RESUMEN
BACKGROUND: Granulomatous mycosis fungoides (GMF) is a rare form of cutaneous T-cell lymphoma characterized by a granulomatous inflammatory infiltrate. OBJECTIVE: The impact of granulomatous inflammation on the prognosis of the disease remains controversial as there have been both favorable and unfavorable outcomes documented. METHODS: We performed a systematic review of 116 GMF cases previously described in the literature. RESULTS: In contrast to the classic Alibert-Bazin type of mycosis fungoides (MF), cutaneous lesions in GMF tend to involve distal extremities (lower legs, feet, hands) early in the disease course. In the literature, 30% of GMF patients developed organ metastasis, most frequently to the lung. The median time to stage progression was 25 months. CONCLUSION: GMF is an aggressive form of MF. Therefore, screening for distant metastases should be considered at presentation and repeated during follow-up.
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Micosis Fungoide , Neoplasias Cutáneas , Humanos , Micosis Fungoide/patología , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/secundario , Neoplasias Pulmonares/patología , Pronóstico , Progresión de la EnfermedadAsunto(s)
Linfoma de Células del Manto , Receptores Quiméricos de Antígenos , Adulto , Humanos , Linfoma de Células del Manto/tratamiento farmacológico , Linfoma de Células del Manto/patología , Clorhidrato de Bendamustina/uso terapéutico , Receptores Quiméricos de Antígenos/uso terapéutico , Estudios de Factibilidad , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Tratamiento Basado en Trasplante de Células y TejidosRESUMEN
Malnutrition and poor health are common among recently resettled refugees and may be differentially associated with pre-migration exposure to refugee camp versus non-camp dwelling. We aimed to investigate the associations of iron deficiency (ID), anemia, and ID anemia (IDA) with pre-migration refugee camp exposure among recently arrived refugees to Canada. To this end, we conducted a retrospective cohort study of 1032 adult refugees who received care between January 1, 2011, and December 31, 2015, within a specialized refugee health clinic in Calgary, Canada. We evaluated the prevalence, severity, and predictors of ID, anemia, and IDA, stratified by sex. Using multivariable logistic regression, we estimated the association of refugee camp exposure with these outcomes, adjusting for age, months in Canada prior to investigations, global region of origin, and parity. Among female refugees, the prevalence of ID, anemia, and IDA was 25% (134/534), 21% (110/534), and 14% (76/534), respectively; among males, 0.8% (4/494), 1.8% (9/494), and 0% (0/494), respectively. Anemia was mild, moderate, and severe in 55% (60/110), 44% (48/110) and 1.8% (2/110) of anemic females. Refugee camp exposure was not associated with ID, anemia, or IDA while age by year (ID OR = 0.96, 95% CI 0.93-0.98; anemia OR = 0.98, 95% CI 0.96-1.00; IDA OR = 0.96, 95% CI 0.94-0.99) and months in Canada prior to investigations (ID OR = 0.85, 95% CI 0.72-1.01; anemia OR = 0.81, 95% CI 0.67-0.97; IDA OR = 0.80, 95% CI 0.64-1.00) were inversely correlated with these outcomes. ID, anemia, and IDA are common among recently arrived refugee women irrespective of refugee camp exposure. Our findings suggest these outcomes likely improve after resettlement; however, given proportionally few refugees are resettled globally, likely millions of refugee women and girls are affected.
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Anemia Ferropénica , Deficiencias de Hierro , Refugiados , Masculino , Adulto , Humanos , Femenino , Campos de Refugiados , Estudios Retrospectivos , Canadá/epidemiología , Anemia Ferropénica/epidemiologíaRESUMEN
B-cell non-Hodgkin lymphoma (B-NHL) encompasses multiple clinically and phenotypically distinct subtypes of malignancy with unique molecular etiologies. Common subtypes of B-NHL, such as diffuse large B-cell lymphoma, have been comprehensively interrogated at the genomic level, but rarer subtypes, such as mantle cell lymphoma, remain less extensively characterized. Furthermore, multiple B-NHL subtypes have thus far not been comprehensively compared using the same methodology to identify conserved or subtype-specific patterns of genomic alterations. Here, we employed a large targeted hybrid-capture sequencing approach encompassing 380 genes to interrogate the genomic landscapes of 685 B-NHL tumors at high depth, including diffuse large B-cell lymphoma, mantle cell lymphoma, follicular lymphoma, and Burkitt lymphoma. We identified conserved hallmarks of B-NHL that were deregulated in the majority of tumors from each subtype, including frequent genetic deregulation of the ubiquitin proteasome system. In addition, we identified subtype-specific patterns of genetic alterations, including clusters of co-occurring mutations and DNA copy number alterations. The cumulative burden of mutations within a single cluster were more discriminatory of B-NHL subtypes than individual mutations, implicating likely patterns of genetic cooperation that contribute to disease etiology. We therefore provide the first cross-sectional analysis of mutations and DNA copy number alterations across major B-NHL subtypes and a framework of co-occurring genetic alterations that deregulate genetic hallmarks and likely cooperate in lymphomagenesis.
