Síndrome de hiperviscosidade em paciente com mieloma múltiplo / Hyperviscosity syndrome in multiple myeloma patients

O mieloma múltiplo é uma neoplasia progressiva e incurável de células B, caracterizado pela proliferação desregulada e clonal de plasmócitos na medula óssea. A síndrome de hiperviscosidade é uma das complicações relacionadas às gamopatias monoclonais, sendo considerada emergência oncológica. O objetivo deste estudo foi descrever o quadro clínico de um paciente diagnosticado com mieloma múltiplo que apresentou síndrome de hiperviscosidade, avaliando a prevalência de sinais e sintomas, bem como características fisiopatológicas dessa entidade clínica. Foi revisado o prontuário de um paciente internado na enfermaria da Clínica Médica do Hospital Regional do Cariri (CE) no período de junho a julho de 2018. Além disso, foi realizada revisão de literatura em base de dados (PubMed®) direcionada ao tema proposto. O diagnóstico de mieloma múltiplo foi comprovado por mielograma, sendo prontamente iniciada a corticoterapia e avaliada a resposta clínica após essa terapêutica. Apesar de incomum e menos frequentemente relacionada ao mieloma múltiplo, a síndrome de hiperviscosidade está relacionada a uma grande taxa de mortalidade quando apresenta diagnóstico tardio. A terapia de primeira linha indicada para a síndrome de hiperviscosidade foi a plasmaferese, no entanto, as condições clínicas (instabilidade hemodinâmica) impossibilitaram sua realização. O desfecho deste caso foi o óbito do paciente. Concluiu-se que o diagnóstico precoce e a intervenção terapêutica estão diretamente relacionados à ocorrência de menor incidência de complicações relacionadas ao mieloma múltiplo e à síndrome de hiperviscosidade.

Multiple myeloma is a progressive and incurable B-cell neoplasm characterized by unregulated and clonal proliferation of plasmocytes in the bone marrow. Hyperviscosity syndrome is one of the complications related to monoclonal gammopathies and is considered an oncological emergency. The aim of this study was to describe the clinical condition of a patient diagnosed with multiple myeloma who presented hyperviscosity syndrome, evaluating the prevalence of symptoms and signs, as well as the pathophysiological characteristics of this clinical entity. The medical records of a patient admitted to the Internal Medicine ward of the Hospital Regional do Cariri (CE) from June to July of 2018 were reviewed. In addition, we conducted a literature review in a database (PubMed®) directed to the theme proposed. The diagnosis of multiple myeloma was confirmed by myelogram, and corticosteroid therapy was promptly initiated and the clinical response was evaluated after this therapy. Although uncommon and less frequently related to multiple myeoloma, hyperviscosity syndrome is related to a high mortality rate when diagnosed late. The first line therapy indicated to hyperviscosity syndrome was plasmapheresis; however, the clinical conditions (hemodynamic instability) precluded its performance. The outcome of this case was the patient's death. Thus, it was concluded that early diagnosis and therapeutic intervention are directly related to the occurrence of lower incidence of complications related to multiple myeloma and hyperviscosity syndrome.

Comportamiento de las inmunoglobulinas en el seguimiento de pacientes con mieloma múltiple. Hospital Universitario Comandante Faustino Pérez. Matanzas / Behavior of the immunoglobulines in the follow-up of patients with multiple mieloma. University Hospital Comandante Faustino Pérez. Matanzas

Introducción: las gammapatías monoclonales son un grupo de desórdenes caracterizados por la proliferación de un clon de células plasmáticas que sintetiza una inmunoglobulina monoclonal, dentro de las que se encuentra como ejemplo de neoplasia de células plasmáticas el mieloma múltiple, entidad que se caracteriza por la producción anormal de inmunoglobulinas. Objetivo: describir el comportamiento de las inmunoglobulinas en el seguimiento de pacientes con mieloma múltiple, en el Servicio de Hematología del Hospital "Comandante Faustino Pérez" de Matanzas. Materiales y Métodos: estudio descriptivo-prospectivo-longitudinal. El universo de estudio fue abierto y la muestra fueron todos los pacientes con mieloma múltiple de debut, durante el período del 1ro de junio del 2013 al 31 de mayo del 2014, a los cuales se les realizó la determinación de inmunoglobulinas IgA, IgG e IgM. Resultados: los valores de IgA e IgG disminuidos presentaron una respuesta al tratamiento muy buena ya desde los seis meses, aunque continuó mejorando a los 12 meses. La IgM a los seis meses de tratamiento se modificó hacia valores aumentados clasificando como refractario revirtiéndose este comportamiento a los 12 meses alcanzando un 13% más que antes del tratamiento. Conclusiones: los marcadores de mejor respuesta al tratamiento fueron las inmunoglobulinas IgA e IgG (AU).

