Case Report: Mycosis fungoides as an exclusive manifestation of common variable immunodeficiency in a family with a NFKB2 gene mutation.

Background: Common variable immunodeficiency disorders (CVIDs), which are primary immunodeficiencies characterized by the failure of primary antibody production, typically present with recurrent bacterial infections, decreased antibody levels, autoimmune features, and rare atypical manifestations that can complicate diagnosis and management. Although most cases are sporadic, approximately 10% of the patients may have a family history of immunodeficiency. Genetic causes involving genes related to B-cell development and survival have been identified in only a small percentage of cases. Case presentation: We present the case of a family with two brothers who presented with mycosis fungoides as an exclusive symptom of a common variable immunodeficiency disorder (CVID). Whole-exome sequencing of the index patient revealed a pathogenic variant of the NFKB2 gene. Based on this diagnosis and re-evaluation of other family members, the father and brother were diagnosed with this rare immune and preneoplastic syndrome. All CVID-affected family members presented with mycosis fungoides as their only symptom, which is, to the best of our knowledge, the first case to be reported. Conclusion: This case highlights the importance of high-throughput sequencing techniques for the proper diagnosis and treatment of hereditary hematological disorders.

Endothelium-biomarkers for postthrombotic syndrome: a case-control study.

BACKGROUND: The postthrombotic syndrome (PTS) is a long-term complication of deep venous thrombosis (DVT). Increase knowledge on the PTS pathophysiology and novel biomarkers are needed in order to predict PTS development and to improve treatment results. The aim of this study was to analyze novel endothelium-biomarkers for PTS in patients with DVT out of the acute phase. METHODS: A case-control study was conducted. Inclusion criteria were symptomatic and confirmed DVT patients treated with anticoagulants for at least 3 months. Villalta score was performed at the time of inclusion and used to diagnose and classify the severity of PTS. Plasma inter-cellular adhesion molecule 1 (ICAM-1), P-selectin, fractalkine and vascular endothelial growth factor (VEGF) were quantified using cytometric bead array. Endothelial progenitor cells (EPCs) and circulating endothelial cells (CEC) level were quantified by flow cytometry. RESULTS: Thirty two patients and 61 controls were included. PTS patients showed higher levels of CEC (0.56/µl (0.34-1.5) vs. 0.20/µl (0.11-0.77); P  = 0.04) and EPC (0.75/µl (0.38-1.52) vs. 0.09/µl (0.05-0.82); P  = 0.0021) compared to no PTS patients. Patients with PTS had significantly higher levels of fractalkine (387.60 pg/ml (222.30-597.90) vs. 98.00 pg/ml (82.30-193.02); P  = 0.044) than patients without PTS. Fracktalkine levels showed a strong linear correlation with Villalta score, r  = 0.86, P  < 0.0001. No differences were observed in P-selectin, ICAM-1 and VEGF between studied groups. CONCLUSIONS: The formation and early resolution of DVT are characterized by inflammation and endothelial/platelet activation. We have identified possible novel biomarkers such as CEC, EPC and fractalkine for the development of PTS. These results suggest a possible role of these mediators in the maintenance and worsening of PTS turning them into potential therapeutic targets.

[18F-fluorodesoxyglucose positron emission tomography/computed tomography in extramedullary multiple myeloma]. / Aportes de la tomografía por emisión de positrones con 18F-fluorodesoxiglucosa/tomografía computada en el diagnóstico de compromiso extramedular por mieloma múltiple en Uruguay.

BACKGROUND: 18F-fluorodesoxyglucose positron emission tomography/ computed tomography (PET-CT) has a high sensitivity and specificity to detect medullary and extramedullary lesions in multiple myeloma (MM). AIM: To describe the findings of PET-CT in extramedullary multiple myeloma (EMM) at diagnosis and at relapse, and correlate its results with clinical variables, response to treatment and survival. MATERIALS AND METHODS: Review of medical records and PET-CT reports of 39 patients with multiple myeloma (MM) who had at least one PET-CT study, treated between January 1, 2015, and January 1, 2019 at a clinical hospital. RESULTS: The Standard Uptake Values for each hypermetabolic lesion were not described in PET-CT reports. Fifteen patients had an EMM and in eight, without a previous clinical suspicion, PET-TC lead to the diagnosis. The mortality rate in the 39 patients with MM was 46%. Sixty seven percent of deaths occurred in patients with EMM. CONCLUSIONS: PET-TC was useful to diagnose EMM. However, a standardization in PETCT reports would be required to unify criteria. As previously reported, EMM had a greater aggressiveness and lower survival.

