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1.
Leuk Lymphoma ; : 1-8, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38625039

RESUMO

There is limited knowledge regarding the prevalence of geriatric impairments and frailty among patients with multiple myeloma (MM) in a real-world setting. This study evaluated the distribution of frailty profiles among 116 patients with newly diagnosed or relapsed MM, using four common frailty scales. The proportion of patients classified as frail varied significantly, ranging from 15.5% to 56.9%, due to differences in how frailty was operationalized between each frailty measure. Functional, cognitive, and mobility impairments were common overall and irrespective of performance status. Analyses between frailty and treatment selection (dose reduction and doublet vs. triplet therapy) demonstrated significant differences in non-steroid MM drug dose reductions between frail vs. non-frail patients, as scored by the International Myeloma Working Group (IMWG) Frailty Index and Simplified Frailty Score (p < .05). A standardized approach to frailty assessment that is practical in application, and beneficial in guiding treatment selection and minimizing treatment related toxicity is necessary to provide optimal tailored care.

2.
J Geriatr Oncol ; 15(3): 101735, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38460399

RESUMO

INTRODUCTION: Many of the newer treatments for adults with newly-diagnosed and relapsed multiple myeloma (MM) are orally administered. Adherence is a challenge, and little is known about strategies to optimize adherence. MATERIALS AND METHODS: Forty-seven patients initiating orally-administered anti-myeloma therapy were enrolled and randomized in a pilot study to receive either standard of care teaching or the Multinational Association of Supportive Care in Cancer Oral agent Teaching Tool (MOATT), a structured teaching tool. Adherence was measured electronically with a Medication Event Monitoring System (MEMS) cap. Optimal adherence was defined as an adherence rate of ≥90% over the six months study duration. Patients completed surveys regarding cancer therapy satisfaction and self-efficacy for medication management at one month and six months following the initiation of treatment in both arms. RESULTS: The mean adherence of patients over six months was 86.9%; 43.9% of the cohort were classified as non-adherent using the 90% threshold of adherence. Mean adherence was similar among standard of care teaching (87.9%) versus the MOATT intervention tool (85.6%) as was cancer therapy satisfaction and self-efficacy for medication management. DISCUSSION: In our pilot, the MOATT tool was not found to be feasible or acceptable. There were no preliminary differences noted between standard of care teaching versus the structured MOATT teaching tool with regards to overall adherence rates, cancer therapy satisfaction, or self-efficacy in medication management. Overall adherence rates were suboptimal in our study. Future research should work to identify aspects of educational interventions which are effective, and investigate different strategies which can be used to supplement patient education and potentially optimize medication adherence in patients with MM.


Assuntos
Mieloma Múltiplo , Humanos , Mieloma Múltiplo/tratamento farmacológico , Projetos Piloto , Adesão à Medicação , Inquéritos e Questionários , Administração Oral
4.
Leuk Res ; 131: 107324, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37285641

RESUMO

Anti-CD38 monoclonal antibodies (mAbs) are commonly used for treating newly diagnosed and relapsed/refractory (r/r) multiple myeloma (MM). However, concerns have been raised about the occurrence of second primary malignancies (SPMs) in patients receiving anti-CD38 mAbs. Assessing the safety data for rare adverse events like SPMs is challenging because individual clinical trials are typically focused on the primary endpoint. Therefore, we conducted a meta-analysis of randomized controlled trials (RCTs) published between January 2005 and April 2022, including patients with newly diagnosed or r/r MM. Our aim was to compare SPM rate with the use of anti-CD38 mAb-based regimens with other anti-myeloma regimens. After a median follow-up of 35.3 months (range: 8.2-56.2), we found that exposure to anti-CD38 mAbs was associated with an increased risk of developing SPMs compared to the control group (6.8% vs. 5.2%; Peto odds ratio [OR]: 1.53 [95% confidence interval (CI): 1.20-1.95]; I2= 0%, p-value for heterogeneity= 0.44). This increased risk was primarily driven by non-melanoma cutaneous cancers (92 vs. 47; Peto OR: 1.77 [95% CI: 1.25-2.51]; I2 = 0%, p-value for heterogeneity = 0.54). However, there was no significant difference in the incidence of solid tumors (including malignant melanoma) (OR: 1.28 [95% CI: 0.85-1.95]) or hematologic SPMs (OR: 1.86; [95% CI: 0.81-4.27]). In conclusion, the use of anti-CD38 mAb-based combination regimens is associated with a higher risk of non-invasive cutaneous SPMs, but not solid tumors or hematologic SPMs. The increased occurrence of non-invasive cutaneous SPMs may be due to enhanced monitoring resulting from longer treatment duration with anti-CD38 mAbs.


