RESUMO
BACKGROUND: Plasma cell dyscrasias (PCD) are a heterogeneous group of diseases characterized by the expansion of monoclonal bone marrow plasma cells that produce a monoclonal immunoglobulin (M-component). PURPOSE: This is a retrospective study that describes the epidemiological, immunochemical features and etiology of monoclonal gammopathies diagnosed between 1998 and 2016 in the Teaching Hospital Beni-Messous of Algiers. PATIENTS AND METHODS: 2121 cases of monoclonal gammopathies (MG) were collected during this period. Serum/urine protein electrophoresis, serum/urine immunofixation and serum free light chain measurements were used to demonstrate M protein. RESULTS: The middle age of the patients at the time of the diagnosis were 62.96 ± 13.19 years with extremes ranging from 07 to 99 years. The study included 1013 (47, 76 %) men and 1108 (52, 23 %) women with a sex ratio 0,91. Isotypes repartition was: IgG (60.91 %), IgA (17.91 %), light chain (10.46 %), IgM (6.6 %), IgD (1.03 %) and IgE (0.09 %) of cases. The most frequent diagnosis was: Multiple Myeloma (55.20 %), followed by monoclonal gammopathy of undetermined significance (34.13 %). CONCLUSION: In our study, two particularities were noted. There is no male predominance in Algerian PCD patients. Moreover, we observed a higher frequency of light chain multiple myeloma and lower frequency of IgM isotype compared to western studies.
Assuntos
Isotipos de Imunoglobulinas/sangue , Paraproteinemias/epidemiologia , Paraproteínas/análise , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Argélia/epidemiologia , Criança , Comorbidade , Feminino , Humanos , Isotipos de Imunoglobulinas/urina , Cadeias Leves de Imunoglobulina/sangue , Cadeias Leves de Imunoglobulina/urina , Imunoglobulina M/sangue , Imunoglobulina M/urina , Masculino , Pessoa de Meia-Idade , Gamopatia Monoclonal de Significância Indeterminada/sangue , Gamopatia Monoclonal de Significância Indeterminada/epidemiologia , Mieloma Múltiplo/sangue , Mieloma Múltiplo/epidemiologia , Mieloma Múltiplo/urina , Paraproteinemias/sangue , Paraproteinemias/urina , Paraproteínas/urina , Estudos Retrospectivos , Distribuição por Sexo , Adulto JovemAssuntos
Análise Química do Sangue , Paraproteinemias/sangue , Paraproteinemias/urina , Paraproteínas/análise , Paraproteínas/urina , Guias de Prática Clínica como Assunto , Urinálise , Análise Química do Sangue/normas , Eletroforese das Proteínas Sanguíneas/normas , Humanos , Internacionalidade , Prontuários Médicos/normas , Paraproteinemias/diagnóstico , Reprodutibilidade dos Testes , Terminologia como Assunto , Urinálise/normasAssuntos
Medula Óssea/metabolismo , Cadeias lambda de Imunoglobulina/metabolismo , Síndrome Nefrótica/etiologia , Paraproteinemias/metabolismo , Paraproteinemias/fisiopatologia , Paraproteínas/metabolismo , Eletroforese das Proteínas Sanguíneas , Medula Óssea/imunologia , Exame de Medula Óssea , Humanos , Imunoeletroforese , Amiloidose de Cadeia Leve de Imunoglobulina/etiologia , Cadeias lambda de Imunoglobulina/análise , Cadeias lambda de Imunoglobulina/urina , Masculino , Pessoa de Meia-Idade , Paraproteinemias/sangue , Paraproteinemias/urina , Paraproteínas/análise , Paraproteínas/urina , Reprodutibilidade dos TestesAssuntos
Anticorpos Monoclonais/análise , Imunoglobulina M/análise , Cadeias kappa de Imunoglobulina/análise , Paraproteinemias/diagnóstico , Paraproteínas/análise , Idoso , Anticorpos Monoclonais/química , Anticorpos Monoclonais/urina , Eletroforese das Proteínas Sanguíneas , Humanos , Imunoeletroforese , Imunoglobulina M/química , Imunoglobulina M/urina , Cadeias kappa de Imunoglobulina/química , Cadeias kappa de Imunoglobulina/urina , Masculino , Mercaptoetanol/química , Peso Molecular , Oxirredução , Paraproteinemias/sangue , Paraproteinemias/urina , Paraproteínas/química , Paraproteínas/urina , Substâncias Redutoras/química , Reprodutibilidade dos Testes , Reagentes de Sulfidrila/químicaAssuntos
Eletroforese Capilar/métodos , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico , Imunofenotipagem/métodos , Paraproteínas/urina , Eletroforese em Gel de Ágar/instrumentação , Eletroforese em Gel de Ágar/métodos , Eletroforese Capilar/instrumentação , Taxa de Filtração Glomerular , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/imunologia , Amiloidose de Cadeia Leve de Imunoglobulina/patologia , Amiloidose de Cadeia Leve de Imunoglobulina/urina , Rim/imunologia , Rim/patologia , Miocárdio/imunologia , Miocárdio/patologia , Paraproteínas/imunologia , Estudos ProspectivosRESUMO
