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Оценка в реальном мире физиотерапевтических упражнений в процессе предварительной абилитации и реабилитации во время аутологической трансплантации стволовых клеток в миэломе: опыт работы в одном центре.

СПРАВОЧНАЯ ИНФОРМАЦИЯ: Имеются новые данные, свидетельствующие о роли упражнений в оптимизации функций, качестве жизни (QoL) и сокращении продолжительности пребывания в больнице, если они начались до пересадки аутологических стволовых клеток (ASCT). Проведенное на местном уровне экспериментальное исследование в области предабилитации и реабилитации пациентов миломы в ходе АОПП показало обнадеживающие результаты и было адаптировано к местным медицинским услугам. Цель настоящего доклада состоит в том, чтобы дать общее представление о недавно внедренной физиотерапевтической службе предварительной

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… Patients with transplant-eligible myeloma are considered to be physically ‘fitter’ than their non-transplant eligible counterparts, in order to tolerate high-dose treatment with melphalan. 26 At baseline, patients assessed in this evaluation had lower than expected QoL scores. … The higher-than-expected levels of impaired functional capacity evident in our patients prior to ASCT highlight the impact of haematological malignancies and disease-related morbidity on overall fitness, even for those deemed suitable to proceed to transplant with high-dose melphalan. …

Автономная трансплантация стволовых клеток с помощью гематопоиетической гематомии для множественных склерозов в Соединенном Королевстве: A 20-year Ретроспективный анализ деятельности и гематологических результатов Британского общества трансплантации крови и мозга и клеточной терапии (BSBMTCT).

Автологическая трансплантация стволовых клеток (AHSCT) была разработана в качестве средства лечения множественных склерозов (MS) с тех пор. 1995. Соединенное Королевство one :: из наиболее активных стран Европы, осуществляющих АХСХТ для НР. Мы сообщаем об опыте Соединенного Королевства в области AHSCT для MS 364 :: пациенты, имеющие MS, которые лечатся AHSCT между 2002 и 2023. Мы представляем данные о смертности, связанной с трансплантацией (ТМР), осложнениях и эффективности АХСПП, определяемых расширенной шкалой показателей инвалидности (ЭДСС) в условиях бесперебойного выживания (ПФС) 2 годы

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… Conditioning was cyclophosphamide/ATG with cyclophosphamide 200 mg/kg based on ideal body weight and rabbit‐ATG (r‐ATG, Thymoglobulin, Sanofi) at either 6.0 mg/kg or 7.5 mg/kg or carmustine/etoposide/cytarabine/melphalan regimen plus an equivalent dose of rATG (BEAM‐ATG). … 0 Dose of ATG ≤6 mg/kg 141 39% 23 28% 8 17% 96 46% >6 mg/kg 219 61% 58 72% 39 83% 111 54% No ATG/not reported 4 2 0 2 Abbreviations: AHSCT, autologous haematopoietic stem cell transplantation; ATG, anti‐thymocyte globulin; BEAM, bis‐chloro‐ethyl‐nitrosourea (BCNU), cytosine arabinoside, etoposide, melphalan …

Best Practice for the Administration of Daratumumab in Multiple Myeloma: Australian Myeloma Nurse Expert Opinion.

Patients with multiple myeloma (MM) are typically of an advanced age and may have significant co-existing medical conditions. They have often had multiple lines of therapy and as such experience disease-related effects alongside associated treatment toxicities. Daratumumab is a monoclonal antibody approved for the treatment of MM in the relapsed/refractory setting. Clinical studies found that daratumumab showed good tolerability as a monotherapy and in combination with current standard therapies. However, the administration of daratumumab does require specific management considerations. It is

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… cyclophosphamide, and etoposide, PIs: Proteasome inhibitors, IMiDs: Immunomodulatory drugs, mAbs: Monoclonal antibodies, PBS: Pharmaceutical Benefits Scheme Class of drug | Drug name PIs | Bortezomib Carfilzomib Ixazomib* IMiDs | Thalidomide Lenalidomide Pomalidomide Cytotoxic agents | Cyclophosphamide Melphalan … Daratumumab plus bortezomib, melphalan, and prednisone for untreated myeloma. N Engl J Med. 2018;378:518–28. doi: 10.1056/NEJMoa1714678. 27. Chapuy CI, Nicholson RT, Aguad MD, Chapuy B, Laubach JP, Richardson PG, et al. Resolving the daratumumab interference with blood compatibility testing. …

Updated analysis of CALGB (Alliance) 100104 assessing lenalidomide versus placebo maintenance after single autologous stem-cell transplantation for multiple myeloma: a randomised, double-blind, phase 3 trial.