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Linfoma de Burkitt , Linfoma Folicular , Linfoma de Células B Grandes Difuso , Adulto , Estudios Transversales , Humanos , Linfoma Folicular/genética , MutaciónRESUMEN
Background: Patients with monoclonal gammopathy of undetermined significance (MGUS) have clinical features including older age, presence of medical comorbidities, susceptibility to infections, and thrombotic tendencies which are relevant when assessing their risk during the coronavirus disease (COVID-19) pandemic. Objective: To study the vulnerability of patients with MGUS during the COVID-19 pandemic, we assessed the local management of MGUS patients and their clinical outcomes. Methods: Retrospective chart reviews were performed for all patients with MGUS seen at a university medical center clinic (2014-2020). Results: A total of 228 MGUS patients were included; 211 patients are alive, 7 patients died before the pandemic, and 10 patients died since the pandemic declaration. The mean age and the overall survival (OS) of the patients who died before versus during the pandemic were 83.0 versus 75.2 years, p = 0.4, and OS 40.6 versus 53.2 months, p = 0.3, respectively. One patient died of COVID-19. Nine patients had venous thromboembolisms (VTE), all of which occurred before the pandemic onset. Conclusions: There were no significant differences found in the mean age or OS of the MGUS patients who died before versus after the pandemic onset. An increase in VTE rates was not seen. Study results are limited by small patient numbers.
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Humanos , Masculino , Femenino , Anciano , Anciano de 80 o más Años , Gammopatía Monoclonal de Relevancia Indeterminada/terapia , Tromboembolia Venosa/epidemiología , COVID-19 , Gammopatía Monoclonal de Relevancia Indeterminada/mortalidad , Gammopatía Monoclonal de Relevancia Indeterminada/epidemiología , Tasa de Supervivencia , Estudios Retrospectivos , Factores de Edad , Poblaciones Vulnerables , Centros Médicos Académicos , Tromboembolia Venosa/etiologíaRESUMEN
BACKGROUND: Patients with monoclonal gammopathy of undetermined significance (MGUS) have clinical features including older age, presence of medical comorbidities, susceptibility to infections, and thrombotic tendencies which are relevant when assessing their risk during the coronavirus disease (COVID-19) pandemic. OBJECTIVE: To study the vulnerability of patients with MGUS during the COVID-19 pandemic, we assessed the local management of MGUS patients and their clinical outcomes. METHODS: Retrospective chart reviews were performed for all patients with MGUS seen at a university medical center clinic (2014-2020). RESULTS: A total of 228 MGUS patients were included; 211 patients are alive, 7 patients died before the pandemic, and 10 patients died since the pandemic declaration. The mean age and the overall survival (OS) of the patients who died before versus during the pandemic were 83.0 versus 75.2 years, p = 0.4, and OS 40.6 versus 53.2 months, p = 0.3, respectively. One patient died of COVID-19. Nine patients had venous thromboembolisms (VTE), all of which occurred before the pandemic onset. CONCLUSIONS: There were no significant differences found in the mean age or OS of the MGUS patients who died before versus after the pandemic onset. An increase in VTE rates was not seen. Study results are limited by small patient numbers.