Introduction: monoclonal gammopathies are a group of disorders characterized for the proliferation of a clone of plasmatic cells that synthesize a monoclonal immunoglobulin; among them, an example of plasmatic cells neoplasias is the multiple myeloma, an entity characterized by the abnormal production of immunoglobulins. Objective: to describe the behavior of immunoglobulins in the follow-up of patients with multiple myeloma in the Hematology Service of the University Hospital "Comandante Faustino Pérez", of Matanzas. Materials and methods: longitudinal-prospective-descriptive study. The universe of study was open and the sample was all the patients with debuting multiple myeloma, during the period from June 1st 2013 to May 31st 2014, to whom the determination of IgA, IgG and IgM immunoglobulins was carried out. Results: the diminished values of IgA and IgG showed a very good answer to the treatment after six and 12 months. At the sixth months of the treatment the IgM was modified to augmented values classifying as refractory; this behavior relapsed at the twelfth month, reaching 13 % more than before the treatment. Conclusions: the markers of better answer to the treatment were the IgA and IgG immunoglobulins (AU).

Changes in circulating endothelial progenitor cells predict responses of multiple myeloma patients to treatment with bortezomib and dexamethasone

Four cycles of chemotherapy are required to assess responses of multiple myeloma (MM) patients. We investigated whether circulating endothelial progenitor cells (cEPCs) could be a biomarker for predicting patient response in the first cycle of chemotherapy with bortezomib and dexamethasone, so patients might avoid ineffective and costly treatments and reduce exposure to unwanted side effects. We measured cEPCs and stromal cell-derived factor-1α (SDF-1α) in 46 MM patients in the first cycle of treatment with bortezomib and dexamethasone, and investigated clinical relevance based on patient response after four 21-day cycles. The mononuclear cell fraction was analyzed for cEPC by FACS analysis, and SDF-1α was analyzed by ELISA. The study population was divided into 3 groups according to the response to chemotherapy: good responders (n=16), common responders (n=12), and non-responders (n=18). There were no significant differences among these groups at baseline day 1 (P>0.05). cEPC levels decreased slightly at day 21 (8.2±3.3 cEPCs/μL) vs day 1 (8.4±2.9 cEPCs/μL) in good responders (P>0.05). In contrast, cEPC levels increased significantly in the other two groups (P<0.05). SDF-1α changes were closely related to changes in cEPCs. These findings indicate that change in cEPCs at day 21 in the first cycle might be considered a noninvasive biomarker for predicting a later response, and extent of change could help decide whether to continue this costly chemotherapy. cEPCs and the SDF-1α/CXCR4 axis are potential therapeutic targets for improved response and outcomes in MM patients.

The prognostic impact of inflammatory factors in patients with multiple myeloma treated with thalidomide in Korea

BACKGROUND/AIMS: The purpose of this study was to determine the correlations between inflammatory factors-including absolute lymphocyte count, lactate dehydrogenase, beta2-microglobulin, albumin, C-reactive protein, and ferritin-and the prognosis for survival in patients with multiple myeloma (MM) treated with induction chemotherapy containing thalidomide and who underwent autologous stem cell transplantation (ASCT). METHODS: Data from patients at 13 university hospitals in South Korea were collected retrospectively between December 2005 and May 2013. RESULTS: The median age of the 232 patients was 57 years (range, 33 to 77) and the male to female ratio was 1.09:1. In the multivariate analysis, fewer than two combined abnormal inflammatory factors was the only independent prognostic factor for superior progression-free survival (relative risk [RR], 0.618; 95% confidence interval [CI], 0.409 to 0.933; p = 0.022), and platelet count > 100 x 109/L and fewer than two combined abnormal inflammatory factors were independent prognostic factors for superior overall survival (RR, 4.739; 95% CI, 1.897 to 11.839; p = 0.001 and RR, 0.263; 95% CI, 0.113 to 0.612; p = 0.002, respectively). CONCLUSIONS: Patients with two or more than two combined inflammatory factors who were treated with thalidomide induction chemotherapy and who underwent ASCT showed significantly shorter survival compared to those with fewer than two combined inflammatory factors. These results could be helpful for predicting prognosis in patients with MM.

