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1.
Hematol Oncol ; 37(5): 595-600, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31486522

RESUMO

Daratumumab, an anti-CD38 antibody, is effective in AL amyloidosis with low tumor burden. Data of daratumumab treatment in patients with AL amyloidosis but high tumor burden (≥10% bone marrow plasma cells) are limited. We report retrospective data of 10 consecutive patients with high tumor burden treated with daratumumab for relapsed/refractory AL amyloidosis. The median age at diagnosis was 62.3 years; all patients had cardiac involvement, and six (60%) patients had renal involvement. Median bone marrow plasma cell infiltration was 15% (range 10%-40%), and the median difference between involved and noninvolved free light-chains (dFLC) was 446 mg/L (range 102-1392 mg/L). Patients had a median of three prior lines of therapy, including bortezomib in all patients and lenalidomide in seven (70%) patients. The median time to first hematological response was 14 days (range 7-28 days), and the median time to best hematological response was 64 days (range 7-301 days). The hematological overall response was 90%, with high-quality response (≥ very good partial remission [VGPR]) in 70% of the patients. Fifty percent of the patients had a cardiac response after a median of 3.8 months (range 0.7-9.1). Infusion-related adverse events ≤ grade 2 occurred in seven (70%) patients and grade 3 adverse events in one patient. After a median follow-up time of 10 months, eight (80%) patients continued to receive daratumumab. We conclude that daratumumab is a very effective and safe treatment option in AL patients with relapsed/refractory disease and high disease burden at diagnosis. Daratumumab leads to rapid disease control and improvement of organ function.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico , Amiloidose de Cadeia Leve de Imunoglobulina/tratamento farmacológico , Contagem de Linfócitos , Plasmócitos/patologia , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Medula Óssea/metabolismo , Medula Óssea/patologia , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/mortalidade , /terapia , Masculino , Pessoa de Meia-Idade , Recidiva , Retratamento , Índice de Gravidade de Doença , Resultado do Tratamento
3.
Amyloid ; 26(3): 128-138, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31172799

RESUMO

Background: Atrial fibrillation (AF) commonly affects patients with cardiac amyloidosis (CA). Amyloid deposition within the left atrium may be responsible for the subtype of AF in either permanent or non-permanent form. The prognostic implications of AF and its clinical subtype according to the type of CA are still controversial in this population. This study sought to investigate the prevalence, incidence and prognostic implications of AF and the clinical subtype of AF (permanent or non-permanent) in patients with CA. Methods: Two hundred and thirty-eight patients with CA and full medical records were retrospectively enrolled in the study: About 115 (48%) with light chain (AL) amyloidosis and 123 (52%) with transthyretin amyloidosis (ATTR). Patient's medical records were reviewed to establish baseline prevalence, incidence and impact on all-cause and cardiovascular mortality during follow-up of AF. Results: One hundred and four (44%) patients had history of AF at the time of diagnosis: 62 (60%) permanent and 42 (40%) non-permanent. There were 30 (26%) and 74 (60%) patients with history of AF among patients with AL and ATTR (including 5 hereditary and 69 wild-type), respectively (p<.0001). During the follow-up, 48 new patients developed AF (29, 12 and 7 among patients with AL, wild-type ATTR and hereditary ATTR). After adjustment for age, survival was similar in patients with or without history of AF (HR 0.87 (95% CI, 0.60 to 1.27; p = .467). AF had no impact on cardiovascular mortality. Among the 152 patients with history of AF included in the whole study, there were 75 (49%) patients with permanent AF. After adjustment for age, survival was similar in patients with permanent and non-permanent AF: HR 1.29 (95% CI, 0.84 to 1.99; p = .251). The results were the same among patients with AL or wild-type amyloidosis. Subtype of AF had no impact on cardiovascular mortality. Conclusions: AF is common in patients with CA. However, AF and clinical subtype of AF have no impact on all-cause mortality, whatever the type of amyloidosis.


