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1.
J Cancer Res Clin Oncol ; 145(11): 2779-2791, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31446489

RESUMO

PURPOSE: To evaluate serum procalcitonin (PCT) and C-reactive protein (CRP) as diagnostic biomarkers of transplant-related adverse events (TRAE) in pediatric patients undergoing hematopoietic stem cell transplantation (HSCT). METHODS: This study analyzed PCT and CRP levels of 214 pediatric patients with a median age of 8.5 years (0.4-17.8 years) undergoing allogeneic HSCT with respect to major TRAE. RESULTS: 26 patients (12.1%) did not experience TRAE (control group), and 188 (87.9%) experienced median 2 (range 1-4) TRAE. Median CRP and PCT were highly and significantly increased during sepsis/SIRS and bacteremia (17.24 mg/dl | 6.30 ng/ml; p < 0.0001 vs. prior values), graft rejection (14.73 mg/dl | 3.20 ng/ml; p < 0.0001), and liver GvHD (6.88 mg/dl | 2.29 ng/ml; p < 0.01). Strong CRP increases and slight/minimal/no PCT increases occurred during fungemia (8.85 mg/dl | 0.72 ng/ml; p < 0.001), intestinal GvHD (8.73 mg/dl | 1.06 ng/ml; p < 0.0001), VOD (10.84 mg/dl | 0.59 ng/ml; p < 0.01), mucositis (8.84 mg/dl | 0.81 ng/ml; p < 0.0001), and viremia (3.62 mg/dl; p < 0.0001 | 0.43 ng/ml; below normal limit). During skin GvHD, CRP and PCT were slightly increased (2.03 mg/dl | 0.93 ng/ml; p < 0.0001). CONCLUSIONS: CRP and PCT did not show congruent changes during TRAE. PCT was a clinically relevant marker for the early detection and differentiation of severe mucositis and sepsis/SIRS and bacteremia during the critical neutropenic period after HSCT. PCT helped to discriminate acute intestinal GvHD from adenovirus viremia and liver GvHD from hepatic VOD. Thus, PCT may be a valuable parameter to enable a prompt and appropriate treatment during these complications, improving patient outcomes.


Assuntos
Bacteriemia/diagnóstico , Proteína C-Reativa/análise , Rejeição de Enxerto/diagnóstico , Doença Enxerto-Hospedeiro/diagnóstico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Pró-Calcitonina/sangue , Sepse/diagnóstico , Adolescente , Bacteriemia/sangue , Bacteriemia/etiologia , Biomarcadores/sangue , Estudos de Casos e Controles , Criança , Pré-Escolar , Diagnóstico Precoce , Feminino , Seguimentos , Rejeição de Enxerto/sangue , Rejeição de Enxerto/etiologia , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/etiologia , Neoplasias Hematológicas/patologia , Neoplasias Hematológicas/terapia , Humanos , Lactente , Masculino , Prognóstico , Estudos Retrospectivos , Sepse/sangue , Sepse/etiologia , Transplante Homólogo
2.
Medicine (Baltimore) ; 98(29): e16390, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31335688

RESUMO

INTRODUCTION: Sjögren's syndrome (SS) often causes lymphoproliferative disorders such as malignant lymphoma and macroglobrinemia. Approximately 5% of long-term follow-up SS patients develop malignant lymphoma. Recently, the tumor necrosis factor receptor superfamily cluster of differentiation 30 (CD30) has been thought to be implicated in malignant cells in organs affected by Hodgikin lymphoma or in a prognostic marker of diffuse large B cell lymphoma. In this study, we investigated CD30 expression in lacrimal gland and conjunctiva in patients with SS. METHODS: We examined lacrimal gland and conjunctival tissues for the diagnosis from 3 female SS patients with a median age of 51 and 3 female chronic graft-versus-host disease (cGVHD) patients with a median age of 41. Histological analysis of these tissues of the remaining samples was conducted by methods including immunohistochemistry and electron microscopy (#20090277). We analyzed the expression and localization of cluster of differentiation 4 (CD4), cluster of differentiation 8 (CD8), cluster of differentiation 20 (CD20), CD30, and Interferon-γ in tissue sections prepared from lacrimal glands and conjunctiva in 3 each of SS and cGVHD patients. RESULTS: There were more B cells and plasma cells in lobules of SS-affected lacrimal glands than in those of their cGVHD-affected counterparts. Interferon-γ was expressed on endothelia of capillaries in SS-affected lacrimal gland and conjunctival tissues whereas it was expressed on fibroblasts in their GVHD-affected equivalents. Furthermore, lacrimal glands and conjunctiva disordered by SS had a greater number of CD30 cells than those disordered by cGVHD. CONCLUSION: Our results suggest that CD30 cells are increased in lacrimal glands and conjunctiva affected by SS and that a subset of SS patients are thereby at risk of development malignant lymphoma.