BackgroundIn the CALGB (Alliance) 100104 study, lenalidomide versus placebo after autologous stem-cell transplantation (ASCT) was investigated for patients with newly diagnosed myeloma. That study showed improved time to progression and overall survival and an increase in second primary malignancies for lenalidomide at a median follow-up of 34 months. Here we report an updated intention-to-treat analysis of CALGB (Alliance) 100104 at a median follow-up of 91 months.MethodsPatients were eligible for this randomised, double-blind, placebo-controlled, phase 3 trial if they had symptomatic disease

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… Introduction Despite improvements in survival of newly diagnosed myeloma patients as a consequence of induction therapy with novel agents followed by consolidation with high dose melphalan and autologous stem cell transplant (ASCT), the majority of patients will suffer disease relapse/progression. … While MDS/AML has previously been associated with high-dose melphalan and myeloma therapy, the appearance of B-cell ALL SPMs has been somewhat unexpected. …

Effect of the specific proteasome inhibitor bortezomib on cancer-related muscle wasting.

BACKGROUND: Muscle wasting, a prominent feature of cancer cachexia, is mainly caused by sustained protein hypercatabolism. The enhanced muscle protein degradation rates rely on the activity of different proteolytic systems, although the Adenosine triphosphate (ATP)-ubiquitin-proteasome-dependent pathway and autophagy have been shown to play a pivotal role. Bortezomib is a potent reversible and selective proteasome and NF-κB inhibitor approved for the clinical use, which has been shown to be effective in preventing muscle wasting in different catabolic conditions. The aim of the present study h

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… San Miguel JF, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, Kropff M, et al Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med 2008;359:906–17. 22. … Mateos MV, Richardson PG, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, et al Bortezomib plus melphalan and prednisone compared with melphalan and prednisone in previously untreated multiple myeloma: updated follow‐up and impact of subsequent therapy in the phase III VISTA trial. …

Факторы риска, связанные с карфилзомибными вредными сердечно-сосудистыми явлениями у китайских пациентов с множественной миеломой: ретроспективное когортное исследование в реальном мире.

Хотя связь между карфилзомибами и сердечно-сосудистыми заболеваниями хорошо задокументирована, факторы риска, связанные с карфилзомибами, по-прежнему неясны. Цель этого исследования заключалась в оценке распространенности и выявлении факторов риска для сердечно-сосудистых неблагоприятных явлений, связанных с карфилзомибом у китайских пациентов с множественной миеломой в реальном мире. " Methods " Мы провели ретроспективное когортное исследование сердечно-сосудистых заболеваний у пациентов с множественной миеломой, обработанных карфилзомибом в первом центральном госпитале Тьянцзин в а

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… History of autologous hematopoietic stem cell transplantation (auto-HSCT) (prior auto-HSCT and auto-HSCT-naïve) and prior exposure to anthracyclines, cyclophosphamide/melphalan (CTX/MEL), IMiDs, daratumumab, dexamethasone, and bortezomib/ixazomib; Carfilzomib treatment regimen. … CVAEs: cardiovascular adverse events; BMI: body mass index; CTX/MEL: cyclophosphamide/melphalan; IMiDs: immunomodulatory drugs; SCr: serum creatinine; NT-proBNP: N-terminal pro-B-type natriuretic peptide; OR: odds ratio; CI: confidence interval. …

Morphofunctional parameters as predictors of autologous hematopoietic stem cell transplantation outcomes.

IntroductionThere is a lack of predictive factors for specific complications in patients who undergo autologous hematopoietic stem cell transplantation. A complete morphofunctional assessment is not usually performed before the procedure. Malnutrition is related to lower survival in cancer patients. Our aim is to identify both risk and protective factors for such complications to refine management and improve outcomes.MethodsWe have implemented the program 'RHeNutrir', which involves a systematic malnutrition and sarcopenia screening, as well as a complete nutritional and functional assessment

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… 200 mg/m2 was used as the conditioning regimen, while in the lymphoma cohort, a combination of carmustine 300 mg/m2, etoposide 200 mg/m2, cytarabine 200 mg/m2/12 h and melphalan 140 mg/m2 (BEAM) was used. … Glossary Glossary Arm circumference Autologous hematopoietic stem cell transplantation BCNU (Carmustine)/Etoposide/AraC/Melphalan Bioelectrical Impedance Analysis Body mass index Calf circumference Chronic Obstructive Pulmonary Disease C-reactive protein Cardiovascular risk factor Fat free …

Daratumumab plus bortezomib, lenalidomide and dexamethasone for transplant-ineligible or transplant-deferred newly diagnosed multiple myeloma: the randomized phase 3 CEPHEUS trial.

