cox proportional hazards regression analyses identified predictors of overall survival (OS) for each subtype and B-cell subgroup. RESULTS: OS differed significantly between monomorphic T-cell neoplasms (median, 9 months) and polymorphic, monomorphic B-cell, and Hodgkin-type neoplasms, for which the median OS was not reached (P = .0001). Significant differences in OS among B subgroups were not detected, but there was a trend toward decreased survival for patients with Burkitt-type PTLD. Kidney transplantation and a reduction of immunosuppression were associated with increased OS for patients with B-cell neoplasms in a multivariate analysis. Immunosuppression with azathioprine was associated with decreased OS for patients with T-cell neoplasms, whereas radiotherapy was associated with improved OS for patients with that subtype. CONCLUSIONS: The histologic subtype represents an important prognostic factor in PTLD, with patients with T-cell neoplasms exhibiting very poor OS. Possibly lower survival for certain subsets of patients with B-cell PTLD should be explored further and suggests the need for subtype-specific therapies to improve outcomes. Cancer 2018;124:2327-36. © 2018 American Cancer Society.


Assuntos
Imunossupressão/efeitos adversos , Transtornos Linfoproliferativos/mortalidade , Transplante de Órgãos/efeitos adversos , Complicações Pós-Operatórias/mortalidade , Antineoplásicos Imunológicos/uso terapêutico , Quimiorradioterapia/métodos , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Humanos , Hospedeiro Imunocomprometido/efeitos dos fármacos , Hospedeiro Imunocomprometido/imunologia , Imunossupressão/métodos , Imunossupressores/efeitos adversos , Incidência , Estimativa de Kaplan-Meier , Transtornos Linfoproliferativos/imunologia , Transtornos Linfoproliferativos/terapia , Complicações Pós-Operatórias/etiologia , Intervalo Livre de Progressão , Fatores de Risco
15.
Eur J Haematol ; 100(1): 98-103, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29094407

RESUMO

OBJECTIVE: To evaluate response rates and survival in adults developing post-transplant lymphoproliferative disorder (PTLD) following liver transplantation. METHODS: Patients were identified retrospectively and data collected through local liver and haematology electronic databases and pharmacy records. RESULTS: Forty-five patients were identified. The median age at first transplant and at development of PTLD was 48 and 54 years, respectively, with the median time from transplant to PTLD diagnosis of 56 months. The majority of cases (76%) were monomorphic B-cell lymphomas, and 36% of tumours were EBV positive. Treatment involved reduction in immune-suppression (RIS) in 30 (67%) with RIS the only treatment in 3. Ten (22%) patients were treated with rituximab alone, 13 (29%) with chemotherapy alone and 14 (31%) patients were treated with rituximab and chemotherapy. Twenty-six (58%) patients achieved a complete response (CR). At a median follow-up of 27 months, the median overall survival (OS) was 50 months. Response and OS were not associated with clinical factors or the use of rituximab. CONCLUSION: Outcomes reported in this study are favourable and comparable to those reported previously. The addition of rituximab did not appear to have improved outcomes in this series, although a significant proportion of patients were able to avoid chemotherapy.


Assuntos
Transplante de Fígado/efeitos adversos , Transtornos Linfoproliferativos/epidemiologia , Transtornos Linfoproliferativos/etiologia , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Bases de Dados Factuais , Feminino , Humanos , Estimativa de Kaplan-Meier , Transtornos Linfoproliferativos/mortalidade , Transtornos Linfoproliferativos/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
16.
Scott Med J ; 63(1): 3-10, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29073846