Assuntos
Túnica Conjuntiva , Doença Enxerto-Hospedeiro , Antígeno Ki-1 , Aparelho Lacrimal , Linfoma/diagnóstico , Síndrome de Sjogren , Adulto , Linfócitos B/imunologia , Túnica Conjuntiva/imunologia , Túnica Conjuntiva/patologia , Feminino , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/patologia , Humanos , Imuno-Histoquímica , Interferon gama/sangue , Antígeno Ki-1/análise , Antígeno Ki-1/imunologia , Aparelho Lacrimal/imunologia , Aparelho Lacrimal/patologia , Microscopia Eletrônica/métodos , Pessoa de Meia-Idade , Fragmentos de Peptídeos/sangue , Plasmócitos/imunologia , Prognóstico , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/imunologia , Síndrome de Sjogren/patologia
3.
Ann Hematol ; 98(8): 1877-1883, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31144019

RESUMO

Secondary poor graft function (sPGF) is defined as secondary cytopenia after initial engraftment of allogeneic stem cell transplantation (allo-SCT). It has been shown to be associated with poor prognosis; however, there are very few reports on the incidence, risk factors, and outcomes of sPGF. Between January 2015 and December 2015, 564 patients, who received transplantation at Peking University People's Hospital, were retrospectively reviewed. Among the 490 patients who achieved initial engraftment of both neutrophils and platelets, 28 patients developed sPGF. The cumulative incidence of sPGF on day 100 was 5.7%. The median time of sPGF was 54.5 (34-91) days after transplantation. Low (< median) CD34+ cell dose (p = 0.019, HR 3.07 (95% CI, 1.207-7.813)), Epstein-Barr Virus (EBV) reactivation (p = 0.009, HR 3.648 (95%CI, 1.382-9.629)), and cytomegalovirus (CMV) reactivation (p = 0.003, HR 7.827 (95%CI, 2.002-30.602)) were identified as independent risk factors for sPGF. There was no significant difference in PGF incidence between the matched sibling donor (MSD) group and haploidentical donor (HID) group (p = 0.44). The overall survival of patients with sPGF at 1 year after transplantation was significantly poorer than that of patients with good graft function (GGF) (50.5% versus 87.2%, p < 0.001). In conclusion, sPGF developed in 5.7% patients after allo-SCT, especially in patients with CMV, EBV reactivation, or infusion with a low dose of CD34+ cells. The prognosis of sPGF is still poor owing to a lack of standard treatment.


Assuntos
Infecções por Citomegalovirus/virologia , Infecções por Vírus Epstein-Barr/virologia , Doença Enxerto-Hospedeiro/virologia , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia/terapia , Síndromes Mielodisplásicas/terapia , Ativação Viral/imunologia , Adolescente , Adulto , Idoso , Antígenos CD34/imunologia , Criança , Pré-Escolar , Citomegalovirus/imunologia , Citomegalovirus/patogenicidade , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/mortalidade , Infecções por Citomegalovirus/patologia , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/mortalidade , Infecções por Vírus Epstein-Barr/patologia , Feminino , Sobrevivência de Enxerto/fisiologia , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/patologia , Transplante de Células-Tronco Hematopoéticas/mortalidade , Células-Tronco Hematopoéticas/imunologia , Células-Tronco Hematopoéticas/virologia , Herpesvirus Humano 4/imunologia , Herpesvirus Humano 4/patogenicidade , Humanos , Leucemia/mortalidade , Leucemia/patologia , Leucemia/virologia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/patologia , Síndromes Mielodisplásicas/virologia , Prognóstico , Estudos Prospectivos , Fatores de Risco , Análise de Sobrevida , Transplante Haploidêntico
4.
Clin Dermatol ; 37(2): 148-158, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30981295

