RESUMO
Proliferation and apoptosis of neoplastic cells are prognostic biomarkers in plasma cell neoplasms (PCNs). The prognostic capacity of proliferation to apoptosis ratio (Ratio-PA) in the era of immunomodulatory treatments is re-evaluated in 316 gammopathy of undetermined significance (MGUS), 57 smoldering multiple myeloma (SMM), and 266 multiple myeloma (MM) patients. Ratio-PA of 0.77 ± 0.12, 1.94 ± 0.52, and 11.2 ± 0.7 (p < 0.0001) were observed in MGUS, SMM, and MM patients. Ten-year overall survival (10y-OS) rates for patients with low/high Ratio-PA were 93.5%/77.3% p < 0.0001) for MGUS, 82.5%/64.7% (p < 0.05) for SMM, and 62.3%/47.0% (p < 0.05) for MM. For patients with low, intermediate, and high risk, 10y-OS for low/high Ratio-PA were 95.5%/72.9% (p < 0.0001), 74.2%/50.4% (p < 0.0001), and 35.3%/20.0% (p = 0.836), respectively. Ratio-PA was an independent prognostic factor for OS (HR = 2.119, p < 0.0001, Harrell-C-statistic = 0.7440 ± 0.0194) when co-analyzed with sex, age, and standard risk. In patients with Ratio-PAhigh, only first-line therapy with VRd/VTd, but not PAD/VCD, coupled with ASCT was associated with high 10y-OS (82.7%). Tumor cell Ratio-PA estimated at diagnosis offers a prognostic biomarker that complements standard risk stratification and helps to guide the clinical management of pre-malignant and symptomatic PCNs. Every effort should be made to provide first-line therapies including VTd or VRd associated with ASCT to patients with Ratio-PAhigh at higher risk of progression and death.
Assuntos
Apoptose , Biomarcadores Tumorais , Neoplasias de Plasmócitos/diagnóstico , Neoplasias de Plasmócitos/etiologia , Lesões Pré-Cancerosas , Idoso , Biópsia , Medula Óssea/patologia , Proliferação de Células , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Neoplasias de Plasmócitos/mortalidade , Neoplasias de Plasmócitos/terapia , Prognóstico , Curva ROC , Fatores de Risco , Avaliação de SintomasRESUMO
The win ratio method has received much attention in methodological research, ad hoc analyses, and designs of prospective studies. As the primary analysis, it supported the approval of tafamidis for the treatment of cardiomyopathy to reduce cardiovascular mortality and cardiovascular-related hospitalization. However, its dependence on censoring is a potential shortcoming. In this article, we propose the inverse-probability-of-censoring weighting (IPCW) adjusted win ratio statistic (i.e., the IPCW-adjusted win ratio statistic) to overcome censoring issues. We consider independent censoring, common censoring across endpoints, and right censoring. We develop an asymptotic variance estimator for the logarithm of the IPCW-adjusted win ratio statistic and evaluate it via simulation. Our simulation studies show that, as the amount of censoring increases, the unadjusted win proportions may decrease greatly. Consequently, the bias of the unadjusted win ratio estimate may increase greatly, producing either an overestimate or an underestimate. We demonstrate theoretically and through simulation that the IPCW-adjusted win ratio statistic gives an unbiased estimate of treatment effect.
Assuntos
Ensaios Clínicos como Assunto/estatística & dados numéricos , Projetos de Pesquisa/estatística & dados numéricos , Viés , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/terapia , Simulação por Computador , Interpretação Estatística de Dados , Progressão da Doença , Hospitalização/estatística & dados numéricos , Humanos , Modelos Estatísticos , Gamopatia Monoclonal de Significância Indeterminada/mortalidade , Neoplasias de Plasmócitos/mortalidade , Probabilidade , Fatores de Tempo , Resultado do TratamentoRESUMO
The characteristics of the IgA plasma cell neoplasms are not clearly reported in the literature. The main goal of this study is to examine IgA plasma cell neoplasms (PCN) and to compare them to IgG lesions. After at least 5 years from the identification of an M protein, 98 cases were selected, the presentation and clinical evolution of 45 IgA neoplasms were compared to 43 cases of IgG gammopathies. The classification at presentation as monoclonal gammopathy of undermined significance (MGUS)-22 of 45 IgA and 20 of 43 IgG (49 vs 46%), plasma cell myeloma (PCM)-22 of 45 IgA and 22 of 43 IgG (49 vs 51%) and smoldering PCM (SPCM)-1 each (2% for both) was essentially identical. No solitary plasmacytomas were identified. At presentation, IgA patients were younger (66.5 ± 11.3 vs. 69.2 ± 10.7 years), less likely to have bone lesions (12/45 vs 18/43, p < 0.14) or immunoparesis (51% vs. 63%), differences statistically insignificant. Cases with normal fluorescence in-situ hybridization (FISH) results, 27% for IgA vs 61% for IgG (p < 0.037) were statistically different. The IgA patients had worse survival (80 vs 108 months median IgA vs IgG, p < 0.013), difference not detectable in the first 5 years, but substantial after 10. In conclusion, poorer long-term survival and increased genomic complexity by FISH are characteristics of IgA PCNs.
