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1.
Am J Hematol ; 97(7): 877-884, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35389534

RESUMO

Monoclonal gammopathy of renal significance (MGRS) is a recognized clinical entity. Literature regarding treatment and its outcomes in MGRS is sparse due to the rarity and misdiagnosis of MGRS. We retrospectively analyzed 280 adults with an MGRS diagnosis from 2003 to 2020 across 19 clinical centers from 12 countries. All cases required renal biopsy for the pathological diagnosis of MGRS. Amyloidosis-related to MGRS (MGRS-A) was present in 180 patients; nonamyloidosis MGRS (MGRS-NA), including a broad spectrum of renal pathologies, was diagnosed in 100 patients. The median overall survival in the studied cohort was 121.0 months (95% CI: 105.0-121.0). Patients with MGRS-A had a shorter overall survival than patients with MGRS-NA (HR = 0.41, 95%CI: 0.25-0.69; p = 0.0007). Both hematologic and renal responses were associated with longer survival. Achievement of ≥VGPR was generally predictive of a renal response (OR = 8.03 95%CI: 4.04-115.96; p < 0.0001), one-fourth of patients with ≥VGPR were renal nonresponders. In MGRS-A, factors associated with poor prognosis included elevated levels of creatinine, beta-2-microglobulin, and hemodialysis at diagnosis. In MGRS-NA, only age >65 years was associated with increased risk of death. Treatments provided similar hematologic response rates in both types of MGRS. Autologous stem cell transplantation led to better response than other treatments. This multicenter and international effort is currently the largest report on MGRS.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Nefropatias , Gamopatia Monoclonal de Significância Indeterminada , Paraproteinemias , Lesões Pré-Cancerosas , Adulto , Idoso , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Nefropatias/etiologia , Nefropatias/patologia , Nefropatias/terapia , Gamopatia Monoclonal de Significância Indeterminada/complicações , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Gamopatia Monoclonal de Significância Indeterminada/terapia , Paraproteinemias/diagnóstico , Prognóstico , Estudos Retrospectivos , Transplante Autólogo/efeitos adversos
2.
J Clin Apher ; 36(1): 59-66, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32942343

RESUMO

INTRODUCTION: Factor XIII (FXIII) deficiency may cause bleeding under certain clinical circumstances. Therapeutic plasma exchange (TPE) may lead to a transient deficiency. OBJECTIVES: To describe the clinical evolution of patients with acquired FXIII deficiency secondary to TPE. METHODS: We respectively studied a cohort of consecutive patients from 2014 to 2019 who were treated with TPE with FXIII levels <50%. The FXIII was measured after the start of the TPE course, on days between the TPE sessions, due to suspected acquired deficiency. All TPE were performed using continuous flow cell separator. In all cases, the initial replacement fluid applied was albumin. Apheresis procedures were held at 24to 48 hours intervals. RESULTS: Eighteen patients were included, 13 of them were recipients of kidney transplants. The main TPE prescription was humoral rejection. Median FXIII at diagnosis (measured on days between sessions of the TPE course) was 19%(IQR17-25). The median of apheresis procedures before measurement of FXIII was 3(IQR2-4). Among the total cohort, 10 patients suffered hemorrhages. None of the patients without history of kidney transplants had bleeding (n = 5), however, 10/13 with kidney transplants did. Five kidney transplant patients received therapy with FXIII concentrate because of life-threatening bleeding. In all cases, the bleeding stopped within the first 24 hours. All patients had their FXIII levels measured again after finishing the TPE course, with normal results. CONCLUSIONS: TPE is an under-diagnosed cause of acquired FXIII deficiency since routine coagulation tests remain unaltered. It might cause major bleeding, particularly in patients with a recent history of surgery like kidney transplants.


Assuntos
Deficiência do Fator XIII/etiologia , Troca Plasmática/efeitos adversos , Adulto , Fator XIII/análise , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
3.
Hematol Oncol ; 38(3): 363-371, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32196120

