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INTRODUCTION: POEMS syndrome is a rare paraneoplastic syndrome caused by an underlying plasma cell disorder. The acronym refers to the following features: polyradiculoneuropathy, organomegaly, endocrinopathy, monoclonal paraproteinemia, and skin changes. METHODS: The study was conducted at 24 hematological centers across 8 Latin-American countries. The study included a total of 46 patients (median age was 52 years (IQR: 42 - 61.5), 30 males and 16 females) fulfilling the POEMS syndrome criteria diagnosed over a period of 12 years (January 1, 2011, through July 31, 2023). Epidemiological and clinical data were collected in an ad-hoc database sent to the members of GELAMM, as well as the Kolmogorov-Smirnov test and Kaplan-Meier estimates. RESULTS: All patients had polyneuropathy; 89% had monoclonal gammopathy, 33% had sclerotic bone lesions. Only ten patients underwent vascular endothelial growth factor (VEGF) testing in plasma samples. The paraproteinemia was IgG λ in 32% and IgA λ in 30%. 59% patients presented with cutaneous changes, mainly hyperpigmentation, 54% had organomegaly, and 74% endocrinopathy. The median interval from symptom onset to diagnosis was 7.7 months (IQR: 4.0 - 12.6). 69% of patients received a single line of treatment. The median follow-up period was 25 months (IQR: 9.37 - 52.0) and the 2-year overall survival rate was 100%. All patients who underwent transplantation (43%) are alive, with a median follow-up of 45.62 months (IQR: 15.46 - 70). CONCLUSION: This study investigates POEMS syndrome in Latin America and presents an initial overview of the disease in the region. VEGF usage is recommended for accurate diagnosis, but only 7 hematology centers in the region used it. Survival rate in Latin America is comparable with those observed internationally.
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Autologous hematopoietic cell transplantation (AHCT) is a commonly used treatment in multiple myeloma (MM). However, real-world global demographic and outcome data are scarce. We collected data on baseline characteristics and outcomes from 61 725 patients with newly diagnosed MM who underwent upfront AHCT between 2013 and 2017 from nine national/international registries. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), relapse incidence (RI) and non-relapse mortality (NRM). Median OS amounted to 90.2 months (95% CI 88.2-93.6) and median PFS 36.5 months (95% CI 36.1-37.0). At 24 months, cumulative RI was 33% (95% CI 32.5%-33.4%) and NRM was 2.5% (95% CI 2.3%-2.6%). In the multivariate analysis, superior outcomes were associated with younger age, IgG subtype, complete hematological response at auto-HCT, Karnofsky score of 100%, international staging scoring (ISS) stage 1, HCT-comorbidity index (CI) 0, standard cytogenetic risk, auto-HCT in recent years, and use of lenalidomide maintenance. There were differences in the baseline characteristics and outcomes between registries. While the NRM was 1%-3% at 12 months worldwide, the OS at 36 months was 69%-84%, RI at 12 months was 12%-24% and PFS at 36 months was 43%-63%. The variability in these outcomes is attributable to differences in patient and disease characteristics as well as the use of maintenance and macroeconomic factors. In conclusion, worldwide data indicate that AHCT in MM is a safe and effective therapy with an NRM of 1%-3% with considerable regional differences in OS, PFS, RI, and patient characteristics. Maintenance treatment post-AHCT had a beneficial effect on OS.
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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.
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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 terapêuticoRESUMO
Waldenström macroglobulinemia (WM) is a rare, indolent, and currently incurable B-cell neoplasm characterized by monoclonal immunoglobulin M gammopathy, frequent nodal involvement, and lymphoplasmacytic infiltration of the bone marrow. The clinical pattern at diagnosis is similar to that reported in developed countries but, unfortunately, the tools for a complete diagnosis and access to novel therapies are suboptimal. Older drugs such as bendamustine, cyclophosphamide, and chlorambucil may still play a role in treating WM. Prospective studies in resource-limited regions are required to further evaluate these essential aspects of the disease. In this document, we issue recommendations based on our local reality.