Assuntos
Neuropatias Amiloides Familiares/diagnóstico por imagem , Fibrilação Atrial/diagnóstico por imagem , Átrios do Coração/diagnóstico por imagem , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Neuropatias Amiloides Familiares/sangue , Neuropatias Amiloides Familiares/complicações , Neuropatias Amiloides Familiares/mortalidade , Fibrilação Atrial/sangue , Fibrilação Atrial/complicações , Fibrilação Atrial/mortalidade , Ecocardiografia , Feminino , Átrios do Coração/fisiopatologia , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/sangue , Amiloidose de Cadeia Leve de Imunoglobulina/complicações , Amiloidose de Cadeia Leve de Imunoglobulina/mortalidade , Masculino , Pessoa de Meia-Idade , Pré-Albumina/metabolismo , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida
5.
Amyloid ; 26(3): 125-127, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31145007

RESUMO

Objectives: We aimed to externally validate Lilleness' et al. Boston University (BU) prognostic score that replaced NT-proBNP with brain natriuretic peptide (BNP), which will allow centres without access to NT-proBNP to accurately stage and prognosticate AL amyloidosis. Patients/methods: Forty-four were identified that had BNP, NTpro-BNP and TnI taken simultaneously, with a mean follow up of 7.3 years. Median age of the 44 patients was 67 years and 27% were female, with 61% having cardiac involvement, and 61% having renal involvement. Results: Using the BU BNP-based staging system, we identified 12/44 (27%) of patients as stage I, 18/44 (41%) of patients as stage II and 14/44 (31%) of patients as stage III. This correlated closely with stratification via the Mayo score, with only one patient miscategorised (97.7% agreement, k = 0.98). Median overall survival for our BU stage I was not reached, stage II was 40 months and stage III was 5 months (long rank p = .0012). Mayo 2004 median overall survival was identical for stages I, II and III. Conclusion: We have provided external validation of the BU staging system, a novel prognostic scoring system incorporating BNP, instead of NT-proBNP, for AL amyloidosis.


Assuntos
Cardiomiopatias/diagnóstico , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico , Peptídeo Natriurético Encefálico/sangue , Nefrite/diagnóstico , Fragmentos de Peptídeos/sangue , Troponina I/sangue , Idoso , Biomarcadores/sangue , Boston , Cardiomiopatias/sangue , Cardiomiopatias/complicações , Cardiomiopatias/mortalidade , Feminino , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/sangue , Amiloidose de Cadeia Leve de Imunoglobulina/complicações , Amiloidose de Cadeia Leve de Imunoglobulina/mortalidade , Masculino , Pessoa de Meia-Idade , Nefrite/sangue , Nefrite/complicações , Nefrite/mortalidade , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Análise de Sobrevida , Universidades
6.
Amyloid ; 26(2): 66-73, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31074308

RESUMO

Background: Patients with amyloid light-chain (AL) amyloidosis who have advanced cardiac damage are at risk of premature mortality. Currently, bortezomib is the mainstay in the treatment of AL amyloidosis, but the benefits of bortezomib in patients with ultra-high-risk (2004 Mayo stage IIIb or 2012 Mayo stage IV) AL amyloidosis have not been proved definitively. Methods: We performed a retrospective analysis of patients newly diagnosed with ultra-high-risk AL amyloidosis who received a bortezomib-based regimen or supportive treatment. We aimed to establish the effects of bortezomib on early mortality and long-term outcomes in this high-risk population. Results: Patients receiving bortezomib-containing chemotherapy (n = 62) and patients receiving no chemotherapy (n = 24) were included. Median overall survival (OS) was 30 months in the bortezomib group and 2 months in the control group (p < .001), and median progression-free survival (PFS) was 15.8 months (bortezomib) and 2 months (control; p < .001). The early-death rate (within 6 months of treatment) was 32.3% (bortezomib) and 66.7% (control; p < .001). In a landmark analysis assessing outcomes in patients surviving beyond 6 months, the 2-year OS and PFS in the bortezomib group were 77.3% and 65.8%, respectively. Conclusions: Bortezomib-based regimens can help to reduce early mortality and improve long-term survival in patients with ultra-high-risk AL amyloidosis.


