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ABSTRACT Objectives Patients with multiple myeloma often require multiple treatment lines. The order in which treatments are sequenced has impact on clinical outcomes. This study aimed to estimate progression‐free survival (PFS) and overall survival (OS) with common treatment sequences used in Portugal and the incremental benefit of an optimal sequence in transplant‐ineligible patients with multiple myeloma. Methods A state‐transition sequential model with a five‐health state conceptual structure was developed to simulate and compare survival outcomes between treatment sequences up to four lines of treatments. Data sources included randomized clinical trials and indirect treatment comparisons. A panel of Portuguese hematologists listed four most common treatment sequences and optimal sequence of choice in transplant‐ineligible patients. Results Our simulation estimated an OS between 6.1 and 7.8 years using the most common sequences, with VMP + DRd + Pd + Kd as the most effective (7.8 years). Optimal sequence of choice (DRd + PVd + Kd + Vd) achieved OS of 9.8 years and may extend OS in 2.0–3.7 years vs. most common sequences (26%–61% increase). This benefit was mostly explained by extended PFS in the first line of treatment. Conclusion Model results demonstrate that choosing the most effective treatment upfront is crucial in delaying disease progression thus yielding better survival outcomes in transplant‐ineligible patients. There was a clear survival benefit in using daratumumab‐based regimens in first line. This modelling exercise highlights the need to raise awareness around the impact of sequencing strategies to improve patient's outcomes.

Using Holter recordings and based on the principle that most of the survivors of acute myocardial infarction who are going to die suddenly after hospital discharge are those who present ventricular premature beats (VPB), the authors have studied the effect of three different antidysrhythmic drugs - procainamide (PA), oxprenolol (OX) and amiodarones. (AMIOD) - in late phase of acute myocardial infarction. All the trials have been controlled Procainamide (47 patients studied), in comparison with placebo (PL), revealed to be effective (a) in supressing and diminishing VPB/hour (p=0.0425), and (b) in maintaining patients with no VPB (PA 89.6% - PL 64.7%). Oxprenolol (27 patients studied), in comparison with placebo, revealed to be effective (a) in maintaining patients with no VPB (p=0.0525), and (b) in avoiding the increase of VPB/hour (p=0.0576). Finally amiodarone (37 patients studied), in comparison with placebo, was effective (a) in maintaining patients with no VPB (AMIOD 50% - PL 39%), (b) in diminishing VPB/hour (AMIOD 29% - PL 9%), and (c) in avoiding the increase of VPB/hour (AMIOD 79% - PL 48%). The authors finish their paper emphasizing that no antidysrhythmic drug should be introduced in clinical practice before being submitted to controlled studies with Holter electrocardiography.

Objectives: Patients with multiple myeloma often require multiple treatment lines. The order in which treatments are sequenced has impact on clinical outcomes. This study aimed to estimate progression-free survival (PFS) and overall survival (OS) with common treatment sequences used in Portugal and the incremental benefit of an optimal sequence in transplant-ineligible patients with multiple myeloma., Methods: A state-transition sequential model with a five-health state conceptual structure was developed to simulate and compare survival outcomes between treatment sequences up to four lines of treatments. Data sources included randomized clinical trials and indirect treatment comparisons. A panel of Portuguese hematologists listed four most common treatment sequences and optimal sequence of choice in transplant-ineligible patients., Results: Our simulation estimated an OS between 6.1 and 7.8 years using the most common sequences, with VMP + DRd + Pd + Kd as the most effective (7.8 years). Optimal sequence of choice (DRd + PVd + Kd + Vd) achieved OS of 9.8 years and may extend OS in 2.0-3.7 years vs. most common sequences (26%-61% increase). This benefit was mostly explained by extended PFS in the first line of treatment., Conclusion: Model results demonstrate that choosing the most effective treatment upfront is crucial in delaying disease progression thus yielding better survival outcomes in transplant-ineligible patients. There was a clear survival benefit in using daratumumab-based regimens in first line. This modelling exercise highlights the need to raise awareness around the impact of sequencing strategies to improve patient's outcomes., (© 2024 The Author(s). Cancer Reports published by Wiley Periodicals LLC.)