RESUMO

Data about treatment outcomes and toxicity in Latin America are scarce. There are differences with central countries based on access to healthcare system and socioeconomic status. Argentinean Society of Hematology recommends bortezomib-based triplets for induction treatment of transplant eligible newly diagnosed multiple myeloma patients. Most common options are CyBorD (cyclophosphamide, bortezomib and dexamethasone) and VTD (bortezomib, thalidomide and dexamethasone). Main goal of our retrospective, multicentric study was to compare very good partial response rate (VGPR) or better after induction treatment in a real-world setting in Argentina. Secondary objectives included comparison of complete response (CR) post-induction and after bone marrow transplantation, grade 3-4 adverse events (AEs), progression-free survival (PFS) and overall survival (OS). Three hundred twenty-two patients were included (median age at diagnosis: 57 years; 52% male; 28% had ISS3; 14% with high-risk cytogenetics; median follow up: 34 months). CyBorD was indicated in 74% and 26% received VTD. In VTD arm, 72.62% of patients achieved at least VGPR vs 53.36% receiving CyBorD (odds ratio, OR: 1.96 [95% confidence interval, CI: 1.08-3.57; P = .026] after adjusting by age, ISS [International Staging System], lactate dehydrogenase levels (LDH) and cytogenetic risk. Difference in VGPR was 19.26% (95% CI: 15-24). CR rate were 35.92% (VTD) vs 22.55% (CyBorD) (adjusted OR: 2.13 [95% CI: 1.12-4.05]). Difference in CR was 13.37% (95% CI: 9.6-17.53). Adverse events (AEs) were more common with VTD (69.05% vs 55.46% for CyBorD; P = .030), especially grade 3-4 neuropathy (P = .005) and thrombosis (P = .001). Thromboprophylaxis was inadequate in 20.24% of patients. Hematological AEs were more common with CyBorD, especially thrombocytopenia (P = .017). PFS and OS at 24 months were not different between treatments. In this real-world setting, VTD was associated with better CR and VGPR than CyBorD. Nevertheless, CyBorD continues to be the preferred induction regimen in Argentina, based on safety profile. Frontline autologous stem cell transplantation improves quality of responses, especially in countries with limited access to new drugs.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia de Indução/mortalidade , Mieloma Múltiplo/mortalidade , Idoso , Bortezomib/administração & dosagem , Ciclofosfamida/administração & dosagem , Dexametasona/administração & dosagem , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/patologia , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Taxa de Sobrevida , Talidomida/administração & dosagem
4.
Nephrology (Carlton) ; 25(6): 442-449, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31825549

RESUMO

BACKGROUND: Monoclonal gammopathy of renal significance (MGRS)-related lesions are infrequent entities. There are no publications on these disorders in Latin America (LA). The aim of this study was to describe epidemiological and clinical characteristics of these patients in LA. METHODS: We performed a multicentre retrospective study. Patients with diagnosis of MGRS between 2012 and 2018 were included. Epidemiological and clinical data were collected from clinical records. RESULTS: Twenty-seven patients from Chile, Argentina, Ecuador and Uruguay were included. Half debuted with a nephrotic syndrome, and 32% required dialysis. Proliferative glomerulonephritis with monoclonal immunoglobulin deposits was found in 33%, amyloidosis in 26% and monoclonal immunoglobulin deposition disease also in 26%. The immunoglobulin most frequently found in renal biopsies was IgG kappa. In 67% a paraprotein was found. Twenty patients received an anti-plasma cell regimen, and 3 a rituximab-based regimen (IgM-MGRS). Renal response (RR) was achieved in 56%. Early treatment (≤3 months) was associated with higher RR (75% vs 43%). Three patients relapsed within 21.5 months, and 3 progressed: 1 to multiple myeloma, 1 to systemic amyloidosis and another to systemic light-chain deposition disease. Two patients died, both due to infection during induction treatment. CONCLUSION: There was a higher than expected frequency of patients requiring dialysis. The most common MGRS-related lesion was PGNMD. Early treatment was associated with better response. As a rare disease, increasing awareness and promoting early diagnosis are necessary in LA to improve outcomes. SUMMARY AT A GLANCE A collection of 27 cases of MGRS from Latin America with information on epidemiology, clinical characteristics, treatment and outcome of patients diagnosed of MGRS-related renal lesions.