Assuntos
Antineoplásicos , Mieloma Múltiplo , Segunda Neoplasia Primária , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/epidemiologia , Mieloma Múltiplo/patologia , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/tratamento farmacológico , Incidência , Antineoplásicos/uso terapêutico , Anticorpos Monoclonais/efeitos adversos
5.
Cancer ; 128(12): 2288-2297, 2022 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-35377484

RESUMO

BACKGROUND: Despite routine evaluation of cytogenetics in myeloma, little is known regarding the impact of high-dose therapy (HDT) consolidation on overall survival (OS) or progression-free survival (PFS) in patients who have high-risk cytogenetics. The authors performed a meta-analysis of randomized controlled trials (RCTs) to assess the heterogeneity of HDT efficacy according to cytogenetic risk. METHODS: All RCTs in patients who had newly diagnosed myeloma from 2000 to 2021 that compared upfront HDT versus standard-dose therapy (SDT) consolidation were included. The primary objective was to assess the difference in HDT efficacy between standard-risk and high-risk cytogenetics in terms of the OS or PFS log(hazard ratio) (HR). The pooled OS and PFS HR was calculated according to cytogenetic-risk subgroup using a random-effects model, and heterogeneity (I2 ) (the percentage of total observed variability explained by between-study differences) was assessed using an interaction test. RESULTS: After screening 3307 citations, 6 RCTs were included for PFS analysis, and 4 were included for OS analysis. The median follow-up ranged from 3.1 to 7.8 years. The pooled OS HR for HDT versus SDT consolidation in patients with standard-risk and high-risk cytogenetics was 0.90 (95% confidence interval [CI], 0.70-1.17; I2 = 0%) and 0.66 (95% CI, 0.45-0.97; I2 = 0%), respectively. The difference in HDT efficacy in terms of OS between standard-risk and high-risk patients was statistically significant in favor of the high-risk group (P for interaction = .03). The pooled PFS HR for HDT versus SDT was 0.65 (95% CI 0.56-0.76; I2 = 0%) versus 0.52 (95% CI, 0.33-0.83; I2 = 55%), respectively. The difference in HDT efficacy in terms of PFS between standard-risk and high-risk patients was not significant (P for interaction = .25). CONCLUSIONS: The magnitude of OS benefit with upfront HDT is cytogenetics-dependent. Patients with high-risk cytogenetics should preferably receive upfront rather than delayed HDT consolidation. LAY SUMMARY: Upfront autologous stem cell transplantation improves overall survival in patients with newly diagnosed myeloma harboring high-risk cytogenetics.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Intervalo Livre de Doença , Humanos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/genética , Mieloma Múltiplo/terapia , Intervalo Livre de Progressão , Ensaios Clínicos Controlados Aleatórios como Assunto , Transplante Autólogo
6.
Cancers (Basel) ; 14(1)2021 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-35008276

RESUMO

Immune dysregulation and alteration of the bone marrow microenvironment allowing plasma cells to escape immune surveillance are well-known factors associated with the proliferation of clonal plasma cells and development of multiple myeloma (MM). Whilst immunotherapeutic approaches are now commonplace in a wide spectrum of malignancies, this aberration of myeloma development gives rise to the biological rationale for the use of immune checkpoint inhibitors (ICIs) in MM. However, the initial experience with these agents has been challenging with limited single agent efficacy, significant toxicity, and side effects. Herein, we review the biological and immunological aspects of MM and ICIs. We discuss the basic biology of immune checkpoint inhibitors, mechanisms of resistance, and drug failure patterns, review the published clinical trial data for ICIs in MM, and look towards the future of ICIs for MM treatment.