Patients with lymphoma who have experienced a first relapse or progression and have disease deemed sensitive to salvage chemotherapy nevertheless have a high likelihood of having a second relapse. To decrease the likelihood of a second relapse after high-dose therapy (HDT) and autologous stem cell transplantation (ASCT), interferon (IFN) α-2b was given in a prospective randomized international trial. Methods. In this trial, 221 patients with varying histologic diagnoses (8 small lymphocytic, 37 follicular, 9 mantle, 90 diffuse large B-cell, 20 peripheral T-cell, 3 high-grade B-cell non-Hodgkin lymphoma, and 54 Hodgkin lymphoma) were randomly assigned to receive no further treatment (arm A: 117 patients) or IFNα-2b, 3 MU three times weekly, for 18 months (arm B: 104 patients). Results. In arm B, 21 patients (20%) did not receive IFNα-2b because of early progression or absence of hematologic recovery, 29 patients (28%) completed the 18 months of treatment, and 54 patients (52%) interrupted treatment because of progression (23%) or toxicity (29%). Event-free survival and overall survival were not different between the two arms on an intent-to-treat analysis and also if analysis was restricted to patients who were alive and had not experienced disease progression three months after transplantation. The study was not sufficiently powered to evaluate effects in histologic subtypes. Conclusion. In this trial, post-autograft IFNα-2b did not improve outcomes in a heterogeneous group of patients with lymphoma.

Infective endocarditis continues to be associated with high mortality, despite the medical and surgical therapeutic options available. Surgical intervention is indicated in cases of heart failure or uncontrolled infection and sometimes for the prevention of embolic phenomena. The authors present the case of a 56-year-old male patient, with fibro-calcific mitral-aortic valve disease, splenectomized and with recently relapsed Hodgkin's lymphoma, who was admitted with infective endocarditis due to Streptococcus dysgalactiae. On the thirtieth day of directed antibiotic therapy, the mitral vegetation showed a significant increase in size and mobility. Surgery was considered at this point. However, given the patient's clinical stability and laboratory results, it was decided to adopt a conservative approach and to extend antibiotic therapy. The vegetation had regressed considerably seven days later. Given this atypical vegetation behavior, with slower than usual regression for the causative agent, the authors suggest that antibiotic therapy should be extended in patients with some degree of immunosuppression., (Copyright © 2011 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.)

Most patients with newly diagnosed multiple myeloma (MM) are aged > 65 years with 30% aged > 75 years. Many elderly patients are also vulnerable because of comorbidities that complicate the management of MM. The prevalence of MM is expected to rise over time because of an aging population. Most elderly patients with MM are ineligible for autologous transplantation, and the standard treatment has, until recently, been melphalan plus prednisone. The introduction of novel agents, such as thalidomide, bortezomib, and lenalidomide, has improved outcomes; however, elderly patients with MM are more susceptible to side effects and are often unable to tolerate full drug doses. For these patients, lower-dose-intensity regimens improve the safety profile and thus optimize treatment outcome. Further research into the best treatment strategies for vulnerable elderly patients is urgently needed. Appropriate screening for vulnerability and an assessment of cardiac, pulmonary, renal, hepatic, and neurologic functions, as well as age > 75 years, at the start of therapy allows treatment strategies to be individualized and drug doses to be tailored to improve tolerability and optimize efficacy. Similarly, occurrence of serious nonhematologic adverse events during treatment should be carefully taken into account to adjust doses and optimize outcomes.