Assuntos
Nefropatias/epidemiologia , Paraproteinemias/complicações , Adulto , Idoso , Progressão da Doença , Feminino , Glomerulonefrite/epidemiologia , Glomerulonefrite/terapia , Humanos , Nefropatias/terapia , América Latina/epidemiologia , Masculino , Pessoa de Meia-Idade , Paraproteinemias/terapia , Diálise Renal , Estudos Retrospectivos
5.
Am J Hematol ; 91(6): 575-80, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26955792

RESUMO

The multicenter retrospective study conducted in 38 centers from 20 countries including 172 adult patients with CNS MM aimed to describe the clinical and pathological characteristics and outcomes of patients with multiple myeloma (MM) involving the central nervous system (CNS). Univariate and multivariate analyses were performed to identify prognostic factors for survival. The median time from MM diagnosis to CNS MM diagnosis was 3 years. Thirty-eight patients (22%) were diagnosed with CNS involvement at the time of initial MM diagnosis and 134 (78%) at relapse/progression. Upon diagnosis of CNS MM, 97% patients received initial therapy for CNS disease, of which 76% received systemic therapy, 36% radiotherapy and 32% intrathecal therapy. After a median follow-up of 3.5 years, the median overall survival (OS) from the onset of CNS involvement for the entire group was 7 months. Untreated and treated patients had median OS of 2 and 8 months, respectively (P < 0.001). At least one previous line of therapy for MM before the diagnosis of CNS disease and >1 cytogenetic abnormality detected by FISH were independently associated with worse OS. The median OS for patients with 0, 1 and 2 of these risk factors were 25 months, 5.5 months and 2 months, respectively (P < 0.001). Neurological manifestations, not considered chemotherapy-related, observed at any time after initial diagnosis of MM should raise a suspicion of CNS involvement. Although prognosis is generally poor, the survival of previously untreated patients and patients with favorable cytogenetic profile might be prolonged due to systemic treatment and/or radiotherapy. Am. J. Hematol. 91:575-580, 2016. © 2016 Wiley Periodicals, Inc.


Assuntos
Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/mortalidade , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Neoplasias do Sistema Nervoso Central/secundário , Neoplasias do Sistema Nervoso Central/terapia , Aberrações Cromossômicas , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , Mieloma Múltiplo/patologia , Prognóstico , Radioterapia , Estudos Retrospectivos , Análise de Sobrevida , Taxa de Sobrevida , Resultado do Tratamento
6.
Medicina (B Aires) ; 76(2): 81-8, 2016.
Artigo em Espanhol | MEDLINE | ID: mdl-27135845

RESUMO

Patients over 60 years old with acute myeloid leukemia (AML) have a worse prognosis due to several factors that determine the therapeutic outcome. The main predictors of mortality in patients with AML reported in the literature were analyzed in our population. The primary objective was to analyze overall survival. The secondary objective was to determine treatment-related mortality, defined as death within eight weeks of starting treatment. It was designed as a retrospective study. A total of 133 treatment naive patients were included, from January 1991 to August 2014. The adjusted analysis showed that the most important variables to determine overall survival were the WBC count = 30 000 at diagnosis [adjusted HR 2.19 (1.06-4.53), p = 0.03)] and the Performance Status (ECOG) 3 or 4 [aHR 4.63 (1.69-12.68), p < 0.001)]. Performance Status 3-4 was the only variable that conditioned treatment related mortality, showing in the univariate analysis an OR 5.44 (CI 1.93-15.28, p < 0.001). It was also the only variable that kept its statistical power in the multivariate analysis adjusted OR (aOR) 12.40 (IC 1.12-137.17, p = 0.04). The inherent poor outcome in elderly patients diagnosed with AML is not fully understood. The best way of assessing these elderly patients should probably include not only age but the best way of assessing these elderly patients should probably include not only age but laboratory, genetic and molecular studies. Especially designed comorbidity and fragility indices should be included, along with functional status. Leukocytosis and poor quality of life were identified as the most powerfull factors for predicting mortality in our study.


Assuntos
Antineoplásicos/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/mortalidade , Leucocitose/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Análise Citogenética , Feminino , Humanos , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/diagnóstico , Masculino , Pessoa de Meia-Idade , Mortalidade , Razão de Chances , Qualidade de Vida , Análise de Regressão , Estudos Retrospectivos , Resultado do Tratamento
7.
Blood Cells Mol Dis ; 53(3): 110-7, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24973170