Assuntos
Imunoglobulina A , Imunoglobulina G , Neoplasias de Plasmócitos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gamopatia Monoclonal de Significância Indeterminada , Neoplasias de Plasmócitos/genética , Neoplasias de Plasmócitos/imunologia , Neoplasias de Plasmócitos/mortalidade , Estudos RetrospectivosRESUMO
We have developed an automated assay to enumerate and characterize circulating multiple myeloma cells (CMMC) from peripheral blood of patients with plasma cell disorders. CMMC show expression of genes characteristic of myeloma and fluorescence in situ hybridisation results on CMMC correlated well with bone marrow results. We enumerated CMMC from over 1000 patient samples including separate cohorts of newly diagnosed multiple myeloma and high/intermediate risk smouldering multiple myeloma (SMM) with clinical follow-up data. In newly diagnosed myeloma patient samples, CMMC counts correlated with other clinical measures of disease burden, including the percentage of bone marrow plasma cells, serum M protein, and International Staging System stage. CMMC counts decreased significantly from baseline when a remission was achieved due to treatment (P < 0·001). Patients with CMMC counts ≥100 at remission showed reduced survival relative to patients with CMMC counts <100. Patients with undetectable CMMC in remission showed further overall survival benefits. In the SMM cohort, there was a trend toward higher CMMC in patients with higher-risk myeloma precursor states. Significantly higher CMMC counts were observed between intermediate/high risk SMM patients that progressed versus those without progression (P = 0·031). CMMC allow a non-invasive means of monitoring tumour biology and may have use as a prognostic test for patients with plasma cell disorders.
Assuntos
Contagem de Células , Mieloma Múltiplo/diagnóstico , Neoplasias de Plasmócitos/diagnóstico , Células Neoplásicas Circulantes/patologia , Adulto , Idoso , Medula Óssea/patologia , Estudos de Coortes , Diagnóstico Diferencial , Feminino , Citometria de Fluxo/métodos , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Mieloma Múltiplo/genética , Mieloma Múltiplo/mortalidade , Neoplasias de Plasmócitos/sangue , Neoplasias de Plasmócitos/genética , Neoplasias de Plasmócitos/mortalidade , Células Neoplásicas Circulantes/metabolismo , Prognóstico , Curva ROC , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: -The values of SEER site recode variables are based on the primary site and histology data fields submitted to SEER by the registries. The site recode variables define the major cancer site/histology groups that are commonly used in the reporting of cancer incidence data and are added to the SEER databases as a convenience for researchers. These codes and definitions are periodically updated and changed by the National Cancer Institute as newer and more applicable information becomes available. Because this myeloma analysis includes cases diagnosed 2010+, the ICD-O-3 recode-updates with adjustment for WHO 2008 hematopoietic histologies that account for changes in the obsolete classification of hematopoietic histology codes, and the assignment of new names (ie, multiple myeloma-MM - to - plasma cell myeloma-PCM) is adhered to and used here. Plasma cell myeloma (PCM) is a bone-marrow based multifocal plasma cell malignancy (primary site C421). PCM is characterized by a single clone of plasma cells, believed to be derived from lymphoid B cells, and spans a clinical spectrum from asymptomatic to aggressive forms, plus disorders caused by the deposition of abnormal immunoglobulin chains in tissue. The