Evaluation of nutritional risk factors in hematopoietic stem cell transplantation-eligible patients / Avaliação dos fatores de riscos nutricionais em pacientes pré-transplante de célula-tronco hematopoiética

ABSTRACT Objective To evaluate the nutritional risk factors in patients eligible for hematopoietic stem cell transplantation. Methods A cross-sectional, descriptive study conducted with patients recruited from an hematology outpatient clinic. Study variables included demographic and clinical data, patient-generated global subjective assessment findings, anthropometric indicators, food intake and oxidative stress levels. The level of significance was set at 5% (p<0.05). Results The sample comprised 72 patients, mean age of 48.93 years (14.5%). Multiple myeloma was the most prevalent condition (51.4%) in this sample. Most patients (55.6%) were overweight according to body mass index and at risk of cardiovascular disease according to waist circumference, conicity index and percentage of body fat. Sarcopenia was associated with risk of cardiovascular disease, hip-to-waist ratio (p=0.021), muscle strength depletion (p<0.001), food intake (p=0.023), reduced functional capacity (p=0.048), self-reported well-nourished status; p=0.044) and inadequate vitamin B6 (p=0.022) and manganese (p=0.026) intake. Elevated oxidative stress, detected in 33.3% of patients in this sample, was not associated with sarcopenia. Conclusion Most patients in this sample were overweight and sarcopenic. Lean mass depletion was associated with risk of cardiovascular disease, reduced muscle strength, food intake changes, reduced functional capacity, self-reported well-nourished status and inadequate intake of vitamin B6 and manganese, but not with oxidative stress.

RESUMO Objetivo Avaliar os fatores de riscos nutricionais em pacientes pré-transplante de célula-tronco hematopoiética. Métodos Estudo transversal, descritivo, realizado com pacientes de um ambulatório de hematologia. As variáveis estudadas foram demográficas, dados clínicos, avaliação subjetiva global produzida pelo próprio paciente, indicadores antropométricos, ingestão alimentar e estresse oxidativo. Os dados foram considerados estatisticamente significativos quando p<0,05. Resultados A amostra do estudo foi constituída por 72 pacientes, com média de idade de 48,93 (14,5%) anos e com mieloma múltiplo (51,4%) como a patologia mais prevalente. Conforme índice de massa corporal, 55,6% dos pacientes encontravam-se com excesso de peso. De acordo com a circunferência da cintura, índice de conicidade e percentual de gordura corporal, houve prevalência de risco para doença cardiovascular. A sarcopenia foi associada ao risco de doença cardiovascular pela relação cintura/quadril (p=0,021), depleção da força muscular (p<0,001), além da ingestão alimentar (p=0,023), da capacidade funcional reduzida (p=0,048) e do diagnóstico de "bem nutrido" (p=0,044), conforme a avaliação subjetiva global, e com consumo inadequado de vitamina B6 (p=0,022) e de manganês (p=0,026). Dentre os avaliados, 33,3% apresentaram estresse oxidativo elevado sem associação com sarcopenia. Conclusão Pacientes do pré-transplante se apresentam, em sua maioria, com excesso de peso, mas com sarcopenia, estando essa ausência de massa magra associada a risco de doença cardiovascular, depleção da força muscular, alteração da ingestão alimentar, redução da capacidade funcional, classificação de "bem nutrido", segundo a avaliação subjetiva global e consumo inadequado de vitamina B6 e manganês, não estando associada a estresse oxidativo.