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COVID-19 , Gammopatía Monoclonal de Relevancia Indeterminada/terapia , Tromboembolia Venosa/epidemiología , Centros Médicos Académicos , Factores de Edad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Gammopatía Monoclonal de Relevancia Indeterminada/epidemiología , Gammopatía Monoclonal de Relevancia Indeterminada/mortalidad , Estudios Retrospectivos , Tasa de Supervivencia , Tromboembolia Venosa/etiología , Poblaciones VulnerablesAsunto(s)
Linfoma Cutáneo de Células T , Papulosis Linfomatoide , Neoplasias Cutáneas , Linfocitos T CD8-positivos/patología , Humanos , Linfoma Cutáneo de Células T/diagnóstico , Linfoma Cutáneo de Células T/etiología , Linfoma Cutáneo de Células T/patología , Papulosis Linfomatoide/complicaciones , Papulosis Linfomatoide/diagnóstico , Papulosis Linfomatoide/patología , Masculino , Persona de Mediana Edad , Piel/patología , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/patologíaRESUMEN
BACKGROUND: Molecular heterogeneity accounts for the variable and often poor prognosis in acute myeloid leukemia (AML). The current risk stratification strategy in clinical practice is limited to karyotyping and limited molecular studies screening for genetic mutations such as FLT-3 and NPM1. There is opportunity to identify further molecular prognostic markers, which may also lay the groundwork for the development of novel targeted therapies. Complex molecular technologies require transition into widely available laboratory platforms, for better integration into routine clinical practice. METHOD: In a defined subset (MYC/BCL2 or MYC/BCL2) of AML patients (n=20), we examined expression signature of several genes (n=12) of established prognostic value in AML. RNA expression and MYC/BCL2 protein pattern was correlated with 3 cytogenetic risk groups and overall survival. RESULTS: K-means++ unsupervised clustering defined 2 distinct groups with high and low transcript levels of BAALC/MN1/MLLT11/EVI1/SOCS2 genes (>2.5-fold difference; P<0.001). This mRNA signature trended with higher prevalence of MYC/BCL2 coexpression (P<0.057) and poor overall survival (P<0.036), but did not correlate with conventional cytogenetic risk groups (P<0.084). CONCLUSIONS: This pilot study provides useful data, which may help further refine the prognostic scheme of AML patients outside conventional cytogenetic risk groups. It also presents some biological rationale for future studies to explore the use of novel agents targeting MYC and/or BCL2 genes in combination with conventional chemotherapy protocols for AML.
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Regulación Leucémica de la Expresión Génica , Leucemia Mieloide Aguda , Proteína del Locus del Complejo MDS1 y EV11/biosíntesis , Familia de Multigenes , Proteínas de Neoplasias/biosíntesis , Proteínas Proto-Oncogénicas c-myc/biosíntesis , Proteínas Proto-Oncogénicas/biosíntesis , Proteínas Supresoras de Tumor/biosíntesis , Regulación hacia Arriba , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/patología , Masculino , Persona de Mediana Edad , Nucleofosmina , Proteínas Proto-Oncogénicas c-bcl-2 , Tasa de Supervivencia , TransactivadoresRESUMEN
Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction, characterized by fatigable weakness of the extraocular, bulbar, and limb musculature; prevalence is estimated at 14 to 32 per 100,000 in North America. Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in adults, resulting from clonal expansion of B-cells in blood, marrow, and secondary lymphoid tissues. The simultaneous presentation of MG and CLL is exceedingly rare. This article presents the case of 71-year-old man diagnosed simultaneously with MG and CLL. His MG was severe and refractory to treatment; therefore, a strategy of treating his coexisting CLL with obinutuzumab and chlorambucil was pursued. Following 6 cycles of obinutuzumab and chlorambucil, his CLL is in remission and his MG is almost entirely undetectable. This is the first case report describing the use of obinutuzumab, a novel anti-CD20 monoclonal antibody, in a patient with concurrent MG and CLL.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Miastenia Gravis/tratamiento farmacológico , Anciano , Anticuerpos Monoclonales Humanizados/administración & dosificación , Clorambucilo/administración & dosificación , Humanos , Leucemia Linfocítica Crónica de Células B/complicaciones , Masculino , Miastenia Gravis/complicaciones , Inducción de Remisión/métodosRESUMEN
