Impact of the lactate dehydrogenase in association with the International Staging System prognostic score in multiple myeloma patients treated in real life

Abstract Introduction Multiple myeloma is characterized by proliferation of clonal plasma cells. The identification of prognostics factors to identify patient's risk is important. Among the studied factors, it was identified of relevant importance the lactic dehydrogenase. Objectives To evaluate the impact of the value of DHL in combination with the score ISS in the medium patients overall survival (OS). Methods It is a retrospective cohort with 252 patients with MM recently-diagnosed that attendance in the institution of the study. Results To evaluate the association between DHL and ISS, we found 6 new groups to be analyzed: ISS I and normal DHL with medium overall survival not reached, and with DHL loud with medium OS of 69,8 months, ISS II and normal DHL with medium overall survival of 78,8 months and with DHL loud with medium OS of 73,9 months, ISS III and normal DHL with medium overall survival of 46,7 months and with DHL loud with medium OS of 45,5 months. Conclusion Through the association of ISS I and normal DHL, ISS III and high DHL and others combinations, we build a new score with superior impact prognostic in our population treated in real life.

Superiority of the triple combination of bortezomib, cyclophosphamide and dexamethasone versus cyclophosphamide, thalidomide and dexamethasone in patients with newly diagnosed multiple myeloma, eligible for transplantation

ABSTRACT Background: The treatment of multiple myeloma (MM) has evolved significantly in the past decade, and new drug combinations have improved the response rates and prolonged survival. Studies comparing different induction chemotherapy regimens have shown that triple combinations have better results than double combinations. However, comparisons among different triple combinations are rare in the literature. Methods: We retrospectively compared two triple combinations comprising bortezomib, cyclophosphamide and dexamethasone (VCD) versus thalidomide, cyclophosphamide and dexamethasone (CTD), and aimed at identifying which of the two combinations would yield better response rates following four induction cycles prior to hematopoietic cell transplantation in patients with untreated multiple myeloma. Results: We retrospectively reviewed the medical records of 311 patients from 24 different centers.The VCD regimen was used as induction therapy by 117 (37.6%) patients, whereas 194 (62.4%) patients received the CTD regimen. After four cycles of induction on an intention-to-treat basis, 54% of the patients in the VCD group achieved at least very good partial response versus 42.8% in the CTD group (p = 0.05). We observed no difference in neuropathy or thrombotic events rates among the two regimens. Conclusion: Our results corroborate the superiority of the triple combination regimes containing bortezomib over the triple combination with thalidomide as pre ASCT induction therapy in MM.

New proteasome inhibitors in the treatment of multiple myeloma

Abstract The treatment of patients with relapsed and/or refractory multiple myeloma has improved considerably in the last 15 years, after the introduction of proteasome inhibitors and immunomodulatory drugs. The first clinical trials with new proteasome inhibitors have produced exciting results, particularly those comparing triplet regimens with standard doublet regimens, with a gain in progression-free survival accompanied by an acceptable safety profile and either similar or better health-related quality of life. New proteasome inhibitors hold the potential to fill unmet needs in multiple myeloma management regarding improvement of clinical outcomes, including delayed progression of disease in high-risk patients. This review summarizes the main pharmacological properties and clinical outcomes of these agents, and discusses their potential to change the whole multiple myeloma therapeutic landscape.

Multiple myeloma and central nervous system involvement: experience of a Brazilian center

Abstract Introduction: The estimated involvement of the central nervous system in patients with multiple myeloma is rare at about 1%. The infiltration can be identified at the time multiple myeloma is diagnosed or during its progression. However, it is more common in refractory disease or during relapse. Methods: This retrospective cohort study reviewed data from medical records of patients followed up at the Gammopathy Outpatient Clinic of Santa Casa de Misericórdia de São Paulo from January 2008 to December 2016. Results: Twenty patients were included, with a median follow-up of 33.5 months after central nervous system infiltration. The prevalence was 7%. The median age at diagnosis of multiple myeloma was 56.1 years, with 70% of participants being female. Sixteen patients had central nervous system infiltration at diagnosis of multiple myeloma. Seventeen patients had exclusive osteodural lesions and three had infiltrations of the leptomeninge, of which one had exclusive involvement and two had associated osteodural lesions. The median overall survival was 40.3 months after central nervous system involvement. The median overall survival in the group with central nervous system infiltration at relapse was 7.4 months. The patients with leptomeningeal involvement had a median overall survival of 5.8 months. Conclusion: Central nervous system infiltration is a rare condition, but it should be considered as a possibility in patients with multiple myeloma and neurological symptoms. The best treatment regimen for this condition remains unknown and, in most cases, the prognosis is unfavorable.

