ABSTRACT
BACKGROUND@#Multiple myeloma is a malignant proliferation of plasma cells that accumulate in the bone marrow and results in several organ dysfunctions that are debilitating and fatal. For the past 20 years, advances in the understanding of genetic abnormalities, interactions in the bone marrow microenvironment, developments in the diagnosis and staging in myeloma and introduction and incorporation of novel agents early in the disease course have been pivotal in the clinical treatment and management of patients with multiple myeloma. However, the burden associated with the disease, including treatment costs, is significant for Filipino patients as it is still incurable. In the Philippines, the introduction of bortezomib in the market in the last decade have brought hope to many patients by expanding the availability of treatment options, improving quality of life and extending survival. @*METHODS@#This paper documents the proceedings of a forum on multiple myeloma conducted last March 2018 at Makati City. The purpose of the forum was to discuss the major clinical presentations of the disease as well as treatment and management of selected patients. Speakers were hematology and medical oncology experts in the Philippines.@*RESULTS@#Five cases of multiple myeloma with different clinical presentations and management were discussed: (1) renal insufficiency, (2) easy fatigability, (3) bone pain, (4) autologous stem cell/bone marrow transplantation and (5) coagulopathy. Short videos of selected patients (or their family members) after each presentation was showed, describing their treatment journey with myeloma. Other patients with multiple myeloma who were treated with bortezomib were present in the forum and briefly shared their experiences.@*CONCLUSION@#As multiple myeloma is a highly heterogeneous molecular disease, approaches and provision of care will need to be individualized for each patient. Because of its impressive performance, bortezomib is likely to continue being an important part of the clinical treatment and management of Filipino patients with myeloma.
Subject(s)
BortezomibABSTRACT
Free light chains (FLCs) are tumour markers of monoclonal gammopathies. Detection of urinary FLC or also known as Bence-Jones protein through urinary protein and its immunofixation electrophoreses (UPE and uIFE, respectively) have been considered the gold standard for its biochemical diagnosis. This is mainly due to their superior detection limits compared to their counterpart investigations in serum. However, urinalysis is limited in many ways. The emergence of serum FLC assay with markedly improved detection limit circumvents many of these problems and has gained much importance in biochemical investigations of monoclonal gammopathies. Nevertheless, they are not without limitations. This review discusses the advantages and limitations of serum and urinary FLC assays.
ABSTRACT
La amiloidosis primaria es una gammapatía monoclonal caracterizada por la formación y depósito de fibrillas insolubles de amiloide en los espacios extracelulares de diversos órganos. El plegamiento y ensamblaje anormal de esta proteína, afecta predominantemente hígado, riñon, bazo y nervios periféricos. Estos pacientes presentan una población monoclonal de células plasmáticas en médula ósea que produce constantemente pequeños fragmentos de cadenas ligeras lambda, kappa, o inmunoglobulinas, que son procesadas de manera anómala. Su infrecuencia y múltiples manifestaciones hacen del diagnóstico un reto para el clínico, quien ante su sospecha, deberá diferenciarla de otras discrasias de células plasmáticas, por lo cual el examen físico minucioso e incisivo juega un papel fundamental en el proceso diagnóstico. En este caso presentamos a un paciente masculino de 54 años cuyo cuadro clínico es caracterizado por edema y máculas hiperpigmentadas circunscritas y descamativas en cabeza y miembros superiores, y laboratorios que revelan anemia, trombocitopenia, hipoalbuminemia, hiperglobulinemia y proteinuria. Ante la sospecha clínica de amiloidosis primaria sistémica se realiza biopsia de grasa periumbilical, donde se visualizan depósitos amiloides en tinción con rojo Congo. Posterior a tratamiento con prednisona, dexametasona y talidomida presenta respuesta hematológica por lo que recibe alta médica al alcanzar mejoría clínica satisfactoria. La ausencia de reporte de casos y revisiones de literatura en nuestra población obliga a presentar este reporte y revisión como referencia diagnóstica y terapéutica.
Primary systemic amyloidosis is a monoclonal gammopathy characterized by the synthesis and extracellular deposition of an insoluble fibrillar protein, the amyloid protein, in a variety of tissues and organs. Its three dimensional beta pleated sheet configuration and abnormal assembly mostly affects liver, kidneys, spleen and peripheral nerves. Patients show free light lambda, kappa and immnoglobulin chains that are abnormally produced by monoclonal plasmatic cell population. Its infrequency and multiple manifestations make its diagnosis a challenge for the physician, who will need to be able to differentiate it from other plasma cell dyscrasias, thus, sharp physical examination plays a key role in diagnostic process. In this case we present a 54 years old male patient consulting for edema and upper limbs descamative and well defined hyperpigmented skin lesions, revaaling anemia, thrombocytopenia, hypoalbuminemia, hyperglobulinemia and proteinuria by laboratory test. In clinical suspect of primary systemic amyloidosis, periumbilical fat biopsy was performed detecting, by Congo red staining, amyloid deposits. Then, after prednisone, dexametasone and thalidomide chemotherapy was stablished, hematologic response and medical discharge was successfully archived. Because no autochthonous case reports have been published, we feel the need to present this one, and its revision, as a diagnostic and therapeutic primary systemic amyloidosis guideline.