Síndrome de hiperviscosidad en pacientes con mieloma múltiple / Hyperviscosity syndrome in patients with multiple myeloma

Objetivos: el mieloma múltiple es una enfermedad de distribución universal. Se determinaron la frecuencia, las características y el tratamiento del síndrome de hiperviscosidad como complicación de esta enfermedad. Método: se realizó un estudio descriptivo retrospectivo que incluyó a 31 pacientes con el diagnóstico de mieloma múltiple atendidos en el servicio de adultos del Instituto de Hematología e Inmunología desde enero del 2007 a junio del 2011. Resultados: la edad media fue de 61 años con un predominio del sexo masculino y el color de la piel blanca. Los pacientes se presentaron con anemia, eritrosedimentación acelerada, hiperproteinemia, hipoalbuminemia, hipergammaglobulinemia, una infiltración media de la médula ósea por células plasmáticas de 63.2 porciento y una viscosidad sérica media de 2.93. El síndrome de hiperviscosidad se observó en 4 (12.9 porciento) pacientes. Las manifestaciones clínicas principales del síndrome de hiperviscosidad fueron los síntomas generales y los síntomas neurológicos y se presentaron con cifras de viscosidad sérica iguales o superiores a 4.5. La proteína monoclonal identificada como responsable del síndrome de hiperviscosidad fue la IgA y la viscosidad sérica fue proporcional a las concentraciones de la paraproteína (p<0.01). Conclusión: el síndrome de hiperviscosidad se presentó en los pacientes estudiados con similares características a lo reportado por otros autores. La plasmaféresis y la quimioterapia fueron los pilares del tratamiento con resultados satisfactorios

Objectives: multiple myeloma is a disease of worldwide distribution. We determined frequency, characteristics and treatment of hyperviscosity syndrome as a complication of this condition. Method: we conducted a retrospective study involving 31 patients with a diagnosis of multiple myeloma treated at the Adult Hematology Service of the Institute of Hematology and Immunology from January 2007 to June 2011. Results: mean age was 61 years with a male predominance and slight predominance in caucasians. The patients presented with anemia, high erythrosedimentation rate, hyperproteinemia, hypoalbuminemia, hypergammaglobulinemia, a median infiltration of bone marrow by plasma cells of 63.2percent and an average serum viscosity of 2.93. Hyperviscosity syndrome was observed in 4 (12.9 percent) patients. The main clinical manifestations of hyperviscosity syndrome were general symptoms and neurological symptoms and presented with serum viscosity at or above 4.5. The monoclonal protein identified as the responsible of the hyperviscosity syndrome was IgA and viscosity was proportional to the concentrations of the paraprotein (p <0.01). Conclusion: the hyperviscosity syndrome is presented in the studied patients with similar characteristics to those reported by other authors. Plasmapheresis and chemotherapy were the mainstays of treatment with satisfactory results

Elevation of Serum Ferritin is Associated with the Outcome of Patients with Newly Diagnosed Multiple Myeloma

BACKGROUND/AIMS: Serum ferritin is a marker of acute phase reactions and iron storage. In addition, hematologic malignancies are associated with elevated serum ferritin levels. Other studies have suggested that ferritin is a surrogate for advanced disease and has an impact on relapse, because elevated serum ferritin predicts overall survival (OS) and relapse-free survival following autologous stem cell transplantation for lymphomas. METHODS: We studied 89 consecutive patients with newly diagnosed multiple myeloma to determine the value of serum ferritin in comparison with known prognostic factors. RESULTS: The OS in the elevated serum ferritin group (> or =300 ng/mL) was shorter than that in the normal serum ferritin group (<300 ng/mL, p<0.001) after a median follow-up of 25 months. In univariate analysis, elevated ferritin was correlated with poor survival in the patients (relative risk [RR], 2.588; 95% confidence interval [CI], 1.536 to 4.358; p<0.001). Furthermore, multivariate analysis showed that elevated serum ferritin was an independent predictor of mortality in patients with multiple myeloma (RR, 2.594; 95% CI, 1.403 to 4.797; p=0.002). CONCLUSIONS: The serum ferritin can a prognostic parameter of survival as well as disease activity in patients with multiple myeloma.