For survival, the emergence of oligoclonal bands after multiple myeloma treatment is less important than achieving complete remission

Abstract Background: The emergence of oligoclonal bands, proteins differing from those originally identified at diagnosis, has been reported in multiple myeloma patients after high-dose chemotherapy followed by autologous stem cell transplantation and after successful conventional chemotherapy. The clinical relevance of oligoclonal bands remains unclear, but their emergence has been associated with better prognosis. The aim of the present study was to determine the prevalence, clinical characteristics and prognostic impact of the presence of oligoclonal bands in multiple myeloma patients. Methods: A retrospective cohort study was conducted. The study included newly diagnosed multiple myeloma patients with at least very good partial response after conventional dose or high-dose chemotherapy followed by autologous stem cell transplantation. The emergence of oligoclonal bands was identified using serum protein electrophoresis as well as serum and urine immunofixation techniques. Results: A total of 101 patients were included with a median follow-up of 42 months. In total, 55% were male, and the median age was 58 years (29-87 years). Fifty-one (50.5%) patients developed oligoclonal bands. They comprised 60% (45/75) of patients treated with autologous stem cell transplantation and 23% (6/26) of those who were not transplanted. Patients with oligoclonal bands showed better progression-free survival than those without the emergence of oligoclonal bands (p-value = 0.0075). Conclusion: The prevalence of oligoclonal bands in this study population was 50.5% with its frequency being greater in cases treated with autologous stem cell transplantation and in those attaining complete remission. Complete remission was more important than the emergence of oligoclonal bands on progression-free survival.

Serum free light chain assays not total light chain assays are the standard of care to assess Monoclonal Gammopathies

Abstract The diagnosis of Multiple Myeloma is a challenge to the physician due to the non-specific symptoms (anemia, bone pain and recurrent infections) that are commonplace in the elderly population. However, early diagnosis is associated with less severe disease, including fewer patients presenting with acute renal injury, pathological fractures and severe anemia. Since 2006, the serum free light chain test Freelite® has been included alongside standard laboratory tests (serum and urine protein electrophoresis, and serum and urine immunofixation) as an aid in the identification of monoclonal proteins, which are a cornerstone for the diagnosis of Multiple Myeloma. The serum free light chain assay recognizes the light chain component of the immunoglobulin in its free form with high sensitivity. Other assays that measure light chains in the free and intact immunoglobulin forms are sensitive, but unfortunately, due to the nomenclature used, these assays (total light chains) are sometimes used in place of the free light chain assay. This paper reviews the available literature comparing the two assays and tries to clarify hypothetical limitations of the total assay to detect Multiple Myeloma. Furthermore, we elaborate on our study comparing the two assays used in 11 Light Chain Multiple Myeloma patients at presentation and 103 patients taken through the course of their disease. The aim of this article is to provide a clear discrimination between the two assays and to provide information to physicians and laboratory technicians so that they can utilize the International Myeloma Working Group guidelines.

Outcomes of autologous transplantation for multiple myeloma according to different induction regimens

Background: Induction therapy followed by high-dose chemotherapy and autologous transplantation is the standard treatment for suitable patients with multiple myeloma. Objective: The aim of this study was to assess whether induction therapy with thalidomidecontaining regimens was associated with improved results compared to vincristine, doxorubicin, and dexamethasone, and whether cyclophosphamide, thalidomide, and dexamethasone were associated with better results than thalidomide and dexamethasone. Methods: The records of 152 patients who underwent autologous transplantation at this institution from August of 2004 to January of 2012 were reviewed, selecting those with at least partial response to a maximum of eight cycles of induction therapy and sufficient follow-up information for analysis. Results: This study included 89 patients; 44 were female, with a mean age of 55 years (there was a significant trend for increasing age over the years of the study).The median number of induction therapy cycles was four, again with a trend of increase over the years.At least a very good partial response to induction therapy was achieved more often in the cyclophosphamide, thalidomide, and dexamethasone group (61.1%) and in the thalidomide and dexamethasone group (59.2%) than in the vincristine, doxorubicin, and dexamethasone group (16.2%). The overall median progression-free survival was 34 months, with no statistically significant difference between the three groups. The overall median survival was not reached, and there was no significant difference between the three groups; the estimated five-year overall survival was 55%. Conclusion: Although the quality of responses appeared to be better with thalidomidecontaining regimens, these improvements did not translate into improved long-term outcomes. Given its track record, cyclophosphamide, thalidomide, and dexamethasone is currently considered the preferred regimen for first-line ...