RESUMO

We have explored the rash that appears as target lesions, with the central and dominant diseases belonging to the Stevens-Johnson syndrome/toxic epidermal necrolysis group. After presenting the clinical patterns of an individual target lesion and classifying them into different types of lesions, the contribution has been organized with groups characterized by such specific findings according to the type of lesion: flat or raised, typical or atypical, presence or absence of fever, presence or absence of mucosal ulcerations, presence or absence of arthralgias, and/or internal organ involvement. Other specific features, such as histologic appearance, immunofluorescence findings, and laboratory changes, are considered. We provide clinicians with an algorithmic, systematic, and logical approach to diagnose the condition of the patients who present with targetoid lesions, and enable them to differentiate between those with serious systemic and life-threatening diseases from others with ordinary skin ailments.


Assuntos
Eritema Multiforme/complicações , Eritema Multiforme/diagnóstico , Exantema/diagnóstico , Exantema/etiologia , Pele/patologia , Síndrome de Stevens-Johnson/complicações , Síndrome de Stevens-Johnson/diagnóstico , Artralgia , Diagnóstico Diferencial , Eritema Multiforme/patologia , Exantema/patologia , Feminino , Febre , Imunofluorescência , Doença Enxerto-Hospedeiro/complicações , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/patologia , Humanos , Masculino , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Síndrome de Linfonodos Mucocutâneos/patologia , Membrana Mucosa , Penfigoide Bolhoso/complicações , Penfigoide Bolhoso/diagnóstico , Penfigoide Bolhoso/patologia , Gravidez , Complicações na Gravidez , Choque Séptico/complicações , Choque Séptico/diagnóstico , Choque Séptico/patologia , Síndrome de Stevens-Johnson/patologia , Sífilis/complicações , Sífilis/diagnóstico , Sífilis/patologia , Úlcera , Urticária/complicações , Urticária/diagnóstico , Urticária/patologia
5.
Eur J Haematol ; 103(1): 10-17, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30958904

RESUMO

OBJECTIVES: This retrospective study analyzed the impact of early cyclosporine A (CsA) initiation (day -3) on the risk of acute graft-vs-host disease (aGvHD) after haploidentical hematopoietic cell transplantation (Haplo-HCT) using post-transplant cyclophosphamide. METHODS: Sixty-one consecutives patients who underwent Haplo-HCT were analyzed. RESULTS: At day +180, the cumulative incidences of grade II-IV and grade III-IV aGvHD were 39% and 18%, respectively. Patients having a lowest CsA concentration (<301 ng/mL; the cutoff value used to segregate the patients between low and high CsA concentrations) in the first week after Haplo-HCT had a significantly higher risk of grade II-IV aGvHD (P = 0.02), severe grade III-IV aGvHD (P = 0.03), cGvHD (P = 0.02), and extensive cGvHD (P = 0.04). In multivariate analysis, a higher CsA concentration (≥301 ng/mL) during the first week following Haplo-HCT was the only parameter significantly associated with a reduced risk of grade II-IV and grade III-IV aGvHD (RR = 0.21; P = 0.049 and RR < 0.001; P < 0.0001, respectively). We find no correlation between CsA concentration and relapse, non-relapse mortality, progression-free survival, GvHD-free and progression-free survival, or overall survival. CONCLUSIONS: CsA could be initiated early before Haplo-HCT with achievement of high CsA concentration to reduce the risk of aGvHD without any detrimental effect on relapse.