Recently, monoclonal gammopathy of renal significance (MGRS) reclassified all monoclonal (M) gammopathies that are associated with the development of a kidney disease but do not meet the definition of symptomatic multiple myeloma (MM) or malignant lymphoma. The purpose was to distinguish the M gammopathy as the nephrotoxic agent independent from the clonal mass. The diagnosis of MGRS obviously depends on the detection of the M-protein. More importantly, the success of treatment is correlated with the reduction of the M-protein. Therefore, familiarity with the M-protein tests is a must. Protein electrophoresis performed in serum or urine is inexpensive and rapid due to automation. However, poor sensitivity especially with the urine is an issue particularly with the low-level M gammopathy often encountered with MGRS. Immunofixation adds to the sensitivity and specificity but also the cost. Serum free light chain (sFLC) assays have significantly increased the sensitivity of M-protein detection and is relatively inexpensive. It is important to recognize that there is more than one assay on the market and their results are not interchangeable. In addition, in certain diseases, immunofixation is more sensitive than sFLC. Finally, novel techniques with promising results are adding to the ability to identify M-proteins. Using the time of flight method, the use of mass spectrometry of serum samples has been shown to dramatically increase the sensitivity of M-protein detection. In another technique, oligomeric LCs are identified on urinary exosomes amplifying the specificity for the nephrotoxic M-protein.
Assuntos
Nefropatias/diagnóstico , Paraproteinemias/diagnóstico , Paraproteínas/urina , Eletroforese das Proteínas Sanguíneas , Humanos , Imunoensaio , Imunoeletroforese , Cadeias Leves de Imunoglobulina/sangue , Cadeias Leves de Imunoglobulina/urina , Nefropatias/sangue , Nefropatias/etiologia , Nefropatias/urina , Limite de Detecção , Proteínas do Mieloma/análise , Paraproteinemias/sangue , Paraproteinemias/complicações , Paraproteinemias/urinaRESUMO
During the last decade, surveys by questionnaire in Canada, Australia and New Zealand revealed wide variation in reporting practices by laboratories and individual practitioners in the interpretation of serum and urine protein electrophoresis (PE). Such variation has potential to adversely impact patient outcomes if report structure is inconsistent or if the messaging is incorrectly perceived by the receiving physician. Concerted efforts have been initiated to promote harmonization in the use of interpretative comments. The primary goal is to add value through clear communication with requesting physicians in the interest of quality patient care. Resistance to a harmonized approach largely reflects longstanding personal reporting habits and preferences but change can be more readily embraced if the new system is intuitive, easy to use and saves time in reporting.
Assuntos
Eletroforese das Proteínas Sanguíneas/normas , Imunoeletroforese/normas , Paraproteínas/urina , Humanos , Projetos de PesquisaRESUMO
The reliable detection of paraprotein in serum and urine is the primary purpose of electrophoretic procedures in clinical laboratories. Screening immunofixation electrophoresis (sIFE) employs a single application of antisera directed against heavy and light chains that facilitates the detection of paraproteins that migrate in the non-γ region or that are below the detection limit of protein electrophoresis. These paraproteins that are missed by routine electrophoresis occur in up to 27.3% of newly investigated and 13.6% of monitored patients. Small paraproteins missed by conventional electrophoretic techniques are clinically important in the diagnosis and monitoring of malignant plasma and B-cell disorders. The superior diagnostic performance of sIFE makes it suitable as the initial laboratory procedure to investigate paraproteins in complex serum and urine matrices.