Mieloma Múltiplo e anemia / Multiple Myeloma and anemia

Anemia é uma complicação comum em pacientes com mieloma múltiplo (MM) e ocorre em mais de 2/3 dos pacientes. Anemia de doença crônica, deficiência de eritropoetina (EPO) devido à insuficiência renal e efeito mielossupressivo da quimioterapia são os principais mecanismos patofisiológicos que contribuem para o desenvolvimento de anemia no MM. Nos pacientes que obtêm remissão completa com tratamento quimioterápico, anemia usualmente se normaliza. Nos pacientes que não respondem ou apresentam recaída do mieloma, anemia freqüentemente persiste. As opções de tratamento dos pacientes anêmicos com MM incluem transfusões de hemácias e EPO recombinante humana. Essa proteína é biologicamente equivalente à EPO endógena e sua administração promove aumento dos valores de hemoglobina por tempo mais prolongado sem os riscos das transfusões de sangue. Vários estudos têm relatado melhora significante da eritropoese, redução da necessidade transfusional e melhora da qualidade de vida com o uso da EPO como tratamento a longo prazo da anemia associada ao mieloma. Nesse artigo, propomos o tratamento da anemia do MM baseado nas recomendações propostas pela Sociedade Americana de Hematologia (ASH) em conjunto com a Sociedade Americana de Oncologia Clínica (ASCO), pela Organização Européia para Pesquisa e Tratamento do Câncer (EORTC), pelo IMF (Internacional Myeloma Foundation) e pelo NCCN (National Comprehensive Cancer Network).

Anemia is a common complication in patients with multiple myeloma (MM) occurring in more than two thirds of all patients. Anemia of chronic diseases, erythropoietin (EPO) deficiency due to renal impairment and the myelosuppressive effect of chemotherapy are the most important pathophysiological mechanisms contributing to the development of anemia in MM. In patients who achieve complete remission after chemotherapy, anemia usually normalizes. Non-responders and relapsing myeloma patients often continue to suffer from anemia. Treatment options for anemic myeloma patients include red blood cell transfusions and recombinant human EPO. This protein is biologically equivalent to the human endogenous hormone EPO, and its application leads to an increase in hemoglobin levels over an extended time without the risks presented by blood transfusions. Several studies reported a significant improvement of erythropoiesis, reduction in transfusion need, and improved quality of life by using EPO as long-term treatment of myeloma-associated anemia. In this article we propose the treatment of myeloma-associated anemia based on recommendations by the American Society of Hematology (ASH) and American Society of Clinical Oncology (ASCO); European Organisation for Research and Treatment of Cancer (EORTC); International Myeloma Foundation (IMF) and the National Comprehensive Cancer Network (NCCN).

Simultaneous complication of multiple myeloma with Sjögren syndrome.

We report a 72-year-old female case of IgG-kappa type multiple myeloma (MM) simultaneously complicated with Sjögren syndrome (SS). She also presented marked hyperamylasemia of salivary-type isozyme. Although she had received sequential chemotherapy completed with high-dose therapy with autologous hematopoietic stem cell transplantation, she died of relapse fifteen months after the initial diagnosis. Various autoantibodies indicated that her sicca symptoms were due to true SS and not caused by MM cell infiltration to exocrine glands. MM cells appeared to produce amylase that fluctuated correspondingly to the disease status of MM. To our knowledge, this is the first English report of simultaneous complication of SS and MM referring to hyperamylasemia. Accumulation of this rare clinical manifestation is important to elucidate the pathogenesis of MM under condition of immunological disorder caused by SS.

Use of simple hematological, biochemical and clinical parameters to monitor response of multiple myeloma patients on high dose thalidomide therapy.