Assuntos
Ciclosporina/administração & dosagem , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Imunossupressores/administração & dosagem , Doença Aguda , Adolescente , Adulto , Idoso , Ciclofosfamida/administração & dosagem , Ciclosporina/farmacocinética , Monitoramento de Medicamentos , Feminino , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/epidemiologia , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/terapia , Humanos , Imunossupressores/farmacocinética , Incidência , Masculino , Pessoa de Meia-Idade , Recidiva , Fatores de Risco , Tempo para o Tratamento , Condicionamento Pré-Transplante , Transplante Haploidêntico , Resultado do Tratamento , Adulto Jovem
6.
Graefes Arch Clin Exp Ophthalmol ; 257(7): 1341-1351, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30944986

RESUMO

PURPOSE: Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cells transplantation, occurring in about half of transplanted patients. This condition seems to be the result of a progressive immune-mediated damage that can involve various tissues, including the eyes. The ocular surface system is the ocular structure most frequently impaired, and dry eye disease is considered the hallmark of ocular GVHD. Given the increasing prevalence and the frequent severe involvement of the ocular surface with vision-threatening complications, ocular GVHD represents a current diagnostic and therapeutic challenge. The purpose of this literature review is to describe all the clinical manifestations occurring in the setting of ocular GVHD, and to further report the outcomes of conventional and novel therapies. METHODS: A literature search about ocular GVHD was performed in PubMed, Scopus, Medline databases, and ClinicalTrials.gov as well as through the reference lists of identified publications until January 2019. We have included RCTs, prospective observational studies, prospective and retrospective cohort studies, pilot studies, and review articles. RESULTS: Overall, 107 articles, 3 book chapters, and 6 ongoing registered clinical trials were collected and analyzed. Ocular GVHD can affect all the structures of the entire ocular surface system, including lacrimal and meibomian glands, cornea, conjunctiva, eyelids, nasolacrimal duct, and tears. Current medical treatment is mainly focused on lubrication and control of drainage, tear evaporation, and ocular surface inflammation. Surgical treatment may be necessary in severe, recalcitrant, or complicated cases. Amniotic membrane and tectonic keratoplasty can be valid options to restore the integrity of the cornea. Recently, conjunctival and limbal transplantation from the same living-related bone marrow donor has been proposed to manage both dry eye and limbal stem cell deficiency, without any risk of immunologic rejection. CONCLUSION: This review provides an up-to-date analysis on clinical findings and current and future management of ocular GVHD. A correct and prompt diagnosis along with an appropriate and aggressive treatment are fundamental for avoiding the occurrence of vision-threatening complications.


Assuntos
Síndromes do Olho Seco/cirurgia , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Imunidade Celular , Túnica Conjuntiva/patologia , Córnea/patologia , Síndromes do Olho Seco/metabolismo , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/metabolismo , Humanos , Lágrimas/metabolismo
7.
J Stroke Cerebrovasc Dis ; 28(6): e73-e74, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30878370

RESUMO

After allogenic hematopoietic stem cell transplantation, cerebrovascular complications are uncommon, occurring in approximately 2%, and typically due to coagulopathy or infection. Graft versus host disease has been rarely reported to affect the central nervous system but these cases typically describe leukoencephalopathy, encephalitis, or perivascular infiltrates or vasculitis with subcortical ischemia or hemorrhage. We report a previously undescribed noninflammatory vasculopathy causing multifocal intracranial arterial occlusions and cerebral infarctions in a man following allogenic hematopoietic stem cell transplantation for chronic lymphocytic leukemia, which we propose to be a central nervous system manifestation of graft versus host disease.


Assuntos
Transtornos Cerebrovasculares/etiologia , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia Linfocítica Crônica de Células B/cirurgia , Biópsia , Transtornos Cerebrovasculares/diagnóstico , Progressão da Doença , Evolução Fatal , Doença Enxerto-Hospedeiro/diagnóstico , Humanos , Hiperplasia , Leucemia Linfocítica Crônica de Células B/diagnóstico , Masculino , Pessoa de Meia-Idade , Neointima , Transplante Homólogo/efeitos adversos
8.
Medicine (Baltimore) ; 98(8): e14474, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30813150