8.
Blood Cancer J ; 10(5): 52, 2020 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-32376870

RESUMO

We conducted a retrospective review of multiple myeloma (MM), smoldering multiple myeloma (SMM), and monoclonal gammopathy of undetermined significance (MGUS) patients seen at Mayo Clinic to determine whether a bone marrow biopsy (BM) is necessary in all patients diagnosed with a monoclonal protein. A total of 2254 MM, 397 SMM, and 5836 MGUS patients were included in the study. A total of 29 (1.3%) MM patients "without CRAB/FLC" were identified where BM or advanced imaging was critical for diagnosis, 8 (0.3% MM cohort) of whom were diagnosed with MM solely on BM findings (plasma cells > 60%). Without BM or advanced imaging none of these patients would be classified low-risk MGUS. A total of 314 (79%) MGUS-like SMM patients were identified where classification of SMM was based on BM findings. Without BM 97 would be classified as low/low-intermediate-risk MGUS and 151 intermediate or high-risk MGUS; 66 had missing information precluding classification. Only three (<1% SMM cohort) were low-risk MGUS without abnormalities in hemoglobin, calcium, and renal function. In patients presenting with low-risk MGUS and normal hemoglobin, calcium, and renal function, the risk of missing a diagnosis of SMM and MM by omitting BM is <1%. BM should be deferred in these patients in preference to clinical and laboratory monitoring.


Assuntos
Medula Óssea/patologia , Gamopatia Monoclonal de Significância Indeterminada/patologia , Mieloma Múltiplo/patologia , Plasmócitos/patologia , Mieloma Múltiplo Latente/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Mieloma Múltiplo/diagnóstico , Estudos Retrospectivos , Mieloma Múltiplo Latente/diagnóstico , Adulto Jovem
9.
Acta Haematol ; 143(2): 118-123, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31311009

RESUMO

The gut microbiota plays a significant role in health and disease, including cancer development and treatment. The importance of the gut microbiota in the efficacy and toxicity of novel therapies and immunotherapy is increasingly recognized. Plasma cells in multiple myeloma have the potential to survive in the gastrointestinal tract for long periods of time. The nature of the gut microbiota impacts the degree of antigen stimulation of these cells and may play a role in mutation development and clonal evolution. Furthermore, myeloma therapies such as proteasome inhibitors and alkylating agents, commonly used to treat patients, are frequently associated with gastrointestinal adverse events. Herein we review the gut microbiota and its role in hematopoiesis, pathogenesis of myeloma, and efficacy/toxicity of anti-myeloma therapies.


Assuntos
Mieloma Múltiplo/tratamento farmacológico , Inibidores de Proteassoma/uso terapêutico , Antineoplásicos Alquilantes/farmacologia , Antineoplásicos Alquilantes/uso terapêutico , Citocinas/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Mieloma Múltiplo/patologia , NF-kappa B/metabolismo , Plasmócitos/metabolismo , Inibidores de Proteassoma/farmacologia , Transdução de Sinais/efeitos dos fármacos
10.
Blood Adv ; 3(8): 1226-1229, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-30975646