Assuntos
Eletroforese das Proteínas Sanguíneas/métodos , Imunoeletroforese/métodos , Paraproteinemias/diagnóstico , Humanos , Cadeias Leves de Imunoglobulina/sangue , Cadeias Leves de Imunoglobulina/urina , Limite de Detecção , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/imunologia , Paraproteinemias/sangue , Paraproteinemias/urina , Paraproteínas/urinaRESUMO
BACKGROUND: The categories of the International Myeloma Working Group (IMWG) response criteria for multiple myeloma are based on the magnitude of the change in paraprotein and the normalization of the free light chain ratio (rFLC). However, the relationship between the response by these biomarkers and clinical outcomes has not been validated with novel compounds in the phase 1 setting. Early response predictors may have prognostic value and speed development plans for new agents. METHODS: The relationship between biomarkers of response and clinical outcomes was examined in 87 relapsed or refractory multiple myeloma patients enrolled in nontransplant phase I clinical trials from January 2004 through November 2011 at 4 time landmarks. Progression-free survival (PFS) was the primary outcome, and overall survival (OS) was also assessed. RESULTS: The normalization of rFLC within 4 months predicted improvement in PFS (11.3 vs 2.8 months, P = .038), whereas the normalization of rFLC within 12 months predicted improvement in PFS (6.1 vs 2.8 months, P = .015) and OS (45 vs 17.4 months, P = .002). The magnitude of response in paraprotein predicted and correlated linearly with PFS at all time landmarks (R(2) = 0.703-0.943) when it was assessed with 2 different boundaries. CONCLUSIONS: These findings suggest that the normalization of rFLC and the magnitude of response are viable biomarkers for surrogate endpoints in early-phase clinical trials, validate the use of current IMWG response criteria in the phase 1 setting, and support the use of these biomarkers for drug development endpoints.
Assuntos
Biomarcadores Tumorais/metabolismo , Cadeias Leves de Imunoglobulina/sangue , Mieloma Múltiplo/metabolismo , Recidiva Local de Neoplasia/metabolismo , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/urina , Ensaios Clínicos Fase I como Assunto/métodos , Intervalo Livre de Doença , Determinação de Ponto Final , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/urina , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/urina , Paraproteinemias/sangue , Paraproteínas/urina , Prognóstico , Resultado do TratamentoRESUMO
AIM: To study the pathomorphology of kidneys in patients with multiple myeloma (MM) and severe renal failure (RF) and to compare the results of morphological, immunohistochemical, and electron microscopic examinations of nephrobiopsy specimens with the pattern of monoclonal secretion and the type of proteinuria and paraproteinuria. SUBJECTS AND METHODS: A study group comprised 25 patients with MM and severe RF; 22 of them underwent programmed hemodialysis. Immunochemical study of serum and urine proteins, renal puncture biopsy with light, immunofluorescence and electron microscopy examination of its specimens were performed in all the patients. RESULTS: Cast nephropathy (CN) is the most common type of renal impairment in patients with MM and severe RF. CN concurrent with monoclonal immunoglobulin deposition disease was identified in 32% of cases. In the mixed lesion, it is CN that is a determinant in the development of acute and chronic RF. Rare variants of nephropathies as fibrillary glomerulonephritis, immunotactoid nephropathy, and crystalline histiocytosis were found in 16% of cases. In most cases, severe RF in MM develops in case of low monoclonal secretion. However, there are a larger number of secreted and excreted monoclonal light chains in CN than in other variants of kidney lesion. Urinary paraprotein G excretion suggests that the glomerular filter is damaged. Degenerative changes in the podocytes and a reduction in their small processes were detected in the majority of cases. In glomerular or mixed proteinuria, there were also unorganized and organized deposits in the glomerular basement membrane. CONCLUSION: The pattern of nephropathy does not determine a renal response after chemotherapy. The reversibility of CN in MM depends on the magnitude of interstitial fibrosis and podocyte changes. The pronounced changes in the podocytes as a reduction in their small processes serves as a poor sign in achieving renal responses following chemotherapy.