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Macroglobulinemia de Waldenstrom , Humanos , Macroglobulinemia de Waldenstrom/diagnóstico , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Estudos Prospectivos , Ciclofosfamida/uso terapêutico , Imunoglobulina M , Medula ÓsseaRESUMO
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.
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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 , DemografiaRESUMO
Cytogenetic abnormalities (CA) such as t(4;14), t(14;16), and del(17p), are associated with a poor prognosis in Multiple Myeloma (MM) patients. However, there is scarce information regarding the Latin-American population. This study aims to analyze the impact of t(4;14), t(14;16), and del(17p) on the progression-free survival (PFS) and overall survival (OS) of transplant-eligible newly-diagnosed MM (NDMM) patients in Latin America. Retrospective survival analysis based on the Grupo de Estudio Latinoamericano de MM (GELAMM) registry, including all adult patients with NDMM harboring CA t(4;14), t(14;16), and/or del(17p). Fifty-nine patients were included; the median age was 57 years, 55.9% males, 22% ISS-I, 25.4% ISS-II, and 47.5% ISS-III. The majority (89.8%) had one alteration, whereas 10.2% had del(17p) and t(4;14). The frequencies of CA were del(17p) in 61.0%, t(4;14) in 25.4%, and t(14;16) in 3,4%. Autologous stem cell transplantation was performed in 36 cases, 20 patients did not use this consolidative strategy, and this data was missed in three cases. Five-year OS for the entire cohort was 60.8% and 5-year PFS was 28.1%. Bortezomib-based induction regimen (BBR) (p=0.029), consolidation with ASCT (p<0.001), and maintenance therapy (p=0.004) were associated with an improved 5-year OS. In the multivariate analysis, ASCT was the only variable with a positive impact on OS (HR 0.11, 95% CI 0.033 to 0.34, p<0.001). The median PFS presented a non-statistically significant benefit in BBR, ASCT, and maintenance therapy groups. BBR induction, ASCT, and maintenance therapy were associated with improved OS in high-risk NDMM patients.
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Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Masculino , Adulto , Humanos , Pessoa de Meia-Idade , Feminino , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/genética , Mieloma Múltiplo/terapia , Prognóstico , Estudos Retrospectivos , Transplante Autólogo , Análise de Sobrevida , Aberrações Cromossômicas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
INTRODUCTION: Autologous stem cell transplantation (ASCT) is the standard consolidation option for transplant-eligible patients with multiple myeloma (MM). The aim of this study is to report the overall survival (OS) and progression-free survival (PFS) outcomes after frontline ASCT in newly-diagnosed MM (NDMM) patients in a real-world setting. METHODS: We conducted a retrospective, survival analysis of all NDMM patients included in the MM Uruguayan Registry. RESULTS: We included 151 NDMM patients treated with induction therapy followed by high-dose melphalan and ASCT as consolidation. The median age at diagnosis was 59 years, and the international staging system (ISS) risk groups were ISS-III 32.9%, ISS-II 37.8%, and ISS-I 29.4%. Frontline induction regimens included bortezomib in 61.6% of cases, and maintenance therapy was used in 63.9% of reported cases. With a median follow-up of 42 months, the 36-month OS and PFS for the whole group were 82.4% (95% CI 75.9% to 89.4%) and 63.8% (95% CI 55.6% to 73.3%), respectively, median OS of 98 months and median PFS of 47 months. The 100-month OS and PFS for the entire group were 48.0% (95% CI 34.9% to 66.0%) and 17.3% (95% CI 8.4% to 35.8%), respectively. CONCLUSION: ASCT is a feasible, safe, and potent strategy that provides a prolonged median OS and PFS in NDMM patients. This approach can be implemented in low-income countries.
