RESUMO
This multicentre study evaluated 5-year progression-free (PFS) and overall survival (OS) in early and advanced Hodgkin lymphoma (HL), where therapy was individualized based on initial prognostic factors and positron emission tomography-computed tomography performed after two cycles (PET-2). Between September 2006 and August 2013, 359 patients aged 18-60 years, were recruited in nine Israeli centres. Early-HL patients initially received ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) ×2. Depending on initial unfavourable prognostic features, PET-2-positive patients received additional ABVD followed by involved-site radiotherapy (ISRT). Patients with negative PET-2 and favourable disease received ISRT or ABVD ×2; those with unfavourable disease received ABVD ×2 with ISRT or, alternatively, ABVD ×4. Advanced-HL patients initially received ABVD ×2 or escalated BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone; EB) ×2 based on their international prognostic score (≤2 or ≥3). PET-2-negative patients further received ABVD ×4; PET-2-positive patients received EB ×4 and ISRT to residual masses. With a median follow-up of 55 (13-119) months, 5-year PFS was 91% and 69% for PET-2-negative and positive early-HL, respectively; 5-year OS was 100% and 95%, respectively. For advanced-HL, the PFS was 81% and 68%, respectively (P = 0·08); 5-year OS was 98% and 91%, respectively. PET-2 positivity is associated with inferior prognosis in early-HL, even with additional ABVD and ISRT. Advanced-HL patients benefit from therapy escalation following positive PET-2. EB can be safely de-escalated to ABVD in PET-2-negative patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/terapia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bleomicina/administração & dosagem , Bleomicina/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Dacarbazina/administração & dosagem , Dacarbazina/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Esquema de Medicação , Monitoramento de Medicamentos/métodos , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/patologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Procarbazina/administração & dosagem , Procarbazina/efeitos adversos , Prognóstico , Estudos Prospectivos , Radioterapia Adjuvante , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Vincristina/administração & dosagem , Vincristina/efeitos adversos , Adulto JovemAssuntos
Medula Óssea/metabolismo , Quimiocina CCL3/biossíntese , Mieloma Múltiplo/metabolismo , Proteínas de Neoplasias/biossíntese , Osteólise/metabolismo , Idoso , Idoso de 80 Anos ou mais , Exame de Medula Óssea/métodos , Quimiocina CCL3/genética , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/metabolismo , Neoplasias Hematológicas/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , Mieloma Múltiplo/genética , Mieloma Múltiplo/patologia , Proteínas de Neoplasias/genética , Células-Tronco Neoplásicas/metabolismo , Osteólise/etiologia , Osteólise/genética , Plasmócitos/metabolismo , Células Estromais/metabolismo , Fixação de Tecidos/métodos , Células Tumorais CultivadasRESUMO
BACKGROUND: Transfusion guidelines advocate restrictive rather than liberal use of red blood cells (RBC) and are based mostly on randomized trials in intensive care and surgical departments. We aimed to study RBC transfusion practice in the medical patients' population. METHODS: The data in this study were collected from patients over the age of 18 years admitted to an Internal Medicine department between 2009 and 2014 who received at least one unit of packed red blood cells (RBC). In addition, data on demographics, patients' diagnoses, laboratory tests and number of transfused RBC units were extracted from the electronic health records. RESULTS: One thousand three hundred and twenty eight patients were included, having mean age of 75 ± 14 years. The median hemoglobin (Hb) trigger for RBC transfusion was 8.0 g/dl (IQR 7.3-8.7g/dl), and most patients received either one (43.4%) or two (33.4%) RBC units. There was no significant difference in Hb trigger between males and females (Hb 8.0 g/dl and 7.9 g/dl, respectively, p = 0.098), and a weak correlation with age (r = 0.108 p = 0.001). Patients with cardiovascular and lung diseases had a statistically significant higher Hb trigger compared to patients without those diagnoses, however the median difference between them was 0.5 g/dl or less. CONCLUSIONS: These "real world" data we collected show a Hb trigger compliant with the upper limit of published guidelines and influenced by medical patients' common diagnoses. Prospective trials addressing patients hospitalized in internal medicine departments could further contribute to transfusion decision algorithms.