Frontline daratumumab-based triplet and quadruplet standard-of-care regimens have demonstrated improved survival outcomes in newly diagnosed multiple myeloma (NDMM). For patients with transplant-ineligible NDMM, triplet therapy with either daratumumab plus lenalidomide and dexamethasone (D-Rd) or bortezomib, lenalidomide and dexamethasone (VRd) is the current standard of care. This phase 3 trial evaluated subcutaneous daratumumab plus VRd (D-VRd) in patients with transplant-ineligible NDMM or for whom transplant was not planned as the initial therapy (transplant deferred). Some 395 patients wi

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… In the phase 3 ALCYONE study, adding daratumumab to bortezomib, melphalan and prednisone did not increase overall toxicity versus triplet therapy alone, and the incidence of peripheral neuropathy was lower in the daratumumab group 18 . … Overall survival with daratumumab, bortezomib, melphalan, and prednisone in newly diagnosed multiple myeloma (ALCYONE): a randomised, open-label, phase 3 trial. Lancet 395 , 132–141 (2020). 10. Moreau, P. et al. …

Efficacy and Safety of Ixazomib Plus Lenalidomide and Dexamethasone Following Injectable PI-Based Therapy in Relapsed/Refractory Multiple Myeloma.

This nationwide, multicenter, open-label, single-arm study evaluated the efficacy and safety of the oral proteasome inhibitor (PI), ixazomib plus lenalidomide (LEN) and dexamethasone (DEX) (IRd) following injectable PI-based therapy for relapsed/refractory multiple myeloma (RRMM). Of 45 patients enrolled, 36 patients received IRd after achieving at least a minor response to 3 cycles of bortezomib or carfilzomib plus LEN + DEX (VRd, n=6; KRd, n=30). At median follow-up of 20.8 months, the 12-month event-free survival rate (primary endpoint) was 49% (90% CI: 35.9-62.0), counting 11 events of pro

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… Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med. 2008;359(9):906–917. doi: 10.1056/NEJMoa0801479. 3. … Persistent overall survival benefit and no increased risk of second malignancies with bortezomib-melphalan-prednisone versus melphalan-prednisone in patients with previously untreated multiple myeloma. J Clin Oncol. 2013;31(4):448–455. doi: 10.1200/jco.2012.41.6180. 4. …

A phase 2, open-label, multicenter study of ixazomib plus lenalidomide and dexamethasone in adult Japanese patients with relapsed and/or refractory multiple myeloma.

BackgroundTOURMALINE-MM1 was a global study that demonstrated a significant improvement in progression-free survival with ixazomib plus lenalidomide and dexamethasone compared with placebo plus lenalidomide and dexamethasone, in patients with relapsed and/or refractory multiple myeloma. The current study was conducted to evaluate further the efficacy and safety of ixazomib plus lenalidomide and dexamethasone in Japanese patients.MethodsThis phase 2, open-label, single-arm, multicenter study enrolled patients aged ≥ 20 years with relapsed and/or refractory multiple myeloma at 16 sites in Japan.

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… Facon T Mary JY Hulin C Melphalan and prednisone plus thalidomide versus melphalan and prednisone alone or reduced-intensity autologous stem cell transplantation in elderly patients with multiple myeloma (IFM 99–06): a randomised trial Lancet 2007 370 9594 1209 1218 10.1016/S0140-6736(07)61537-2 17920916 … San Miguel JF Schlag R Khuageva NK Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma N Engl J Med 2008 359 9 906 917 10.1056/NEJMoa0801479 18753647 7. …

Changing paradigm in the treatment of amyloidosis: From disease-modifying drugs to anti-fibril therapy.

Cardiac amyloidosis is a rare, debilitating, and usually fatal disease increasingly recognized in clinical practice despite patients presenting with non-specific symptoms of cardiomyopathy. The current standard of care (SoC) focuses on preventing further amyloid formation and deposition, either with anti-plasma cell dyscrasia (anti-PCD) therapies in light-chain (AL) amyloidosis or stabilizers of transthyretin (TTR) in transthyretin amyloidosis (ATTR). The SoC is supplemented by therapies to treat the complications arising from organ dysfunction; for example, heart failure, arrhythmia, and prot

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… In a small group of patients with AL amyloidosis, median survival was 655 days for those treated with CyBorD ( n = 15) compared with 178 days for those treated with melphalan-dexamethasone ( n = 10) ( 44 ). … Alkylating agents like cyclophosphamide and melphalan can have severe side effects, including hematopoietic, gastrointestinal, hepatic, gonadal, pulmonary, renal, cardiac, and neural toxicity ( 30 ). Treatment with bortezomib can result in peripheral neuropathy ( 49 ). …

Health-related quality of life in the ENDEAVOR study: carfilzomib-dexamethasone vs bortezomib-dexamethasone in relapsed/refractory multiple myeloma.