Assuntos
Mieloma Múltiplo/patologia , Insuficiência Renal/patologia , Adulto , Idoso , Anticorpos Monoclonais/biossíntese , Anticorpos Monoclonais/sangue , Feminino , Fibrose/patologia , Glomerulonefrite/sangue , Glomerulonefrite/patologia , Glomerulonefrite/urina , Humanos , Cadeias Leves de Imunoglobulina/biossíntese , Cadeias Leves de Imunoglobulina/sangue , Cadeias Leves de Imunoglobulina/urina , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Mieloma Múltiplo/urina , Paraproteinemias/sangue , Paraproteinemias/patologia , Paraproteinemias/urina , Paraproteínas/metabolismo , Paraproteínas/urina , Podócitos/patologia , Insuficiência Renal/sangue , Insuficiência Renal/urina , Índice de Gravidade de DoençaRESUMO
BACKGROUND: The objective of this study was to review the outcome of patients with solitary plasmacytoma (SP) after definitive radiation therapy. METHODS: The authors retrospectively reviewed 84 patients with SP who were diagnosed and treated at The University of Texas MD Anderson Cancer Center during 1988 to 2008. The impact of tumor anatomic site, tumor size, and the presence of serum and urinary paraprotein at diagnosis was assessed on local control, survival, and the risk of developing multiple myeloma (MM). RESULTS: Fifty-nine patients (70%) had bone SP, and 25 patients (30%) had extramedullary SP. Serum paraprotein was present in 39 patients (46%). The median radiation dose was 45 grays (Gy) (range, 36-53.4 Gy). Local control was achieved in 77 patients (92%). Neither radiation dose nor tumor size predicted local control. The 5-year rate of progression to MM was 47% and was higher for patients with bone SP (56% vs 30% for extramedullary SP; P = .021), and patients who had serum paraprotein detected at diagnosis (60% vs 39%; P = .016). On univariate analysis, patients aged <60 years and men had higher rates of progression to MM, although the differences were not significant (P = .048 and P = .29, respectively). Multivariate analysis revealed that bone location and serum protein at diagnosis were associated statistically with progression to MM. The 5-year overall survival rate for the entire patient cohort was 78%, and no difference was observed between patients who had bone SP versus extramedullary SP (76% vs 85%, respectively; P = .274). CONCLUSIONS: The current results indicated that definitive radiation therapy for SP can provide excellent local control. Progression to MM remains the main problem and is more common among patients with bone SP and those who have serum paraprotein detected at diagnosis.
Assuntos
Neoplasias Ósseas/diagnóstico , Mieloma Múltiplo/diagnóstico , Neoplasias Induzidas por Radiação/diagnóstico , Paraproteínas/metabolismo , Paraproteínas/urina , Plasmocitoma/radioterapia , Radioterapia/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/sangue , Neoplasias Ósseas/etiologia , Neoplasias Ósseas/urina , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Mieloma Múltiplo/etiologia , Mieloma Múltiplo/urina , Neoplasias Induzidas por Radiação/sangue , Neoplasias Induzidas por Radiação/etiologia , Neoplasias Induzidas por Radiação/urina , Plasmocitoma/mortalidade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Monoclonal components (MCs) are frequently detected in the sera of patients with B-cell malignancies, by techniques that are getting more and more sensitive. Only few chronic lymphocytic leukemia (CLL) patients with multiple serum paraproteins are reported in the literature. METHODS: In this case report we present a 71-year-old woman with CLL and serum MCs. Immunofixation was performed on agarose film using anti-sera monospecific for the heavy and light chains of human immunoglobulins (anti-gamma, -alpha, -mu, -delta, -epsilon, -kappa, -lambda). Serum free light chains (FLCs) were quantified nephelometrically. Immunofluorescence analysis was performed using fluorochrome-conjugated goat antibodies specific for human mu, gamma or alpha immunoglobulin heavy chains and K or lamda light chains. RESULTS: Immunofixation revealed two different MCs (IgGlambda + lambda light-chains) in the serum and only one MC (lambda light chains) in concentrated urine. Serum lamda FLCs were 206 mg/L. The bone marrow aspiration and biopsy revealed a 38 % interstitial and nodular infiltration of mature small lymphocytes expressing IgG lambda surface immunoglobulins CD 19, CD20, CD5, and CD23, with negative BCL-1, t(11, 14) and cyclin D1. The plasma cells were less than 1%. Final diagnosis was CLL (Rai stage I) with IgG lamda plus lamda serum paraproteins. Three years later, the patient died because of myocardial infarction after a follow-up period with no need for CLL therapy. CONCLUSIONS: Our hypothesis is that the double MC may be the result of an unbalanced immunoglobulin chain synthesis by the leukemic B-cell clone, resulting in IgGlamda and excess of lambda FLCs.