RESUMO

In this study, we have examined CKS1B gene expression and copy number in a total of 114- patients at diagnosis: 83 with multiple myeloma (MM) and 31 with monoclonal gammopathy of undetermined significance (MGUS). Results were correlated with cytogenetics, FISH and clinical characteristic. Significant CKS1B mRNA levels in MM compared to MGUS cases (p<0.048) were detected. In MM, the frequency of 1q21 (CKS1B) copy gain was significantly higher in cases with abnormal karyotype compared to patients with normal karyotype (p=0.021). Global analysis showed a positive correlation between CKS1B expression and 1q21 copy number (p<0.0001). No association between CKS1B mRNA expression and clinical parameters was found. However, a significantly higher level of ß2 microglobulin in cases with 1q21 gains than those without (p=0.0094) was observed. Overall survival was shorter in cases with 1q21 gain compared to those with normal 1q21 region (p=0.0082). Our results suggest a role for CKS1B in the multiple step process of progression of MGUS to MM and show that CKS1B copy gain has a more significant prognostic value than its overexpression. This adverse impact on survival probably reflects the genetic instability associated to chromosome 1q alterations resulting in a more aggressive behavior of the disease.


Assuntos
Quinases relacionadas a CDC2 e CDC28/genética , Dosagem de Genes , Gamopatia Monoclonal de Significância Indeterminada/genética , Mieloma Múltiplo/genética , RNA Mensageiro/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Aberrações Cromossômicas , Cromossomos Humanos Par 1 , Progressão da Doença , Feminino , Perfilação da Expressão Gênica , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Gamopatia Monoclonal de Significância Indeterminada/mortalidade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/mortalidade , Estadiamento de Neoplasias , Prognóstico , Adulto Jovem
8.
Medicina (B Aires) ; 73 Suppl 2: 1-26, 2013.
Artigo em Espanhol | MEDLINE | ID: mdl-24192583

RESUMO

The venous thromboembolic disease (VTD) in adults has a high morbidity and mortality. It can be also associated to disabling chronic conditions. In spite of this, prophylaxis in healthcare assistance is still underused. In this article, the available evidence in thromboprophylaxis was analyzed to offer recommendations (1) or suggestions (2) classified according to different levels of evidence (A, B or C). Different medical scenarios and types of thromboprophylaxis were analyzed. In major orthopedic surgeries low molecular weight heparins, LMWH, inhibitors of the Xa and IIa factors are recommended (1B) to be started during hospitalization and continued for 35 days in hip replacement surgery and for 10 days in total knee replacement surgery. Knee arthroscopy and spine surgery do not require pharmacologic treatment (2B) unless the patient has other risks factors for thrombosis. In such cases, LMWH are recommended. Non-surgical patients who have at least one risk factor should receive LMWH, NFH or fondaparinux (1B) if they are to be bedridden or unable to walk for three or more days. Patients undergoing neurosurgery or with intracranial hemorrhage should receive mechanic prophylaxis (2C), and accordingly they should start LMWH or NFH 24 to 72 hours afterwards (2C). The latter two drugs are recommended for critically ill patients. Patients with low risk for VTD undergoing other type of surgeries should be prescribed with mechanical prophylaxis (2C) and encouraged to walk promptly (2C), while those with high risk should be prescribed with LMWH or NFH (1B or 2C according to bleeding risk factors).


Assuntos
Anticoagulantes/uso terapêutico , Fibrinolíticos/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Trombose Venosa/prevenção & controle , Adulto , Argentina , Fidelidade a Diretrizes , Humanos , Incidência , Procedimentos Ortopédicos/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Fatores de Risco , Trombose Venosa/epidemiologia
9.
Artigo em Inglês | MEDLINE | ID: mdl-37739860

RESUMO

INTRODUCTION: The treatment of elderly multiple myeloma (MM) patients with autologous stem cell transplantation (ASCT) is a controversial procedure. Most clinical trials evaluating the safety and efficacy of ASCT have primarily included patients younger than 65 years. DESIGN AND METHODS: This was a retrospective analysis of patients with MM who underwent ASCT between 2008 and 2018. Patients at or over 65 years were compared with patients under 65 years. We analyzed treatment-related mortality (TRM), response rate, progression-free survival (PFS) and overall survival (OS). RESULTS: Two hundred and twenty-one patients were included: 50 patients at or over 65 years, (median age 68 years), including 7 patients over 70 years and 151 patients under 65 years, (median age 57 years). No differences were found in the neutrophil and platelet engraftment, median days of hospitalization and life support requirement during the hospitalization period for the ASCT. No statistically significant differences were found in the incidence of TRM between both groups at 100 days post-transplant (2% vs. 2.9%, p = 0.322). The ASCT improved complete response and stringent complete response rates (44% vs. 37%, p < 0.001). Survival was not modified by age: after a median follow-up of 53 months, the estimated PFS rates at three years were 63% and 60% (p = 0.88) and the OS rates at five years were 75% and 74% (p = 0.72), respectively. CONCLUSIONS: Our data suggest that the ASCT is feasible in selected elderly patients with MM over 65 years of age, achieving response and survival rates similar to those of younger patients.