Background: High dose chemotherapy with autologous stem cell transplantation (HDCT-ASCT) has been administered to patients with high-risk germ cell tumours (GCT). The role of this treatment for GCT still remains unclear, including the identification of subgroups more likely to benefit from such strategy., Methods: A retrospective review was conducted of all male patients with gonadal and extra gonadal GCT treated with HDCT-ASCT between 1996 and 2008 at the Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG)., Results: Twenty patients were treated with HDCT-ASCT, 17 with primary testicular tumours, two mediastinal and one retroperitoneal GCT. According to the International Germ Cell Cancer Consensus Group (IGCCCG) classification, at diagnosis three patients had good risk, four intermediate, eight poor but for the patients left the risk group could not be ascertained. In eight patients HDCT-ASCT was used upfront, after induction with first-line conventional chemotherapy, and in the remaining 12 for relapsed GCT. One patient had platinum-resistant and another platinum-refractory disease. Only two patients had Beyer score > 2. All but one patient were treated with ICE (Ifosfamide, Carboplatin, Etoposide). Six patients underwent a second HDCT-ASCT course. The 5-year overall survival and progression free survival were respectively 53% and 44%; both patients with mediastinal GCT are long term survivors., Conclusion: Randomized studies to date have failed to indicate a survival advantage for HDCT-ASCT in GCT. This series is small and heterogeneous which prevents us from drawing conclusions regarding the benefit of this treatment for GCT. However, we could confirm the lack of benefit of HDCT-ASCT for platinum-resistant GCT and to question the absolute contraindication to this therapeutic modality in mediastinal GCT. HDCT-ASCT should therefore be performed exclusively in experienced centers and, preferably, in the setting of clinical trials.

The arrival of the novel agents thalidomide, bortezomib, and lenalidomide has significantly changed our approach to the management of multiple myeloma and, importantly, patient outcomes have improved. These agents have been investigated intensively in different treatment settings, providing us with data to make evidence-based decisions regarding the optimal management of patients. This review is an update to a previous summary of European treatment practices that examines new data that have been published or presented at congresses up to the end of 2010 and assesses their impact on treatment practices.

Thalidomide has received approval from the European Agency for the Evaluation of Medicinal Products for the treatment of newly diagnosed multiple myeloma (MM) patients older than 65 years or ineligible for transplant. The results of five phase III trials assessing thalidomide in combination with melphalan and prednisone (MPT) have demonstrated significantly improved response rates compared with melphalan and prednisone (MP) alone. Additionally, two of these studies showed that survival was extended by approximately 18 months in patients treated with MPT compared with MP alone. Thalidomide, in combination with MP, is associated with adverse events (AEs) including peripheral neuropathy and venous thromboembolism. In order to optimize the efficacy of MPT, a good awareness of these AEs is imperative. This manuscript outlines both evidence- and consensus-based recommendations discussed by a panel of experts, to provide a practical guide for physicians addressing the effective management of newly diagnosed, transplant-ineligible MM patients receiving thalidomide therapy.

The development of biotechnology drugs represents one of the great advances in medical therapy and it was observed an exponential growth in its use. The resource to these drugs in Oncology and Hematology is no exception and it soon became an essential element of an integrated and directed therapy strategy. The expiry of the first biotechnology drugs patents has opened the door for the development and marketing of biosimilars, which entry in the Portuguese market was recently approved. This article was built on the analysis of the available state-of-the-art information on biotechnology drugs, biosimilars and current legislation and it expresses the opinion of Oncology and Hematology experts about the substituition of biological drugs by biosimilars in clinical practice.

The administration of cytotoxic chemotherapy may be complicated by the emergence of neutropenia and febrile neutropenia, frequently determining hospital admission and intravenous treatment with broad spectrum antibiotics. Frequently, it is necessary to reduce the dose or to delay the administration of the cytotoxic drugs reducing the relative dose intensity of the chemotherapy regimen. Granulocyte growth factors stimulate the proliferation and differentiation of neutrophils and reduce the number of days of severe neutropenia and febrile neutropenia associated with cytotoxic chemotherapy. They are also indicated for the collection of hematopoietic progenitors for autologous and allogeneic transplantation, as well as in non malignant diseases associated with chronic neutropenia. This article reviews the evidence supporting the use of granulocyte growth factors in Hematology.

A 44-month old girl with congenital amegakaryocytic thrombocytopenia, already with pancytopenia, underwent an unrelated allogeneic cord blood transplantation with recovery of normal blood cell counts. The patient was a compound heterozygote for two c-mpl missense mutations inherited from both parents, one of them, a G578A exon 4 mutation leading to a cysteine to tyrosine replacement of codon 193, previously unreported., (Copyright (c) 2006 Wiley-Liss, Inc.)