RESUMO

BACKGROUND: Numerous reports have explored the prognostic value of pretransplant serum C-reactive protein (CRP) in patients receiving allogeneic stem cell transplant (ASCT), but the results remain conflicting. Therefore, we performed a meta-analysis to comprehensively assess the prognostic value of pretransplant serum CRP in patients receiving ASCT. METHODS: We systematically searched eligible studies in PubMed, Embase, and Web of Science from 1999 to September 2018. The pooled hazard ratios (HRs) and their corresponding 95% CIs were used to synthetically assess the prognostic value of pre-ASCT CRP in terms of overall survival (OS), non-relapse mortality (NRM), and acute graft versus host disease (aGVHD). RESULTS: A total of 14 articles with 15 studies containing 3458 patients were included in this meta-analysis. The pooled results showed that high pre-ASCT CRP level was significantly related to worse OS (HR = 1.63; 95% CI: 1.34-1.98; P < .05), to an increased risk of NRM (HR = 2.06; 95% CI: 1.62-2.62; P < .05), and aGVHD (HR = 1.35; 95% CI: 1.07-1.71; P < .05). Additionally, sensitivity and subgroup analyses demonstrated that our pooled results were stable and reliable. CONCLUSIONS: High pre-ASCT serum CRP was significantly associated with worse OS, as well as higher risk of NRM and aGVHD. CRP may be a candidate factor of updating the existing risk scoring systems or establishing a novel risk scoring systems, which has the potential of guiding patient selection for ASCT and proceeding with risk-adapted therapeutic strategies. However, more high-quality clinical studies and basic research are required to further validate our findings in view of several limitations in our meta-analysis.


Assuntos
Biomarcadores/sangue , Proteína C-Reativa/análise , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/epidemiologia , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Prognóstico , Medição de Risco/métodos , Taxa de Sobrevida , Transplante Homólogo/efeitos adversos , Transplante Homólogo/mortalidade
10.
Clin Lab Med ; 39(1): 61-72, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30709509

RESUMO

Advances in the field of omics have led to a significant expansion in biomarkers identified for complications after hematopoietic stem cell transplantation (HSCT). Biomarkers can offer an effective method for early identification of a specific disease and can be used to guide therapies. Ongoing investigations to discover biomarkers for acute graft-versus-host disease as well as other post-HSCT complications may improve early diagnosis, prognosis, and the development of new therapeutic targets. The authors review the most recent and validated diagnostic, prognostic, predictive, and response to treatment biomarkers for early complications following HSCT consistent with 2014 NIH consensus on biomarker criteria.


Assuntos
Doença Enxerto-Hospedeiro/diagnóstico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hepatopatia Veno-Oclusiva/complicações , Pneumopatias/complicações , Biomarcadores/sangue , Doença Enxerto-Hospedeiro/imunologia , Hepatopatia Veno-Oclusiva/diagnóstico , Pneumopatias/diagnóstico , Prognóstico , Resultado do Tratamento
11.
Chest ; 155(1): e1-e4, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30616741

RESUMO

Bronchiolitis obliterans (BO) is a significant life-threatening complication that occurs after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and it is associated with increased morbidity and mortality. BO responds poorly to corticosteroids or immunosuppressants, and there are currently no established treatment approaches. We herein describe a patient with biopsy-proven BO after allo-HSCT who was successfully treated with tamibarotene, a novel synthetic retinobenzoic acid. Tamibarotene led to a dramatic improvement in lung function as well as cutaneous manifestations of chronic graft-vs-host disease. A large prospective clinical trial is therefore warranted to confirm the efficacy of tamibarotene in BO.


Assuntos
Benzoatos/uso terapêutico , Bronquiolite Obliterante/tratamento farmacológico , Doença Enxerto-Hospedeiro/complicações , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Tetra-Hidronaftalenos/uso terapêutico , Aloenxertos , Biópsia , Bronquiolite Obliterante/diagnóstico , Bronquiolite Obliterante/etiologia , Doença Crônica , Seguimentos , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Humanos , Leucemia Promielocítica Aguda/terapia , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
12.
J Am Acad Dermatol ; 80(3): 608-616, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30612984

