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Оптимизация использования мелфлюфена (melphalan flufenamide) в реанимированных или рефрактных миеломах: рекомендации для клинической практики.

В настоящем докладе группа экспертов по миеломе, состоящая из нескольких экспертов, оценивает роль мелфлюфена (Melphalan flufenamide) в лечении пациентов с повторной или рефрактной множественной миеломой (RRMMM). На основе имеющихся данных приводятся рекомендации по управлению мелфлюфеном, управлению неблагоприятными явлениями и оптимальному отбору пациентов. Мелфлюфен, первый в классе пиптидный матрос, утверждается в Европейском союзе и Соединенном Королевстве в сочетании с дексаметазоном для лечения взрослых пациентов с множественной миеломой (ММ), которые получили по крайней мере three :: п

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… In HORIZON, 43% of the patients received platelet transfusions [ 14 ]. Bleeding events Bleeding events of any grade occurred in 21% of patients in the safety population, whereas a Grade 3 bleeding was reported in 2% [ 1 ]. … The threshold for platelet transfusions depends on clinical signs, co-morbidity and, if present, anti-coagulant co-medication. Expert consensus suggests weekly monitoring in the first cycle, then adaption, depending on cytopenia, to biweekly or four-weekly controls. …

36th International Symposium on Intensive Care and Emergency Medicine : Brussels, Belgium. 15-18 March 2016.

P001 - Sepsis impairs the capillary response within hypoxic capillaries and decreases erythrocyte oxygen-dependent ATP efflux R. M. Bateman, M. D. Sharpe, J. E. Jagger, C. G. Ellis P002 - Lower serum immunoglobulin G2 level does not predispose to severe flu. J. Solé-Violán, M. López-Rodríguez, E. Herrera-Ramos, J. Ruíz-Hernández, L. Borderías, J. Horcajada, N. González-Quevedo, O. Rajas, M. Briones, F. Rodríguez de Castro, C. Rodríguez Gallego P003 - Brain protective effects of intravenous immunoglobulin through inhibition of complement activation and apoptosis in a rat model of sepsis F. Esen

Aptamers: Potential Diagnostic and Therapeutic Agents for Blood Diseases.

Aptamers are RNA/DNA oligonucleotide molecules that specifically bind to a targeted complementary molecule. As potential recognition elements with promising diagnostic and therapeutic applications, aptamers, such as monoclonal antibodies, could provide many treatment and diagnostic options for blood diseases. Aptamers present several superior features over antibodies, including a simple in vitro selection and production, ease of modification and conjugation, high stability, and low immunogenicity. Emerging as promising alternatives to antibodies, aptamers could overcome the present limitations

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… pathway of coagulation | [ 73 ] Direct oral anticoagulants (dabigatran) | DGB-1, DBG-2, DBG-4, and DBG-5 | ssDNA aptamers | Direct oral anticoagulants (dabigatran) | Pre-clinical studies (proof of concept) for monitoring direct oral anticoagulants (dabigatran) | [ 74 , 75 ] Refrigerated platelets (for platelet … transfusion) | Anti-VWF aptamer | von Willebrand factor | Refrigerated platelets (for platelet transfusion) | Pre-clinical studies (proof of concept) for the use of ARC1779 to refrigerated platelets; improves post-transfusion recovery and preserves the long-term hemostatic function of refrigerated platelets …

Selinexor plus ruxolitinib in JAK inhibitor-naïve patients with myelofibrosis: a multicenter, open-label, phase 1 study.

AbstractThe phase 1 portion of SENTRY/XPORT-MF-034 (NCT04562389) evaluated the exportin 1 inhibitor selinexor (40 mg/60 mg once weekly) plus ruxolitinib in JAK inhibitor-naïve patients with myelofibrosis (n = 24). Primary end points were maximum tolerated selinexor dose, recommended clinical trial dose, and safety. No dose-limiting toxicities were reported. Common adverse events were nausea, fatigue, anemia, thrombocytopenia, constipation, vomiting, and headache. Nausea was transient, mainly grade 1, and managed by prophylactic antiemetics. Four deaths occurred, all unrelated to study treatmen

Women with Gaucher Disease.