RESUMO

Background Immunosuppression helps prevent acute rejection post-cardiac transplant but has been linked to malignancy development. This may be due to a reduction in T-lymphocyte function, a direct oncogenic effect or the increased impact of environmental carcinogens. There has been shown to be significant increases in non-melanoma skin cancers and post-transplant lympho-proliferative disorders, particularly in those treated with OKT3. Aim To investigate the survival and incidence of malignancy in the Scottish cardiac transplant population and whether rates of non-melanoma skin cancers justify the provision of specialist dermatological follow-up. Methods and results Retrospective case note analysis of patients transplanted (363) or followed up (2) in Scotland from 1992 to 2016. Kaplan-Meier survival analysis generated a survival curve. Patients had a 1-year survival of 82% and a median survival of 10.9 years. There were 60 (95% CI 47.5, 75.2) NMSCs and 8 (3.7, 12.4) post-transplant lympho-proliferative disorders diagnosed in the cohort (3110 person years follow-up). Fisher's exact test was employed to analyse the association between induction therapy (via OKT3 or rabbit antithymocyte globulin) and post-transplant lympho-proliferative disorder development. Patients treated with OKT3 had a 6.7 times greater risk ( P = 0.014) and a shorter experience of patients treated with rabbit antithymocyte globulin has so far shown no significantly altered risk ( P = 1.00) of developing a post-transplant lympho-proliferative disorder. Conclusion Incidences of non-melanoma skin cancers and post-transplant lympho-proliferative disorders were increased in the Scottish cardiac transplant population and there was a significant association between post-transplant lympho-proliferative disorder development and OKT3 therapy but not rabbit antithymocyte globulin therapy. These findings in Scottish patients reflect what is published in wider literature and support the provision of a dedicated post-transplant dermatology clinic.


Assuntos
Rejeição de Enxerto/prevenção & controle , Transplante de Coração , Imunossupressão , Imunossupressores/efeitos adversos , Transtornos Linfoproliferativos/induzido quimicamente , Neoplasias Cutâneas/induzido quimicamente , Seguimentos , Rejeição de Enxerto/imunologia , Humanos , Imunossupressão/efeitos adversos , Incidência , Estimativa de Kaplan-Meier , Transtornos Linfoproliferativos/imunologia , Transtornos Linfoproliferativos/mortalidade , Transtornos Linfoproliferativos/patologia , Complicações Pós-Operatórias/imunologia , Complicações Pós-Operatórias/mortalidade , Estudos Retrospectivos , Escócia/epidemiologia , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Linfócitos T/imunologia
17.
Haematologica ; 103(6): 1018-1028, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29242302

RESUMO

The characteristics of adult patients with chronic active Epstein-Barr virus infection are poorly recognized, hindering early diagnosis and an improved prognosis. We studied 54 patients with adult-onset chronic active Epstein-Barr virus infection diagnosed between 2005 and 2015. Adult onset was defined as an estimated age of onset of 15 years or older. To characterize the clinical features of these adults, we compared them to those of 75 pediatric cases (estimated age of onset <15 years). We compared the prognosis of adult-onset chronic active Epstein-Barr virus infection with that of patients with nasal-type (n=37) and non-nasal-type (n=45) extranodal NK/T-cell lymphoma. The median estimated age of onset of these lymphomas was 39 years (range, 16-86 years). Compared to patients with pediatric-onset disease, those in whom the chronic active Epstein-Barr virus infection developed in adulthood had a significantly decreased incidence of fever (P=0.005), but greater frequency of skin lesions (P<0.001). Moreover, hypersensitivity to mosquito bites and the occurrence of hydroa vacciniforme were less frequent in patients with adult-onset disease (P<0.001 and P=0.0238, respectively). Thrombocytopenia, high Epstein-Barr virus nuclear antigen antibody titer, and the presence of hemophagocytic syndrome were associated with a poor prognosis (P=0.0087, P=0.0236, and P=0.0149, respectively). Allogeneic hematopoietic stem cell transplantation may improve survival (P=0.0289). Compared to pediatric-onset chronic active Epstein-Barr virus infection and extranodal NK/T-cell lymphoma, adult-onset chronic active Epstein-Barr virus infection had a poorer prognosis (P<0.001 and P=0.0484, respectively). Chronic active Epstein-Barr virus infection can develop in a wide age range, with clinical differences between adult-onset and pediatric-onset disease. Adult-onset chronic active Epstein-Barr virus infection is a disease with a poor prognosis. Further research will be needed.