RESUMO

BACKGROUND: Severe cutaneous adverse reactions (SCARs) are frequent in inpatient oncology. Early intervention might reduce morbidity, mortality, and hospitalization costs; however, current clinical and histologic features are unreliable SCAR predictors. There is a need to identify rational markers of SCARs that could lead to effective therapeutic interventions. OBJECTIVE: To characterize the clinical and serologic features of hospitalized patients with cancer who developed SCARs. METHODS: Retrospective review of 49 hospitalized cancer patients with a morbilliform rash, recorded testing for serum cytokines (interleukin [IL] 6, IL-10, and tumor necrosis factor [TNF] α) or elafin, and a prior dermatology consultation. Patients were categorized as having a simple morbilliform rash without systemic involvement or complex morbilliform rash with systemic involvement. RESULTS: Fifteen out of 49 patients (30.6%) were deceased at 6 months from time of dermatologic consultation. Elafin, IL-6, and TNF-α were significantly higher in patients who died compared with patients who were still alive at 6 months. IL-6 and IL-10 were significantly higher in patients with a drug-related complex rash. LIMITATIONS: Retrospective design, limited sample size, and high-risk patient population. CONCLUSION: In cancer patients with SCARs, elafin, IL-6, and TNF-α levels might predict a poor outcome. Agents directed against these targets might represent rational treatments for the prevention of fatal SCARs.


Assuntos
Citocinas/sangue , Síndrome de Hipersensibilidade a Medicamentos/sangue , Elafina/sangue , Mortalidade Hospitalar , Neoplasias/tratamento farmacológico , Síndrome de Stevens-Johnson/sangue , Adulto , Antineoplásicos/efeitos adversos , Biomarcadores/sangue , Superfície Corporal , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Edema/etiologia , Eosinofilia/etiologia , Face , Feminino , Febre/etiologia , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/diagnóstico , Hospitalização , Humanos , Interleucina-10/sangue , Interleucina-6/sangue , Linfócitos/patologia , Masculino , Púrpura/etiologia , Estudos Retrospectivos , Síndrome de Stevens-Johnson/etiologia , Fator de Necrose Tumoral alfa/sangue
13.
Pediatr Transplant ; 23(2): e13350, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30672115

RESUMO

GVHD as a complication of SOT presents both a diagnostic and therapeutic challenge. Typically affecting the skin, gastrointestinal tract, and liver, GVHD occurs when donor lymphocytes engrafted in recipient tissues are activated by host antigen-presenting cells resulting in cytokine release and donor cell-mediated cytotoxicity to host tissue. Here, we describe a 5-year-old girl who developed fatal, refractory GVHD after isolated intestinal transplantation when recipient immune cells failed to repopulate the allograft in the setting of CMV viremia. Persistence of the donor immune cells in the allograft mucosa, rather than engraftment in the recipient bone marrow, likely perpetuated this refractory GVHD. Early diagnosis and intervention are critical to reduce morbidity and mortality. Thus, periodic monitoring of peripheral blood and allograft mucosal chimerism with sensitive detection methods may allow early detection and potentially curative enterectomy in similar cases of refractory GVHD.


Assuntos
Doença Enxerto-Hospedeiro/imunologia , Mucosa Intestinal/imunologia , Intestinos/transplante , Síndrome do Intestino Curto/cirurgia , Medula Óssea/imunologia , Pré-Escolar , Quimerismo , Evolução Fatal , Feminino , Doença Enxerto-Hospedeiro/diagnóstico , Humanos , Mucosa Intestinal/transplante , Intestinos/imunologia , Masculino , Doadores de Tecidos
14.
Blood Cells Mol Dis ; 74: 5-12, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30344086

RESUMO

Predictive biomarkers for acute graft-versus-host disease (aGVHD) is currently lacking. In this study, we employed an unbiased proteome profiling method to prospectively collected plasma samples from allogeneic hematopoietic stem cell transplantation (alloHSCT) recipients to identify protein biomarkers that predict the risk of aGVHD and non-relapse mortality (NRM). In the discovery set, including five aGVHD patients and five controls, we identified seven candidate proteins. Patients with high levels of these proteins tended to exhibit a higher risk of aGVHD and NRM compared to patients with low levels in post-engraftment plasma samples from an independent validation set (n = 89). Tissue inhibitor of metalloproteinase 1, plastin-2, and regenerating islet-derived protein 3-α were selected as the most-predictive biomarkers via an exhaustive variable screening algorithm and were collectively used to develop a biomarker panel score ranging from 0 to 3. The biomarker panel score correlated significantly with aGVHD and NRM risk in univariable and multivariable Cox models. Furthermore, using the biomarker panel score in conjunction with clinical predictors significantly improved the discriminatory performance of the Cox model in predicting aGVHD and NRM risk. Our findings suggest that plasma-derived protein biomarkers can be used to predict aGVHD and NRM before the onset of clinical manifestations.