Mobilized and apheresis-collected endothelial progenitor cells with plerixafor.

BACKGROUND: Endothelial progenitor cells (EPCs) are immature cells able to proliferate and contribute to endothelial repair, vascular homeostasis, neovascularization, and angiogenesis. It therefore seems likely that circulating EPCs have therapeutic potential in ischemic and vascular diseases. In this study we evaluated the efficiency of EPC mobilization and collection by large volume leukapheresis in subjects with hematological diseases, treated with plerixafor in association with G-CSF. METHODS: Twenty-two patients with lymphoid malignancies underwent rHuG-CSF and plerixafor treatment followed by leukapheresis. Blood samples before and after treatment and apheresis liquid sample were taken and analyzed by flow cytometry in order to quantified EPC. RESULTS: The percentage of CD34+ cells and EPCs among circulating total nuclear cells (TNCs) increased significantly by approximately 2-fold and 3-fold, respectively, after plerixafor treatment. Consequently, the absolute number of CD34+ cells and EPCs were increased 4-fold after plerixafor treatment. The median PB concentration of EPCs before and after treatment were 0.77/µL (0.31-2.15) and 3.41/µL (1.78-4.54), respectively, P < .0001. The total EPCs collected per patient were 3.3×107 (0.8×107 -6.8×107 ). CONCLUSION: We have shown that plerixafor in combination with G-CSF allows the mobilization and collection of large amounts of EPCs along with CD34+ cells in lymphoid neoplasm patients. The possibility to collect and to store these cells could represent a promising therapeutic tool for the treatment of ischemic complications without the need of in vitro expansion.

Aportes de la tomografía por emisión de positrones con 18F-fluorodesoxiglucosa/tomografía computada en el diagnóstico de compromiso extramedular por mieloma múltiple en Uruguay / 18F-fluorodesoxyglucose positron emission tomography/computed tomography in extramedullary multiple myeloma

BACKGROUND: 18F-fluorodesoxyglucose positron emission tomography/ computed tomography (PET-CT) has a high sensitivity and specificity to detect medullary and extramedullary lesions in multiple myeloma (MM). AIM: To describe the findings of PET-CT in extramedullary multiple myeloma (EMM) at diagnosis and at relapse, and correlate its results with clinical variables, response to treatment and survival. MATERIALS AND METHODS: Review of medical records and PET-CT reports of 39 patients with multiple myeloma (MM) who had at least one PET-CT study, treated between January 1, 2015, and January 1, 2019 at a clinical hospital. RESULTS: The Standard Uptake Values for each hypermetabolic lesion were not described in PET-CT reports. Fifteen patients had an EMM and in eight, without a previous clinical suspicion, PET-TC lead to the diagnosis. The mortality rate in the 39 patients with MM was 46%. Sixty seven percent of deaths occurred in patients with EMM. CONCLUSIONS: PET-TC was useful to diagnose EMM. However, a standardization in PETCT reports would be required to unify criteria. As previously reported, EMM had a greater aggressiveness and lower survival.

Efectividad del tratamiento con bortezomib en pacientes con mieloma múltiple en el Hospital de Clínicas en el período 2009-2016. Montevideo, Uruguay / Effectiveness of bortezomib treatment in patients with multiple myeloma at the Clínicas Hospital between 2009 and 2016. Montevideo, Uruguay