Assuntos
Imunoglobulina G/sangue , Cadeias lambda de Imunoglobulina/sangue , Leucemia Linfocítica Crônica de Células B/imunologia , Paraproteinemias/sangue , Paraproteínas/análise , Idoso , Eletroforese em Gel de Ágar , Feminino , Imunofluorescência , Humanos , Imunoglobulina G/urina , Cadeias lambda de Imunoglobulina/urina , Leucemia Linfocítica Crônica de Células B/sangue , Leucemia Linfocítica Crônica de Células B/urina , Nefelometria e Turbidimetria , Paraproteinemias/urina , Paraproteínas/urinaAssuntos
Imunoglobulina M/sangue , Cadeias kappa de Imunoglobulina/sangue , Cadeias lambda de Imunoglobulina/sangue , Paraproteinemias/sangue , Idoso , Eletroforese das Proteínas Sanguíneas , Humanos , Imunoglobulina M/urina , Cadeias kappa de Imunoglobulina/urina , Cadeias lambda de Imunoglobulina/urina , Masculino , Paraproteinemias/diagnóstico , Paraproteinemias/urina , Paraproteínas/análise , Paraproteínas/urina , Valores de ReferênciaAssuntos
Cadeias Leves de Imunoglobulina/urina , Paraproteínas/urina , Humanos , Imunoensaio , Cadeias Leves de Imunoglobulina/sangue , Cadeias kappa de Imunoglobulina/sangue , Cadeias kappa de Imunoglobulina/urina , Cadeias lambda de Imunoglobulina/sangue , Cadeias lambda de Imunoglobulina/urina , Sensibilidade e EspecificidadeRESUMO
Salvage therapy of patients with advanced, relapsed and refractory multiple myeloma (MM) is often limited by poor marrow reserve and multi-organ impairment. In particular, renal failure occurs in up to 50% of such patients, and this further limits the use of conventional chemotherapy. Thalidomide, both alone and in combination with dexamethasone, has been demonstrated to be useful in patients with advanced MM, as responses could be achieved in 30-60% of the cases. From May 2000 to November 2003, 20 consecutive MM patients (15 males, five females, median age 66.5 yr) with stage III relapsed/refractory MM and renal failure, defined as serum creatinine >130 mmol/L, gave their informed consent to be enrolled in a clinical trial aimed at evaluating the efficacy and the toxic effects of thalidomide. Three patients were undergoing chronic haemodialysis during the time of entry in the study. Eight patients have been treated with thalidomide as a single agent, at a starting dose of 100 mg/d, that was to be increased to 400 mg/d in case of good tolerance. Twelve patients have been treated with thalidomide at the maximum dose of 200 mg/d plus dexamethasone 40 mg/d for four consecutive days every 4 wk. A >50% decrease in serum or urine M component was observed in nine patients (45%), seven of whom have been treated with thalidomide + dexamethasone and three with thalidomide alone. Six additional patients achieved a minor response (>25% paraprotein decrease); the total response rate was thus 75%. Median response duration was 7 months (range 2-24 months). Four patients were refractory to treatment. Recovery of a normal renal function was observed in 12 of 15 responsive patients, two additional patients, in chronic haemodialysis, showed a reduction of serum creatinine. Toxicity profile of thalidomide with or without dexamethasone was comparable with that observed in patients with a normal renal function. In conclusion, our data show that thalidomide can be safely administered in patients with advanced MM and renal failure.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Insuficiência Renal/etiologia , Terapia de Salvação/métodos , Talidomida/administração & dosagem , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Dexametasona/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , Mieloma Múltiplo/mortalidade , Proteínas do Mieloma/urina , Paraproteínas/urina , Diálise Renal , Insuficiência Renal/tratamento farmacológico , Talidomida/toxicidade , Resultado do TratamentoRESUMO
Investigation of effective biomarkers for cancers is currently a popular area of study in clinical and cancer researches, because it can potentially lead to pre-cancer screening or pre-cancer diagnosis and may provide useful information on cancer type and the disease's stage of progression. More and more biochemical or chemical fluid components of the human body such as urine, blood, and cerebrospinal fluid have been considered to contain biomarkers, which are useful in cancer researches, pre-cancer diagnosis, and cancer follow-ups during or after cancer treatment. Several modern analytical techniques, such as gas chromatography (GC), high-performance liquid chromatography (HPLC), capillary electrophoresis (CE), and other separation techniques as well as hyphenated techniques, have been extensively used in study of cancer biomarkers. Among these techniques, CE is considered to be a highly efficient and practical analytical technique because of the small sample volume requirement and its wide separation versatility, ranging from small inorganic molecules to large biomolecules. This review discusses the latest developments involving biomarkers and their analysis by CE, including a discussion of instrumental conditions, method developments, and data analysis.