Assuntos
Bortezomib/uso terapêutico , Amiloidose de Cadeia Leve de Imunoglobulina/tratamento farmacológico , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
7.
Amyloid ; 26(1): 45-51, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30931628

RESUMO

BACKGROUND: T1 mapping allows quantitative assessment of "diffuse" deposition of amyloid protein in the myocardium. Early detection of cardiac involvement and potential prognostic improvement could benefit patients with AL amyloidosis. OBJECTIVES: This study aims to evaluate the regional variation of amyloid infiltration in the left ventricle and the prognostic value of T1 mapping in patients with AL amyloidosis. METHODS: We prospectively enrolled 77 patients with AL amyloidosis who underwent cardiac magnetic resonance on a 3.0-T scanner. Native T1 and extracellular volume (ECV) were quantitated on the basal, mid, and apical levels of the left ventricle. Late gadolinium enhancement (LGE) pattern (no or non-specific LGE, sub-endocardial LGE, and transmural LGE) was also assessed. Forty healthy subjects served as controls. The primary end point was all-cause mortality. RESULTS: Basal ECV (26.9 ± 2.8% versus 31.1 ± 4.9%, p < .001) were lower than apical ECV in the healthy controls; however, basal ECV (60.6 ± 11.5% versus 53.0 ± 9.6%, p = .003) were significantly higher than apical ECV in patients with transmural LGE. During the follow-up period (median duration, 28 months; 25th-75th percentile, 13.5-38.0 months), 46 patients died. Basal ECV has the largest area under the curve of 0.845 (95% CI, 0.747-0.917) to predict all-cause mortality. Multivariable Cox analysis indicated that basal ECV was an independent prognostic factor and showed incremental prognostic value beyond NYHA class, Mayo stage, and LGE pattern. CONCLUSION: We demonstrated that T1 mapping may have the potential to detect a characteristic amyloid deposition with a decreasing gradient from base to apex. Furthermore, myocardial ECV indicated that basal amyloid infiltration provided robust and incremental prognostic value in patients with AL amyloidosis.


Assuntos
Coração/diagnóstico por imagem , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico por imagem , Imagem por Ressonância Magnética , Adulto , Idoso , Idoso de 80 Anos ou mais , Meios de Contraste , Feminino , Gadolínio , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico , Amiloidose de Cadeia Leve de Imunoglobulina/mortalidade , Amiloidose de Cadeia Leve de Imunoglobulina/patologia , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Prognóstico , Estudos Prospectivos
8.
Hematol Oncol Stem Cell Ther ; 12(1): 10-14, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30879471

RESUMO

INTRODUCTION: Systemic light chain (AL) amyloidosis can lead to an acquired coagulopathy secondary to acquired factor X (aFX) deficiency. However, it is not very clear who develops aFX deficiency in AL amyloidosis. METHODS: We therefore undertook this single centre, retrospective study to better characterize AL amyloidosis-associated aFX deficiency. RESULTS: Out of 121 AL patients who had FX testing at the time of their first evaluation at our institution, including 17 patients on warfarin at the time of testing, 10 out of 104 patients (9.6%) with systemic AL amyloidosis were found to have FX levels below 50%. Acquired FX deficiency was associated with advanced stage of AL amyloidosis and elevated cardiac biomarkers. Lower FX activity, advanced stage, and cardiac involvement by disease were associated with higher hazard of death on univariate analysis. On multivariate analysis, stage of AL amyloidosis was the only significant predictor of survival. Median survival time of patients with FX deficiency was 9.3 months compared to 118.4 months in those without. CONCLUSIONS: We conclude that while aFX deficiency is rare in systemic AL amyloidosis, it is a marker of advanced disease.


Assuntos
Deficiência do Fator X , Fator X/metabolismo , Amiloidose de Cadeia Leve de Imunoglobulina , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Deficiência do Fator X/sangue , Deficiência do Fator X/etiologia , Deficiência do Fator X/mortalidade , Feminino , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/sangue , Amiloidose de Cadeia Leve de Imunoglobulina/complicações , Amiloidose de Cadeia Leve de Imunoglobulina/mortalidade , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida
9.
Leukemia ; 33(5): 1268-1272, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30737485