Plasmocitoma solitario de costilla como presentación inicial de mieloma múltiple: reporte de un caso / Lone rib plasmacytoma as a presentation of initial multiple myeloma: a case report

Resumen Introducción: El 50% de los tumores de pared torácica son malignos, dentro de los que destaca el plasmocitoma de costilla. Objetivo: Presentar un caso clínico que debutó inicialmente como un plasmocitoma de costilla, y que terminó presentándose como mieloma múltiple. Materiales y Método: Registro clínico de un paciente sometido a resección de tumor de parrilla costal. Resultados: Paciente masculino de 58 años, con un año de dolor costal, asociado a aumento de volumen a nivel de la octava costilla derecha en línea media axilar, indurada. TC de tórax que demuestra imagen sugerente de plasmocitoma de 79 × 44 mm. Se realiza resección quirúrgica, con instalación de malla de prolene en el defecto. Biopsia diferida con compromiso neoplásico por lesión monoclonal de células plasmáticas. Se complementa estudio con biopsia de médula ósea confirmando mieloma múltiple. Se inicia tratamiento con quimioterapia adyuvante. Conclusiones: El plasmocitoma óseo solitario es una entidad de baja frecuencia, que se asocia a la presencia de mieloma múltiple. Es por esto que al momento de la sospecha se hace necesario descartar su presencia, con el fin de mejorar el pronóstico del paciente.

Introduction: Up to 50% of chest wall tumors are malignant; among which rib plasmocytoma stand out. Aim: Showcase a clinical case that debuted as a rib plasmacytoma, and that ended up presenting as Multiple Myeloma. Materials and Method: Records of a patient with resection of chest wall tumor. Results: Male patient of 58 years, with one year of costal pain, associated with an indurated increase in volume at the level of the eighth right rib in the mid-axillary line. Chest CT scan demonstrated a suggestive image of plasmacytoma of 79 × 44 mm. Surgical resection was performed, with prolene mesh installation in the defect. Biopsy showed neoplastic compromise due to monoclonal lesion of plasma cells. Study is complemented with bone marrow biopsy confirming multiple myeloma. The patient was treated with adjuvant chemotherapy. Conclusions: Solitary bone plasmacytoma is a low frequency entity, which is associated with the presence of multiple myeloma. At the moment of suspicion, it is necessary to rule out their presence, in order to improve the patient's prognosis.

Skp2 inhibitor SKPin C1 decreased viability and proliferation of multiple myeloma cells and induced apoptosis

Multiple myeloma (MM) is a malignant neoplasm of plasma, and exhibits several harmful effects including osteolytic injuries, hypercalcemia, and immune dysfunction. Many patients with MM succumb to the underlying malignancy. An S-phase kinase-related protein 2 (Skp2) inhibitor, designated SKPin C1, has been developed and confirmed to have an inhibitory effect on metastatic melanoma cells. This study aimed to determine the effect of SKPin C1 on MM. Normal B lymphocytes, THP-1 cells, and MM U266 and RPMI 8226 cells were exposed to various dosages of SKPin C1 for 48 h. Cell proliferation was determined by MTT, EdU staining, and cell cycle assays. Western blot assays were performed to assess intracellular protein levels of Skp2, p27, and cleaved caspase-3. The amount of ubiquitin attached to p27 was determined using an immunoprecipitation assay. The viability of U266 and RPMI 8226 cells was significantly inhibited by 10 μM SKPin C1 and the inhibitory effect was enhanced with increasing doses of SKPin C1. In contrast, 50 μM SKPin C1 only marginally decreased viability of normal B lymphocytes in 12 h. Skp2 and p27 expression in U266 and RPMI 8226 cells was higher and lower, respectively, than that in the normal B lymphocytes. Treatment with SKPin C1 or Skp2 knockdown increased p27 protein levels in U266 and RPMI 8226 cells by preventing p27 from being ubiquitinated, which slowed the cell cycle, inhibited cell proliferation, and triggered apoptosis. Therefore, this study suggested SKPin C1 as a potent inhibitor against aberrant proliferation and immortalization of MM.

Hipertensión pulmonar como presentación en mieloma múltiple / Pulmonary hypertension as presentation in multiple myeloma

El mieloma múltiple es una enfermedad oncohematológica, que representa el 15% de las enfermedades hematológicas malignas. La edad media de aparición es entre los 65-70 años, siendo muy poco frecuente en pacientes jóvenes; 2% son menores de 40 años. Presentamos el caso de una mujer de 36 años con antecedente de tabaquismo de 20 paquetes año. Consultó por disnea asociada a signos de insuficiencia cardíaca derecha, anemia, proteinuria, elevación de reactantes de fase aguda y patrón sugestivo de restricción moderadamente grave en la espirometría y caída de la capacidad de difusión de monóxido de carbono (DLco). El ecocardiograma doppler evidenció dilatación de cavidades derechas y signos de hipertensión pulmonar que se confirmó con cateterismo cardiaco derecho. En busca de la etiología se arribó al diagnóstico de mieloma múltiple.