RESUMO

We retrospectively reviewed the utility of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and transthoracic echocardiogram (TTE) in diagnosing cardiac involvement in patients with biopsy-proven systemic immunoglobulin light chain amyloidosis seen at the Mayo Clinic between 1 January 2006 and 30 December 2015. We analyzed 2 cohorts: patients undergoing endomyocardial biopsy for suspicion of cardiac involvement (cohort 1) and patients who had serum NT-proBNP and comprehensive echocardiographic evaluation at diagnosis (cohort 2). Of 179 patients undergoing endomyocardial biopsy (cohort 1), 173 (97%) had evidence of amyloid deposition, with 159 having NT-proBNP performed at the time of the procedure. The NT-proBNP was elevated (>300 pg/mL) in all 159 patients (sensitivity, 100%; median NT-proBNP, 4917 pg/mL; range, 355-69 541). The left ventricular ejection fraction, interventricular septal thickness, and strain rate were abnormal in 89/168 (53%), 102/64 (61%) and 92/95 (97%), respectively. Among cohort 2 (n = 342), 259 (76%) had an elevated NT-proBNP, of whom 237 (92%) had an abnormality detected on TTE. Of 83 patients with normal NT-proBNP <300 pg/mL, 27 (33%) had an abnormality on TTE (all with borderline strain rate -18% to -15%). Only 5/27 patients were considered to have possible early cardiac involvement and none had any other diagnostic or classical features of amyloidosis on TTE. The combination of NT-proBNP and comprehensive echocardiographic evaluation can diagnose cardiac amyloidosis negating the need for endomyocardial biopsy. A negative NT-proBNP rules out clinically meaningful cardiac involvement and may obviate the routine use of TTE in patients with a low clinical suspicion of cardiac amyloidosis.


Assuntos
Ecocardiografia , Cardiopatias , Amiloidose de Cadeia Leve de Imunoglobulina , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Volume Sistólico , Função Ventricular Esquerda , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Cardiopatias/sangue , Cardiopatias/diagnóstico por imagem , Cardiopatias/etiologia , Cardiopatias/fisiopatologia , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/sangue , Amiloidose de Cadeia Leve de Imunoglobulina/complicações , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico por imagem , Amiloidose de Cadeia Leve de Imunoglobulina/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
11.
Bone Marrow Transplant ; 54(3): 442-447, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30087461

RESUMO

Myeloma patients failing to achieve a complete response post autologous stem cell transplantation are heterogeneous, some ultimately achieving deeper responses and prolonged remission, whilst others relapse rapidly with poor outcomes. We evaluated the prognostic impact of the plasma cell proliferative index (PCPI) post-therapy, in 382 patients with myeloma failing to achieve complete response at 100 days post-transplant. Sixty percent (n = 230) of patients had zero clonal or too few clonal plasma cells to accurately assess PCPI (No PCPI). The remaining 40% (n = 152) of patients had PCPI performed with 79% (n = 120) having a low PCPI and 21% (n = 32) having an elevated PCPI. Patients with an elevated PCPI had significantly shorter progression free and overall survival. The median PFS was 8 months for elevated PCPI vs. 19 months for low PCPI vs. 24 months for no PCPI (p < 0.0001). The median OS was 27 months for elevated PCPI vs. 79 months for low PCPI vs. not reached for no PCPI, p < 0.0001). On multivariable analysis post-therapy PCPI was an independent predictor of progression free and overall survival. The PCPI post-therapy is a powerful predictor of survival and risk stratifies myeloma patients failing to achieve complete response early in the disease course.


Assuntos
Mieloma Múltiplo/metabolismo , Plasmócitos/metabolismo , Idoso , Proliferação de Células , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Prognóstico , Análise de Sobrevida
13.
Bone Marrow Transplant ; 54(7): 1077-1081, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30390060