Mieloma múltiplo no Brasil: aspectos clínicos, demográficos e validação do Sistema de Estadiamento Internacional (ISS) em pacientes brasileiros / Multiple myeloma in Brazil: clinicl and demographic aspects and International Staging System (ISS) validations for Brazilian patients

Durante o VI Simpóso Ítalo Brasileiro em Onco-Hematologia e Transplante de Medula Óssea apresentarei os resultados do estudo epidemiológico do mieloma múltiplo no Brasil. O mieloma múltiplo é a segunda neoplasia hemaológica mais frequente. Há poucos registros sobre a incidência e aspectos clínicos do mieloma múltiplo em grupos étnicos da Aérica Latina. No Brasil, por exemplo, a incidência de mielma múltiplo é desconhecida, uma vez que a doença não aparece nas estimtivas anuais fornecidas pelo Instituto Nacional de Câncer. A sobrevida mediana atual de pacientes com mieloma múltiplo é de aproximdamente três ano, mas há uma alta variabildade no prognóstico devido à heterogeneidade na biologia do mieloma múltiplo e nos fatores relacionados ao hospedeiro. O sistema de estadiamnto clínico de Durie-Salmon é preditivo de sobrevida global, permanecendo como o sistema de estadiamento mais amplamente utilizado por mais de 25 anos. Durante esse tempo, poucos parâmetros prognósticos novos surgiram com a beta2 microglobulina emergindo como o fator prognóstico mais poderoso, sendo simples e confiável na previsão de sobrevida. Estudos subsequentes sugeriram que a abumina era um outro indicaor prognóstico poderoso e de fácil aplicacação para o mieloma múltiplo. Recentemente, um painel internacional de investigadores apresentou o Sistema de Estadiamnto Internacional (International Staging System, ISS) par o mieloma múltiplo, uma escala de prognóstico que leva em conta a beta2 microglobulina sérica e a albumina como fatores significativos em análise multivariada, classificando então os pacientes em três grupos de risco. O Sistema ISS foi validado com pacientes da América do Norte, Europa e Ásia, mas não foi aplicado em um banco de dados do Brasil. Para avaliar os aspectos demográficos e clínicos dos pacientes com mieloma múltiplo no Brasil e observar se estas características são semelhantes às encontradas nos diferentes países da América do Sul e a outros países da Europa...

During the VI Italo-Brasilian Syposium on Onco-Hematology and Bone Marrow Transplatation, I will present the findings of the Epidemiological Study of Multiple Myeloma in Brazil. Multiple Myeloma is the second most frequent hematologic neoplasia. There are few records on the incidence and clinical aspects of multiple myeloma in ethic groups in Latin America. In Brasil, for example, the incidence of multiple myeloma is is unknown, as the disease does not appear in the annual estimates supplied by the National Cancer Institute. The current median survival of patients with multiple myeloma is approximately three years, but there is a high variability in the prognosis due to the heterogeneity of the biology of multiple myeloma and factors related to the host. The Durie-Salmon clinical staging system is predictive of the global survival, remaining as the staging sytem which has been most amply used for more than 25 years. During this fime, few new prognostic parameters have appeared, with beta-2-microglobulin emerging as the most powerful prognostic factor, it being a simple and realible forecast of survival . Subsequent studies suggested that albumin was another powerful indicator of easy application for multiple myeloma. Recently, an international panel of investigators presented the International Staging System, ISS, for multiple myeloma, a prognostic scale which takes serum beta-2-microglobulin and albumin into account as significant factors in multivariate analysis, thus classifying the patients into three risk groups. The ISS system was validated in patients in North America, Europe and Asia, but was not applied in a database in Brazil. To evaluated the demographic and clinical aspects of multiple myeloma patients in Brazil, and to observe if these characteristics are similar to the ones found in different countries of Latin America and other countries of Europe , North America and continents, we retrospectively analyzed all the cases of multiple...