Multiple myeloma is a hematologic disease, which accounts for 15% of hematologic malignancies. The average age of onset is between 65-70 years and is very rare in young patients, as 2% are under 40 years old. We present a case of 36-year-old women with history of 20 pack years (p/y) smoking, who complaints of dyspnea associated with signs of right cardiac overload, anemia, proteinuria, elevated acute phase reactants and spirometry pattern suggestive of moderately-severe restriction and severe drop in diffusing capacity for carbon monoxide (DLCO). Echocardiogram evidence dilated right heart cavities and signs of pulmonary hypertension which is confirmed by right heart catheterization. In search of the etiology we arrive to the diagnosis of multiple myeloma.

Mieloma múltiple IgA en paciente obstétrica / Multiple Myeloma in an obstetric patient

El mieloma múltiple es una neoplasia caracterizada por la proliferación anómala de células plasmáticas en la médula ósea, usualmente diagnosticada en pacientes mayores de 60 años, siendo rara su presentación antes de los 40 años de edad. Se presenta el caso de paciente femenina de 29 años de edad, sin antecedentes patológicos conocidos, a quien se le realiza el diagnóstico de mieloma múltiple IgA lambda en el primer trimestre del embarazo. Durante su estancia hospitalaria presenta hipercalcemia en rango de malignidad, con falla renal expresada en elevación de azoados y acidosis metabólica compensada. Se realizó serie radiológica ósea que mostró lesiones líticas en bóveda craneana. En la RMN de columna lumbar se evidencian fracturas patológicas de en columna lumbar (L4). Asimismo se solicitó electroforesis de proteínas en suero y orina e inmunofenotipo, corroborándose el diagnóstico de mieloma múltiple IgA lambda estadío IIIA según criterios de Durie Salmon. La paciente fue tratada con esteroides, evidenciándose disminución de la lesión en región frontal y mejoría de la función renal. El MM durante el embarazo es raro, habiendo sólo 42 casos descritos desde 1968 hasta la actualidad; de los cuales 4 corresponden a MM IgA. Reportamos el quinto caso en la literatura de mieloma múltiple IgA en una paciente obstétrica(AU)

Multiple myeloma is a hematologic malignancy characterized by the abnormal proliferation of plasma cells in the bone marrow. This disease is usually diagnosed in patients older than 60 years, with rare presentation before 40 years of age. We present the case of a female, 29 years - old patient, with no medical history, with IgA lambda myeloma diagnosed in the first trimester of pregnancy and who, during her hospitalization, presented malignant hypercalcemia, with renal failure. Bone survey revealed litic lesions in the skull. The MRI scan showed pathologic fractures of lumbar spine. The patient was treated with steroids, with a decrease of the frontal lesion and improvement of renal function. A protein electrophoresis is also requested in serum and urine, and immunophenotype, corroborating diagnosis of multiple myeloma IgA lambda IIIA stage according to Durie Salmon criteria. Myeloma multiple during pregnancy is extremely rare and there are 42 cases described from 1968 to date, and 4 of them are IgA MM. We report the fifth case in the literature of IgA multiple myeloma in an obstetric patient(AU)

Changes in Renal Function after Different Tandem Hematopoietic Stem-cell Transplantation Approaches in Patients with Multiple Myeloma