Gaucher disease is an inherited disorder in which there is a deficiency of the enzyme glucocerebrosidase, which leads to the accumulation of glucosylceramide. Although much scientific evidence is now available, there is still limited data on the impact on the different life stages of women with this disease. Among other alterations, a delay in menarche has been described, although it has not been related to fertility problems. Menorrhagia is relatively frequent, being related to the presence of thrombocytopenia, thrombocytopathies or coagulation disorders. On the other hand, pregnancy planning

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… There is little evidence on the management of hemostatic coverage in these patients, and the recommendations established for pregnant patients with congenital or acquired alterations of hemostasis are generally applied, mainly using tranexamic acid for situations of low bleeding risk and platelet transfusion … transfusion, fresh frozen plasma…) Check immunization Menopause | Early onset of menopause Osteoporosis, osteopenia | HRT 2 DXA 3 /densitometry monitoring Consider initiation or adjustment of treatment Support treatment (oral bisphosphonates, vitamin D, and calcium supplementation) 4. …

Расположение Мелфлюфа в организме пациентов, прошедших курс интенсивной предварительной терапии: реальные данные в мире в быстро меняющемся терапевтическом ландшафте.

Современная терапия явно ознаменовала историю множественной миэломы (ММ), что привело к неоспоримым преимуществам с точки зрения устойчивых мер реагирования и продолжительного выживания при постепенном повышении качества жизни пациентов. Тем не менее повторение заболеваний и устойчивость к имеющимся методам лечения подчеркивают важность выявления дополнительных вариантов лечения, особенно у пациентов с тяжелыми условиями лечения или в тех случаях, когда доступ к современной иммунотерапии ограничен. Мелфлюфен (мельфалан-флюфенамид) плюс дексаметасон были утверждены Европейским агентством по мед

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… Supportive care (Table 2 ) was frequently required, with six (35%) patients receiving red blood cell transfusions, four (24%) platelet transfusions, and 10 (59%) granulocyte colony‐stimulating factor (G‐CSF) support. …

SEOM clinical guidelines for anaemia treatment in cancer patients (2020).

Anaemia is defined by the presence of haemoglobin (Hb) levels < 13 g/dL in men and 12 g/dL in women. Up to 39% of cancer patients present it at the time of diagnosis and up to 40% have iron deficiency. Anaemia causes fatigue, functional deterioration and a reduction in the quality of life; it has also been associated with a poorer response to anti-tumour treatment and lower survival. Basic diagnostic tests for anaemia are simple and should be a routine part of clinical practice. These guidelines review the available evidence on the use of different therapies for treating anaemia: erythropoiesi

Exploring Affordable Curative Therapy for Sickle Cell Disease in Africa: A Comprehensive Overview.

The practical aspects of developing curative treatments for sickle cell disease (SCD) in Africa, such as gene therapy and hematopoietic stem cell transplantation, involve strengthening healthcare infrastructure, training healthcare professionals, establishing regional treatment centers, and creating national SCD programs. The costs associated with gene therapy and stem cell transplants can be prohibitive, especially in low- and middle-income countries. Strategies to address affordability, including local manufacturing, government funding, and partnerships with global health agencies, are essen

Extramedullary disease is associated with severe toxicities following B-cell maturation antigen CAR T-cell therapy in multiple myeloma.

Extramedullary disease (EMD) in multiple myeloma (MM) is associated with poor outcomes following B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR) T therapy, yet its impact on treatment-related toxicity remains unclear. This study evaluates the impact of active EMD on toxicity, efficacy, and survival in patients with MM treated with idecabtagene vicleucel (ide-cel) or ciltacabtagene autoleucel (cilta-cel). We conducted a retrospective cohort study of all patients with MM who received ide-cel (N=32) or cilta-cel (N=76) as standard-of-care therapy at our institution from

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… The severity of cytopenias further compounded these challenges, increasing the need for red blood cell and platelet transfusions to support hematologic recovery. Managing these complications required intensive supportive care, including greater use of antibiotics, steroids, and anakinra. …

Oral Graft-Versus-Host Disease: A Pictorial Review and a Guide for Dental Practitioners.