Assuntos
Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4/fisiologia , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/etiologia , Células T Matadoras Naturais/metabolismo , Células T Matadoras Naturais/virologia , Adolescente , Adulto , Fatores Etários , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Biópsia , Feminino , Humanos , Transtornos Linfoproliferativos/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida , Avaliação de Sintomas , Carga Viral , Adulto Jovem
18.
Br J Haematol ; 182(3): 429-433, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-28643365
19.
Leuk Lymphoma ; 59(5): 1172-1179, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-28831836

RESUMO

We studied retrospectively the outcome of Epstein-Barr virus (EBV)-related disease with EBV monitoring and preemptive rituximab to prevent post-transplant lymphoproliferative disorder (PTLD) in 319 consecutive allogeneic stem cell transplantations 2004-2012. Patients who received anti-thymocyte globulin (ATG) or alemtuzumab were regarded as high-risk for PTLD (n = 214). EBV DNAemia ≥1000 copies/mL plasma was observed in 50 (23%) of the high-risk patients. Thirty-three of the high-risk (15%) and one of the low-risk (1%) patients received rituximab, in combination with reduction of immunosuppression (n = 24) or chemotherapy (n = 4). Although rituximab was initiated only 5 d after first EBV load ≥1000 copies/mL, 85% of the rituximab-treated patients developed symptoms (lymphadenopathy 50%, fever 76%, and encephalitis/meningitis 12%). Response-rate to EBV treatment was 88%. Overall survival at 1- and 5-year was 71 and 52% for rituximab-treated patients, which was not inferior to all other patients post-transplant. In conclusion, rituximab therapy for EBV DNAemia does not affect long-term survival negatively.


Assuntos
DNA Viral/sangue , Infecções por Vírus Epstein-Barr/complicações , Transplante de Células-Tronco Hematopoéticas/mortalidade , Transtornos Linfoproliferativos/mortalidade , Rituximab/uso terapêutico , Viremia/mortalidade , Adolescente , Antineoplásicos Imunológicos/uso terapêutico , Criança , Pré-Escolar , Terapia Combinada , DNA Viral/genética , Infecções por Vírus Epstein-Barr/virologia , Feminino , Seguimentos , Herpesvirus Humano 4/isolamento & purificação , Humanos , Lactente , Transtornos Linfoproliferativos/etiologia , Transtornos Linfoproliferativos/terapia , Masculino , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Transplante Homólogo , Carga Viral , Viremia/etiologia , Viremia/terapia
20.
Rev Esp Enferm Dig ; 109(6): 406-413, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28508661

RESUMO

INTRODUCTION: Post-transplant lymphoproliferative syndrome (PTLD) is a rare and potentially life-threatening complication after liver transplantation. The aim of this study was to analyze the clinicopathologic features related to PTLD in a single institution after liver transplantation. METHODS: Observational study where we have retrospectively analyzed 851 cases who underwent liver transplantation. Ten cases have developed PTLD. Their clinical-pathological characteristics and the treatment received have been analyzed. RESULTS: PTLD incidence was 1.2% (10/851). The mean time from liver transplantation to PTLD diagnosis was 36 months (range 1.2 to 144 months). PTLD localization was extranodal in all cases, the most frequent location being intestinal. Seven cases showed a monomorphic lymphoma which in all cases was differentiated B cell lymphomas. Fifty per cent of the series were seropositive for Epstein-Barr virus. Five patients were alive at the time of the review. Among these patients, we observed three cases of complete remission and two cases of disease stabilization. The death rate was higher in the first year after diagnosis of PTLD. CONCLUSION: PTLD is a rare complication after liver transplantation, but it may pose a threat to the life of a liver transplant recipient. It is essential to identify patients at risk, to establish an early diagnosis and treatment that can change the outcome of the disease.


Assuntos
Transplante de Fígado/efeitos adversos , Transtornos Linfoproliferativos/etiologia , Transtornos Linfoproliferativos/terapia , Adulto , Idoso , Diagnóstico Precoce , Feminino , Humanos , Incidência , Transplante de Fígado/mortalidade , Transtornos Linfoproliferativos/mortalidade , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/terapia , Estudos Retrospectivos , Análise de Sobrevida
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