RESUMO

It is well known that staging of patients with AL amyloidosis at diagnosis predicts for survival, but there is a paucity of literature delineating the prognostic value of these systems at relapse. We evaluated the prognostic value of AL staging among 413 patients initiated with second-line therapy between 2000 and 2015. Both the Revised Mayo 2012 and the European revision of Mayo 2004 staging systems were used. The median time from initial treatment to second-line therapy was 11.7 months. The first-line therapy was autologous stem cell transplant (ASCT) in 179 (43%) patients and non-ASCT therapies in 234 patients. Median survival from the institution of second-line therapy was 61 months. Both the Mayo 2004 and 2012 staging systems were of prognostic benefit at second-line therapy with respective risk ratios of 2.78 (95% CI: 2.15, 3.58) and 3.03 (95% CI: 2.33, 3.93) for patients with > stage 2 disease. On multivariate analysis, the predictive value of staging at second-line therapy was independent of stage at diagnosis and prior ASCT as first-line therapy. This study indicates that the Mayo staging systems work well at second-line therapy. Consequently, it is suitable for the stratification of patients in trials for relapsed, refractory AL amyloidosis.


Assuntos
Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/tratamento farmacológico , Amiloidose de Cadeia Leve de Imunoglobulina/mortalidade , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Retratamento , Estudos Retrospectivos , Resultado do Tratamento
10.
Mayo Clin Proc ; 94(3): 455-464, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30718070

RESUMO

OBJECTIVE: To evaluate the prognostic impact of Holter findings in patients with light chain amyloidosis. PATIENTS AND METHODS: We evaluated 239 patients in whom light chain amyloidosis was diagnosed from January 1, 2010, through December 31, 2015, who underwent 24-hour Holter monitoring. RESULTS: Holter testing was done before stem cell transplant evaluation in 183 of the 239 patients (76.6%) and at diagnosis in 50 (20.9%). Holter findings were nonsustained ventricular tachycardia (NSVT) in 60 patients (25.1%), ventricular couplets in 103 (43.1)%, accelerated idioventricular rhythm in 32 (13.4%), and atrial fibrillation (AF) in 18 (7.5%). Overall survival (OS) at 3 and 6 months after Holter monitoring in patients with AF vs without AF was 78% (95% CI, 54%-91%) vs 96% (95% CI, 92%-98%) (P=.002) and 61% (95% CI, 38%-80%) vs 92% (95% CI, 87%-95%), (P<.001), respectively. In patients with and without NSVT, 3- and 6-month OS after Holter testing was 90% (95% CI, 80%-94%) vs 96% (95% CI, 91%-98%) (P=.12) and 77% (95% CI, 64%-85%) vs 94% (95% CI, 89%-97%) (P<.001), respectively. For patients with and without ventricular couplets, 3- and 6-month OS was 94% (95% CI, 88%-97%) vs 94% (95% CI, 89%-97%) (P=.98) and 84% (95% CI, 75%-89%) vs 94% (95% CI, 89%-97%) (P=.01), respectively. Atrial fibrillation (hazard ratio, 2.5; 95% CI, 1.2-5.0; P=.02) and NSVT (hazard ratio, 2.0; 95% CI, 1.1-3.5; P=.02) were independent predictors for OS after accounting for age and Mayo stage. For patients undergoing routine testing before stem cell transplant, AF (P=.002) and NSVT (P=.02) were associated with inferior OS at 6 months but did not retain statistical significance after adjusting for Mayo stage (P=.10 and P=.54, respectively). CONCLUSION: Atrial fibrillation and NSVT on 24-hour Holter monitoring are associated with inferior short-term OS outcomes but do not impact peritransplant mortality.


Assuntos
Fibrilação Atrial/fisiopatologia , Eletrocardiografia Ambulatorial/métodos , Amiloidose de Cadeia Leve de Imunoglobulina/fisiopatologia , Amiloidose de Cadeia Leve de Imunoglobulina/terapia , Idoso , Fibrilação Atrial/mortalidade , Eletrocardiografia , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico
12.
Leukemia ; 33(5): 1256-1267, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30542145