10.
Leuk Lymphoma ; 64(4): 816-821, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36695519

RESUMO

Primary plasma cell leukemia (pPCL) is an infrequent and aggressive plasma cell disorder. The prognosis is still very poor, and the optimal treatment remains to be established. A retrospective, multicentric, international observational study was performed. Patients from 9 countries of Latin America (LATAM) with a diagnosis of pPCL between 2012 and 2020 were included. 72 patients were included. Treatment was based on thalidomide in 15%, proteasome inhibitors (PI)-based triplets in 38% and chemotherapy plus IMIDs and/or PI in 29%. The mortality rate at 3 months was 30%. The median overall survival (OS) was 18 months. In the multivariate analysis, frontline PI-based triplets, chemotherapy plus IMIDs and/or PI therapy, and maintenance were independent factors of better OS. In conclusion, the OS of pPCL is still poor in LATAM, with high early mortality. PI triplets, chemotherapy plus IMIDs, and/or PI and maintenance therapy were associated with improved survival.


Assuntos
Leucemia Plasmocitária , Humanos , Leucemia Plasmocitária/diagnóstico , Leucemia Plasmocitária/epidemiologia , Leucemia Plasmocitária/terapia , Prognóstico , Bortezomib/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento , América Latina/epidemiologia , Agentes de Imunomodulação , Demografia
11.
Indian J Hematol Blood Transfus ; 39(1): 7-14, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36699429

RESUMO

A program for the hematologic patient at very high risk of infections (HAR, from its initials in Spanish) was implemented, based on a multidisciplinary team and six measures intended to reduce the colonization and subsequent sepsis by multidrug-resistant organisms (MDRO). We aimed at evaluating the effectiveness of the HAR program in terms of MDRO infections mainly caused by Klebsiella pneumoniae carbapenemase-producing and multidrug-resistant Pseudomona aeruginosa, and sepsis-related mortality. We established retrospective comparisons between the pre-HAR period (2016-2018) and the post-HAR period (2018-2019), in patients who received a hematopoietic stem cell transplant (HSCT) and/or intensive chemotherapy to treat non-M3 acute myeloid leukemia (CH-AML). We included 262 patients: 176 pre-HAR and 86 post-HAR. MDRO infection was 4.6% at 30 days and 6.1% at 90 days (all the cases during the pre-HAR period). Sepsis-related mortality was 6.5%, considering a median follow-up of 608 days: 6.1% in the HSCT group and 12.4% in the CH-AML group (p = 0.306). Sepsis-related mortality was 8.7% in the pre-HAR period and 0% in the post-HAR period (p = 0.014). The implementation of this multidisciplinary program based in preventive measures and the appropriate use of antibiotics enabled a decrease in sepsis-related mortality in very high-risk hematologic patients.

12.
JCO Glob Oncol ; 9: e2300182, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38060975

RESUMO

PURPOSE: Multiple myeloma (MM) is a highly heterogeneous, incurable disease most frequently diagnosed in the elderly. Therefore, data on clinical characteristics and outcomes in the very young population are scarce. PATIENTS AND METHODS: We analyzed clinical characteristics, response to treatment, and survival in 103 patients with newly diagnosed MM age 40 years or younger compared with 256 patients age 41-50 years and 957 patients age 51 years or older. RESULTS: There were no statistical differences in sex, isotype, International Scoring System, renal involvement, hypercalcemia, anemia, dialysis, bony lesions, extramedullary disease, and lactate dehydrogenase (LDH). The most used regimen in young patients was cyclophosphamide, bortezomib, dexamethasone, followed by cyclophosphamide, thalidomide, dexamethasone and bortezomib, thalidomide, dexamethasone. Of the patients age 40 years or younger, only 53% received autologous stem-cell transplant (ASCT) and 71.1% received maintenance. There were no differences in overall survival (OS) in the three patient cohorts. In the multivariate analysis, only high LDH, high cytogenetic risk, and ASCT were statistically associated with survival. CONCLUSION: In conclusion, younger patients with MM in Latin America have similar clinical characteristics, responses, and OS compared with the elderly.