Mantle cell lymphoma (MCL) is an aggressive disease with frequent relapse. Targeted therapies against B-cell receptor (BCR) molecules have demonstrated improved outcomes in relapsed cases. However, clinical responses are slow and selective, with failure to attain complete remission in a significant subset of patients. Complex interaction of BCR signal transduction with toll-like receptor (TLR) and other pathways in MCL remains unknown, thus averting progress in development of targeted therapies. We have performed detailed digital quantification of BCR/TLR signalling molecules and their effector pathways in a cohort (n = 81) of MCL patients and correlated these data with overall survival. Hierarchical clustering model based on BCR/TLR genes revealed two distinct (BCRhigh and BCRlow ) subsets of patients (n = 32; 40%) with significant differences in expression (>1.5-fold change; p < 0.05). Higher levels of BTK/SYK/BLNK/CARD11/PLCG signalosome and lower expression of MALT1/BCL10 genes suggested tonic pattern of BCR activation. Amplified expression of TLR6/TLR7/TLR9 was noted in concert with hyper-responsiveness of BCR machinery. MYD88, a key TLR adaptor molecule, was not upregulated in any of these clusters, which may suggest a 'cross-talk' between BCR and TLR pathways. In sync with BCR/TLR signalling, we recorded significantly enhanced expression of genes associated with NF-kB pathway in BCRhigh subset of MCL patients. On univariate analysis, the BCRhigh patients showed a trend towards inferior clinical response to a standardized treatment protocol, compared with the BCRlow group (log rank, p = 0.043). In conclusion, we have identified hyperactive BCR/TLR signalling pathways and their effector downstream targets in a subset of MCL patients and associated it with poor clinical outcomes. Our study provides quantitative evidence at RNA expression level of possible concomitant collaboration between TLR and BCR signalling molecules in MCL. These data will provide further insights for future functional studies and, hence, development of targeted therapies for MCL patients. Copyright © 2015 John Wiley & Sons, Ltd.
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Linfocitos B/metabolismo , Regulación Neoplásica de la Expresión Génica , Linfoma de Células del Manto/metabolismo , Receptores de Antígenos de Linfocitos B/metabolismo , Receptores Toll-Like/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Análisis por Conglomerados , Estudios de Cohortes , Biología Computacional , Femenino , Perfilación de la Expresión Génica , Humanos , Linfoma de Células del Manto/mortalidad , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Inducción de Remisión , Transducción de Señal , Resultado del Tratamiento , Regulación hacia ArribaRESUMEN
Acute myeloid leukaemia (AML) is a clinically aggressive disease with marked genetic heterogeneity. Cytogenetic abnormalities provide the basis for risk stratification into clinically favourable, intermediate, and unfavourable groups. There are additional genetic mutations, which further influence the prognosis of patients with AML. Most of these result in molecular aberrations whose downstream target is MYC. It is therefore logical to study the relationship between MYC protein expression and cytogenetic risk groups. We studied MYC expression by immunohistochemistry in a large cohort (n = 199) of AML patients and correlated these results with cytogenetic risk profile and overall survival (OS). We illustrated differential expression of MYC protein across various cytogenetic risk groups (p = 0.03). Highest expression of MYC was noted in AML patients with favourable cytogenetic risk group. In univariate analysis, MYC expression showed significant negative influence of OS in favourable and intermediate cytogenetic risk group (p = 0.001). Interestingly, MYC expression had a protective effect in the unfavourable cytogenetic risk group. In multivariate analysis, while age and cytogenetic risk group were significant factors influencing survival, MYC expression by immunohistochemistry methods also showed some marginal impact (p = 0.069). In conclusion, we have identified differential expression of MYC protein in relation to cytogenetic risk groups in AML patients and documented its possible impact on OS in favourable and intermediate cytogenetic risk groups. These preliminary observations mandate additional studies to further investigate the routine clinical use of MYC protein expression in AML risk stratification. Copyright © 2016 John Wiley & Sons, Ltd.