BACKGROUND: Evidence of increased bone marrow vascularity in multiple myeloma (MM) has led to the use of anti-angiogenic drugs especially thalidomide in relapsed or refractory patients. Currently, parameters such as serum/ urine electrophoresis for M (monoclonal) proteins, bone marrow biopsy with touch preparation and b2 microglobulin are routinely used to assess response to therapy. These investigations are expensive, invasive and require high technical setup. AIM: To correlate simple and routine hematological and biochemical parameters with the key marker of disease i.e. M proteins. SETTINGS AND DESIGN: This is an open label, uncontrolled, single-arm study. MATERIALS AND METHODS: Twenty nine refractory or relapsed multiple myeloma patients of both sexes (M=20, F=9) with age ranging between 35-72 years were initiated on 200 mg/day of thalidomide with fortnightly increments of 200 mg to a maximum tolerated dose not exceeding 800 mg/day. All hematological and biochemical parameters were monitored at monthly intervals for one year. STATISTICAL ANALYSIS: Correlation analysis was performed between hemoglobin (Hb), total leukocyte count (TLC), absolute neutrophil count (ANC), platelet count (PC), total proteins (TP), serum albumin and serum globulin on one hand and M protein levels on the other using Pearsons Correlation test by SPSS version 7.5. RESULT: Hb, TLC, ANC, PC and serum albumin levels showed a significant negative correlation with M proteins. A highly significant positive correlation existed between M proteins on one hand and TP and globulin levels on the other. Dryness of skin indicated positive response to therapy. These correlations were found to be significant at the end of one month of therapy in all the above-mentioned parameters except in TLC where it was significant after 2 months of thalidomide therapy. CONCLUSION: Results suggest that sustained efficacy of thalidomide therapy may be amenable to monitoring by these simple, inexpensive and easily available investigations after ascertaining an initial response by M protein and marrow plasmacytosis as these parameters closely follow M protein levels. However more studies are required to further substantiate these findings.

Light chain multiple myeloma: a lesson to learn

This case report is to emphasise the importance of investigating urine as well as the serum for monoclonal band if multiple myeloma [MM] is suspected. On many occasions a specimen of serum is sent alone without the urine specimen to exclude myelomatosis. It is important to note that in light chain myeloma, which contributes to about 20% of myelomatosis, the diagnosis could be easily missed or unnecessarily delayed if only serum is investigated as it happened with the present case

Paraproteins: a regional South Australian experience.

We have performed a systematic review of all new serum and urinary paraproteins detected over a six year period in an immunodiagnostic laboratory serving a population of 400,000 people. Clinical diagnoses and associated laboratory features were ascertained from a computerized laboratory database or from clinical notes. Over the period of study, serum or urine paraproteins were detected in 613 new patients. These consisted of 568 patients with serum paraproteins and 45 patients with urinary monoclonal free light chain (in the absence of a serum paraprotein). These paraproteins occurred more commonly in males and the frequency increased with age. Approximately 30% of the serum paraproteins and 60% of urinary monoclonal free light chain were associated with B cell lymphoproliferative disorders (multiple myeloma, plasmacytoma, Waldenstrom's macroglobulinemia, non-Hodgkins lymphoma, chronic lymphocytic leukemia, etc) with the remainder being labeled as monoclonal gammopathies of uncertain significance (MGUS). At clinical presentation, patients with lymphoproliferative disorders tended to have higher levels of paraprotein, B2 microglobulin, the presence of free urinary light chain and demonstrated molecular size heterogeneity of the paraprotein but there was considerable overlap. A good correlation was noted between paraprotein concentration and viscosity in most patients. In conclusion paraproteins were most frequently encountered in the context of a gammopathy of uncertain significance. Features which suggested lymphoproliferative disorders included higher levels of serum paraprotein (> 15 g/l), elevated levels of B2-microglobulin and the presence of urinary free high chain. However, as much overlap was seen with patients with MGUS, regular monitoring of paraprotein level is considered mandatory in the management of these patients.