IntroductionGraft-versus-host disease (GVHD) is a complication of haematopoietic stem cell transplantation (HSCT). GVHD may also develop following solid transplants or blood transfusions if white blood cells are transferred. GVHD affects multiple organs, including the oral tissues.ObjectiveThis pictorial review provides a background of GVHD to dental practitioners, describes the most common oral manifestations of GVHD and highlights the main treatment modifications needed to deliver dental care to patients with GVHD.MethodsA narrative review enhanced with clinical photographs.ResultsAcute GVHD

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… If surgery is necessary, a platelet transfusion may be needed. …

Frailty-adjusted therapy in Transplant Non-Eligible patients with newly diagnosed Multiple Myeloma (FiTNEss (UK-MRA Myeloma XIV Trial)): a study protocol for a randomised phase III trial.

INTRODUCTION: Multiple myeloma is a bone marrow cancer, which predominantly affects older people. The incidence is increasing in an ageing population.Over the last 10 years, patient outcomes have improved. However, this is less apparent in older, less fit patients, who are ineligible for stem cell transplant. Research is required in this patient group, taking into account frailty and aiming to improve: treatment tolerability, clinical outcomes and quality of life. METHODS AND ANALYSIS: Frailty-adjusted therapy in Transplant Non-Eligible patients with newly diagnosed Multiple Myeloma is a nati

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… Please note: Platelet transfusions are not allowed ≤3 days prior to randomisation in order to meet these values. Haemoglobin≥80 g/L. The use of red blood cell transfusions is permitted. Biochemical: Total bilirubin≤3× upper limit of normal (ULN). … Please note: Platelet transfusions are not allowed ≤3 days prior to randomisation in order to meet these values. Haemoglobin≥80 g/L. The use of red blood cell transfusions is permitted. Biochemical: Total bilirubin≤3× upper limit of normal (ULN). …

Lenalidomide for the Treatment of Low- or Intermediate-1-Risk Myelodysplastic Syndromes Associated with Deletion 5q Cytogenetic Abnormality: An Evidence Review of the NICE Submission from Celgene.

The National Institute for Health and Care Excellence (NICE) invited the manufacturer of lenalidomide (Celgene) to submit evidence of the clinical and cost effectiveness of the drug for treating adults with myelodysplastic syndromes (MDS) associated with deletion 5q cytogenetic abnormality, as part of the Institute's single technology appraisal (STA) process. Kleijnen Systematic Reviews Ltd (KSR), in collaboration with Erasmus University Rotterdam, was commissioned to act as the Evidence Review Group (ERG). This paper describes the company's submission, the ERG review, and the NICE's subsequen

Bortezomib-based therapy for transplant-ineligible East Asian patients with newly diagnosed mantle-cell lymphoma.

IntroductionThis subgroup analysis of the LYM-3002 Phase III study (NCT00722137) investigated whether substituting bortezomib for vincristine in frontline R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) therapy could improve outcomes in East Asian patients with newly diagnosed mantle-cell lymphoma (MCL).Materials and methodsA total of 121 East Asian patients from China, Taiwan, Japan, and the Republic of Korea with stage II-IV MCL who were ineligible or not considered for stem-cell transplantation were enrolled to six to eight 21-day cycles of R-CHOP or VR-CA

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… The rates of red blood cell (RBC) transfusions were 15% with VR-CAP and 13% with R-CHOP, and platelet transfusions with VR-CAP were 35% and 4% with R-CHOP. Rates of any-grade bleeding events were 3% for VR-CAP and 2% for R-CHOP. … The higher thrombocytopenia rates observed with VR-CAP were reflected in a higher rate of platelet transfusions, but rates of clinically significant bleeding events were similar between arms, indicating no sequelae. …

Impact of tandem autologous stem cell transplantation and response to transplant in the outcome of multiple myeloma.

UnlabelledBackgroundMultiple Myeloma (MM) is the commonest indication for autologous stem cell transplantation (ASCT).MethodsWe retrospectively analysed data from 85 patients with MM submitted to ASCT in our centre from 2000 to 2010: 132 ASCT were realized, 80 of them as tandem.ResultsAfter induction, 17.6% were in complete remission (CR), 41.2% in very good partial remission (VGPR) and 41.2% in partial remission (PR). After transplant 44.7% were in CR, 15.3% in VGPR and 40% in PR. With 22 months (range - 3 to 117 months) of median follow-up, median overall survival (OS) was 43 months and prog

Characteristics and Outcomes of Intracranial Hemorrhage in Cancer Patients Visiting the Emergency Department.