We examined effects of carfilzomib-dexamethasone (Kd56) versus bortezomib-dexamethasone (Vd) on health-related quality of life (HR-QoL) in relapsed/refractory multiple myeloma (MM) patients from the ENDEAVOR study. HR-QoL was assessed by the European Organisation for Research and Treatment of Cancer QoL Questionnaire (QLQ-C30), MM-specific module (QLQ-MY20), and Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT-GOG-Ntx) "Additional Concerns" neurotoxicity subscale. The QLQ-C30 Global Health Status (GHS)/QoL scale and seven prespecified subscales were compar

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… The phase 3 FIRST trial evaluated the impact of continuous lenalidomide and low-dose dexamethasone compared with melphalan, prednisone, and thalidomide on HR-QoL 31 . … Lenalidomide, melphalan, and prednisone, followed by lenalidomide maintenance, improves health-related quality of life in newly diagnosed multiple myeloma patients aged 65 years or older: results of a randomized phase III trial. …

Assessing Cachexia Acutely after Autologous Stem Cell Transplant.

Autologous hematopoietic stem cell transplantation (AHCT) is an accepted strategy for various hematologic malignancies that can lead to functional impairment, fatigue, muscle wasting, and reduced quality of life (QOL). In cancer cachexia, these symptoms are associated with inflammation, hypermetabolism, and decreased anabolic hormones. The relative significance of these factors soon after AHCT setting is unclear. The purpose of this study was to characterize the acute effects of AHCT on physical function, body composition, QOL, energy expenditure, cytokines, and testosterone. Outcomes were ass

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… For the conditioning regimens, patients with multiple myeloma received 350 (250, 435) mg melphalan and patients with lymphoma received BEAM (carmustine, etoposide, cyratabine, and melphalan) or mini-BEAM regimens: 582.5 (440, 645) mg carmustine, 3080 (1200, 3450) mg cyratabine, 3080 (1200, 3450) mg etoposide … , and 272.5 (200, 290) mg melphalan. …

Clinical developments in the treatment of relapsed or relapsed and refractory multiple myeloma: impact of panobinostat, the first-in-class histone deacetylase inhibitor.

BackgroundPanobinostat is a new agent for the treatment of relapsed and refractory multiple myeloma (rrMM) as part of a combination regimen. This article presents an overview of the mechanism of action, pharmacokinetics, safety, efficacy, patient care strategies, and role of the agent in treating rrMM patients.ResultsPanobinostat belongs to the class of drugs known as histone deacetylase inhibitors, and has high activity against Class I, II, and IV nonhistone deacetylases and histone deacetylases. It represents the first of its class to receive approval for use in MM, and received priority rev

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… promising results for combining this class with anti-CD38 MAbs, such as those targeted by daratumumab (approved by the US FDA in November 2015). 48 Conditioning regimens for autologous stem cell transplant (ASCT) A Phase II trial examining the role of PAN combined with high-dose gemcitabine/busulfan/melphalan … Panobinostat Combined With High-Dose Gemcitabine/Busulfan/Melphalan With Autologous Stem Cell Transplant for Patients With Refractory/Relapsed Myeloma. [Accessed December 11, 2015]. Available from: https://clinicaltrials.gov/ct2/show/NCT02506959?term=nct02506959&rank=1 . 50. …

Role of bone-anabolic agents in the treatment of breast cancer bone metastases.

Skeletal metastases are an incurable complication afflicting the majority of patients who die from advanced breast cancer. They are most often osteolytic, characterized by net bone destruction and suppressed new bone formation. Life expectancy from first diagnosis of breast cancer bone metastases is several years, during which time skeletal-related events - including pain, fracture, hypercalcemia, and spinal cord compression - significantly degrade quality of life. The bone marrow niche can also confer hormonal and chemo-resistance. Most treatments for skeletal metastases target bone-destroyin

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… and prednisone, compared with melphalan + prednisone controls, in bisphosphonate-naïve patients. … The combination of bortezomib, melphalan, dexamethasone and intermittent thalidomide is an effective regimen for relapsed/refractory myeloma and is associated with improvement of abnormal bone metabolism and angiogenesis. Leukemia. 2008;22:2247–2256. doi: 10.1038/leu.2008.235. 26. …

Oral mucositis induced by anticancer treatments: physiopathology and treatments.