current myeloma group ICD-O-3 histologic morphology types consists of: ICD-O-3 9731: Plasmacytoma, NOS, occurring in bone (osseous plasmacytoma malignancy data reportable to SEER only beginning since 1986); ICD-O-3 9732: Plasma cell myeloma - composed of three clinical variants: a) asymptomatic, b) Non-secretory myeloma, and c) Plasma cell leukemia (all coded to 9732); ICD-O-3 9734: Extramedullary plasmacytoma; anatomic sites other than bone. OBJECTIVE: -Using the statistical database of SEER*Stat 8.3.4 (produced 4/14/2017 for diagnosis years 1973-2014), to assess, determine, compare, and summarize the occurrence, long-term survival and mortality indices of the three morphologic types of myeloma by age, sex, race and stage in two-cohort entry time-periods (1973-1994 and 1995-2014). All analyses are accomplished within the context of current SEER Site Recode ICD-O-3 (1/27/2003) definitions, terminologies and descriptions, and also in accordance with the rules of the consolidated Hematopoietic and Lymphoid Neoplasm Coding Manual data base (effective 1/1/2010 - release date January 2015). METHODS: -Population data including 111,041 cases collected by the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Frequency Database (18 SEER Registries Research Data + Hurricane Katrina Impacted Louisiana Cases, November 2016 Submission, 1973-2014 varying) for diagnosis years 1973-2014: Relative Survival Statistics were analyzed in two cohorts: 1973-1994 and 1995-2014. Survival statistics were derived from: SEER*Stat Database: Incidence - SEER 9 Regs Research Data, November 2016 Submission (1973-2014)
Assuntos
Neoplasias Ósseas , Neoplasias de Plasmócitos , Plasmocitoma , Programa de SEER , Adolescente , Adulto , Idoso , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/terapia , Estudos de Coortes , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo , Neoplasias de Plasmócitos/mortalidade , Neoplasias de Plasmócitos/terapia , Fenótipo , Plasmocitoma/mortalidade , Plasmocitoma/terapia , Sistema de Registros , Estudos Retrospectivos , Estados Unidos/epidemiologia , Adulto JovemRESUMO
Population-based plasmacytoma incidence and survival data are sparse. We analyzed incidence rates (IRs), IR ratios (IRRs), and 5-year relative survival for plasmacytoma overall and by site -- bone (P-bone) and extramedullary (P-extramedullary) -- in the Surveillance, Epidemiology and End Results (SEER) Program (1992-2004). For comparison, we included cases of multiple myeloma (MM) diagnosed over the same time period in SEER. Incidence of MM (n = 23,544; IR 5.35/100,000 person-years) was 16-times higher than plasmacytoma overall (n = 1543; IR = 0.34), and incidence of P-bone was 40% higher than P-extramedullary (P < 0.0001). The male-to-female IRRs for P-bone, P-extramedullary, and MM were 2.0, 2.6, and 1.5, respectively. For plasmacytoma and MM, IRs were highest in Blacks, intermediate in Whites, and lowest in Asian/Pacific Islanders. Compared with Whites, the Black IR was approximately 30% higher for P-extramedullary and P-bone and 120% higher for MM. IRs for all neoplasms increased exponentially with advancing age, less prominently at older ages for plasmacytoma than MM. Distinct age, gender, and race incidence patterns of plasma cell disorders suggest underlying differences in clinical detection, susceptibility, disease biology and/or aetiological heterogeneity. Five-year relative survival for P-bone, P-extramedullary, and MM varied significantly by age (<60/60+ years), supporting age-related differences in disease burden at presentation, disease biology, and/or treatment approaches.