RESUMO

Early diagnosis and risk stratification are key to improve outcomes in light-chain (AL) amyloidosis. Here we used multidimensional-flow-cytometry (MFC) to characterize bone marrow (BM) plasma cells (PCs) from a series of 166 patients including newly-diagnosed AL amyloidosis (N = 94), MGUS (N = 20) and multiple myeloma (MM, N = 52) vs. healthy adults (N = 30). MFC detected clonality in virtually all AL amyloidosis (99%) patients. Furthermore, we developed an automated risk-stratification system based on BMPCs features, with independent prognostic impact on progression-free and overall survival of AL amyloidosis patients (hazard ratio: ≥ 2.9;P ≤ .03). Simultaneous assessment of the clonal PCs immunophenotypic protein expression profile and the BM cellular composition, mapped AL amyloidosis in the crossroad between MGUS and MM; however, lack of homogenously-positive CD56 expression, reduction of B-cell precursors and a predominantly-clonal PC compartment in the absence of an MM-like tumor PC expansion, emerged as hallmarks of AL amyloidosis (ROC-AUC = 0.74;P < .001), and might potentially be used as biomarkers for the identification of MGUS and MM patients, who are candidates for monitoring pre-symptomatic organ damage related to AL amyloidosis. Altogether, this study addressed the need for consensus on how to use flow cytometry in AL amyloidosis, and proposes a standardized MFC-based automated risk classification ready for implementation in clinical practice.


Assuntos
Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico , Amiloidose de Cadeia Leve de Imunoglobulina/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Medula Óssea/metabolismo , Evolução Clonal , Feminino , Citometria de Fluxo , Humanos , Isotipos de Imunoglobulinas/sangue , Amiloidose de Cadeia Leve de Imunoglobulina/mortalidade , Imunofenotipagem , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Medição de Risco
13.
Blood ; 133(3): 215-223, 2019 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-30333122

RESUMO

Immunoglobulin light chain amyloidosis (AL amyloidosis) is caused by misfolded light chains that form soluble toxic aggregates that deposit in tissues and organs, leading to organ dysfunction. The leading determinant of survival is cardiac involvement. Current staging systems use N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac troponins T and I (TnT and TnI) for prognostication, but many centers do not offer NT-proBNP. We sought to derive a new staging system using brain natriuretic peptide (BNP) that would correlate with the Mayo 2004 staging system and be predictive for survival in AL amyloidosis. Two cohorts of patients were created: a derivation cohort of 249 consecutive patients who had BNP, NT-proBNP, and TnI drawn simultaneously to create the staging system and a complementary cohort of 592 patients with 10 years of follow-up to determine survival. In the derivation cohort, we found that a BNP threshold of more than 81 pg/mL best associated with Mayo 2004 stage and also best identified cardiac involvement. Three stages were developed based on a BNP higher than 81 pg/mL and a TnI higher than 0.1 ng/mL and compared with Mayo 2004 with high concordance (κ = 0.854). In the complementary cohort, 25% of patients had stage I, 44% had stage II, 15% had stage III, and 16% had stage IIIb disease with a median survival not reached in stage I, 9.4 years in stage II, 4.3 years in stage III, and 1 year in stage IIIb. This new Boston University biomarker scoring system will allow centers without access to NT-proBNP the ability to appropriately stage patients with AL amyloidosis. This trial was registered at www.clinicaltrials.gov as #NCT00898235.


Assuntos
Biomarcadores Tumorais/sangue , Amiloidose de Cadeia Leve de Imunoglobulina/mortalidade , Amiloidose de Cadeia Leve de Imunoglobulina/patologia , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Troponina T/sangue , Idoso , Feminino , Seguimentos , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/sangue , Amiloidose de Cadeia Leve de Imunoglobulina/classificação , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Taxa de Sobrevida
14.
Amyloid ; 25(4): 227-233, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30513220