This study was done to observe the alteration of the estimated glomerular filtration rate (eGFR) in multiple myeloma patients according to type of tandem hematopoietic stem cell transplantation (HSCT). Forty-one patients were enrolled in this study. Twenty patients underwent autologous HSCT (auto-HSCT) and 21 patients underwent allogeneic HSCT (allo-HSCT). The changes in eGFR after the two tandem HSCT modalities were different between the two groups, according to the donor of stem cells (P = 0.016). In the auto-HSCT group, the eGFR, recorded 12 months after secondary HSCT, was significantly decreased compared with the eGFR recorded before stem cell mobilization (P = 0.005). Although there was no significant difference, the trend showed that the eGFR after allo-HSCT decreased from the previous HSCT until a month after secondary HSCT. In addition, after 6 months of secondary HSCT, the eGFR recovered to the level recorded prior to the HSCT (P = 0.062). This difference may be due to total body irradiation, a calcineurin inhibitor, or maintemance therapy. Changes in renal function would be monitored closely for these patients. The recovery of the eGFR would be a main focus for the patients treated with the total body irradiation or the calcineurin inhibitor, a progressive decline of the eGFR would be also crucial for the patients treated with maintenance therapy.

Autologous stem cell transplantation improves quality of life in economically challenged, brazilian multiple myeloma patients

OBJECTIVES: 1) To characterize the impact of multiple myeloma on the quality of life of patients treated in two public institutions in São Paulo State, Brazil, using a generic Short Form 36 Health Survey and a questionnaire specific for oncologic patients (QLQ-C30) upon diagnosis, after the clinical treatment, and at day +100 after autologous stem cell transplantation; 2) to evaluate whether autologous stem cell transplantation can improve the quality of life of our economically challenged population aside from providing a clinical benefit and disease control. METHODS: We evaluated 49 patients with multiple myeloma (a total of 70 interviews) using the two questionnaires. The scores upon diagnosis, post-treatment/pre-autologous stem cell transplantation, and at D+100 were compared using ANOVA (a comparison of the three groups), post hoc tests (two-by-two comparisons of the three groups), and paired t-tests (the same case at two different times). RESULTS: Of the included patients, 87.8 percent had a family budget under US $600 (economic class C, D, or E) per month. The generic Short Form 36 Health Survey questionnaire demonstrated that physical function, role-physical, and bodily pain indices were statistically different across all three groups, favoring the D+100 autologous stem cell transplantation group (ANOVA). The questionnaire specific for oncologic patients, the QLQ-C30 questionnaire, confirmed what had been demonstrated by the Short Form 36 Health Survey with respect to physical function and bodily pain, with improvements in role functioning, fatigue, and lack of appetite and constipation, favoring the D+100 autologous stem cell transplant group (ANOVA). The post hoc tests and paired t-tests confirmed a better outcome after autologous stem cell transplantation CONCLUSION: The questionnaire specific for cancer patients seems to be more informative than the generic Short Form 36 Health Survey questionnaire and reflects the real benefit of autologous stem cell transplantation in the quality of life of multiple myeloma patients in two public Brazilian institutions that provide assistance for economically challenged patients.

[Cellular and molecular aspects of multiple myeloma]

Multiple Myeloma [MM] is a plasma cell disorder witch accounts for about 10% of all hematologic cancers; 99% of patients diagnosed are older than 40 years of age. The aim of this study is to evaluate the recognized cellular and molecular factors effective on the emergence and development of MM. In the present study, 150 articles about genetic translocation, osteoclast and osteoblast cells, chemokines, signaling pathways, and Multiple Myeloma published in recent years were firstly selected to be reviewed. Out of this number, 69 which applied to cellular and molecular biology of MM were selected to be studied. Bone lesions and pathological fractures are the most important complications of Multiple Myeloma. Recurrent infection, renal insufficiency, hyperproteinemia, amyloidosis, hypercalcemia, decrease of alkaline phosphatase, and osteocalcin are other complications which are mostly caused by cell-cell interaction, chemokine, and immunoglobulin signal induction. The results show that infiltration of tumor cells like myeloma cells is due to secretion of some factors from BM cells as well as the presence of calcium and iron whose concentration is high in BM

New acquisitions in the physiopathology of multiple myeloma: role of the bone microenvironment / Novos conhecimentos da fisiopatologia do mieloma múltiplo: o papel do microambiente medular

