RESUMO
The treatment of older patients with Hodgkin lymphoma (HL) remains a challenge. We sought to identify the treatment patterns and outcomes in older HL patients included in the Brazilian HL registry (NCT02589548). A total of 136 patients with HIV-negative classic HL, aged ≥ 60 years, diagnosed between 2009 and 2018, were analyzed. The median age was 66 years old (60-90), 72% had advanced disease, 62% had a high IPS, and 49% had a nodular sclerosis subtype. Median follow-up was 64 months for alive patients. ABVD was the front-line treatment in 96% of patients. Twenty-one patients (15%) died during front-line treatment. The 5-year PFS and 5-year OS rates were 55% and 59%, respectively. The 5-year OS rates in localized and advanced disease were 81% and 51% (p=0.013). Lung toxicity developed in 11% of the patients treated with ABVD. Bleomycin was administered for > 2 cycles in 65% of patients. Compared with 2009-2014, there was a decrease in the use of bleomycin for > 2 cycles in 2015-2018 (88% × 45%, p<0.0001). The impact of socioeconomic status (SES) on outcomes was studied in patients treated with ABVD. After adjusting for potential confounders, lower SES remained independently associated with poorer survival (HR 2.22 [1.14-4.31] for OS and HR 2.84 [1.48-5.45] for PFS). Treatment outcomes were inferior to those observed in developed countries. These inferior outcomes were due to an excess of deaths during front-line treatment and the excessive use of bleomycin. SES was an independent factor for shorter survival.
Assuntos
Doença de Hodgkin , Idoso , Humanos , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/uso terapêutico , Brasil/epidemiologia , Dacarbazina/uso terapêutico , Doxorrubicina/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/epidemiologia , Estadiamento de Neoplasias , Estudos Prospectivos , Sistema de Registros , Resultado do Tratamento , Vimblastina/uso terapêutico , Idoso de 80 Anos ou mais , Estudos Clínicos como AssuntoRESUMO
Invasive fungal disease (IFD) is frequent in patients with haematologic malignancies and in recipients of haematopoietic cell transplantation (HCT). An epidemiologic study conducted in Brazil reported a high incidence of IFD in haematologic patients, and invasive fusariosis was the leading IFD. A limitation of that study was that galactomannan was not available for at least half of the study period. In order to characterise the epidemiology and burden of IFD in three cohorts, HCT, acute myeloid leukaemia (AML) or myelodysplasia (MDS), and acute lymphoid leukaemia (ALL), we conducted a prospective multicentre cohort study in four haematologic Brazilian centres. From August 2015 to July 2016, all patients receiving induction chemotherapy for newly diagnosed or relapsed AML, MDS or ALL, and all HCT recipients receiving conditioning regimen were followed during the period of neutropenia following chemotherapy or the conditioning regimen. During a 1-year period, 192 patients were enrolled: 122 HCT recipients (71 allogeneic, 51 autologous), 46 with AML, and 24 with ALL. The global incidence of IFD was 13.0% (25 cases, 11 proven and 14 probable). Invasive aspergillosis (14 cases) was the leading IFD, followed by candidemia (6 cases) and fusariosis (3 cases). The incidence of IFD was 26.1% in AML/MDS, 16.7% in ALL, 11.3% in allogeneic HCT, and 2.0% in autologous HCT. The burden of IFD in haematologic patients in Brazil is high, with a higher frequency in AML and ALL. Invasive aspergillosis is the leading IFD, followed by invasive candidiasis and fusariosis.