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Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Estudos Retrospectivos , Intervalo Livre de Doença , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante Autólogo , Análise de Sobrevida , Transplante de Células-TroncoRESUMO
INTRODUCTION: Infections represent a significant cause of morbidity and mortality in patients with multiple myeloma (MM). In Latin America, data on infectious complications in newly diagnosed MM (NDMM) patients are limited. METHODS: We conducted a multicenter, prospective cohort study of patients with NDMM in Uruguay between June 2019 and December 2020. Patients with active disease, on active therapy and who provided written informed consent were included. Elegible patients were followed for 6 months from the time of diagnosis and before proceeding to autologous stem cell transplantation or until death, whichever occurred first. Our primary endpoint was the number of infectious events that required hospitalization for ≥ 24 h. MAIN RESULTS: Of 124 patients with NDMM, 54 (43.5 %) had infectious complications (74 infectious events), the majority (74.3 %) within the first 3 months from diagnosis. The most common sites of infection were urinary (39.2 %) and respiratory tracts (33.8 %). The microbial agent was identified in 60.8 % of patients with Gram-negative bacteria (71.4 %) as the most common pathogen. Viral and fungal infections were infrequent. In the multivariable analysis, the Eastern Cooperative Oncology Group (ECOG) performance status was ≥ 2 (odds ratio [OR], 2.16; 95 % confidence interval [95 %CI], 1.23 - 3.79; p = 0.008) and creatinine ≥ 2 mg/dl (OR, 2.33; 95 %CI, 1.33 - 4.07; p = 0.003) were independent factors associated with bacterial infections. At 6 months, 14 patients (11.3 %) had died, 50 % related to infectious complications. CONCLUSION: Bacterial infections are a substantial cause of hospital admissions and early death in patients with NDMM. Antibiotic prophylaxis should be considered to reduce infectious complications in patients with MM.
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BACKGROUND: 18F-fluorodesoxyglucose positron emission tomography/ computed tomography (PET-CT) has a high sensitivity and specificity to detect medullary and extramedullary lesions in multiple myeloma (MM). AIM: To describe the findings of PET-CT in extramedullary multiple myeloma (EMM) at diagnosis and at relapse, and correlate its results with clinical variables, response to treatment and survival. MATERIALS AND METHODS: Review of medical records and PET-CT reports of 39 patients with multiple myeloma (MM) who had at least one PET-CT study, treated between January 1, 2015, and January 1, 2019 at a clinical hospital. RESULTS: The Standard Uptake Values for each hypermetabolic lesion were not described in PET-CT reports. Fifteen patients had an EMM and in eight, without a previous clinical suspicion, PET-TC lead to the diagnosis. The mortality rate in the 39 patients with MM was 46%. Sixty seven percent of deaths occurred in patients with EMM. CONCLUSIONS: PET-TC was useful to diagnose EMM. However, a standardization in PETCT reports would be required to unify criteria. As previously reported, EMM had a greater aggressiveness and lower survival.
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Mieloma Múltiplo , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Fluordesoxiglucose F18 , Humanos , Mieloma Múltiplo/diagnóstico por imagem , Mieloma Múltiplo/tratamento farmacológico , Recidiva Local de Neoplasia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia por Emissão de Pósitrons/métodos , Compostos RadiofarmacêuticosRESUMO
PURPOSE: Waldenstrom Macroglobulinemia (WM) is a rare lymphoma with distinct clinical features, and data from Latin American patients are lacking. Therefore, we aim to investigate the clinical, therapy, and outcome patterns of WM in Latin America. METHODS: We retrospectively analyzed patients with WM diagnosed between 1991 and 2019 from 24 centers in seven Latin American countries. The study outcomes were overall survival (OS) and progression-free survival (PFS). RESULTS: We identified 159 cases (median age 67 years, male 62%). Most patients (95%) were symptomatic at diagnosis. The International Prognostic Scoring System for WM (IPSSWM) at diagnosis was available in 141 (89%) patients (high-risk 40%, intermediate-risk 37%, and low-risk 23%). Twenty-seven (17%) patients were tested for MYD88L265P, with 89% (n = 24 of 27) carrying the mutation. First-line and second-line therapies were administered to 142 (89%) and 53 (33%) patients, respectively. Chemoimmunotherapy was the most commonly used first-line (66%) and second-line (45%) approach; only 18 (11%) patients received ibrutinib. With a median follow-up of 69 months, the 5-year OS rate was 81%. In treated patients, the 5-year OS and PFS rates were 78% and 59%, respectively. High-risk IPSSWM at treatment initiation was an independent risk factor for OS (adjusted hazard ratio: 4.73, 95% CI, 1.67 to 13.41, P = .003) and PFS (adjusted hazard ratio: 2.43, 95% CI, 1.31 to 4.50, P = .005). CONCLUSION: In Latin America, the management of WM is heterogeneous, with limited access to molecular testing and novel agents. However, outcomes were similar to those reported internationally. We validated the IPSSWM score as a prognostic factor for OS and PFS. There is an unmet need to improve access to recommended diagnostic approaches and therapies in Latin America.