Assuntos
Neoplasias Ósseas/epidemiologia , Neoplasias de Plasmócitos/epidemiologia , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/mortalidade , Intervalos de Confiança , Etnicidade , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/epidemiologia , Neoplasias Bucais/mortalidade , Mieloma Múltiplo/epidemiologia , Mieloma Múltiplo/mortalidade , Neoplasias de Plasmócitos/mortalidade , Neoplasias Faríngeas/epidemiologia , Neoplasias Faríngeas/mortalidade , Plasmocitoma/epidemiologia , Plasmocitoma/mortalidade , Neoplasias do Sistema Respiratório/epidemiologia , Neoplasias do Sistema Respiratório/mortalidade , Distribuição por Sexo , Taxa de Sobrevida , Estados Unidos/epidemiologiaRESUMO
The clinical and pathological findings of plasmablastic lymphoma (PBL) have been described in the literature but the etiology is not well established, and treatment options are poorly defined. We reviewed patients with PBL in our institution to characterize the clinicopathologic features in our patient population. In this retrospective analysis from a single academic institution, five patients with PBL were identified and analyzed. Human immunodeficiency virus and human herpesvirus 8 (HHV-8) were identified in 40% (two out of five) and 80% (four out of five) of these patients, respectively. Central nervous system (CNS) involvement was identified in four out of five (80%) patients. Interestingly, three out of five patients had a concurrent or preceding second primary malignancy including small lymphocytic lymphoma, endometrial cancer, and nonsmall cell lung cancer. Most of the patients had advanced disease and a poor performance status at diagnosis. Only two of the patients received systemic chemotherapy with an initial partial response. All five patients died; the median overall survival was 1 month. Our experience in patients with PBL indicates that CNS involvement is more common than reported in the literature. Coexistence of a second primary malignancy may be frequent, and prognosis remains dismal with standard lymphoma therapy. Lastly, the role of HHV-8 in the etiopathogenesis needs further trials.
Assuntos
Neoplasias do Sistema Nervoso Central/etiologia , Linfoma não Hodgkin/etiologia , Neoplasias de Plasmócitos/etiologia , Adulto , Neoplasias do Sistema Nervoso Central/virologia , Feminino , HIV/isolamento & purificação , Herpesvirus Humano 8/isolamento & purificação , Humanos , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/virologia , Masculino , Pessoa de Meia-Idade , Neoplasias de Plasmócitos/mortalidade , Neoplasias de Plasmócitos/virologia , Segunda Neoplasia Primária/classificação , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Presented is a retrospective analysis of 27 patients with plasma cell neoplasms of the spine treated by surgery. Multiple myeloma was confirmed in 22 (81%) and solitary plasmacytoma in 5 patients (19%), assessed at the time of surgery. Nineteen patients (70%) with the preliminary diagnosis of malignancy of unknown etiology were admitted for surgery. In 23 patients (85%) the essential symptom was back pain, which preceded surgery by an average of 4 months. Thirteen patients (48%) were bedridden due to tumor spinal cord compression, on average for 7 days before undergoing surgery. Only 5 out of 13 bedridden patients (38%) regained the ability to walk after surgery and 8 patients (62%) remained bedridden despite successful surgical decompression of the spinal cord. The difference of survival of the patients between bedridden and able to walk prior to surgery was statistically significant (Cox's F-Test = 0.005). Key words: plasma cell neoplasia, spinal cord compression, late diagnosis, outcome.
Assuntos
Neoplasias de Plasmócitos/diagnóstico , Neoplasias de Plasmócitos/cirurgia , Neoplasias da Coluna Vertebral/diagnóstico , Neoplasias da Coluna Vertebral/cirurgia , Adulto , Idoso , Descompressão Cirúrgica , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias de Plasmócitos/mortalidade , Procedimentos Neurocirúrgicos , Recuperação de Função Fisiológica , Estudos Retrospectivos , Compressão da Medula Espinal/etiologia , Compressão da Medula Espinal/cirurgia , Neoplasias da Coluna Vertebral/mortalidade , Resultado do TratamentoRESUMO
Non-immunoglobulin (Ig)-M monoclonal gammopathy of undetermined significance (MGUS) is a precursor lesion with the potential to evolve into a malignant plasma cell neoplasm. The prevalence of MGUS differs by ethnicity and is lower in the Japanese population than in the Western population. However, there is limited evidence about the clinical course of MGUS in Asian races. The present study aims at elucidating the clinical course and prognosis of Japanese patients with non-IgM MGUS in the clinical setting. We retrospectively examined 1009 patients with non-IgM MGUS identified by screening procedures. The median overall survival of these patients was > 20 years, and only one-fifth patients died of plasma cell neoplasms. The cumulative incidence of plasma cell neoplasms requiring treatment was 19%. Multivariate analysis revealed that immunoparesis and female gender were independent factors affecting treatment requirement. Although the characteristics and clinical course of patients with non-IgM MGUS obtained in this study were found to be essentially similar to those of previous studies, we report here for the first time that female gender is a significant independent factor for requiring treatment.