RESUMO

High-dose melphalan is the standard conditioning regimen for patients with AL amyloidosis receiving autologous stem cell transplantation. Conventional formulations require propylene glycol (PG) as a co-solvent and melphalan has limited solubility and chemical stability after reconstitution, with potential risks for propylene glycol-related complications. Captisol-stabilized propylene glycol-free (PG-free) melphalan has been developed with improved solubility and chemical stability. We compared a cohort of patients with AL amyloidosis receiving PG melphalan (n = 96) to those receiving PG-free melphalan (n = 48) as conditioning for autologous stem cell transplantation. Median time to neutrophil and platelet engraftment was the same; 14 days PG melphalan vs 14 days PG-free melphalan, p = 0.73 and 16 days PG melphalan vs 16 days PG-free melphalan, p = 0.52, respectively. Hospitalization rate was similar in both cohorts, 68% PG melphalan vs 58% PG-free melphalan, p = 0.27. All-cause mortality at 100 days was not statistically significant, 3% PG melphalan vs 2% PG-free melphalan, p > 0.99. Overall response rate (ORR) and rates of complete response (CR) were similar (ORR 93% PG melphalan vs 94% PG-free melphalan, p > 0.99 and CR 39% PG melphalan vs 32% PG-free melphalan, p = 0.46). PG-free melphalan showed a comparable safety and efficacy profile to PG melphalan in patients with AL amyloidosis receiving stem cell transplantation.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Amiloidose de Cadeia Leve de Imunoglobulina/tratamento farmacológico , Amiloidose de Cadeia Leve de Imunoglobulina/terapia , Melfalan/uso terapêutico , Condicionamento Pré-Transplante/métodos , Transplante Autólogo/métodos , Idoso , Antineoplásicos Alquilantes/farmacologia , Feminino , Humanos , Masculino , Melfalan/farmacologia , Pessoa de Meia-Idade
14.
Blood Adv ; 2(22): 3149-3154, 2018 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-30463914

RESUMO

The plasma cell proliferative index (PCPI), determined by a slide technique or by flow cytometry, detects cells in the S phase of the cell cycle and is a useful prognostic tool in patients with plasma cell disorders such as multiple myeloma and amyloidosis. We conducted a retrospective review analyzing the prognostic effect of PCPI in 306 patients with smoldering multiple myeloma (SMM). Seventy-nine (26%) patients had an elevated PCPI (>0.5). An elevated PCPI predicted an inferior time to progression (median, 3.0 vs 7.1 years for those with a low PCPI; P = .0004). Within 24 months, the progression rate was significantly higher for patients with an elevated PCPI (49% vs. 20%; P < .0001). PCPI is a valuable tool in risk stratifying patients with SMM and identifies patients with earlier progression who may benefit from closer follow-up and consideration of early intervention trials.


Assuntos
Plasmócitos/patologia , Mieloma Múltiplo Latente/patologia , Idoso , Anemia/diagnóstico , Anemia/etiologia , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Plasmócitos/citologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Mieloma Múltiplo Latente/complicações
15.
Blood Cancer J ; 8(11): 106, 2018 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-30409963

RESUMO

We retrospectively reviewed all patients (n = 243) receiving bortezomib, lenalidomide, and dexamethasone (VRd) induction followed by autologous stem cell transplantation (ASCT) for multiple myeloma at the Mayo Clinic between January 2010 and April of 2017. Median age was 61 (interquartile range, 55-67) with 62% of patients being male. High-risk cytogenetic abnormalities (HRA) were present in 34% of patients. A total of 166 (68%) patients received some form of maintenance/other therapy post transplant (no maintenance (NM, n = 77), lenalidomide maintenance (LM, n = 108), bortezomib maintenance (BM, n = 39), and other therapy (OT, n = 19)). Overall response rate at day 100 post ASCT was 99% (CR 42%) with CR rate increasing to 62% at time of best response post transplant. Two year and 5 year overall survival rates were 90% and 67%, respectively, with an estimated median overall survival (OS) and progression-free survival (PFS) of 96 and 28 months, respectively. HRA was associated with a worse OS but not PFS (median OS: not reached for standard risk vs 60 months for HRA, P = 0.0006; median PFS: 27 months for standard risk vs 22 months for HRA, P = 0.70). The combination of VRd followed by ASCT is a highly effective regimen producing deep and durable responses in many patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/terapia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bortezomib/administração & dosagem , Terapia Combinada , Dexametasona/administração & dosagem , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Lenalidomida/administração & dosagem , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/etiologia , Mieloma Múltiplo/mortalidade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Transplante Autólogo , Resultado do Tratamento
16.
Panminerva Med ; 60(4): 174-184, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30303355

RESUMO

Despite significant progress in our understanding and the development of novel therapies, most patients with multiple myeloma will experience relapse of their disease. Therapy of relapsed myeloma has improved due to the availability of novel agents that are highly active against the disease. However, the selection of therapy can be challenging due to the emergence of toxicities, comorbidities and frailty. In the following we discuss our approach to the treatment of the patient with relapsed myeloma.