RESUMO

BACKGROUND: Although survival has improved in recent decades, the short-term prognosis of patients with immunoglobulin light chain (AL) amyloidosis remains grim. We aimed to assess overall survival (OS) of AL amyloidosis patients by comparing cohorts in two consecutive time periods. METHODS: Data were collected and compared on 126 patients from two tertiary referral centres in The Netherlands during the time periods 2008-2012 and 2013-2016. RESULTS: There was a non-significant trend to improved 6-month OS in the last cohort (78% vs. 67%, p = .216, crude odds ratio 1.66, 95%CI 0.74-3.70, adjusted odds ratio 2.22, 95%CI 0.88-5.56). Patients in this cohort had higher Mayo risk scores (stage III 40% vs. 24%, p < .001 and revised stage IV 14% vs. 11%, p < .001), higher use of bortezomib (50% vs. 30%), and better haematological response (complete response/very good partial response in 39% vs. 27%, p < .001). Diagnostic delay was similar in both time periods. CONCLUSIONS: In the 2013-2016 cohort there was a trend toward improved 6-month OS, and an improved haematological response. Patients in this cohort had more advanced cardiac disease and received bortezomib more frequently, but diagnostic delay was similar to the 2008-2012 cohort. For further prognostic improvement, practitioners should be more alert, especially for cardiac amyloidosis.


Assuntos
Antineoplásicos/uso terapêutico , Biomarcadores/análise , Bortezomib/uso terapêutico , Testes Hematológicos , Amiloidose de Cadeia Leve de Imunoglobulina/mortalidade , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Seguimentos , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico , Amiloidose de Cadeia Leve de Imunoglobulina/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida
15.
Blood Cancer J ; 8(11): 101, 2018 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-30397193

RESUMO

High-dose melphalan with autologous stem cell transplantation (ASCT) can induce durable haematological and organ responses in systemic AL amyloidosis (AL). Stringent selection criteria have improved safety of ASCT in AL but most patients are transplant-ineligible. We report our experience of deferred ASCT in AL patients who were transplant-ineligible at presentation but had improvements in organ function after induction chemotherapy, enabling them to undergo ASCT. Twenty-two AL patients underwent deferred ASCT from 2011 to 2017. All had serial organ function and clonal response assessment. Organ involvement and responses were defined by amyloidosis consensus criteria. All patients were transplant-ineligible at presentation, predominantly due to advanced cardiac involvement. All received bortezomib-based therapy, with 100% haematologic response (86% complete response (CR)/very good partial response (VGPR)), enabling reversal of ASCT exclusion criteria. Patients underwent deferred ASCT for haematologic progression (45%) or consolidation (55%). There was no transplant-related mortality. Haematologic responses post-ASCT: CR 50%, VGPR 27%, PR 18%, non-response 5%. In all, 85.7% achieved cardiac responses. Median overall survival (OS) was not reached. Median progression-free survival (PFS) was 54 months. This selected cohort achieved excellent haematologic responses, organ responses, PFS and OS with deferred ASCT. If larger studies confirm these findings, this may widen the applicability of ASCT in AL.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Amiloidose de Cadeia Leve de Imunoglobulina/terapia , Adulto , Idoso , Biomarcadores , Seguimentos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico , Amiloidose de Cadeia Leve de Imunoglobulina/metabolismo , Amiloidose de Cadeia Leve de Imunoglobulina/mortalidade , Pessoa de Meia-Idade , Prognóstico , Índice de Gravidade de Doença , Transplante Autólogo , Resultado do Tratamento
16.
J Comp Eff Res ; 7(11): 1053-1062, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30354284

RESUMO

AIMS: Examine mortality and healthcare costs in Medicare beneficiaries with newly diagnosed immunoglobulin light chain (AL) amyloidosis. PATIENTS & METHODS: Cases were identified in 2012-2015 Medicare 5% data with ≥1 inpatient/≥2 outpatient claims consistent with AL amyloidosis and ≥1 AL-specific treatment. Cases were matched 3:1 with disease-free controls. Descriptive statistics were reported. RESULTS: A total of 249 (33.3%) cases were matched to 747 (66.7%) controls. A total of 19.7% of cases died within 1 year of follow-up versus 5.5% of controls; 30.6 versus 11.8% died within 2 years (p < 0.001). Mean (SD) costs in 1-year of follow-up were significantly higher among cases versus controls ($71,040 [65,766] vs $13,722 [27,493]; p < 0.001). CONCLUSION: Mortality was nearly four-times higher, and costs nearly five-times higher in beneficiaries with AL amyloidosis versus controls.