El mieloma múltiple representa la segunda neoplasia hematológica en frecuencia. Es una enfermedad incurable, cuya sobrevida se ha duplicado en los últimos años, vinculado esto a la aparición de nuevos fármacos. Los planes con bortezomib mejoran la respuesta, sobrevida libre de progresión y sobrevida global. En Uruguay, desde 2009, este fármaco tiene cobertura por parte del Fondo Nacional de Recursos. Este estudio tiene como objetivo analizar la efectividad y toxicidad de bortezomib en pacientes con diagnóstico de mieloma múltiple asistidos en el Hospital de Clínicas. Método: estudio observacional, retrospectivo y descriptivo en el que se incluyeron todos los pacientes con diagnóstico de mieloma múltiple que recibieron tratamiento con bortezomib en primera, segunda o tercera línea en el Hospital de Clínicas de Montevideo, Uruguay, desde 2009 a 2016. Resultados: 36 pacientes recibieron bortezomib. El plan más utilizado fue ciclofosfamida-bortezomib-dexametasona. La vía de administración fue subcutánea en 53,8%. La tasa de respuesta global fue de 79,5% (87% en primera línea y 68,8% en segunda o tercera línea). El 47,2% desarrolló polineuropatía y 30,6% citopenias. Con una mediana de seguimiento de 26 meses la sobrevida global fue de 61% y la sobrevida libre de progresión de 35 meses (IC 95%, 22,6-47,4). Conclusión: el tratamiento con bortezomib logró buena tasa de respuesta. La neuropatía fue la toxicidad más frecuente. Bortezomib es un fármaco efectivo y con adecuado perfil de seguridad para el tratamiento del mieloma múltiple en primera, segunda y tercera línea. (AU)

Multiple mieloma represents the secon neoplasis in terms of frequency. It is an incurable disease, whose survival has doubled in recent years with the emergence of new drugs. Plan including bortezomib improve response, progression free survival and global survival. In Uruguay this drig is covered by the National Resources Find (FNR) since 2009. This study aims to analyse the experience of using bortezomib in patients with a diagnosis of multiple myeloma at the Clínicas Hospital. Method: observational, retrospective and descriptive study that included all patients with a diagnosis of multiple myeloma who received bortezomib treatment in the first, second and/or third line at the Clínicas Hospital of Montevideo; Uruguay from 2009 and 2016. Results: 36 patients received bortezomib. The most frequently used plan was cyclophosphamide-bortezomib-dexamethasone, subcutaneously administered in 54% of cases. Global response rate was 79.5% (87% in the first line, 68.8% in the second or third line). 43.6% of patients developed polineuropahty and 28.2 % cytopenia. With a median follow up of 26 months, global survival was 61% and progression free survival was 35 months, (CI 95%, 22.6-47.4). Conclusion: bortezomib treatment achieved a good reponse rate. Neuropathy was the most frequent toxicity. Bortezomib is an effective drug and it has the adequate safety profile to treat MM in the first, second and third line.

O mieloma múltiplo é a segunda neoplasia hematológica mais frequente. É uma doença incurável, cuja sobrevida se duplicou nos últimos anos graças aparecimento de novos fármacos. Os esquemas terapêuticos com bortezomibe melhoram a resposta, sobrevida livre de progressão e a sobrevida global. Desde 2009 no Uruguai este fármaco é parcialmente financiado pelo Fondo Nacional de Recursos (FNR). O objetivo deste estudo é analisar a experiência com o uso de bortezomibe em pacientes com diagnóstico de mieloma múltiplo atendidos no Hospital de Clínicas. Método: estudo observacional, retrospectivo e descritivo; foram incluídos todos os pacientes com diagnóstico de mieloma múltiplo que receberam tratamento com bortezomibe em primeira, segunda e/ou terceira linha no Hospital de Clínicas de Montevidéu Uruguai, de 2009 a 2016. Resultados: 36 pacientes receberam bortezomibe. O esquema mais utilizado foi ciclofosfamida - bortezomibe - dexametasona. Em 54% dos pacientes a vida de administração foi subcutânea. A taxa de resposta global foi de 79,5% (87% em primeira linha e 68,8% em segunda ou terceira linha). 43,6% apresentou polineuropatia e 28,2% citopenias. Com uma mediana de seguimento de 26 meses a sobrevida global foi de 61% e a sobrevida livre de progressão de 35 meses (IC 95%, 22,6-47,4). Conclusão: o tratamento com bortezomibe apresentou uma boa taxa de resposta. A neuropatia foi o efeito tóxico mais frequente. Bortezomibe é um fármaco efetivo e com perfil de seguridade adequado para o tratamento do MM em primeira, segunda e terceira linha.