Assuntos
Mieloma Múltiplo , Humanos , Idoso , Adulto , Pessoa de Meia-Idade , Mieloma Múltiplo/terapia , Mieloma Múltiplo/tratamento farmacológico , Bortezomib/uso terapêutico , Talidomida/uso terapêutico , América Latina/epidemiologia , Resultado do Tratamento , Dexametasona/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Prognóstico , Ciclofosfamida/uso terapêutico
13.
Life Sci ; 268: 118979, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33421528

RESUMO

The challenge in classical Hodgkin Lymphoma (cHL) management is the 30-40% of refractory/relapsed cases. AIMS: The aim of this work was to determine whether NIK and BCL-2 could be useful as prognosis biomarkers in cHL. In addition, we evaluated BCL-2 as a directed-therapy in cHL cell lines using venetoclax. MAIN METHODS: We evaluated NIK and BCL-2 expression in 112 untreated cHL patients' lymph-node biopsies by immunohistochemistry. cHL cell lines were treated with venetoclax alone or combined with vincristine or doxorubicin. Cell viability, metabolic activity and cell death were analyzed by trypan-blue exclusion method, MTS assay and FDA/IP staining respectively. KEY FINDINGS: No correlation between NIK or BCL-2 expression and the majority of the clinical parameters was found. Patients with ≥60% BCL-2+ HRS-cells had a shorter disease-free survival (DFS) and overall survival (OS) (p = 0.002, p = 0.02 respectively). A decision tree analysis, in a 30 patients subgroup, showed that patients with <60% NIK+ HRS-cells but with ≥60% BCL-2+ HRS-cells had a worse outcome in terms of DFS and OS. These parameters performed better as prognosis indicators as compared to the diagnosis bone marrow status. Human cHL cell lines U-H01, KM-H2, L1236, SUPHD1, L540 showed sensitivity to venetoclax. The co-treatment effect of venetoclax and vincristine or doxorubicin on cell viability was diverse depending on the cell line evaluated. SIGNIFICANCE: BCL-2 should be considered as a prognosis biomarker as well as a potential new therapeutic target in cHL. We report for the first time the cytotoxic effect of venetoclax in human cHL cell lines.


Assuntos
Antineoplásicos/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Doença de Hodgkin/tratamento farmacológico , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Sulfonamidas/farmacologia , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/metabolismo , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Linhagem Celular Tumoral , Criança , Feminino , Doença de Hodgkin/mortalidade , Doença de Hodgkin/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular/métodos , Proteínas Serina-Treonina Quinases/metabolismo , Sulfonamidas/administração & dosagem , Adulto Jovem , Quinase Induzida por NF-kappaB
14.
Expert Rev Hematol ; 14(3): 315-322, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33541156

RESUMO

OBJECTIVES: We compared the efficacy of lenalidomide-dexamethasone (Rd) based treatments for relapsed/refractory multiple myeloma patients (pts), in a real-world setting. In addition, we evaluated adverse events (AE), progression-free survival (PFS) and overall survival (OS). METHODS: In our retrospective, multicentric study, 156 pts with RRMM were included. 74/156 pts (47%) were refractory to bortezomib (V) and 43/156 (27%) pts to lenalidomide (R), with 24/156 (15%) of pts double refractory. Eighty-six pts (55%) received Rd with carfilzomib (KRd), 30 pts (19%) bortezomib (VRd), 30 pts (19%) daratumumab (DRd), and 10 pts (6%) ixazomib (IRd). RESULTS: The overall response (ORR) (≥ partial response) for the entire cohort was 71%, with a very good partial response rate or better (≥VGPR) of 35%. We found no significant differences in CR or ≥VGRP rates between treatments (p:0.229). Regardless of the combination received, those patients who achieved CR had significantly improved PFS (p: 0.007). The most frequent cause of treatment discontinuation was disease progression in 55/156 pts (35%). 8 pts (5%) discontinued treatment due to treatment-related adverse events (AE). CONCLUSION: This is the first report of Rd combinations for the treatment of RRMM in Latin America. All combinations proved to be effective with an acceptable toxicity.