Assuntos
Biomarcadores Tumorais/análise , Proteínas Sanguíneas/análise , Ácido N-Acetilneuramínico/análise , Nucleosídeos/análise , Paraproteínas/análise , Biomarcadores Tumorais/urina , Proteínas Sanguíneas/urina , Dano ao DNA/fisiologia , Eletroforese Capilar , Humanos , Ácido N-Acetilneuramínico/urina , Nucleosídeos/urina , Paraproteínas/urina , Proteoglicanas , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
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.
Assuntos
Paraproteínas/imunologia , Paraproteínas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Viscosidade Sanguínea/fisiologia , Crioglobulinas/metabolismo , Feminino , Seguimentos , Humanos , Imunoglobulina A/imunologia , Imunoglobulina A/metabolismo , Imunoglobulina G/imunologia , Imunoglobulina G/metabolismo , Imunoglobulina M/imunologia , Imunoglobulina M/metabolismo , Linfoma não Hodgkin/sangue , Linfoma não Hodgkin/imunologia , Linfoma não Hodgkin/urina , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/urina , Paraproteínas/urina , Austrália do Sul/epidemiologia , Macroglobulinemia de Waldenstrom/sangue , Macroglobulinemia de Waldenstrom/imunologia , Macroglobulinemia de Waldenstrom/urinaRESUMO
AIM: Bisphosphonates are potent inhibitors of osteoclastic activity and are used in the treatment of multiple myeloma (MM) in combination with chemotherapy. The effect of pamidronate on markers of bone resorption [cross-linked N-telopeptides of type I collagen (NTx)], markers of bone formation [serum alkaline phosphatase (BAP) and osteocalcin (OSC)], interleukin-6 (IL-6), beta2-microglobulin, CRP, paraprotein and disease-related pain and skeletal events has been evaluated in 62 newly diagnosed patients with MM. PATIENTS AND METHODS: The patients were randomly assigned to two groups: the first included 32 patients under chemotherapy and pamidronate (group I) and the second 30 patients on chemotherapy only (group II). Pamidronate was administered at a monthly dose of 90 mg iv, and the above parameters were evaluated at the beginning of this study and after 1, 3, 6, 9, 12 and 14 months of treatment. RESULTS: The addition of pamidronate to chemotherapy resulted in a significant reduction of NTx, IL-6 and paraprotein from the 3rd month and of beta2-microglobulin, CRP and pain from the 6th month of treatment. No changes of NTx, IL-6, beta2-microglobulin, CRP or skeletal events were observed in patients of group II, while paraprotein was significantly reduced after 6 months of treatment. The differences in NTx, IL-6, paraprotein and beta2-microglobulin were statistically significant between the two groups. Multivariate analysis revealed a significant correlation between changes of NTx, changes of IL-6 in both groups and reduction of pain and paraprotein in group I. CONCLUSIONS: These results suggest that pamidronate may have a synergistic action with chemotherapy in decreasing osteoclastic activity, in reducing markers of myeloma activity and myeloma related pain and in improving the quality of life in patients with MM.