Manejo de un algoritmo para la detección de gamopatías monoclonales en suero: experiencia del Instituto Nacional de Cancerología en México / Management of an algorythm for serum monoclonal gammopathies detection: experience of Instituto Nacional de Cancerología in Mexico

Most patients with multiple myeloma have an abnormal band in the gamma region of protein electrophoresis. To correlate the clinical diagnosis with patterns of protein electrophoresis. Retrospective analysis of all protein electrophoresis or immunoglobulin quantification requested during 1992 and review of clinical charts of patients. During 1992, 553 protein electrophoresis were requested. Of these, 344 were repetitions and 209 came from patients seen for the first time. Among the latter, we found a monoclonal component in 40. Of these 40 patients, 35 had a multiple myeloma, one had a plasmocytoma and four a non-Hodgkin lymphoma. 14 patients with diagnosis of myeloma did not have a monoclonal component in protein electrophoresis. These figures resulted in a 71 percent sensitivity and 97 percent specificity for monoclonal components in the diagnosis of multiple myeloma. The monoclonal component of patients with myeloma was characterized as IgG in 29 (60 percent), IgA in 5 (10 percent) and IgM in one. A monoclonal component present in a protein electrophoresis has a high diagnostic accuracy for multiple myeloma

Xanthoma of the liver in a patient with multiple myeloma associated with hyperlipidemia: A case report

A case of xanthoma of the liver in a 61-year-old Korean woman with multiple myeloma, hyperlipidemia and xanthoma of the skin is described. Microscopically, the liver showed a multiple xanthomatous collection of foamy histiocytes as well as diffuse sinusoidal infiltration of the foam cells. This hepatic accumulation of foam cells seems to be related to hyperlipidemia of the patient. The mechanism of hyperlipidemia in multiple myeloma is discussed.

Importancia pronóstica de la beta 2-microglobulina en mieloma múltiple / Prognostic value of beta 2-microglobulin in multiple myeloma

La beta 2 microglobulina es una proteína de bajo peso molecular relacionada con el sistema HL-A, que se encuentra virtualmente en todas las células nucleadas. En pacientes con mieloma múltiple (MM) se ha encontrado que niveles elevados de esta proteína se asocian con un pobre pronóstico tanto para obtener respuesta terapéutica como en la duración de la supervivencia. Con el fin de determinar la importancia de la misma, en 70 pacientes con MM sin tratamiento previo, se determinaron niveles séricos de beta 2 microglobulina y se efectuó un análisis multivariable con otros factores pronósticos. Se encontró que los factores asociados a un mal pronóstico en pacientes con MM fueron niveles elevados de beta 2 microglobulina y estadio, independientemente de otros factores analizados, ya que la supervivencia fue significativamente mejor: 80 porciento a 5 años del grupo de pacientes con estadio I y niveles normales de beta 2 microglobulina, cuando se compara con pacientes en estadio III y niveles elevados de beta 2 microglobulina (> 8.0 *g/mL) en las que todos los pacientes estaban muertos a los 27 meses del diagnóstico. Se puede considerar que los niveles séricos de beta 2 microglobulina son un indicador de mal pronóstico en pacientes con MM y que su determinación debe hacerse como parte fundamental del estudio inicial de estos pacientes.

Lepracticien devant une gammapathie monoclonale

Monoclonal gammopathies are usually observed in myeloma and in the course of the other B lymphocyte Neoplasia. However, gammopathies can occur in the serum of people apparently in good healthy [asymptomatic gammopathie]. So, when malignant lymphoplasmocytary etiology is not proved, the patient should be kept under a follow up clinical and biological control

Viscosidad sanguínea humana implementación de un método sencillo para sangre total y plasma valores normales / Human blood viscosity use of a simple method for total blood and plasma normal values

Se implementa una técnica sencilla para medir la viscosidad sanguínea y plasmática, midiendo el tiempo que demora una cantidad determinada de sangre o plasma en recorrer un segmento de tubo, a temperatura y presión constante. Se analizan 100 muestras de sujetos normales, de acuerdo a parámetros determinados al inicio del estudio. Se concluyen valores expresados en viscosidad relativa similares a los encontrados en viscosímetros por otros autores. Promedio 4,5 u de viscosidad sanguínea para hombres y mujeres, y 1,9 u de viscosidad plasmática en mujeres y hombres, respectivamente. De esto concluimos que no hay diferencias significativas entre viscosidad sanguínea y viscosidad plasmática según sexo, edad, hematocrito normal y el tiempo transcurrido entre la toma de muestra y la medición en laboratorio para el grupo en estudio. Se deja planteada la inquietud de continuar analizando la viscosidad sanguínea de acuerdo a otros parámetros, como diabetes descompensada, accidentes vasculares u otras patologías o cuadros clínicos en que se describen alteraciones de viscosidad sanguínea