Intracranial hemorrhage (ICH) is a dreaded complication of both cancer and its treatment. To evaluate the characteristics and clinical outcomes of cancer patients with ICH, we identified all patients with ICH who visited The University of Texas MD Anderson Cancer Center emergency department between 1 September 2006 and 16 February 2016. Clinical and radiologic data were collected and compared. Logistic regression analyses were used to determine the association between clinical variables and various outcomes. During the period studied, 704 confirmed acute ICH cases were identified. In-hospital,

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… Treatment was initiated in most patients (93.8%), and platelet transfusion was the most common treatment modality (30%), followed by dexamethasone (20.3%), whereas early surgical intervention was uncommon (11.7%, Table 2 ). Table 2 Management and outcome of ICH in cancer patients. … The risk of spontaneous hemorrhage in severe thrombocytopenia is well recognized, and this is the rationale behind prophylactic platelet transfusions. …

Venous thromboembolism in the cancer population: pathology, risk, and prevention.

Patients with cancer have an increased risk of developing venous thromboembolism (VTE) and the incidence of these events has been increasing over the past decade. Venous thromboembolic events include both deep venous thrombosis and pulmonary embolism. These events contribute to higher morbidity and mortality rates. Understanding the complex pathogenesis of and risk factors for cancer-associated VTE will help guide advanced practitioners to improve outcomes with prophylaxis. The American Society of Clinical Oncology, the National Comprehensive Cancer Network, and the European Society of Medical

Therapeutic approaches in myelofibrosis and myelodysplastic/myeloproliferative overlap syndromes.

The discovery of JAK2 (V617F) a decade ago led to optimism for a rapidly developing treatment revolution in Ph(-) myeloproliferative neoplasms. Unlike BCR-ABL, however, JAK2 was found to have a more heterogeneous role in carcinogenesis. Therefore, for years, development of new therapies was slow, despite standard treatment options that did not address the overwhelming symptom burden in patients with primary myelofibrosis (MF), post-essential thrombocythemia MF, post-polycythemia vera MF, and myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN) syndromes. JAK-STAT inhibitors have ch

Moving forward from spleen response as an endpoint in randomized controlled trials in myelofibrosis.

Anticancer drugs should make patients live longer and/or feel better. Ideally, endpoints of cancer randomized controlled trials (RCT) should demonstrate that a drug leads to an increase in overall survival and/or improvement in quality of life. With the aim of including smaller numbers of patients, running shorter trials and thus getting new drugs to patients faster, cancer RCT are increasingly using (putative) surrogate endpoints. However, changes in surrogate endpoints often do not reliably predict improvements in overall survival and/or quality of life. Furthermore, especially in later line

A phase I study of single-agent perifosine for recurrent or refractory pediatric CNS and solid tumors.

The PI3K/Akt/mTOR signaling pathway is aberrantly activated in various pediatric tumors. We conducted a phase I study of the Akt inhibitor perifosine in patients with recurrent/refractory pediatric CNS and solid tumors. This was a standard 3+3 open-label dose-escalation study to assess pharmacokinetics, describe toxicities, and identify the MTD for single-agent perifosine. Five dose levels were investigated, ranging from 25 to 125 mg/m2/day for 28 days per cycle. Twenty-three patients (median age 10 years, range 4-18 years) with CNS tumors (DIPG [n = 3], high-grade glioma [n = 5], medulloblast

Research progress on venous thrombosis development in patients with malignant tumors.

The coexistence of venous thromboembolism (VTE) within patients with cancer, known as cancer-associated thrombosis (CAT), stands as a prominent cause of mortality in this population. Over recent years, the incidence of VTE has demonstrated a steady increase across diverse tumor types, influenced by several factors such as patient management, tumor-specific risks, and treatment-related aspects. Furthermore, mutations in specific genes have been identified as potential contributors to increased CAT occurrence in particular cancer subtypes. We conducted an extensive review encompassing pivotal hi