Subject(s)
Humans , Male , Middle Aged , Amyloidosis/diagnosis , Amyloidosis/pathology , Dexamethasone/therapeutic use , /diagnosis , Fibril-Associated Collagens , Salmonella Infections/etiology , Paraproteinemias/pathology , Prednisone/therapeutic useABSTRACT
O transplante de células-tronco hematopoéticas (TCTH) é um procedimento de fundamental importância na estratégia terapêutica das gamopatias monoclonais. No mieloma múltiplo, em particular, o TCTH autólogo está indicado como estratégia de primeira linha para pacientes até 70 anos de idade. Nesta capítulo serão discutidas as indicações, estratégias e recomendações envolvendo o TCTH em gamopatias monoclonais, amiloidose e POEMS, frutos da Reunião de Consenso da Sociedade Brasileira de Transplante de Medula Óssea.
Hematopoietic stem cell transplantation (HSCT) is an important strategy in the treatment of monoclonal gammopathies. For multiple myeloma, in particular, autologous HSCT is indicated as first line therapy for under 70-year-old patients. In this chapter we will discuss indications, strategies and recommendations involving HSCT for monoclonal gammopathies from the Consensus Meeting of the Brazilian Society of Bone Marrow Transplantation.
Subject(s)
Humans , Hematopoietic Stem Cell Transplantation , Multiple Myeloma , ParaproteinemiasABSTRACT
Objective To explore the outcome of monoclonal gammopathy of undetermined significance (MGUS). Methods The data from 14 MGUS patients in our hospital including clinical features, outcome and change of M protein concentration were analyzed retrospectively. Results The MGUS didn't have the clinical manifestations of multiple myeloma (MM), the time of outcome from MGUS to MM was about 4-20 years (mean time, 10 years). The most types of MM were IgA and IgG, 6 cases were IgA type, 6 cases were IgG type and 2 cases were light chain type. The concentration of immune globulin in general showed an upward trend year by year. A few showed fold lines ascend. Conclusions The elevated monoclonal immunoglobulin may develop into MM after many years. We must follow up frequently to avoid error diagnosis and missed diagnosis.
ABSTRACT
As gamopatias monoclonais constituem um grupo de desordens caracterizado pela proliferação monoclonal de plasmócitos, que produzem e secretam imunoglobulina ou fragmento de imunoglobulina monoclonal (proteína M) . Este artigo propõe uma revisão dos critérios diagnósticos das principais gamopatias monoclonais e diagnósticos diferenciais, uma vez que é comum a sobreposição de muitas características clínicas entre suas variantes. A gamopatia monoclonal de significado indeterminado (MGUS) é definida pela presença de proteína M sérica < 3,0 g/dL e/ou urinária < 1g/24h, infiltração plasmocitária medular menor que 10 por cento e ausência de danos aos órgãos e tecidos. O mieloma múltiplo (MM) assintomático caracteriza-se pela presença de proteína M, infiltração plasmocitária na medula óssea ou em tecido biopsiado e ausência de critérios para MGUS, MM sintomático e plasmocitoma solitário. O MM sintomático é uma neoplasia plasmocitária associada à proteína M sérica e/ou urinária, infiltração medular por plasmócitos e presença de dano orgânico relacionado: hipercalcemia, insuficiência renal, anemia e lesões ósseas. Se a proteína M não é detectada (MM não secretor), a plasmocitose medular precisa ser > 30 por cento ou plasmocitoma documentado por biópsia. Se a lesão óssea decorre de plasmocitoma solitário ou somente osteoporose, sem fratura, a plasmocitose medular também precisa ser > 30 por cento, para preencher critérios de MM. As gamopatias monoclonais podem estar associadas a diversas doenças, incluindo desordens linfoproliferativas, reumatológicas, neurológicas, dermatológicas e infecciosas. A definição das características clínicas e laboratoriais de cada entidade, maligna ou benigna, facilita o diagnóstico das gamopatias monoclonais e, como conseqüência, seu manejo clínico pelos médicos assistentes.