Assuntos
Antineoplásicos/uso terapêutico , Mieloma Múltiplo/terapia , Protocolos de Quimioterapia Combinada Antineoplásica , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Ensaios Clínicos Fase III como Assunto , Tomada de Decisões , Perfilação da Expressão Gênica , Humanos , Hidrazinas/uso terapêutico , Imunoterapia , Hibridização in Situ Fluorescente , Mieloma Múltiplo/diagnóstico , Recidiva Local de Neoplasia , Transplante de Células-Tronco , Sulfonamidas/uso terapêutico , Avaliação de Sintomas , Transplante Autólogo , Triazóis/uso terapêutico , Conduta Expectante
17.
Am J Hematol ; 93(12): 1518-1523, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30194770

RESUMO

Positron emission tomography-computed tomography (PET-CT) can identify bony lesions, assess disease burden, and detect extramedullary disease (EMD) in patients with multiple myeloma. We retrospectively reviewed records of patients who underwent PET-CT within 60 days of a new diagnosis (before therapy commenced) to identify the nature and prognostic impact of PET-CT abnormalities. Patients (N = 313) were seen from April 2005 through June 2017. Of the 234 patients (75%) with focal lesions (FLs), 182 (58%) had at least 3 FLs, 38 (12%) had EMD, and 204 (65%) had documented myelomatous lytic lesions. The median maximum standardized uptake value (SUVmax ) for the entire cohort was 5.9 (range 1.5-48.3). Presence of at least 3 FLs and EMD predicted inferior overall survival (OS); median OS was 57.8 months for patients with 3 or more FLs and 103.6 months for patients with fewer than 3 FLs (P = .003). The median OS was 45.5 and 71.8 months for patients with and without EMD, respectively (P = .004). No clear SUVmax cutoff was predictive of progression-free survival or OS. PET-CT is a valuable tool for assessing disease burden and could provide prognostic information about a contemporary cohort of patients with newly diagnosed myeloma who received treatment with novel agents.


Assuntos
Fluordesoxiglucose F18/farmacocinética , Mieloma Múltiplo/diagnóstico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico por imagem , Mieloma Múltiplo/mortalidade , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida
18.
Biol Blood Marrow Transplant ; 24(11): 2360-2364, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29964192

RESUMO

Hematologic response has emerged as a powerful prognostic factor for survival in patients with immunoglobulin light chain (AL) amyloidosis. Patients achieving a complete response (CR), based on serum and urine analysis, survive longest. However, data regarding the impact of bone marrow features post-therapy on response and survival are limited. We evaluated the impact of achieving a stringent CR (sCR), defined as undetectable bone marrow clonal plasma cells by flow cytometry, in patients with AL amyloidosis receiving an autologous stem cell transplant. A total of 573 consecutive patients transplanted for AL amyloidosis at the Mayo Clinic between April 2002 and August 2016 were included in the analysis. Of 540 patients in whom response was assessable, 220 patients (41%) achieved a CR, of whom 212 (96%) had a bone marrow biopsy at time of response assessment and were further analyzed for determination of sCR; 166 patients (78%) with a CR achieved an sCR, representing 31% of the whole cohort. Patients achieving a CR had a higher median percentage of bone marrow plasma cells (10% for CR versus 6% for sCR, P = .03), more patients with bone marrow plasma cells ≥ 10% (50% for CR versus 33% for sCR, P = .04), and were less likely to receive chemotherapy before transplantation (30% for CR versus 49% for sCR, P = .03) compared with those achieving sCR. Median overall survival for all patients achieving a CR was 175 months and was not statistically different between those achieving an sCR compared with those achieving a CR only (median not reached for sCR versus 175 months for CR, P = .65). Progression-free survival, however, was significantly shorter in patients failing to achieve an sCR (151 months for sCR versus 72 months for CR, P = .0003). Bone marrow examination post-transplant in AL amyloidosis is important and identifies patients who fail to achieve an sCR and progress earlier.