Assuntos
Remodelação Óssea/efeitos dos fármacos , Difosfonatos/farmacologia , Mieloma Múltiplo/complicações , Mieloma Múltiplo/tratamento farmacológico , Idoso , Fosfatase Alcalina/urina , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Biomarcadores/urina , Reabsorção Óssea/tratamento farmacológico , Reabsorção Óssea/etiologia , Reabsorção Óssea/urina , Proteína C-Reativa/urina , Colágeno/urina , Colágeno Tipo I , Difosfonatos/administração & dosagem , Difosfonatos/toxicidade , Avaliação de Medicamentos , Feminino , Humanos , Interleucina-6/urina , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/metabolismo , Análise Multivariada , Osteocalcina/urina , Medição da Dor/efeitos dos fármacos , Pamidronato , Paraproteínas/urina , Peptídeos/urina , Fatores de Tempo , Microglobulina beta-2/urinaRESUMO
Pseudoparaproteins were observed in 129 (10.5%) of 1,229 high resolution protein electrophoretic fractionations of serum (N = 847), urine (N = 368), or cerebrospinal fluid (N = 14) performed in this laboratory during a 12-month period. The pseudoparaproteins identified in serum electrophoretic patterns included fibrinogen, C-reactive protein, hemoglobin-haptoglobin complex, elevated beta-globulins (transferrin and C3), lysozyme (muramidase), and an extended migration artifact. In the electrophoretic patterns of urine, the pseudoparaproteins consisted of nonspecific gamma zone bands of varying intensity. Gamma zone trace protein in the cerebrospinal fluid was often of sufficient intensity to cause potential confusion with oligoclonal bands. Awareness of the characteristic electrophoretic migration positions of these pseudoparaproteins helps to avoid unnecessary ancillary testing and expense.
Assuntos
Artefatos , Paraproteínas/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas Sanguíneas/análise , Proteínas do Líquido Cefalorraquidiano/análise , Eletroforese em Gel de Ágar/métodos , Feminino , Hospitais Comunitários , Humanos , Masculino , Pessoa de Meia-Idade , Ohio , Paraproteínas/urina , Estudos RetrospectivosRESUMO
We have retrospectively analysed 344 multiple myeloma (MM) patients (202 de novo patients) treated in a non-uniform way in whom high-dose therapy and autologous stem cell transplantation (ASCT) response was simultaneously measured by both electrophoresis (EP) and immunofixation (IF). Patients in complete remission (CR) by EP were further subclassified as CR1 when IF was negative and CR2 when it remained positive. Partial responders (PR) were also subclassified as PR1 (very good PR, > 90% reduction in M-component) or PR2 (50-90% reduction). CR1 patients showed a significantly better event-free survival (EFS) [35% at 5 years, 95% confidence interval (CI) 17-53, median 46 months] and overall survival (OS) (72% at 5 years, CI 57-86, median not reached) compared with any other response group (univariate comparison P < 0.00000 to P = 0. 004). In contrast, comparison of CR2 with PR1 and with PR2 did not define different prognostic subgroups (median EFS 30, 30 and 26 months respectively, P = 0.6; median survival 56, 44 and 42 months respectively, P = 0.5). The non-responding patients had the worst outcome (5-year OS 8%, median 7 months). Multivariate analysis confirmed both the absence of differences among CR2, PR1 and PR2 and the highly discriminatory prognostic capacity of a three-category classification: (i) CR1 (ii) CR2 + PR1 + PR2, and (iii) non-response (EFS P < 0.00000; OS P < 0.00000; both Cox models P < 0.00000). In the logistic regression analysis, the factors significantly associated with failure to achieve CR1 were the use of two or more up-front chemotherapy lines, status of non-response pre-ASCT and inclusion of total body irradiation (TBI) in the preparative regimen. Tandem transplants or the use of multiple agents (busulphan and melphalan) in the preparative regimen resulted in a higher CR1 level; none of the biological factors explored influenced the possibility of achieving CR1. These results confirm that, in MM patients undergoing ASCT, achieving a negative IF identifies the patient subset with the best prognosis; accordingly, therapeutic strategies should be specifically designed to achieve negative IF.