Assuntos
Doenças Hematológicas/complicações , Infecções Fúngicas Invasivas/epidemiologia , Adolescente , Adulto , Idoso , Antifúngicos/uso terapêutico , Brasil/epidemiologia , Criança , Pré-Escolar , Efeitos Psicossociais da Doença , Feminino , Doenças Hematológicas/epidemiologia , Doenças Hematológicas/microbiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Incidência , Lactente , Infecções Fúngicas Invasivas/classificação , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Fúngicas Invasivas/microbiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Transplantados/estatística & dados numéricos , Transplante Autólogo/efeitos adversos , Adulto JovemRESUMO
BACKGROUND: Patients treated for invasive aspergillosis may relapse during subsequent periods of immunosuppression and should receive secondary prophylaxis. Little is known about the frequency of relapse and practices of secondary prophylaxis for invasive fusariosis (IF). OBJECTIVES: Evaluate practices of secondary prophylaxis and the frequency of relapse in patients who survived IF and were exposed to subsequent periods of immunosuppression. METHODS: Multicentre retrospective study of patients with haematological malignancies who developed IF, survived the initial fungal disease period, and were exposed to subsequent periods of immunosuppression. RESULTS: Among 40 patients, 35 received additional chemotherapy and developed neutropenia (median, 24 days; range, 4-104), and five received glucocorticoids for the treatment of graft-vs-host disease. Overall, 32 patients received secondary prophylaxis (voriconazole in 24) for a median of 112 days (range, 12-468). IF relapsed in five patients (12.5%): 2/8 (25%) not on prophylaxis and 3/32 (9.4%) receiving prophylaxis. Among 28 patients with disseminated IF, relapse occurred in 2/2 (100%) not on prophylaxis and in 3/26 (11.5%) on prophylaxis (P = 0.03). All patients who relapsed IF died. CONCLUSIONS: Patients with IF who survive the initial disease may relapse if exposed to subsequent episodes of immunosuppressive therapies. Secondary prophylaxis should be considered, especially if IF was disseminated.
Assuntos
Quimioprevenção/métodos , Fusariose/tratamento farmacológico , Fusariose/prevenção & controle , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Prevenção Secundária/métodos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Fusariose/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Adulto JovemRESUMO
Socioeconomic status (SES) is a well-known determinant of outcomes in cancer. The purpose of this study was to analyze the impact of the SES on the outcomes of Hodgkin lymphoma (HL) patients from the Brazilian Prospective HL Registry. SES stratification was done using an individual asset/education-based household index. A total of 624 classical HL patients with diagnosis from January/2009 to December/2014, and treated with ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine), were analyzed. The median follow-up was 35.6 months, and 33% were classified as lower SES. The 3-year progression- free survival (PFS) in higher and lower SES were 78 and 64% (p < 0.0001), respectively. The 3-year overall survival (OS) in higher and lower SES were 94 and 82% (p < 0.0001), respectively. Lower SES patients were more likely to be ≥ 60 years (16 vs. 8%, p = 0.003), and to present higher risk International Prognostic score (IPS) (44 vs. 31%, p = 0.004) and advanced disease (71 vs. 58%, p = 0.003). After adjustments for potential confounders, lower SES remained independently associated with poorer survival (HR = 3.12 [1.86-5.22] for OS and HR = 1.66 [1.19-2.32] for PFS). The fatality ratio during treatment was 7.5 and 1.3% for lower and higher SES (p = 0.0001). Infections and treatment toxicity accounted for 81% of these deaths. SES is an independent factor associated with shorter survival in HL in Brazil. Potential underlying mechanisms associated with the impact of SES are delayed diagnosis and poorer education. Educational and socio-economic support interventions must be tested in this vulnerable population.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/economia , Doença de Hodgkin/economia , Doença de Hodgkin/mortalidade , Sistema de Registros/estatística & dados numéricos , Classe Social , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Brasil , Feminino , Seguimentos , Doença de Hodgkin/tratamento farmacológico , Humanos , Renda , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Adulto JovemRESUMO
Data about Hodgkin lymphoma (HL) in developing countries are scarce and suggest the existence of substantial disparities in healthcare and outcomes in large areas of the world. In 2009, a prospective registry of HL was implemented in Brazil. Web-based data were contributed by 20 institutions across the country participating in the Brazilian Prospective Hodgkin's Lymphoma Registry. The aim of this study was to present the clinical features and outcomes of newly diagnosed patients with HL aged 13 to 90 years. Multivariate Cox regression models were used to estimate progression-free (PFS) and overall survival (OS) by clinical factors. A total of 674 patients with classical HL were analysed, with a median follow-up of 37 months. Median age was 30 years (13-90). The median time from the onset of symptoms to diagnosis was 6 months (0-60). Only 6% of patients had early favourable disease, while 65% had advanced disease. Stage IVB was present in 26% and a high-risk International Prognostic Score in 38%. Doxorubicin, bleomycin, vinblastine, and dacarbazine was used in 93%. The median dose of radiotherapy was 36 Gy for localized disease and 32 Gy for advanced disease. The 3 year PFS in early favourable, early unfavourable, and advanced disease were 95%, 88%, and 66%, respectively. High-risk International Prognostic Score, advanced disease, and age greater than or equal to 60 were independently associated with poorer PFS and OS; performance status greater than or equal to 2 was also associated with a poorer OS. Poor-risk patients predominated. Radiation doses for localized disease appear higher than current recommendations. Outcomes appear inferior in developing countries than in developed countries. Delayed diagnosis is probably a major factor underlying these findings. Scattered reports from developing nations suggest that many aspects of standard care in developed countries remain unmet needs for populations living in developing countries. The present report contributes to this body of data, with a proper description of what is currently achieved in urban areas in Brazil.