Monoclonal gammopathies are a group of disorders characterized by proliferation of monoclonal plasma cells, which produce and secrete monoclonal immunoglobulin or fragments of monoclonal immunoglobulin (M protein). This paper proposes to review diagnostic criteria of the most important monoclonal gammopathies and their differential diagnosis, because superposition of many clinical characteristics is common between variants. The monoclonal gammopathy of undetermined significance (MGUS) is defined by the presence of serum M protein < 3g/dL and/or urinary M protein < 1g/24h, bone marrow plasma cell < 10 percent, and absence of organ and tissue damage. Asymptomatic multiple myeloma (MM) is characterized by the presence of M protein, bone marrow or tissue biopsy plasma cell infiltration, and non-compliance of the criteria for MGUS, symptomatic MM and solitary plasmacytoma. Symptomatic MM is a plasma cell neoplasm associated with serum or urinary M protein, bone marrow or tissue biopsy plasma cell infiltration and related organ or tissue damage: elevated calcium levels, renal insufficiency, anemia and bone lesions. If no M protein is detected (nonsecretory MM), then at least 30 percent monoclonal bone marrow plasma cell infiltration and/or a biopsy-proven plasmacytoma is required for MM diagnosis. If a solitary (biopsy-proven) plasmacytoma or osteoporosis (without fractures) are the sole defining criteria, then at least 30 percent plasma cells are required in the bone marrow for MM diagnosis. Monoclonal gammopathies may be associated with many different diseases, including lymphoproliferative disorders, connective tissue disorders, neurologic, dermatologic and infectious diseases. The clinical and laboratorial characteristics should be very well defined in each variant, malign or benign, easily determining the diagnosis of monoclonal gammopathies and then their clinical management.
Subject(s)
Humans , Diagnosis, Differential , Paraproteinemias , Paraproteinemias/diagnosisABSTRACT
As gamopatias monoclonais resultam de hiperprodução de um único clone anormal de células plasmocitárias ou linfócitos B. O objetivo da avaliação laboratorial nas gamopatias é demonstrar a presença, a quantidade e o tipo de proteína anormal presente no soro e/ou na urina através do estudo do perfil protéico, quantificação das imunoglobulinas e cadeias leves e avaliação da proteinúria. Este artigo descreve as principais técnicas laboratoriais disponíveis, bem como suas indicações e limitações.
Monoclonal gammopathies result from an overproduction of a single abnormal clone of a plasma cell or B lymphocyte. The purpose of the laboratory protocols in these situations is to demonstrate the presence, the characterization and the concentration of an abnormal protein detected in serum and/or urine samples. The laboratory investigation is based on the electrophoretic protein profile, quantification of immunoglobulins, free light chains and proteinuria. This paper describes the major available laboratory methods as well their indications and limitations.
Subject(s)
Humans , Blood Protein Electrophoresis , Electrophoresis , Immunoelectrophoresis , Immunoglobulin kappa-Chains , Immunoglobulin lambda-Chains , Immunoglobulins , Paraproteinemias , Diagnostic Techniques and ProceduresABSTRACT
Extramedullary plasmacytoma of the liver is a very rare tumor. Although a few cases of extramedullary plasmacytoma of the liver have been reported, we could not find any report on truly localized extramedullary plasmacytoma of the liver in the literature. The patient was a 63-yr-old man who exhibited a solitary liver mass on dynamic computed tomography and magnetic resonance imaging. Histologically, the tumor was composed of mature plasma cells with mild atypia. Immunohistochemistry demonstrated monoclonal IgG and Kappa light chain expression. Bone marrow examination revealed no abnormalities. There was no evidence of a monoclonal protein in the serum and urine, lytic bone lesions, anemia, renal insufficiency, and hypercalcemia. The patient was treated with 5,000 cGy of radiotherapy, and the tumor disappeared 6 months after treatment.
Subject(s)
Humans , Male , Middle Aged , Immunoglobulin G/analysis , Immunoglobulin kappa-Chains/analysis , Immunohistochemistry , Liver Neoplasms/immunology , Magnetic Resonance Imaging , Monoclonal Gammopathy of Undetermined Significance/immunology , Plasmacytoma/immunology , Tomography, X-Ray ComputedABSTRACT
Monoclonal gammopathies are associated with a wide range of renal diseases, including cast nephropathy, light chain amyloidosis, monoclonal immunoglobulin deposition diseases, and so on. We describe seven cases of monoclonal gammopathies involving kidney. The mean age was 61.6+/-3.6 years and male to female ratio was 1:1.3. Among 7 patients, diagnoses were cast nephropathy with light chain deposition disease, two light chain deposition diseases, three light chain amyloidosis and light chain deposition disease with light chain amyloidosis. Two cases were monoclonal gammopathy of undetermined significance and three cases were multiple myeloma in five cases underwent bone marrow biopsy. It showed that renal function was severly decreased in light chain deposition disease. It is clear that monoclonal gammopathies show various renal disease and clinical course in our cases. It is necessary to do renal biospy for adequate diagnosis and treatment even to old patients suspecting monoclonal gammopathy.