Assuntos
Mieloma Múltiplo , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Dexametasona/uso terapêutico , Humanos , América Latina , Lenalidomida/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Intervalo Livre de Progressão , Estudos Retrospectivos
15.
Medwave ; 21(11): e8504, 2021 Dec 28.
Artigo em Espanhol, Inglês | MEDLINE | ID: mdl-34964447

RESUMO

OBJECTIVE: We aim to evaluate factors associated with the recurrence of thromboembolic episodes among patients with a first episode of venous thromboembolic disease during anticoagulation treatment and at least one year after treatment suspension. METHODS: A prospective cohort of patients with a first episode of deep vein thrombosis confirmed by Doppler ultrasound and initiated anticoagulation treatment. Participants were registered in the Institutional Registry of Thromboembolic Disease between June 2015 and March 2019. Patients with cancer, with permanent inferior vena cava filter implant, and those who refused to participate or did not provide informed consent were excluded. All patients were evaluated within treatment at 30 days and at least one year after the suspension of anticoagulation with a D-dimer study and an ultrasound. All patients were evaluated for recurrence, bleeding (major and minor), and death. RESULTS: A total of 304 patients were recruited during the study period. Seventy-three percent were female, and the median age was 80 years. The rate of recurrence rate during anticoagulation treatment was 5% (N = 16/303; 95% confidence interval: 3 to 8), and 5% during post-suspension follow-up (N = 11/202; 95%CI: 3 to 9). The overall bleeding rate was 13% (N = 39; 95%CI: 9 to 17), and 5% for major bleeding. Patients who recurred had higher basal D-dimer mean, higher neutrophils and monocytes, and a higher prevalence of age-adjusted D-dimer ratio greater than 0.5 before discontinuation. In addition, they more frequently had complete leg involvement by ultrasound and received a shorter treatment. CONCLUSIONS: Although some baseline and pre-suspension parameters had a higher recurrence incidence, statistical significance was not reached, probably due to small statistical power and a short-term follow-up.


OBJETIVO: Evaluar factores asociados a la recurrencia de episodios tromboembólicos en pacientes con un primer evento de enfermedad tromboembólica venosa intra-tratamiento, al año de suspendida la anticoagulación. MÉTODO: Cohorte prospectiva con todos los pacientes consecutivos con un primer episodio de trombosis venosa profunda confirmado por eco Doppler, que iniciaron tratamiento anticoagulante incluidos en el Registro Institucional de Enfermedad Tromboembólica, entre junio de 2015 y marzo de 2019. Se excluyeron los pacientes con cáncer, con implante de filtro de vena cava inferior permanente y quienes se negaron a participar o no entregaron el consentimiento informado. Todos los pacientes fueron evaluados a los 30 días, pre-suspensión de anticoagulación con estudio de dímero D y la realización de una ecografía, y al menos un año de suspendida la anticoagulación. Todos los pacientes fueron evaluados para recurrencia, sangrado (mayor y menor) y muerte. RESULTADOS: Se reclutó a 304 pacientes durante el periodo de estudio. La tasa de recurrencia durante la anticoagulación fue de 5% (N = 16/303; intervalo de confianza 95%: 3 a 8), y durante el seguimiento post suspensión fue también 5% (N = 11/220; 95%: 2 a 9). La tasa de sangrado global fue del 13% (N = 39; 95%: 9 a 17), siendo mayor del 5% para sangrado. Los pacientes que recurrieron tenían una media más elevada de dímero D, neutrófilos, monocitos basales y mayor prevalencia de razón de dímero D ajustada por edad mayor a 0,5 previo a la suspensión. Además, presentaban más afectación de la pierna completa por ecografía y recibieron tratamiento anticoagulante de menor duración. CONCLUSIÓN: Si bien algunos parámetros basales y pre-suspensión dieron valores más altos, no se alcanzó significación estadística, probablemente debido al tamaño muestral y a la baja tasa de recurrencia post suspensión asociada al corto seguimiento.


Assuntos
Embolia Pulmonar , Tromboembolia , Filtros de Veia Cava , Trombose Venosa , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Feminino , Humanos , Estudos Prospectivos , Recidiva , Trombose Venosa/tratamento farmacológico , Trombose Venosa/epidemiologia
16.
Medicina (B Aires) ; 70(4): 311-5, 2010.
Artigo em Espanhol | MEDLINE | ID: mdl-20679049

RESUMO

Multiple myeloma is characterized by the neoplastic proliferation of a single clone of plasma cells producing a monoclonal immunoglobulin. Myelomatous nodular lesions of the liver are infrequent. We describe 3 cases with histological confirmation and we review the bibliography.