Oral mucositis is a frequent and devastating side effect of anticancer treatments. It impairs the patient's quality of life and also can be life threatening because severe infections and delayed or incomplete anticancer treatments may result. This problem has been largely overlooked and underestimated in the past. However, recently studies have been performed to precisely identify the epidemiology, cost, consequences, physiopathology, and treatments of oral mucositis. Clinical guidelines have recently been published to help the daily management of this frequent complication. In addition, some

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… Conditioning regimens including melphalan are associated with high rates of oral mucositis ( Wardley et al 2000 ). In this setting, mucositis has been reported by patients as the most distressing side effect they had to cope with ( Bellm et al 2000 ). … The study by Spencer and colleagues (2005) also suggested that amifostine reduced the median grade of oral mucositis and the severity of mucositis, but not the requirement of parenteral nutrition or analgesic use after high-dose melphalan and HSCT for multiple myeloma. …

Targeted immunotherapy: harnessing the immune system to battle multiple myeloma.

Multiple myeloma (MM) remains an incurable hematological malignancy disease characterized by the progressive dysfunction of the patient's immune system. In this context, immunotherapy for MM has emerged as a prominent area of research in recent years. Various targeted immunotherapy strategies, such as monoclonal antibodies, antibody-drug conjugates, bispecific antibodies, chimeric antigen receptor T cells/natural killer (NK) cells, and checkpoint inhibitors have been developed for MM. This review aims to discuss promising experimental and clinical evidence as well as the mechanisms of action u

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… Anti-CD19 CAR T cells with high-dose melphalan and autologous stem cell transplantation for refractory multiple myeloma. JCI Insight. 2018;3:e120505. doi: 10.1172/jci.insight.120505. 21. Yan L, Qu S, Shang J, Shi X, Kang L, Xu N, et al. … Daratumumab plus bortezomib, melphalan, and prednisone for untreated myeloma. N. Engl J Med. 2018;378:518–28. doi: 10.1056/NEJMoa1714678. 69. Facon T, Kumar SK, Plesner T, Orlowski RZ, Moreau P, Bahlis N, et al. …

Position Statement on Diagnosis and Treatment of Cardiac Amyloidosis - 2021.

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Investigating the Interplay between Myeloma Cells and Bone Marrow Stromal Cells in the Development of Drug Resistance: Dissecting the Role of Epigenetic Modifications.

Multiple Myeloma (MM) is a malignancy of plasma cells infiltrating the bone marrow (BM). Many studies have demonstrated the crucial involvement of bone marrow stromal cells in MM progression and drug resistance. Together with the BM microenvironment (BMME), epigenetics also plays a crucial role in MM development. A variety of epigenetic regulators, including histone acetyltransferases (HATs), histone methyltransferases (HMTs) and lysine demethylases (KDMs), are altered in MM, contributing to the disease progression and prognosis. In addition to histone modifications, DNA methylation also plays

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… Myeloma cells with a high MMSET expression are able to repair chemotherapy-induced DNA damage faster, and MMSET silencing was shown to increase melphalan sensitivity in vivo [ 67 ]. … A phase 1/2 study of oral panobinostat combined with melphalan for patients with relapsed or refractory multiple myeloma. Ann. Hematol. 2014;93:89–98. doi: 10.1007/s00277-013-1910-2. 141. …

An overview of multiple myeloma: A monoclonal plasma cell malignancy's diagnosis, management, and treatment modalities.

Multiple Myeloma (MM) is a plasma cell cancer with high mortality and morbidity rates. Its incidence rate has increased by 143% since 1975. Adipokines, cytokines, chemokines, and genetic variations influence the development and progression of MM. Chromosomal translocations cause mutations associated with MM. The pathogenesis of MM is complicated by novel issues like miRNAs, RANKL, Wnt/DKK1, Wnt, and OPG. Conventional diagnosis methods include bone marrow biopsy, sPEP or uPEP, sIFE and uIFE, and sFLC assay, along with advanced techniques such as FISH, SNPA, and gene expression technologies. A n

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… Research is being done on Melphalan fulafenamide melflufen, a peptide pharmaceutical molecule, as a potential novel treatment for triple-refractory MM. … Melphalan flufenamide was considered a potential treatment for triple-class refractory MM in the HORIZON and O-12-M1 studies. …