Assuntos
Transfusão de Eritrócitos/normas , Hemoglobinas/análise , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Contagem de Células Sanguíneas , Estudos Transversais , Grupos Diagnósticos Relacionados , Transfusão de Eritrócitos/estatística & dados numéricos , Feminino , Fidelidade a Diretrizes , Departamentos Hospitalares , Hospitais de Ensino/estatística & dados numéricos , Humanos , Pacientes Internados/estatística & dados numéricos , Medicina Interna , Israel , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , Procedimentos Desnecessários , Adulto JovemRESUMO
BACKGROUND: A lack of aspirin effect on platelets after a myocardial infarction (MI) is associated with poor health outcome. This lack of effect may be due to biological resistance to aspirin or due to nonadherence (the patient is not taking the aspirin, hence it has no effect). Determining which of these factors predicts poor outcome would inform potential intervention strategies. METHODS: Aspirin effect on platelets was assessed in a cohort of MI survivors who were divided into three groups: group A ("adherent"), patients whose platelets were affected by aspirin; group B ("nonadherent"), patients whose platelets showed no aspirin effect and who admitted in an interview that they were not taking their medications; and group C (potentially biologically resistant to aspirin), patients whose platelets showed no aspirin effect but maintained that they were taking their aspirin. Two health outcome measures (death, reinfarction, or rehospitalization for unstable angina; or admission for any cardiovascular causes) were assessed 12 months after enrollment. RESULTS: Seventy-three patients were enrolled and classified into groups A ("adherent," 52 patients), B ("nonadherent," 12 patients), and C ("potentially aspirin resistant," 9 patients). Adverse events and readmission were more common in the nonadherent group (B)-42% and 67%, respectively, when compared with the adherent group (A)-6% and 11%, and with the potentially biologically resistant group (C)-11% and 11%. CONCLUSIONS: Nonadherence is a significant mediator of poor outcome. It is important to evaluate whether or not patients are taking their medications in clinical settings and in studies that evaluate the effect of prescribed medications.
Assuntos
Aspirina/uso terapêutico , Plaquetas/efeitos dos fármacos , Inibidores da Agregação Plaquetária/uso terapêutico , Tromboxano B2/biossíntese , Recusa do Paciente ao Tratamento , Aspirina/efeitos adversos , Aspirina/farmacologia , Plaquetas/metabolismo , Doenças Cardiovasculares/prevenção & controle , Estudos de Coortes , Intervalo Livre de Doença , Resistência a Medicamentos , Seguimentos , Humanos , Avaliação de Resultados em Cuidados de Saúde , Cooperação do Paciente , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/farmacologia , Fatores de Risco , Tromboxano B2/sangueRESUMO
In recording the changes acquired in gene expression profile during culture of fresh bone marrow samples from patients with multiple myeloma or acute myeloid leukemia, the most remarkable finding in both instances was widespread downregulation of mitotic and transcriptional genes (e.g. MKI67, CCNB1, ASPM, SGOL1, DLGAP5, CENPF, BUB1, KIF23, KIF18a, KIF11, KIF14, KIF4, NUF2, KIF1, AE2FB, TOP2A, NCAPG, TTK, CDC20, and AURKB), which could account for the ensuing proliferation arrest. Many of these genes were also underexpressed in leukemic cells from the blood or myeloma cells from an extramedullary site compared with their expression in the aspirates. Taken together, our results exhibited mitotic and transcriptional gene subsets where their expression appears to be coordinated and niche dependent. In addition, the genes induced during culture specified a variety of angiogenic factors (e.g. interleukin-8 and CXCL-5) and extracellular matrix proteins (e.g. osteopontin and fibronectin) probably released by the tumor cells while generating their favored microenvironment.
Assuntos
Pontos de Checagem do Ciclo Celular/genética , Regulação Neoplásica da Expressão Gênica , Mitose/genética , Neoplasias/genética , Medula Óssea/patologia , Proliferação de Células , Análise por Conglomerados , Biologia Computacional , Perfilação da Expressão Gênica , Humanos , Anotação de Sequência Molecular , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/genéticaRESUMO
In a comparison of gene expression profile in unsorted bone marrow (BM) samples from patients with multiple myeloma (MM), acute leukemia, and diffuse large B-cell lymphoma infiltrating the BM, the leading myeloma distinguishing gene was GPRC5D. This gene was highly expressed in BM samples from the 10 MM cases examined as opposed to minimal expression in samples from the eight cases with other hematological malignancies. Moreover, following antimyeloma treatment the expression of GPRC5D decreased several folds. The strong and selective expression of GPRC5D in MM cells makes this gene and its encoded surface protein as promising markers for monitoring the tumor load and hopefully also as targets for antimyeloma antibodies.