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Macroglobulinemia de Waldenstrom , Idoso , Humanos , América Latina/epidemiologia , Masculino , Mutação , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/uso terapêutico , Estudos Retrospectivos , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Macroglobulinemia de Waldenstrom/terapiaRESUMO
PURPOSE: Infections are a significant cause of morbidity and mortality in patients with multiple myeloma (MM). In Latin America, data on infectious complications in this patient population are lacking. METHODS: We conducted a prospective cohort study of patients with newly diagnosed MM (NDMM) in seven Latin American countries between June 2019 and May 2020. Patients with active disease, on active therapy, and with a follow-up of 6 months from the time of diagnosis were included. Our primary end point was the number of infectious events that required hospitalization for ≥ 24 hours. RESULTS: Of 248 patients with NDMM, 89 (35.9%) had infectious complications (113 infectious events), the majority (67.3%) within the first 3 months from diagnosis. The most common sites of infection were respiratory (38%) and urinary tract (31%). The microbial agent was identified in 57.5% of patients with gram-negative bacteria (73.5%) as the most common pathogen. Viral infections were infrequent, and no patients with fungal infection were reported. In the multivariable analysis, diabetes mellitus (odds ratio [OR], 2.71; 95% CI, 1.23 to 6.00; P = .014), creatinine ≥ 2 mg/dL (OR, 4.87; 95% CI, 2.29 to 10.35; P < .001), no use of trimethoprim-sulfamethoxazole prophylaxis (OR, 6.66; 95% CI, 3.43 to 12.92; P < .001), and treatment with immunomodulatory drugs (OR, 3.02; 95% CI, 1.24 to 6.29; P = .003) were independent factors associated with bacterial infections. At 6 months, 21 patients (8.5%) had died, 47.6% related to infectious complications. CONCLUSION: Bacterial infections are a substantial cause of hospital admissions and early death in patients with NDMM. Antibiotic prophylaxis should be considered to reduce infectious complications in patients with MM.
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Infecções Bacterianas , Mieloma Múltiplo , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/epidemiologia , Humanos , América Latina/epidemiologia , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/epidemiologia , Estudos Prospectivos , Fatores de RiscoRESUMO
INTRODUCTION: Bortezomib is proteasome inhibitor used in multiple myeloma treatment. The reactivation of herpes simplex virus (HSV) and varicella-zoster virus (VZV) during bortezomib-based therapy is a well-known adverse event. Antiviral prophylaxis is mandatory. Nevertheless, reports of herpesviral encephalitis are scarce. CASE REPORT: A 57-year-old multiple myeloma patient who during CyBorD protocol (Bortezomib, cyclophosphamide, and dexamethasone), after a transient suspension of antiviral prophylaxis presented progressive headaches unresponsive to conventional analgesics, asthenia, fever, episodic visual hallucinations, and vesicular lesions in the right supraorbital and frontal region. Herpetic encephalitis was diagnosed after detecting herpes zoster in cerebrospinal fluid. MANAGEMENT & OUTCOME: The patient was treated with acyclovir 500mg every 6 hours for 21 days, and subsequent valacyclovir prophylaxis achieving an excellent clinical evolution. Anti-myeloma treatment was changed to lenalidomide and dexamethasone achieving a durable complete response. Herpesviral encephalitis is a rare but severe complication associated with the use of Bortezomib, especially when patients did not receive acyclovir prophylaxis. However, a rapid detection based on the clinical suspicion, and the prompt start of treatment, may lead to overcome this adverse event.