Assuntos
Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Adulto , Idoso , Povo Asiático , Progressão da Doença , Feminino , Humanos , Imunoglobulina M , Masculino , Pessoa de Meia-Idade , Gamopatia Monoclonal de Significância Indeterminada/epidemiologia , Gamopatia Monoclonal de Significância Indeterminada/mortalidade , Neoplasias de Plasmócitos/mortalidade , Prognóstico , Estudos Retrospectivos , Fatores Sexuais , Análise de SobrevidaAssuntos
Neoplasias do Sistema Nervoso Central/mortalidade , Neoplasias de Plasmócitos/mortalidade , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/terapia , Gerenciamento Clínico , Humanos , Neoplasias de Plasmócitos/diagnóstico , Neoplasias de Plasmócitos/terapia , PrognósticoRESUMO
The European Society for Blood and Marrow Transplantation Chronic Malignancies Working Party held a preceptorship meeting in Turin, Italy on 25-26 September 2014, to discuss the role of stem cell transplantation (SCT) in the treatment of multiple myeloma and other plasma cell disorders. Scientists and clinicians working in the field gathered to discuss a variety of topics including the results of recent clinical trials, basic research, the concept of minimal residual disease, and immune modulation. As individual presentations revealed, important advances have occurred in our understanding of the pathophysiology of myeloma and the role that SCT, along with other forms of immunotherapy, plays in treating it. Each presentation stimulated discussion and exchange of ideas among the attendants. We decided to summarize and, importantly, to update the meeting proceedings in this review to share stimulating discussions and ideas on potentially novel treatment strategies among clinicians.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/terapia , Neoplasias de Plasmócitos/terapia , Fatores Etários , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Separação Celular , Terapia Combinada , Quimioterapia de Consolidação , Mobilização de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/metabolismo , Humanos , Quimioterapia de Manutenção , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/mortalidade , Neoplasia Residual , Neoplasias de Plasmócitos/diagnóstico , Neoplasias de Plasmócitos/mortalidade , Recidiva , Transplante Autólogo , Transplante Homólogo , Resultado do TratamentoRESUMO
Concomitant plasma cell (PCN) and B-cell neoplasms (BCN) in a single patient have been infrequently reported. This study reviewed nine such patients at the institution - six had multiple myeloma (MM) associated with a BCN (MM/B group) and three had AL amyloidosis (ALA) with a BCN (ALA/B group). This study describes two syndromes of MM/B - three patients presented with CLL and subsequently developed MM, while three presented with MM and monoclonal B-cell lymphocytosis. In the ALA/B group, all three patients had systemic ALA and a BCN. Responses of the BCN and PCN to treatment correlated. In the two patients whose MM relapsed, the BCN simultaneously relapsed. The finding that the BCN may relapse in tandem with the MM argues against a coincidental relationship between the two.
Assuntos
Leucemia de Células B/complicações , Leucemia de Células B/diagnóstico , Linfoma de Células B/complicações , Linfoma de Células B/diagnóstico , Neoplasias de Plasmócitos/complicações , Neoplasias de Plasmócitos/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Biópsia , Medula Óssea/patologia , Terapia Combinada , Progressão da Doença , Feminino , Humanos , Imunofenotipagem , Leucemia de Células B/mortalidade , Leucemia de Células B/terapia , Linfoma de Células B/mortalidade , Linfoma de Células B/terapia , Masculino , Pessoa de Meia-Idade , Neoplasias de Plasmócitos/mortalidade , Neoplasias de Plasmócitos/terapia , Fenótipo , Resultado do TratamentoRESUMO
Blastic plasmacytoid DC neoplasm (BPDCN) is a rare haematopoietic malignancy with an aggressive behaviour. We evaluated five patients allografted as consolidative treatment with an unrelated donor in first or subsequent remission. Four patients received a reduced intensity-conditioning regimen because of age or co-morbidities. As the stem cell sources, two umbilical cord blood-(UCB), two PBSC- and one BM graft were used. No GVHD was observed in the patients who received a UCB graft. However, both developed a post-transplant-associated lymphoproliferative disease. So far, only one patient has experienced relapse and was consecutively treated by escalated donor lymphocyte infusions (DLI). A potent graft-versus-leukaemia (GVL) effect was induced leading to a 17-month-long CR. Four patients are still in ongoing CR with median disease-free and overall survivals of 17 and 21 months. Thus, allogeneic SCT in BPDCN offers a potential curative option for patients with a compatible donor. UCB is an attractive alternative as a stem cell source. For relapsing patients, DLI can exert a powerful GVL effect.