Liposomal daunorubicin and dexamethasone as a treatment for multiple myeloma: the DD Protocol

CONTEXTO E OBJETIVO: A daunorrubicina lipossomal tem sido usada no tratamento em várias doenças hematológicas malignas, incluindo mieloma múltiplo (MM). O objetivo deste estudo foi avaliar a eficácia, efeitos colaterais e toxicidade da daunorrubicina lipossomal and dexametasona no Protocolo DD. TIPO DE ESTUDO E LOCAL: Estudo prospectivo, realizado nos hospitais Sírio Libanês, São Camilo, Brasil e no Hospital Alemão Oswaldo Cruz. MÉTODOS: 20 pacientes com MM ativo receberam daunoxome (25-30 mg/m²/dia) por três dias consecutivos, mensal, por quatro meses (total de quatro ciclos), e dexametasona, 10 mg a cada seis horas por quatro dias consecutivos (dia 1 - 4, 9 - 12 e 17 - 20), também mensal. RESULTADOS: A mediana entre o diagnóstico e o início do protocolo DD foi de 13 meses. Quinze pacientes receberam alguma quimioterapia anterior ao protocolo DD. Uma redução maior que 50% do pico monoclonal sérico foi observada em seis paciente após o primeiro ciclo do DD (30%), em seis pacientes após o segundo ciclo (30%), em quatro pacientes após o terceiro ciclo (20%) e em quatro pacientes não houve redução (20%). No início do protocolo, 17 pacientes (85%) apresentavam anemia e em 12 destes pacientes (70%) a anemia foi corrigida. Doença progressiva foi observada em três pacientes (15%), um apresentava resposta mínima, quatro pacientes (20%) apresentaram resposta parcial e 12 (60%) apresentaram resposta completa. A toxicidade hematológica foi aceitável.Toxicidade em trato gastrointestinal foi leve, consistindo em náusea (10%) e anorexia (15%), sem episódios de vômito. CONCLUSÃO: Este tratamento apresentou uma baixa toxicidade, uma boa taxa de resposta e pode ser usado previamente ao transplante de medula óssea autogênico.

A importância da citometria de fluxo no diagnóstico raro de mieloma mielomonocítico / The importance of flow cytometry in the rare diagnosis of myelomonocytic myeloma

O mieloma múltiplo consiste na proliferação de células plasmáticas. Raramente apresenta, ao diagnóstico, morfologia de células imaturas com citoplasma amplo basofílico, sugerindo quadro leucêmico inicial. O objetivo deste artigo é mostrar a importância da imunofenotipagem na elucidação destes achados, morfológicos, pela expressão simultânea de antígenos plasmocíticos, mielomonocíticos e de linhagem linfóide T, confirmando a hipótese diagnóstica de mieloma mielomonocítico. Apresentamos dois casos de mieloma mielomonocítico através de análise morfológica (coloração pancromática de Romanovsky), citoquímica (PAS, peroxidase, sudan black, alfanaftil acetato esterase e oil red), citogenética e imunofenotipagem por citometria de fluxo em sangue periférico e medula óssea, de acordo com as técnicas recomendadas. Foram utilizados os anticorpos monoclonais: CD2, CD3, CD4, CD5, CD7, CD10, CD13, CD15, CD19, CD20, CD25, CD33, CD34, CD38, CD45, CD56, CD71, HLAðDR, TCR alfa/beta, TCR gama/delta, kappa, lambda, IgM e IgD de superfície e intracitoplasmática, assim com MPO, CD79a e CD3 intracitoplasmático. Utilizamos as técnicas de banda G e FISH nas análises citogenéticas. Foram observadas alterações clonais em ambos os casos, sendo uma com trissomia do cromossomo 8 e outro caso com deleção do braço longo do cromossomo 7 e do braço curto do cromossomos 6. Os percentuais de positivadade encontrados nos anticorpos monoclonais CD4, CD7, CD10, CD13, CD14, CD15, CD33, CD38 E CD56 de forte expressão, HLAðDR, TCR gama/delta, MPO e IgM intracitoplasmático no histograma de volume x complexidade e no histograma de CD45 x complexidade permitiram concluir este diagnóstico em ambos os casos, demonstrando a importância do método