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Amiloidose , Antineoplásicos , Encefalite por Herpes Simples , Mieloma Múltiplo , Aciclovir/efeitos adversos , Amiloidose/induzido quimicamente , Amiloidose/complicações , Amiloidose/tratamento farmacológico , Antineoplásicos/efeitos adversos , Antivirais/efeitos adversos , Ácidos Borônicos/efeitos adversos , Bortezomib/efeitos adversos , Dexametasona/efeitos adversos , Encefalite por Herpes Simples/induzido quimicamente , Encefalite por Herpes Simples/complicações , Encefalite por Herpes Simples/tratamento farmacológico , Herpesvirus Humano 3/fisiologia , Humanos , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , Mieloma Múltiplo/tratamento farmacológico , PirazinasRESUMO
BACKGROUND: 18F-fluorodesoxyglucose positron emission tomography/ computed tomography (PET-CT) has a high sensitivity and specificity to detect medullary and extramedullary lesions in multiple myeloma (MM). AIM: To describe the findings of PET-CT in extramedullary multiple myeloma (EMM) at diagnosis and at relapse, and correlate its results with clinical variables, response to treatment and survival. MATERIALS AND METHODS: Review of medical records and PET-CT reports of 39 patients with multiple myeloma (MM) who had at least one PET-CT study, treated between January 1, 2015, and January 1, 2019 at a clinical hospital. RESULTS: The Standard Uptake Values for each hypermetabolic lesion were not described in PET-CT reports. Fifteen patients had an EMM and in eight, without a previous clinical suspicion, PET-TC lead to the diagnosis. The mortality rate in the 39 patients with MM was 46%. Sixty seven percent of deaths occurred in patients with EMM. CONCLUSIONS: PET-TC was useful to diagnose EMM. However, a standardization in PETCT reports would be required to unify criteria. As previously reported, EMM had a greater aggressiveness and lower survival.
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Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/diagnóstico por imagem , Compostos Radiofarmacêuticos , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons/métodos , Recidiva Local de NeoplasiaRESUMO
PURPOSE: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive disease caused by the human T-cell leukemia virus type 1. Real-world data of ATLL in Latin America are lacking. PATIENTS AND METHODS: We analyzed patients with ATLL (acute, lymphomatous, chronic, and smoldering) encountered in 11 Latin American countries between 1995 and 2019. Treatment response was assessed according to the 2009 consensus report. Survival curves were estimated using the Kaplan-Meier method and log-rank test. RESULTS: We identified 253 patients; 226 (lymphomatous: n = 122, acute: n = 73, chronic: n = 26, and smoldering: n = 5) had sufficient data for analysis (median age 57 years). Most patients with ATLL were from Peru (63%), Chile (17%), Argentina (8%), and Colombia (7%). Hypercalcemia was positively associated with acute type (57% v lymphomatous 27%, P = .014). The median survival times (months) were 4.3, 7.9, 21.1, and not reached for acute, lymphomatous, chronic, and smoldering forms, with 4-year survival rates of 8%, 22%, 40%, and 80%, respectively. First-line zidovudine (AZT)-interferon alfa (IFN) resulted in an overall response rate of 63% (complete response [CR] 24%) for acute. First-line chemotherapy yielded an overall response rate of 41% (CR 29%) for lymphomatous. CR rate was 42% for etoposide, cyclophosphamide, vincristine, doxorubicin, and prednisone versus 12% for cyclophosphamide, vincristine, doxorubicin, and prednisone-like regimen (P < .001). Progression-free survival at 1 year for acute type patients treated with AZT-IFN was 67%, whereas 2-year progression-free survival in lymphomatous type patients who achieved CR after chemotherapy was 77%. CONCLUSION: This study confirms Latin American ATLL presents at a younger age and has a high incidence of lymphomatous type, low incidence of indolent subtypes, and worse survival rates as compared with Japanese patients. In aggressive ATLL, chemotherapy remains the preferred choice for lymphomatous favoring etoposide-based regimen (etoposide, cyclophosphamide, vincristine, doxorubicin, and prednisone), whereas AZT-IFN remains a good first-line option for acute subtype.