Assuntos
Biomarcadores/sangue , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/mortalidade , Doença Aguda , Adulto , Estudos de Casos e Controles , Doença Enxerto-Hospedeiro/diagnóstico , Humanos , Glicoproteínas de Membrana/sangue , Proteínas dos Microfilamentos/sangue , Proteínas/análise , Proteômica , Risco , Inibidor Tecidual de Metaloproteinase-1/sangue , Transplante Homólogo
15.
Front Immunol ; 9: 2853, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30574143

RESUMO

Graft-vs.-host disease (GVHD) remains a major obstacle to the success of allogeneic hematopoietic stem cell transplantation (HSCT). GVHD occurs because donor T cells in the allograft recognize the genetically disparate host as foreign and attack the transplant recipient's tissues. While genetic incompatibility between donor and recipient is the primary determinant for the extent of alloimmune response, GVHD incidence and severity are also influenced by non-genetic factors. Recent advances in immunology establish that environmental factors, including dietary micronutrients, contribute significantly to modulating various immune responses and may influence the susceptibility to autoimmune and inflammatory diseases of experimental animals and humans. Emerging clinical and preclinical evidence indicates that certain micronutrients may participate in regulating GVHD risk after allogeneic HSCT. In this review, we summarize recent advances in our understanding with respect to the potential role of micronutrients in the pathogenesis of acute and chronic GVHD, focusing on vitamins A and D.


Assuntos
Doença Enxerto-Hospedeiro/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Micronutrientes/administração & dosagem , Linfócitos T/efeitos dos fármacos , Vitamina A/administração & dosagem , Vitamina D/administração & dosagem , Animais , Movimento Celular/efeitos dos fármacos , Movimento Celular/imunologia , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Incidência , Micronutrientes/efeitos adversos , Estado Nutricional/imunologia , Índice de Gravidade de Doença , Linfócitos T/imunologia , Transplante Homólogo/efeitos adversos , Vitamina A/efeitos adversos , Vitamina D/efeitos adversos
16.
BMJ Case Rep ; 11(1)2018 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-30567271

RESUMO

A 24-year-old man with previous matched unrelated donor allogenic bone marrow transplant for aplastic anaemia and chronic graft versus host disease on steroid taper presented with progressively worsening anasarca. CT revealed large pericardial effusion, while echocardiogram was concerning for early tamponade physiology. He underwent emergent pericardiocentesis with pericardial drain placement. Extensive rheumatological and infectious work-up was unrevealing with patient's presentation attributed to pericardial graft versus host disease. This highlights the need of physicians to be aware of pericardial serositis as a complication of graft versus host disease due to its life-threatening complications, which require immediate intervention.


Assuntos
Anemia Aplástica/terapia , Transplante de Medula Óssea/efeitos adversos , Tamponamento Cardíaco/diagnóstico , Edema/etiologia , Doença Enxerto-Hospedeiro/diagnóstico , Derrame Pericárdico/diagnóstico , Pericardiocentese/métodos , Anti-Inflamatórios/uso terapêutico , Tamponamento Cardíaco/fisiopatologia , Tamponamento Cardíaco/terapia , Ecocardiografia , Edema/fisiopatologia , Edema/terapia , Doença Enxerto-Hospedeiro/fisiopatologia , Doença Enxerto-Hospedeiro/terapia , Humanos , Masculino , Metilprednisolona/uso terapêutico , Derrame Pericárdico/etiologia , Derrame Pericárdico/fisiopatologia , Derrame Pericárdico/terapia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto Jovem
17.
Transplant Proc ; 50(10): 4028-4032, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30577308