Assuntos
Doença de Hodgkin/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sistema de Registros , Resultado do Tratamento , Adulto JovemRESUMO
INTRODUCTION: Constitutional symptoms and thrombohemorrhagic events are common in patients with myeloproliferative neoplasms (MPNs). Hence, the treatment's primary goal is to control symptoms and improve the quality of life (QoL). In order to assess response to therapy, symptom burden, and QoL among patients with MPN, the "Myeloproliferative Neoplasm Symptom Assessment Form - Total Symptom Score (MPN-SAF TSS)" questionnaire was developed in the USA in 2012. Herein, we translated and validated the MPN-SAF TSS questionnaire to Brazilian Portuguese. METHODS: The ten-item questionnaire was translated from the English language and its psychometric properties (reliability, convergent and construct validities) were evaluated in 101 MPN patients. RESULTS: There were 41 patients with essential thrombocythemia, 39 with myelofibrosis and 21 with polycythemia vera. The median age of all patients at diagnosis was 68 years and 59% were female. The Cronbach's alpha coefficient for the overall questionnaire was 0.78, ranging from 0.73 to 0.79, if each item was deleted. Validity analyses showed that the strongest item-item correlation were between early satiety and abdominal discomfort. Strong correlations were also found between physician and patient perceptions of itching (r=0.81) and fatigue (r=0.70). The Pearson coefficient correlation between the MPN-SAF TSS global score and the EORTC QLQ-C30 functional scales ranged from 0.51 to 0.64. The exploratory factor analysis showed that seven of the ten symptoms loaded into one single factor. CONCLUSION: The Brazilian Portuguese version of the MPN-SAF-TSS showed good psychometric properties and can be an available tool to assess symptom burden in this group of patients.
Assuntos
Calreticulina/genética , Janus Quinase 2/genética , Mutação de Sentido Incorreto , Mielofibrose Primária , Trombocitemia Essencial , Adulto , Idoso , Idoso de 80 Anos ou mais , Substituição de Aminoácidos , Calreticulina/metabolismo , Feminino , Humanos , Janus Quinase 2/metabolismo , Masculino , Pessoa de Meia-Idade , Mielofibrose Primária/sangue , Mielofibrose Primária/genética , Mielofibrose Primária/patologia , Trombocitemia Essencial/sangue , Trombocitemia Essencial/genética , Trombocitemia Essencial/patologiaRESUMO
The genetic events associated with transformation of myeloproliferative neoplasms (MPNs) to secondary acute myeloid leukemia (sAML), particularly in the subgroup of essential thrombocythemia (ET) patients, remain incompletely understood. Deep studies using high-throughput methods might lead to a better understanding of genetic landscape of ET patients who transformed to sAML. We performed array-based comparative genomic hybridization (aCGH) and whole exome sequencing (WES) to analyze paired samples from ET and sAML phases. We investigated five patients with previous history of MPN, which four had initial diagnosis of ET (one case harboring JAK2 p.Val617Phe and the remaining three CALR type II p.Lys385fs*47), and one was diagnosed with MPN/myelodysplastic syndrome with thrombocytosis (SF3B1 p.Lys700Glu). All were homogeneously treated with hydroxyurea, but subsequently transformed to sAML (mean time of 6 years/median of 4 years to transformation). Two of them have chromosomal abnormalities, and both acquire 2p gain and 5q deletion at sAML stage. The molecular mechanisms associated with leukemic progression in MPN patients are not clear. Our WES data showed TP53 alterations recurrently observed as mutations (missense and frameshift) and monoallelic loss. On the other hand, aCGH showed novel chromosome abnormalities (+2p and del5q) potentially associated with disease progression. The results reported here add valuable information to the still fragmented molecular basis of ET to sAML evolution. Further studies are necessary to identify minimal deleted/amplified region and genes relevant to sAML transformation.