Multiple myeloma (MM) is a plasma cell malignancy characterized by the accumulation of malignant plasma cells within the bone marrow (BM). MM cells interact with the microenvironment and induce pathological modifications that in turn support the growth and survival of MM cells. The BM microenvironment consists of various extracellular matrix proteins, and cell components as haematopoietic stem cells, progenitor and precursor cells, immune cells, erythrocytes, BM stromal cells (BMSCs), BM endothelial cells, as well as osteoclasts and osteoblasts that are able to secret several growth factors for MM cells. The direct interactions of MM cells with the microenvironment and the secreted cytokines activate signalling pathways mediating growth, survival, drug resistance and the migration of MM cells as well as osteoclastogenesis and angiogenesis. In this article we underline in particular the new evidences at the basis of the interaction between MM cell and bone cells and the potential role of osteoclast and osteoblast in MM pathophysiology.

O mieloma múltiplo (MM) é uma doença maligna das células plasmáticas caracterizada pelo acúmulo de células plasmáticas na medula óssea (MO). As células do MM interagem com o microambiente e induzem modificações patológicas que, por seu turno, propiciam o crescimento e a sobrevida das células do MM. O microambiente da MO consiste de várias proteínas da matriz extracelular e de componentes hematopoéticos: células-tronco, progenitoras e precursoras, células imunes, eritrocitárias, estromais, endoteliais. Possuem também osteoclastos e osteoblastos capazes de secreção de fatores de crescimento das células do MM. A direta interação das células mielomatosas com o microambiente e a secreção de citocinas ativam cascatas sinalizadoras que mediam o crescimento, sobrevida, resistência a drogas e a migração destas células assim como a osteoclastogênese e a angiogênese. Neste artigo explicitamos novas evidências e as bases da interação das células mielomatosas e as células medulares e o provável papel dos osteoclastos e dos osteoblastos na fisiopatologia do MM.

Fatores associados à expressão da molécula de adesão CD56 por plasmócitos tumorais em medula óssea de pacientes com mieloma múltiplo e seu impacto na sobrevida global / Factors associated with expression of CD56 molecule of accession by plasma tumor in bone marrow of patients with multiple myeloma and its impact on overall survival

O Mieloma Múltiplo (MM), a despeito dos avanços tecnológicos e terapêuticos dos últimos anos, mantém-se como uma neoplasia incurável e de prognóstico desfavorável na maioria dos casos. No entanto, estudos a respeito de sua fisiopatologia e dos eventos celulares e moleculares envolvidos têm trazido importantes contribuições para o desenvolvimento da terapêutica da doença. A expressão de moléculas de adesão, em especial CD56, por plasmócitos tumorais, tem sido frequentemente associada ao prognóstico dos pacientes, embora seu papel na fisiopatologia da doença ainda seja controverso. O presente estudo incluiu 97 pacientes com diagnóstico de MM, provenientes da Faculdade de Medicina de Botucatu - UNESP e do Hospital Amaral Carvalho - Jaú. Os materiais histológicos referentes ao diagnóstico foram classificados de acordo com a distribuição de plasmócitos tumorais na medula óssea. Foi realizado estudo imunohistoquímico para detectar a expressão das cadeias leves de imunoglobulina kappa e lambda e da molécula de adesão CD56. Os dados obtidos foram analisados levando-se em consideração fatores prognósticos previamente estabelecidos, como Beta2microglobulina e desidrogenase tática, e tempo de sobrevida dos pacientes. Foi observada expressão mais frequente de CD56 entre pacientes do sexo masculino (p igual 0,013) e associação entre expressão de kappa e CD56 (p igual 0,050), assim como entre expressão de lambda e ausência de expressão de CD56 (p igual 0,042). Não foi observada associação entre expressão da molécula e outros fatores prognósticos, bem como tempo de sobrevida dos pacientes.