RESUMO

Acute graft-vs-host disease (aGVHD) is a rare but deadly complication after liver transplantation (LT). It occurs when donor immunocompetent cells transplanted with the liver allograft repopulate and recognize recipient antigens as foreign and mount an alloreactive response. aGVHD patients can present with skin rash, fever, diarrhea, and pancytopenia. These nonspecific symptoms are usually misleading, delaying the diagnosis of aGVHD. Here, we present a patient who developed severe aGVHD after LT, with neurogenic symptoms as the first manifestation. Symptoms including fever, skin rash, diarrhea, and pancytopenia appeared several days later. A skin biopsy revealed dermal lymphocyte infiltration. A bone marrow chimerism test showed 99.87% liver donor cells. The patient was treated with high doses of methylprednisolone (360 mg a day), Rabbit anti-T lymphocyte immunoglobulin (300 mg per day), and antithymocyte globulin (40 mg per day). Unfortunately, the patient died of multiple organ failure at 47 days after transplantation. To our knowledge, this is the first case of aGVHD after LT with neurogenic symptoms as the single primary manifestation and also with the highest level of donor cells (>99%) in bone marrow chimerism test ever reported.


Assuntos
Confusão/etiologia , Doença Enxerto-Hospedeiro/complicações , Doença Enxerto-Hospedeiro/diagnóstico , Transplante de Fígado/efeitos adversos , Tremor/etiologia , Doença Aguda , Evolução Fatal , Humanos , Masculino , Pessoa de Meia-Idade
18.
J Med Case Rep ; 12(1): 368, 2018 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-30545408

RESUMO

INTRODUCTION: Acquired partial lipoatrophy has been reported after bone marrow transplantation during childhood; however, no adult cases have previously been reported. We herein report two adult cases of acquired partial lipoatrophy after transplantation. CASE PRESENTATION: A 28-year-old Japanese woman developed diabetic ketoacidosis and received insulin therapy after bone marrow transplantation. She manifested partial lipoatrophy of the extremities, prominent insulin resistance, hyperglycemia, hypertriglyceridemia, and fatty liver. A 40-year-old Japanese woman underwent liver transplantation from a living donor for alcoholic liver disease after abstinence from alcohol. She newly developed non-alcoholic steatohepatitis and diabetes. Non-alcoholic steatohepatitis progressed to liver failure, and a second liver transplantation from a brain-dead donor was performed at 42 years of age. She demonstrated loss of subdermal fat of the upper and lower extremities, prominent insulin resistance, hyperglycemia, and hypertriglyceridemia. In both cases, the injection of recombinant methionyl human leptin reversed all of the metabolic abnormalities. CONCLUSIONS: Acquired partial lipoatrophy after transplantation is a manifestation of chronic graft-versus-host disease in adults. This entity is associated with diabetes with prominent insulin resistance and severe hypertriglycemia and can be successfully treated with metreleptin for the long term.


Assuntos
Doença Enxerto-Hospedeiro/complicações , Doença Enxerto-Hospedeiro/terapia , Leptina/análogos & derivados , Lipodistrofia/etiologia , Lipodistrofia/terapia , Adulto , Feminino , Doença Enxerto-Hospedeiro/diagnóstico , Humanos , Leptina/uso terapêutico , Lipodistrofia/diagnóstico , Resultado do Tratamento
19.
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
20.
Gastroenterol Clin North Am ; 47(2): 355-368, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29735029

RESUMO

Pediatric intestinal transplantation has moved from the theoretic to an actual therapy for children with irreversible intestinal failure who are suffering from complications of total parenteral nutrition. Owing to significant advancement in the management of intestinal failure and prevention of parenteral nutrition-related complications that have led to reduction in incidence of parenteral nutrition-associated liver disease and have improved intestinal adaptation, the indications for intestinal transplantation are evolving. Long-term outcomes have improved, but challenges in long-term graft function owing to chronic rejection and immunosuppressant-related complications remain the major opportunities for improvement.


Assuntos
Aloenxertos Compostos , Enteropatias/cirurgia , Intestinos/transplante , Transplante de Órgãos/métodos , Cuidados Pós-Operatórios , Adolescente , Criança , Pré-Escolar , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Humanos , Imunossupressão , Lactente , Recém-Nascido , Infecção/tratamento farmacológico , Infecção/etiologia , Intestinos/fisiopatologia , Transplante de Fígado , Doadores Vivos , Transplante de Órgãos/efeitos adversos , Transplante de Pâncreas , Seleção de Pacientes , Estômago/transplante , Taxa de Sobrevida , Coleta de Tecidos e Órgãos/métodos
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