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Leucemia-Linfoma de Células T do Adulto , Linfoma , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Argentina , Chile , Colômbia , Humanos , América Latina/epidemiologia , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Leucemia-Linfoma de Células T do Adulto/epidemiologia , Pessoa de Meia-Idade , Peru/epidemiologiaRESUMO
Resumen: La anticoncepción en las pacientes con trombofilia es un desafío para el equipo de salud. La función de asesoramiento en materia de planificación familiar va más allá de la simple prescripción, ya que para definir el mejor método anticonceptivo no es suficiente la consideración de los antecedentes médicos y obstétricos de la mujer, sino que es imprescindible considerar las preferencias de la paciente. El asesoramiento sobre anticoncepción en las mujeres con trombofilia hereditaria debe abordar los riesgos de enfermedad tromboembólica venosa, incrementada en este grupo de pacientes, considerando cada uno de los métodos anticonceptivos, así como los de un embarazo no buscado, con el objetivo de contribuir a que la decisión se tome de manera informada. La presente revisión aborda este riesgo según cada tipo anticonceptivo en pacientes con distintos tipos de trombofilia hereditaria.
Abstract: Contraception in patients with thrombophilia is a challenge for the health team. The role of family planning counseling goes beyond simple prescription, since in order to define the best contraceptive method, it is not enough to consider the woman's medical and obstetric history, but rather it is essential to consider the patient's preferences . Counseling on contraception in women with hereditary thrombophilia should address the risks of venous thromboembolic disease, increased in this group of patients, considering each of the contraceptive methods, as well as those of an unintended pregnancy, in order to contribute to the the decision is made in an informed manner. The present review addresses this risk according to each contraceptive type in patients with different types of inherited thrombophilia.
Resumo: A contracepção em pacientes com trombofilia é um desafio para a equipe de saúde. O papel do aconselhamento de planejamento familiar vai além da simples prescrição, pois para definir o melhor método anticoncepcional não basta considerar a história médica e obstétrica da mulher, mas sim considerar as preferências da paciente. O aconselhamento sobre contracepção em mulheres com trombofilia hereditária deve abordar os riscos de doença tromboembólica venosa, aumentados neste grupo de pacientes, considerando cada um dos métodos contraceptivos, bem como os de gravidez indesejada, a fim de contribuir para a tomada de decisão de uma forma informada. A presente revisão aborda esse risco de acordo com cada tipo de contraceptivo em pacientes com diferentes tipos de trombofilia hereditária.
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This Policy Review presents the International Myeloma Working Group's clinical practice recommendations for the treatment of relapsed and refractory multiple myeloma. Based on the results of phase 2 and phase 3 trials, these recommendations are proposed for the treatment of patients with relapsed and refractory disease who have received one previous line of therapy, and for patients with relapsed and refractory multiple myeloma who have received two or more previous lines of therapy. These recommendations integrate the issue of drug access in both low-income and middle-income countries and in high-income countries to help guide real-world practice and thus improve patient outcomes.
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Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Mieloma Múltiplo/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Guias de Prática Clínica como Assunto/normas , Terapia de Salvação , Humanos , Mieloma Múltiplo/patologia , Recidiva Local de Neoplasia/patologiaRESUMO
BACKGROUND AND AIMS: Multiple myeloma is a frequent hematologic malignancy, in which the International Stratification Score (ISS) is widely used to estimate the overall survival. However, there are no studies in Latin America evaluating its performance. This study aims to describe the ISS performance in the overall survival estimation for newly diagnosed multiple myeloma patients in Uruguay. METHODS: This is a retrospective registry-based survival analysis through the Grupo Uruguayo de Mieloma Múltiple (GUMMA) database, including newly diagnosed multiple myeloma patients from January 2001 until May 2019. RESULTS: 249 patients were included, 51.81% males and an average age of 63.49 years. According to ISS and Durie-Salmon score (DSS), 47.79% and 82.3% were ISS III and DSS III, respectively. Also, 32.3% were DSS B. Auto hematopoietic stem cell transplantation was performed in 31.73% of patients, and bortezomib was used in 44.18% as frontline therapy. The overall survival was 80% for ISS1, 64.9% ISS2, and 48.6% ISS3 (Log-Rank; p <0.01). The average overall survival was 116.5 months for ISS 1, 77.6 months for ISS 2, and 57.8 months for ISS 3. The hazard ratio between ISS II and ISS I was 2.42 (95% CI 1.10-5.33; p<0.05), and 3.94 (95% CI 1.88-8.26; p<0.05) between ISS III and ISS II. CONCLUSION: The ISS staging system allows an adequate stratification of patients according to overall survival in the real-practice setting. However, considering the relevance of the new cytogenetic advances, it is necessary to increase the availability and quality of iFISH in Latin America.