Helicobacter pylori associado a linfoma gástrico primário tipo MALT / Helicobacter pylori associated to primary gastric lymphoma type MALT

O trato gastrointestinal é o local mais comum de comprometimento por linfoma näo Hodgkin extranodal primário, sendo o linfoma gástrico primário o mais freqüente, correspondendo a 2/3 dos casos. Isaacson e Wright, em 1983, introduziram o conceito de tecido linfóide associado a mucosa (MALT), relatando que este tecido precede o aparecimento de linfomas de célula B tipo MALT no estômago. Este tecido linfóide é adquirido, provavelmente resultante da infecçäo por Helicobacter pylori na mucosa gástrica. No período de janeiro de 1983 a dezembro de 1994 foram realizados 22 diagnósticos de linfoma gástrico primário, no Serviço de Hematologia e Hemoterapia da Santa Casa de Säo Paulo. Após revisäo histológica foram encontrados 13 casos de linfoma tipo MALT, sendo que o H. pylori foi positivo em 92,3 por cento dos casos. Esse achado é importante, pois há estudos mostrando que em pacientes com linfoma gástrico primário de baixo grau, de célula B, tipo MALT, com H. pylori positivo, após a erradicaçäo do H. pylori houve regressäo do linfoma.

Quantificaçäo do risco mínimo de aquisiçäo de doença de Chagas transfusional, através do xenodiagnóstico em doadores de sangue com sorologia positiva / Quantification of the minimum risk of transfusional Chagas disease acquisition, by xenodiagnosis in blood donors with positive serology

Quantificaçäo do risco mínimo de aquisiçäo de doença de Chagas transfusional através do xenodiagnóstico em doadores de sangue com sorologia positiva. Os autores procuraram quantificar o risco mínimo de aquisiçäo de infecçäo chagásica através de transfusöes, quando o sangue utilizado é proveniente de indivíduos com reaçöes sorológicas positivas para esta parasitose. Para a avaliaçäo da parasitemia, realizaram o xenodiagnóstico em 178 candidatos a doadores de sangue com sorologia positiva para tripanosomíase americana. A positividade revelada pelo xenodiagnóstico, da ordem de 14 por cento, é interpretada como o risco mínimo de ocorrência de novos casos de infecçäo T. cruzi em indivíduos transfundidos com sangue proveniente de doadores chagásicos.

Tratamento de linfomas refratários ou recorrentes com ifosfamida, metotrexato, etoposideo (VP-16) e bleomicina (IMVP-Bleo) / Treatment of refractory or recurrent lymphoma with ifosfamide, methotrexate, etoposide (VP-16) and bleomycin (IMVP-Bleo)

O prognóstico de pacientes com linfoma maligno refratário ou recorrente é ruim. Para melhorar a resposta ao tratamento destes pacientes, um esquema terapêutico com IMVP-Bleo (ifosfamida e mesna, metotrexato, etoposídeo, bleomicina) foi administrado. Dos 18 pacientes tratados, 16 apresentavam linfoma nao-Hodgkin (LNH), 13 de grau intermediário e 3 de baixo grau; 2 pacientes apresentavam doença de Hodgkin (DH). Todos pacientes receberam qumioterapia prévia, sendo que 8 apresentaram recidiva e 10 foram refratários ao tratamento de primeira linha. A taxa de resposta global obtida foi de 83,3 por cento, com 55,6 por cento de remissäo completa (RC) e 27,8 por cento de remissäo parcial (RP). Embora o tempo de estudo seja curto, nossos resultados indicam uma boa efetividade deste protocolo, como terapêutica de resgate com toxicidade aceitável. Baseado em vários estudos que mostram uma boa resposta e tolerabilidade ao esquema IMVP-Bleo; sabendo-se que o tratamento de resgate nunca é täo efetivo como o de primeira linha, e que qualquer esquema de resgate pode ser testado como primeira linha; parece razoável que este esquema possa ser introduzido como parte do tratamento de primeira linha para pacientes portadores de linfoma com fatores prognósticos desfavoráveis.