Parámetros séricos del metabolismo del hierro en mieloma múltiple / Serum iron parameters in multiple myeloma

Las células normales y neoplásicas tienen similares necesidades de hierro, pero las últimas pueden exhibir mecanismos alterados de adquisición y secuestro del metal que les permiten continuar multiplicándose en tejidos del huésped, aun en condiciones de restricción del nutriente. El presente trabajo tuvo como objetivo investigar los parámetros séricos del metabolismo del hierro en pacientes con Mieloma Múltiple (MM), y compararlos con los correspondientes a una población normal. En 48 pacientes con el cáncer hematolègico se determinó Hierro (µ/dl) e Indice de Saturación de la Transferrina (por ciento) por métodos colorimétricos, Ferritina (ng/ml) por IRMA y Transferrina (mg/dl) por inmunodifusión radial. El grupo control estuvo constituido por 40 individuos sanos, correspondientes en edad y sexo. En el grupo pacientes se encontraron valores significativamente elevados (P<0,00001) de Ferritina sérica (x=504,6 ng/ml ± 386,2) y de Indice de Saturación de la Transferrina (x=45 por ciento ± 14,9) comparados con los controles (x=86,7 ng/ml ± 30 y x=29,9 ng/ml ± 8,36, respectivamente). Niveles significativamente más bajos de Transferrina sérica (P<0,00001) se observaron en el grupo pacientes (x=270 mg/dl ± 102,1) respecto a los controles (x=360 mg/dl ± 57,3).No hubo diferencias significativas (P=0,8189) entre la Ferremia del grupo pacientes (x=100,85 µg/dl ± 56,2) y los controles (x=98,6 µg/dl ± 32,4). Los resultados obtenidos mostraron un metabolismo del hierro aberrante en MM, que podría favorecer el crecimiento celular maligno y la susceptibilidad a infecciones, e inhibir funciones inmunes

Mieloma múltiplo: relato de caso / Multiple myeloma: case report

Os autores apresentam um caso clínico de um paciente portador de mieloma múltiplo, com anemia, proteinúria, dores ósseas, velocidade de hemossedimentação elevada, em que faltou a positividade da proteinúria de Bence Jones, e a eletroforese das proteínas plasmáticas não apresentava o pico monocional da doença

Diagnóstico: plasmocitoma / Diagnosis: plasmocytoma

Varón de 49 años, inicia padecimiento cuatro meses antes de internamiento hospitalario, al notar la aparición de una tumoración pequeña, blanda, de bordes lisos y no dolorosa en la región parietal izquierda, con un crecimiento rápidamente progresivo. Se intentó realizar una biopsia excisional que no se logró, debido a que la tumoración presentaba una gran vascularidad

Características clínicas e implicaçöes prognósticas do acometimento renal no mieloma múltiplo / Clinical characteristics and prognosis implications of renal involvement in multiple myeloma

O envolvimento renal no mieloma múltiplo tem sido associado com pior prognóstico destes pacientes. A influência da insuficiência renal no quadro clínico e no prognóstico de portadores de mieloma múltiplo foi estudada, retrospectivamente, em 45 pacientes. Pacientes com insuficiência renal, à primeira visita, apresentaram maior freqüência de perda de peso, proteinúria e hipercalcemia. Entre os pacientes com insuficiência renal, as médias de uricemia e VHS foram maiores e a média do hematócrito foi menor. Näo houve diferença com relaçäo a edema, hipertensäo arterial, fraturas e dores ósseas. A regressäo da insuficiência renal ocorreu em 47% dos casos, o que se deu mais freqüentemente no primeiro mês de seguimento. A média da creatinina foi mais baixa entre os pacientes com insuficiência renal reversível. A mediana da sobrevida foi: pacientes com insuficiência renal: 11 meses; pacientes com funçäo renal normal: 50 meses. Entre os pacientes com insuficiência renal, aqueles que apresentaram recuperaçäo da funçäo renal mostraram uma mediana de sobrevida maior (24 meses) do que aqueles com insuficiência renal irreversível (1 mês). Em conclusäo: o envolvimento renal no mieloma múltiplo é comum e freqüentemente reversível. Pacientes com insuficiência renal tiveram pior prognóstico; entre os pacientes com insuficiência renal, a normalizaçäo da funçäo renal conferiu melhor prognóstico