Assuntos
Custos de Cuidados de Saúde , Amiloidose de Cadeia Leve de Imunoglobulina/economia , Amiloidose de Cadeia Leve de Imunoglobulina/mortalidade , Medicare/economia , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Custos de Cuidados de Saúde/estatística & dados numéricos , Humanos , Pacientes Internados , Masculino , Estudos Retrospectivos , Estados Unidos
17.
Clin Lymphoma Myeloma Leuk ; 18(11): e493-e499, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30104177

RESUMO

INTRODUCTION: Deletion 17p (del 17p) portends a poor prognosis in myeloma, but its significance in light-chain amyloidosis is unknown. PATIENTS AND METHODS: We identified patients with light-chain amyloidosis and del 17p at diagnosis, and analyzed presenting characteristics, treatments, and clinical outcomes. All had baseline biopsy results showing amyloid and serologic and marrow studies, including standard fluorescence in-situ hybridization determinations of del 17p using commercial probes. Consensus criteria for hematologic and organ involvement, progression, and response were used. Kaplan-Meier (log rank) analyses and Cox regression analysis of baseline variables were used to identify predictors of overall and progression-free survival (PFS). Six-month landmark analyses were performed to assess the impact of treatment-related variables. RESULTS: We identified 44 patients from 7 countries with median marrow and del 17p plasma cells of 22% (range, 3%-100%) and 30% (2%-93%). Ninety-five percent had cardiac involvement, including 44% stage III. Two-thirds of the patients initially received bortezomib-based therapy. Forty-nine percent of patients experienced complete response or very good partial response, with median time to best response of 4 months (range, 1-28 months). Median overall survival and PFS were 49 and 32 months. Cardiac stage and hematologic response were the key predictors of outcomes. Patients with > 50% and ≤ 50% del 17p in clonal plasma cells had median survivals of 28 and 52 months, respectively (P = .08). In landmark analyses, only hematologic response predicted both overall survival and PFS. CONCLUSION: Cardiac stage, hematologic response, and del 17p percentage impact outcomes in these cases. Emphasis should be placed on optimizing supportive care and achieving a deep hematologic response.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Deleção Cromossômica , Cromossomos Humanos Par 17/genética , Amiloidose de Cadeia Leve de Imunoglobulina/mortalidade , Transplante de Células-Tronco/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Feminino , Seguimentos , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/genética , Amiloidose de Cadeia Leve de Imunoglobulina/patologia , Amiloidose de Cadeia Leve de Imunoglobulina/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
18.
Br J Haematol ; 183(4): 557-563, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30095161

RESUMO

Pomalidomide is a next-generation immunomodulatory agent with activity in relapsed light chain (AL) amyloidosis, but real world outcomes are lacking. We report the experience of the UK National Amyloidosis Centre. All patients with AL amyloidosis treated with pomalidomide between 2009 and 2017 were included. Data was collected on treatment toxicity and clonal response. Survival was calculated by the Kaplan-Meier method and outcomes reported on an intent-to-treat (ITT) basis. A total of 29 patients treated with pomalidomide were identified. Haematological responses at 3 months were: complete response (CR) nil, very good partial response (VGPR) 10 (35%), partial response (PR) 9 (31%), stable or progressive disease 7 (24%), unevaluable 3 (10%). On an ITT basis (n = 28), responses at 6 months were: CR- nil, VGPR-11 (39%), PR-2 (7%) and the remaining patients were non-responders 15 (53%). Median overall survival was 27 months (95% confidence interval 15·7-38·1 months). Median progression free survival (PFS) was 15 months (95% confidence interval 6·24-23·77). In conclusion, pomalidomide has activity in patients with relapsed AL amyloidosis. Responses are rapid and early responses may be predictive of a sustained overall response. Deep responses (VGPR or better) are seen in only a third of all patients and combination therapy needs to be explored.