Assuntos
Amiloidose de Cadeia Leve de Imunoglobulina/terapia , Transplante de Células-Tronco/métodos , Adulto , Idoso , Feminino , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
19.
Biol Blood Marrow Transplant ; 24(10): 2157-2159, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29933071

RESUMO

Autologous stem cell transplantation (ASCT) has been used in treatment for immunoglobulin light chain (AL) amyloidosis for over 2 decades and is generally reserved for patients younger than 70 years. Herein we report on outcomes of ASCT in a cohort of patients with AL amyloidosis aged 70 years or older. Between August of 2002 and April of 2017, 34 patients aged 70 years or older, with biopsy-proven AL amyloidosis, received an ASCT at the Mayo Clinic Rochester. Seventy percent of patients (n = 24) were transplanted within 6 months of diagnosis, and 74% (n = 25) received reduced-intensity conditioning with melphalan <200 mg/m2. Sixty-five percent of patients (n = 22) required hospitalization with a median duration of hospital admission of 8 days. Common reasons for hospitalization included fever or infection (14%), cardiac arrhythmia (14%), nutritional support (24%), and volume overload (19%). Overall response rate was 75%, with a complete response seen in 25% of patients. Overall survival and progression-free survival for the cohort were 66 months and 40 months, respectively. One patient died within 100 days of transplant, representing a 3% 100-day mortality rate. ASCT is safe and efficacious in carefully screened patients aged 70 or above.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Amiloidose de Cadeia Leve de Imunoglobulina , Melfalan/administração & dosagem , Condicionamento Pré-Transplante , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/mortalidade , Amiloidose de Cadeia Leve de Imunoglobulina/terapia , Masculino , Indução de Remissão , Estudos Retrospectivos , Taxa de Sobrevida , Transplante Autólogo
20.
Blood Adv ; 2(7): 769-776, 2018 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-29615413

RESUMO

We evaluated the impact of light chain type, lambda (λ) or kappa (κ), on disease features and outcomes in patients with immunoglobulin light chain (AL) amyloidosis receiving stem cell transplant at the Mayo Clinic between October 2002 and August 2016. Patients with λ AL amyloidosis had higher rates of renal and neurological involvement (λ 69% vs κ 57%, P = .02 and λ 16% vs κ 9%, P = .03, respectively). Patients with κ AL amyloidosis had more hepatic involvement (λ 7% vs κ 18%, P = .0003). Complete response rate was 43% for both groups and overall response rates were similar (λ 85% vs κ 91%, P = .12). Patients with κ light chain amyloidosis had better progression-free and overall survival (PFS: λ 74 months vs κ 101 months, P = .0064 and OS: λ 121 months vs κ not reached, P = .003). Mayo stage 2004 was more predictive of survival in the λ cohort (median OS of 143 months stage I vs 77 months stage II vs 33 months stage III, P < .0001) than in the κ cohort (median OS not reached for stage I and II and 102 months for stage III, P = .044). Conditioning dose predicted survival in the λ cohort only (median OS 149 months for melphalan 200 mg/m2 vs 50 months for melphalan <200 mg/m2, P < .0001; median OS κ not reached for melphalan 200 mg/m2 or <200 mg/m2, P = .38). On multivariate analysis, light chain type remained an independent predictor of survival. Light chain type predicts organ involvement and survival in patients with AL amyloidosis receiving stem cell transplant.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Cadeias Leves de Imunoglobulina , Amiloidose de Cadeia Leve de Imunoglobulina/mortalidade , Valor Preditivo dos Testes , Idoso , Feminino , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/complicações , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico , Amiloidose de Cadeia Leve de Imunoglobulina/terapia , Cadeias kappa de Imunoglobulina , Cadeias lambda de Imunoglobulina , Nefropatias/etiologia , Hepatopatias/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Condicionamento Pré-Transplante/mortalidade
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