Assuntos
Neoplasias Hepáticas/patologia , Fígado/patologia , Mieloma Múltiplo/patologia , Idoso de 80 Anos ou mais , Biópsia por Agulha Fina , Diferenciação Celular , Células Clonais , Evolução Fatal , Feminino , Humanos , Imunoglobulina G/análise , Masculino , Pessoa de Meia-Idade
17.
Blood Coagul Fibrinolysis ; 31(8): 511-516, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32852328

RESUMO

: Factor XIII (FXIII) levels may decrease because of surgical consumption. Acquired FXIII deficiency could be a cause of postoperative hemorrhage usually underdiagnosed in clinical practice. To determine the diagnosis confirmation rate of acquired FXIII deficiency in postsurgical patients with clinical suspicion and to compare the characteristics and evolution of patients with or without FXIII deficiency. We performed a retrospective cohort study, which included 49 inpatients who were attended at our university hospital from 2014 to 2018 with suspicion of acquired FXIII deficiency because of disproportionate postoperative hemorrhage. FXIIIA levels less than 50% was considered a deficiency. Persistence of bleeding for more than 48 h, drop in hematocrit points, red blood cells transfused units, hemoglobin levels 12-36 h after bleeding, and time elapsed from the procedure to the bleeding were assessed as outcome variables. Logistic regression was employed for both univariate and multivariate analyses. Of the 49 patients included, 27(55%) had FXIII deficiency, with a median level of 34% [interquartile range (IQR) 19-42]. Abdominal surgery was the most common [n = 21 (43%)]. All patients had routine coagulation tests within the hemostatic range. FXIII deficiency was associated with a drop of more than 4 points in hematocrit [OR 59.69 (95% CI 4.71-755.30)], red blood transfused units >2 [OR 45.38 (95% CI 3.48-590.65)], and delayed bleeding >36 h after surgery [OR 100.90 (95% CI 3.78-2695.40)]. Plasma-derived FXIII concentrate was administered to eight patients with life-threatening bleeding with resolution within 24 h. Only one deficient patient died from bleeding. FXIII levels were measured 15 days after diagnosis or more in 20 out of 27 deficient patients, with normal results. Acquired FXIII deficiency may be a frequent underdiagnosed entity that should be considered when high-volume and delayed postoperative hemorrhage is present in patients with hemostatic routine coagulation test results.


Assuntos
Deficiência do Fator XIII/complicações , Hemorragia Pós-Operatória/etiologia , Adulto , Idoso , Coagulação Sanguínea , Testes de Coagulação Sanguínea , Transfusão de Eritrócitos , Deficiência do Fator XIII/sangue , Deficiência do Fator XIII/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hemorragia Pós-Operatória/sangue , Hemorragia Pós-Operatória/terapia , Estudos Retrospectivos
18.
Leuk Lymphoma ; 61(12): 2868-2875, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32623944

RESUMO

This study determined whether 85 patients with multiple myeloma (MM) double-refractory to primary induction therapy with triplet regimens had a homogenous prognosis. The overall response rate (ORR) after the second-line therapy was 51%. Patients who proceeded to immediate autologous stem cell transplantation (ASCT) had better ORR than those who received conventional therapies (62% vs. 31%). The ORR for patients who had ASCT directly after the frontline therapy was higher than for those treated with other regimens as the second line therapy (91% vs. 45%) and offered ASCT as the third-line therapy (91% vs. 55%). The median progression-free survival (PFS) after the second-line therapy and median overall survival were 21.6 months and 35.6 months, respectively. ASCT after the second line treatment (HR = 0.24) was an independent predictor of PFS. Eligible patients with primary refractory MM achieve the most benefit from ASCT, also performed immediately after first line induction therapy.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Intervalo Livre de Doença , Humanos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/terapia , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Transplante Autólogo , Resultado do Tratamento
19.
Leuk Lymphoma ; 61(13): 3112-3119, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32844699

RESUMO

The aim of this study was to describe clinical and survival characteristics of transplant-eligible multiple myeloma (MM) patients in Latin America (LA), with a special focus on differences between public and private healthcare facilities. We included 1293 patients diagnosed between 2010 and 2018. A great disparity in outcomes and survival between both groups was observed. Late diagnosis and low access to adequate frontline therapy and ASCT in public institutions probably explain these differences. Patients treated with novel drug induction protocols, followed by autologous stem cell transplantation (ASCT) and maintenance, have similar overall survival compared to that published internationally.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , América Latina/epidemiologia , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/epidemiologia , Mieloma Múltiplo/terapia , Transplante Autólogo , Resultado do Tratamento
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