RESUMO
Primary myelofibrosis (PMF) is a hematological malignancy characterized by activation of the JAK/STAT pathway and risk of leukemic transformation. In this study, we generated an induced Pluripotent Stem (iPS) cell line derived from a 65-year old male PMF patient carrying the 5-pb insertion in the CALR gene (CALRins5) and the c.437 Gâ¯>â¯A mutation in the TP53 gene (p.W146X). The newly derived PMF3.17 iPS cell line harbors the original mutations and was characterized as bona fide iPS. Resource table.
Assuntos
Mielofibrose Primária/genética , Proteína Supressora de Tumor p53/genética , Idoso , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Masculino , Mutação , Mielofibrose Primária/patologiaRESUMO
ABSTRACT Introduction: Constitutional symptoms and thrombohemorrhagic events are common in patients with myeloproliferative neoplasms (MPNs). Hence, the treatment's primary goal is to control symptoms and improve the quality of life (QoL). In order to assess response to therapy, symptom burden, and QoL among patients with MPN, the "Myeloproliferative Neoplasm Symptom Assessment Form - Total Symptom Score (MPN-SAF TSS)" questionnaire was developed in the USA in 2012. Herein, we translated and validated the MPN-SAF TSS questionnaire to Brazilian Portuguese. Methods: The ten-item questionnaire was translated from the English language and its psychometric properties (reliability, convergent and construct validities) were evaluated in 101 MPN patients. Results: There were 41 patients with essential thrombocythemia, 39 with myelofibrosis and 21 with polycythemia vera. The median age of all patients at diagnosis was 68 years and 59% were female. The Cronbach's alpha coefficient for the overall questionnaire was 0.78, ranging from 0.73 to 0.79, if each item was deleted. Validity analyses showed that the strongest item-item correlation were between early satiety and abdominal discomfort. Strong correlations were also found between physician and patient perceptions of itching (r = 0.81) and fatigue (r = 0.70). The Pearson coefficient correlation between the MPN-SAF TSS global score and the EORTC QLQ-C30 functional scales ranged from 0.51 to 0.64. The exploratory factor analysis showed that seven of the ten symptoms loaded into one single factor. Conclusion: The Brazilian Portuguese version of the MPN-SAF-TSS showed good psychometric properties and can be an available tool to assess symptom burden in this group of patients.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Adulto Jovem , Inquéritos e Questionários , Transtornos Mieloproliferativos , Qualidade de Vida , Sinais e SintomasRESUMO
Although most cases of myeloid neoplasms are sporadic, a small subset has been associated with germline mutations. The 2016 revision of the World Health Organization classification included these cases in a myeloid neoplasm group with a predisposing germline mutational background. These patients must have a different management and their families should get genetic counseling. Cases identification and outline of the major known syndromes characteristics will be discussed in this text.
RESUMO
Peripheral blood sample was donated by a 61years old female patient diagnosed with acute myeloid leukemia secondary to a primary myelofibrosis harboring the 52-bp deletion in the CALR gene (c.1092_1143del, p.L367fs*46) and the R693X mutation in the ASXL1 gene (c.2077C>T, p.R693X). CD34+ cells were isolated from the sample and subjected to the reprogramming procedure by using the Sendai virus carrying the reprogramming factors Oct3/4, Sox2, Klf4 and c-Myc. iPS colonies generated retained the original mutations and displayed all the features of bona fide iPS cells.