Assuntos
Biomarcadores Tumorais/genética , Mieloma Múltiplo/genética , Receptores Acoplados a Proteínas G/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologia , Receptores Acoplados a Proteínas G/metabolismo , Transcriptoma , Carga TumoralAssuntos
Proteínas Sanguíneas/deficiência , Acidente Vascular Cerebral/sangue , Trombose/sangue , Adulto , Idoso , Proteínas Sanguíneas/genética , Proteínas Sanguíneas/fisiologia , Estudos de Casos e Controles , Fator V/genética , Humanos , Pessoa de Meia-Idade , Acidente Vascular Cerebral/etiologia , Trombose/etiologiaRESUMO
Precursor B-ALL blasts may be positive for CD20 in up to 50% of cases. There are few reports on the use of the anti CD20 monoclonal antibody, rituximab, in children with B-ALL. We report on two adult patients with precursor B-ALL who developed significant hepatic toxicity during induction chemotherapy. Single agent rituximab was given until recovery of liver enzymes was established. Both patients were able to continue further chemotherapy, underwent an Allo BMT and are now 10-12 months after diagnosis in a continuous CR.
Assuntos
Anticorpos Monoclonais/administração & dosagem , Antineoplásicos/administração & dosagem , Transplante de Medula Óssea , Linfoma de Burkitt/terapia , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Murinos , Antineoplásicos/efeitos adversos , Linfoma de Burkitt/complicações , Feminino , Seguimentos , Humanos , Hepatopatias/etiologia , Pessoa de Meia-Idade , Indução de Remissão , Rituximab , Transplante HomólogoRESUMO
OBJECTIVES: Central retinal vein occlusion (CRVO) and central retinal artery occlusion (CRAO) are common disorders associated with risk factors for atherosclerosis. Protein Z is a cofactor for the inactivation of activated factor X (Xa) by the protein Z dependent protease inhibitor. Protein Z deficiency was recently linked to increased risk of arterial thrombosis. We investigated whether CRVO and CRAO are associated with low protein Z levels. PATIENTS AND METHODS: Patients with CRVO, CRAO or recurrent branch retinal vein occlusion were recruited to the study. Protein Z level, lupus anticoagulant (LAC), anticardiolipin antibodies (ACA) and activated protein C resistance (APCR) were determined in plasma from patients (n = 36) and healthy controls (n = 42). RESULTS: Thirty patients in the study group had traditional risk factors for retinal vessel occlusion and six patients had none. There was no significant difference in protein Z levels between the whole study group patients and controls (1995 +/- 810 vs. 2010 +/- 603 ng/mL, P = 0.922). However, patients with no risk factors for retinal vessel occlusion had significantly lower protein Z levels than controls (1379 +/- 682 vs. 2010 +/- 603 ng/mL, P = 0.022). Positive LAC was found in six patients and one control subject (P = 0.04). There were three patients and one control subject with abnormal APCR (P = 0.3) and none with positive ACA. Low protein Z level (lower than fifth percentile of control) was not associated with the presence of LAC or APCR. CONCLUSION: Low protein Z level may be another risk factor for retinal vessel occlusion in patients without traditional risk factors for these disorders.
Assuntos
Proteínas Sanguíneas/análise , Oclusão da Artéria Retiniana/sangue , Oclusão da Veia Retiniana/sangue , Adulto , Idoso , Proteínas Sanguíneas/deficiência , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oclusão da Artéria Retiniana/etiologia , Oclusão da Veia Retiniana/etiologia , Fatores de RiscoRESUMO
Hemophagocytic syndrome (HPS) is an unusual acute syndrome presenting with fever, hepatosplenomegaly, and cytopenias. The hallmark of HPS is the accumulation of activated macrophages that engulf hematopoietic cells in the reticuloendothelial system. Most cases of HPS in adults are secondary to infection or malignancy, and thus investigation of the underlying disease is necessary. We describe a patient with prolonged fever, HPS, and chromosomal abnormalities in the bone marrow who underwent thorough evaluation for the cause of his symptoms. A final diagnosis of acute lymphoblastic leukemia (ALL) was established in a fourth, repeated bone marrow biopsy performed more than 2 months after the first presenting symptom appeared. This unusual case demonstrates the importance of cytogenetic abnormalities found in cases of HPS and the importance of repeated testing when an underlying disease is suspected.