Assuntos
Amiloidose de Cadeia Leve de Imunoglobulina , Talidomida/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/tratamento farmacológico , Amiloidose de Cadeia Leve de Imunoglobulina/metabolismo , Amiloidose de Cadeia Leve de Imunoglobulina/mortalidade , Amiloidose de Cadeia Leve de Imunoglobulina/patologia , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Taxa de Sobrevida , Talidomida/administração & dosagem
19.
Virchows Arch ; 473(5): 627-637, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30136180

RESUMO

Immunoglobulin-derived light-chain (AL) amyloidosis of lungs and bronchi can appear as a systemic and a local form. While systemic AL amyloidosis may need haemato-oncological care, the localised form can be treated restrained. We re-evaluated 207 specimens of lungs and bronchi sent in for amyloid diagnostics. Amyloid was diagnosed by polarization microscopy using Congo red-stained tissue specimens and classified immunohistochemically. Histoanatomical amyloid distribution patterns were documented as well as additional histological findings. For 118 patients with AL amyloidosis, we retrieved clinical data. CT scan results were available from 59 patients. AL amyloidosis was the most common type (183 cases). ALλ was found in 141 and of ALκ in 27 cases. Fifteen cases were AL amyloid not otherwise specified. Twenty cases harboured transthyretin and three serum amyloid A derived amyloid. By correlation of histoanatomy, radiological and clinical data, amyloid was rarely in the initial differential diagnosis. Local AL amyloidosis often presented with a nodular pattern on CT scan and showed a significantly better disease-specific 10-year survival compared with systemic AL amyloidosis (96.0 vs. 51.9%). Localised and systemic pulmonary and bronchial AL amyloidosis are having a completely different prognosis. While CT scan might be indicative, histological and clinical assessment are mandatory to reach a proper diagnosis and guide patient care.


Assuntos
Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico , Amiloidose de Cadeia Leve de Imunoglobulina/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/mortalidade , Amiloidose de Cadeia Leve de Imunoglobulina/terapia , Imuno-Histoquímica , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
20.
Am J Hematol ; 93(9): 1169-1180, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30040145

RESUMO

DISEASE OVERVIEW: Immunoglobulin light chain amyloidosis is a clonal, nonproliferative plasma cell disorder in which fragments of immunoglobulin light or heavy chain are deposited in tissues. Clinical features depend on organs involved but can include restrictive cardiomyopathy, nephrotic syndrome, hepatic dysfunction, peripheral/autonomic neuropathy, and "atypical multiple myeloma." DIAGNOSIS: Tissue biopsy stained with Congo red demonstrating amyloid deposits with apple-green birefringence is required for diagnosis. Invasive organ biopsy is not required because amyloid deposits can be found in bone marrow, salivary gland, or subcutaneous fat aspirate in 85% of patients. Verification that amyloid is composed of immunoglobulin light chains is mandatory. The gold standard is laser capture mass spectroscopy. PROGNOSIS: N-terminal pro-brain natriuretic peptide (NT-proBNP), serum troponin T, and difference between involved and uninvolved immunoglobulin free light chain values are used to classify patients into four groups of similar size; median survivals are 94.1, 40.3, 14.0, and 5.8 months. THERAPY: All patients with a systemic amyloid syndrome require therapy to prevent deposition of amyloid in other organs and prevent progressive organ failure. Stem cell transplant (SCT) is preferred, but only 20% of patients are eligible. Requirements for safe SCT include systolic blood pressure >90 mm Hg, troponin T < 0.06 ng/mL, age < 70 years, and serum creatinine ≤1.7 mg/dL. Nontransplant candidates can be offered melphalan-dexamethasone or cyclophosphamide-bortezomib-dexamethasone. Daratumumab appears to be highly active in AL amyloidosis. Antibodies designed to dissolve existing amyloid deposits are under study. FUTURE CHALLENGES: Delayed diagnosis remains a major obstacle to initiating effective therapy. EDUCATIONAL OBJECTIVES: Upon completion of this educational activity, participants will be better able to: Master recognition of clinical presentations that should raise suspicion of amyloidosis. Understand simple techniques for confirming the diagnosis and providing material to classify the protein subunit. Recognize that a tissue diagnosis of amyloidosis does not indicate whether the amyloid is systemic or of immunoglobulin light chain origin. Understand the roles of the newly introduced chemotherapeutic and investigational antibody regimens for the therapy of light chain amyloidosis.


Assuntos
Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico , Fatores Etários , Pressão Sanguínea , Creatinina/sangue , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/mortalidade , Amiloidose de Cadeia Leve de Imunoglobulina/terapia , Espectrometria de Massas/métodos , Prognóstico , Transplante de Células-Tronco , Análise de Sobrevida , Troponina T/sangue
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