Assuntos
Leucemia Mieloide Aguda/terapia , Mielofibrose Primária/terapia , Animais , Diferenciação Celular , Linhagem Celular , Feminino , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Fator 4 Semelhante a Kruppel , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Mielofibrose Primária/patologiaAssuntos
Hidroxiureia/farmacologia , Janus Quinase 2/genética , Policitemia Vera/sangue , Policitemia Vera/genética , Trombocitemia Essencial/sangue , Trombocitemia Essencial/genética , Alelos , Antineoplásicos/farmacologia , Relação Dose-Resposta a Droga , Frequência do Gene , Granulócitos/metabolismo , Testes Hematológicos , Humanos , Janus Quinase 2/metabolismo , Mutação Puntual , Policitemia Vera/tratamento farmacológico , Policitemia Vera/enzimologia , Reação em Cadeia da Polimerase , Estudos Retrospectivos , Trombocitemia Essencial/tratamento farmacológico , Trombocitemia Essencial/enzimologiaRESUMO
Myelodysplastic syndrome (MDS) cases comprise a heterogeneous group of hematological disorders that are characterized by impaired hematopoiesis, with cytopenias of different grades and risk of developing acute myeloid leukemia. MDS may rarely be associated with thrombocytosis. In such cases, myelodysplasia and myeloproliferative disorders may overlap, making correct diagnosis difficult. We herein describe a case of MDS with thrombocytosis, Janus kinase 2 gene mutation-positive and Perls' staining-negative, which was initially classified as essential thrombocythemia (ET). This case highlights that MDS may be misdiagnosed as ET and inappropriate treatment may be initiated. Therefore, it is crucial to carefully combine all available data on morphology and immunophenotyping, and to perform the necessary molecular, cytogenetic and molecular cytogenetic analyses, in order to correctly diagnose this disease.
RESUMO
This report describes the results of a multicenter study designed to determine the efficacy and toxicity of a novel combination (ABVP) in patients with newly diagnosed Hodgkin's disease. The ABVP protocol is a modification of ABVD in which prednisone is substituted for DTIC. In order to attempt an increase in drug intensity, doxorubicin, bleomycin and vinblastine were administered on days 1 and 8 of each cycle, and a new cycle began on day 22. Patients who developed phlebitis were allowed to receive the drugs every two weeks. Patients with bulky mediastinal disease received involved field radiation therapy after chemotherapy. Fifty-one patients were treated. Complete remission was achieved in 40 patients (78%). Actuarial failure-free survival in 55 months was 59%, and overall survival was 81%. The overall survival for the 32 patients treated with the intensified regimen was higher than that for those who switched to the bi-weekly schedule (89% vs. 68%, p=0.03). ABVP appears to be equivalent to ABVD. The higher overall survival rate in patients treated every 21 days suggests that this intensified schedule might be more effective. The placement of a Port catheter is recommended, due to the high incidence of phlebitis.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/uso terapêutico , Doxorrubicina/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Prednisolona/uso terapêutico , Vincristina/uso terapêutico , Adolescente , Adulto , Idoso , Criança , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Flebite/induzido quimicamente , Flebite/tratamento farmacológico , Resultado do TratamentoRESUMO
Assessing the clinical significance of JAK2 V617F mutant allele burden is complicated by a myriad of techniques reported to detect and quantify the mutation. As a consequence, the level of sensitivity and how the data is reported vary. Harmonization of well-defined molecular studies would permit evaluation of the clinical significance of measuring allele burden and rapid determination of the efficacy of novel agents for the treatment of chronic myeloproliferative neoplasia via multicenter clinical trials, at the subclinical level. Here we report a comparison between the widely available TaqMan quantitative real time polymerase chain reaction (Q-PCR) and competitive PCR (C-PCR) assays. We found that the tumor load was invariably greater when measured by C-PCR compared to that recorded by Q-PCR. Furthermore, none of the samples converted from undetectable to detectable when the enriched granulocyte (GR) fraction was tested. While a difference in the V617F allele levels was detected between GR fraction and whole blood, this was not statistically significant.