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Aberraciones Cromosómicas , Expresión Génica , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidad , Proteínas Proto-Oncogénicas c-myc/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Cariotipo , Leucemia Mieloide Aguda/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Proteínas Proto-Oncogénicas c-myc/metabolismo , Medición de Riesgo , Factores de Riesgo , Análisis de Supervivencia , Adulto JovenRESUMEN
Although the survival rates are extremely low for patients with secondary central nervous system lymphoma (SCNSL) treated with conventional chemotherapy and radiotherapy, more encouraging outcomes have recently been reported in small series with high-dose (HD) therapy and autologous stem cell transplant (ASCT). The optimal HD regimen for SCNSL is unknown. Despite reports of thiotepa/busulfan-based conditioning for primary CNS lymphoma, very little data exist regarding the use of this regimen for SCNSL. We analyzed 23 patients with SCNSL (median age 62 years) who underwent ASCT at two Alberta centers using thiotepa, busulfan, cyclophosphamide (TBC) in six patients prior to 2011 and rituximab-busulfan, melphalan, thiotepa (R-BuMelTt) in 17 patients after 2011. At a median follow-up of 27.8 months (4.2-113.6), the 2-year actuarial rate of progression-free survival was 76.1%. In conclusion, our results demonstrate encouraging survival outcomes for patients with SCNSL treated with R-BuMelTt and ASCT.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Trasplante de Células Madre Hematopoyéticas , Linfoma/tratamiento farmacológico , Neoplasias Primarias Secundarias/tratamiento farmacológico , Acondicionamiento Pretrasplante , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Busulfano/administración & dosificación , Neoplasias del Sistema Nervioso Central/diagnóstico , Neoplasias del Sistema Nervioso Central/mortalidad , Terapia Combinada , Femenino , Estudios de Seguimiento , Movilización de Célula Madre Hematopoyética/métodos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Linfoma/diagnóstico , Linfoma/mortalidad , Masculino , Persona de Mediana Edad , Neoplasias Primarias Secundarias/diagnóstico , Neoplasias Primarias Secundarias/mortalidad , Estudios Retrospectivos , Tiotepa/administración & dosificación , Trasplante Autólogo , Resultado del TratamientoRESUMEN
BACKGROUND: Mantle cell lymphoma (MCL) is an aggressive disease with genetic heterogeneity and discrete clinical subtypes. MCL is rarely CD10 positive. These cases raise the question whether a subset of MCL may be germinal centre (GC) derived, and have distinct clinicopathological characteristics. AIMS AND METHODS: A series of nine CD10-positive MCL cases is described herein. The clinicopathological and immunophenotypic features, immunoglobulin somatic hypermutation (SHM) status and gene expression profile (GEP) data are detailed. These features were compared with two independent sets (n=20, each) of CD10-negative MCL cases (controls), which were randomly selected from our institutional registry. RESULTS: GEP showed distinct expression of a GC signature in CD10-positive MCL cases with minimal impact on downstream signalling pathways. There were no significant differences in the clinicopathological features or clinical outcome between our CD10-positive and CD10-negative MCL cases. The frequency of SHM was comparable with established data. CONCLUSIONS: This study provides convincing evidence that CD10 expression is related to a distinct GC signature in MCL cases, but without clinical or biological implications.
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Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Perfilación de la Expresión Génica , Inmunofenotipificación , Linfoma de Células del Manto/genética , Linfoma de Células del Manto/inmunología , Neprilisina/análisis , Estudios de Casos y Controles , Análisis por Conglomerados , Perfilación de la Expresión Génica/métodos , Predisposición Genética a la Enfermedad , Humanos , Inmunohistoquímica , Linfoma de Células del Manto/clasificación , Linfoma de Células del Manto/patología , Fenotipo , Valor Predictivo de las Pruebas , Sistema de RegistrosRESUMEN
OBJECTIVE: The objective of this study was to characterize the use of topical negative pressure therapy in combat wounds. METHODS: This study was a retrospective review of the records of patients whose wounds were managed with topical negative pressure between April 2007 and March 2008. The main outcome measure was episodes of antibiotic prescription, which was used as a surrogate marker of clinically relevant infection. RESULTS: Of the 62 cases identified, 25 clinical notes were unavailable and were excluded from the study leaving 37 included cases. All but one of the cases was male with an average age of 29 (19-39) and New Injury Severity Score (NISS) of 21.3 (14.4-28.1). In 20 cases, topical negative pressure was changed less than once per 4.9 days on average, and in the remaining 17 cases, this was done more frequently. Comparison of the rate of antibiotic prescription between these groups reveals a significantly higher rate in the cohort managed with more frequent topical negative pressure changes. However this relationship was not borne out in a multiple variable analysis. CONCLUSION: This study describes the use of topical negative pressure in the management of a uniquely challenging group of patients. Statistical analysis of relatively small numbers is challenging but these results support the current complex wound management strategies where wounds are temporized with topical negative pressure for several days following thorough wound debridement. This period allows patients to be physiologically stabilized, other injuries to be addressed and appears not to be associated with increased infections.