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BACKGROUND: Multiple Myeloma (MM) is a malignant hematologic disorder and the second most common blood cancer. Interleukin-6 (IL-6) has been identified as a crucial factor for the proliferation and survival of MM cells and the overexpression of IL-6 receptor is being studied as a molecular target for therapeutic and diagnostic use in myelomas and other comorbidities. Tocilizumab is a humanized monoclonal antibody that binds IL-6R. OBJECTIVE: We aim to label and evaluate Fab(Tocilizumab) with 99mTechnetium or Cy7 as potential MM imaging agents. METHODS: IL-6R distribution was analyzed by Laser Confocal Microscopy (LCM) in MM cell lines. Fab(Tocilizumab) was produced by the digestion of Tocilizumab with papain for 24h at 37°C, derivatized with NHS-HYNIC-Tfa and radiolabeled with 99mTc. Radiochemical stability and in vitro cell assays were evaluated. Biodistribution and SPECT/CT were performed. Also, Fab(Tocilizumab) was labeled with Cy7 for in vivo fluorescence imaging up to 72h. RESULTS: LCM analysis demonstrates IL-6R distribution on MM cell lines. Incubation with papain resulted in complete digestion of Tocilizumab and exhibited a good purity and homogeneity. Radiolabeling with 99mTc via NHS-HYNIC-Tfa was found to be fast, easy, reproducible and stable, revealing high radiochemical purity and without interfering with IL-6R recognition. Biodistribution and SPECT/CT studies showed a quick blood clearance and significant kidney and MM engrafted tumor uptake. Cy7-Fab(Tocilizumab) fluorescent imaging allowed MM1S tumor identification up to 72h p.i. CONCLUSION: These new molecular imaging agents could potentially be used in the clinical setting for staging and follow-up of MM through radioactive whole-body IL-6R expression visualization in vivo. The fluorescent version could be used for tissue sample evaluation and to guide surgical excision, if necessary.
Assuntos
Anticorpos Monoclonais Humanizados/química , Carbocianinas/química , Imagem Molecular , Mieloma Múltiplo/diagnóstico por imagem , Compostos de Organotecnécio/química , Compostos Radiofarmacêuticos/química , Humanos , Receptores de Interleucina-6/análiseRESUMO
BACKGROUND: Multiple myeloma is a disease of the elderly. However, 40% of patients are diagnosed before 65 years old. Outcomes regarding age as a prognostic factor in MM are heterogeneous. METHOD: We retrospectively analyzed clinical characteristics, response to treatment and survival of 282 patients with active newly-diagnosed multiple myeloma, comparing results between patients younger and older than 65 years. MAIN RESULTS: The frequency of multiple myeloma in those younger than 66 years was 53.2%. Younger patients presented with a more aggressive disease, more advanced Durie-Salmon stage (85.3% vs 73.5%; p=0.013), extramedullary disease (12.7% vs 0%; p<0.001), osteolytic lesions (78.7% vs 57.6%; p<0.001) and bone plasmacytoma (25.3% vs 11.4%; p=0.003). In spite of this, the overall response rate was similar between groups (80.6% vs 81.4%; p=0.866). The overall survival was significantly longer in young patients (median, 65 months vs 41 months; p=0.001) and higher in those who received autologous hematopoietic stem cell transplantation. The main cause of death was disease progression in both groups. Multivariable analysis revealed that creatinine ≥2mg/dl, extramedullary disease, ≤very good partial remission and non-autologous hematopoietic stem cell transplantation are independent risk factors for shorter survival. CONCLUSION: Although multiple myeloma patients younger than 66 years of age have an aggressive presentation, this did not translate into an inferior overall survival, particularly in those undergoing autologous hematopoietic stem cell transplantation.