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In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 2004-2004

Abstract: Background: Hematogenous extramedullary multiple myeloma (HEMM), though rare, is mainly observed in MM patients at relapse. The current study assesses the characteristics and outcomes of patients with MM who develop HEMM in the novel agent era. Methods: Consecutive patients, treated in 16 participating centers and diagnosed with HEMM, were included. Patient characteristics at diagnosis and at HEMM presentation, treatment regimens, response to therapy, response duration and survival were recorded. Factors predicting time to HEMM and survival from HEMM diagnosis were analyzed. Results: 127 patients were included. Median age at MM diagnosis was 63 years (31-94). 50% of patients had IgG MM, 26% had IgA, 23% had light chain, and 1% had other MM types. 44% had ISS 3 and 57% presented with plasmacytomas. 30% presented with high-risk cytogenetics: 19% with t(4;14),11% had 17p deletion. CD56 was expressed in 72% of cases and CD20 in 16%. 55% of the patients were treated for MM with PI, 55% with IMIDs, 62% with chemotherapy and 59% underwent autologous stem cell transplantation (ASCT) prior to HEMM. The median time to the development of HEMM was 2.8 years (95% CI 2.2-3.6). B2M levels (HR 1.04, 95% CI 1.00-1.07, p=0.03), del17p (HR 3.3, 95% CI 1.6-7.1, p=0.002) and plasmacytomas at MM diagnosis (HR 1.6, 95% CI 1.1-2.4, p=0.01) were associated with a shorter duration from diagnosis to HEMM, while upfront ASCT was associated with a longer period to the development of HEMM disease (HR 0.6, 95% CI 0.4-0.9, p=0.01). 47 patients (38%) patients had no concomitant plasmacytomas at HEMM diagnosis. 33% of patients had ≥2 HEMM sites, in 53% HEMM lesion was ≥5 cm, 20% had non-secretory disease at HEMM, and 59% had an increased LDH. 61% received at least 2 lines for MM prior to HEMM. First treatment for HEMM included PIs in 50%, IMIDs in 39%, MoAbs in 10% and chemotherapy in 53%. Overall response rate (ORR) was 49% and 51% failed to respond to first treatment for HEMM. IMIDs were associated with higher odds for ORR (OR 2.2, 95% CI 1.02-4.7, p=0.04). Median survival from MM diagnosis and from HEMM diagnosis were 4.3 (CI 95% 3-5.5) and 0.5 (CI 95% 0.4-0.6) years, respectively. 5-year OS from HEMM diagnosis was 6% (1-15%)(Figure 1A). Increased LDH level at the time HEMM (HR=2.2, 95% CI 1.3-3.8, p=0.002, Figure 1B), FISH positive for t(4;14) (HR=2.3, 95% CI 1.2-4.2, p=0.01)(Figure 1C), t(14;16) (HR=5.6, 95% CI 1.3-25, p=0.02)(Figure 1D), as well as ≤3 years between MM diagnosis and HEMM (HR=1.6, 95% CI 1.04-2.4, p=0.03(Figure 1E)), were found to be associated with a significantly shorter survival from HEMM diagnosis. The achievement of CR or VGPR to treatment administered for HEMM therapy were both associated with improved OS (HR=0.2, 95% CI 0.1-0.3, p 〈 0.001 and HR=0.5, 95% CI 0.3-0.9, p=0.02, respectively) (Figure 1F). No specific treatment was found to be associated with improved survival in patients that develop HEMM. Conclusion: In MM patients who develop HEMM, the median time from MM to HEMM diagnosis is 2.8 years. Despite the improvement in MM therapy over the last decades, patients with HEMM diagnosis have a dismal outcome. OS is significantly shorter in patients with high-risk cytogenetic abnormalities, increased LDH and time to HEMM 〈 3 years. Further studies assessing best therapy in patients experiencing this complication are warranted. Figure 1. Figure 1. Disclosures Cohen: Neopharm Israel: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Medisson Israel: Consultancy, Honoraria, Research Funding. Garderet:Takeda: Consultancy; Celgene: Consultancy; Amgen: Consultancy. Niesvizky:Amgen Inc.: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Takeda: Consultancy, Research Funding. Castillo:Pharmacyclics: Consultancy, Research Funding; Beigene: Consultancy, Research Funding; Millennium: Research Funding; Genentech: Consultancy; Janssen: Consultancy, Research Funding; Abbvie: Consultancy, Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2018-99-112750

Language: English

Publisher: American Society of Hematology

Publication Date: 2018

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Clinical Lymphoma Myeloma and Leukemia, Elsevier BV, Vol. 22, No. 5 ( 2022-05), p. 297-304

Type of Medium: Online Resource

ISSN: 2152-2650

URL: Article

DOI: 10.1016/j.clml.2021.10.007

Language: English

Publisher: Elsevier BV

Publication Date: 2022

detail.hit.zdb_id: 2540998-0

detail.hit.zdb_id: 2193618-3

In: BMC Cardiovascular Disorders, Springer Science and Business Media LLC, Vol. 21, No. 1 ( 2021-12)

Abstract: The accurate and independent measurement of blood pressure (BP) by patients is essential for home BP monitoring (HBPM) and determining the quality of hypertension (HTN) control. This study aimed to evaluate the BP self-measurement techniques of hypertensive patients and their accuracy in accordance with established guidelines. We sought to identify the common errors that patients make and suggest improvements that can be implemented in the primary healthcare setting to increase the reliability of HBPM conducted by hypertensive patients. Methods One hundred patients diagnosed with HTN completed a questionnaire inquiring about their health and demographic data and BP monitoring practices. Patients were then observed and filmed while measuring their BP on their own devices in five primary healthcare centres in Kraków, Poland. The correctness of their techniques was assessed in accordance with the European Society of Hypertension guidelines on HBPM. Results Only 3% of patients measured their BP without error; 60% made three or more errors. The most frequent error, made by 76% of subjects, was incorrect sphygmomanometer cuff placement (above or below heart level, or/and the indicator mark was not aligned with the brachial artery). Regarding patients’ previous instruction for the correct use of their devices, 36% of patients referred to their monitor’s user manual, 22% did not receive any prior assistance, and only 29% were adequately counselled by physicians on how to measure their BP correctly. Conclusions Our findings suggest that primary healthcare physicians and their personnel often do not adequately instruct patients on how to measure their BP correctly. Therefore, healthcare systems must provide patients with more adequate training and reference materials on the best practices of BP monitoring.

Type of Medium: Online Resource

ISSN: 1471-2261

URL: Article

DOI: 10.1186/s12872-021-02351-5

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2021

detail.hit.zdb_id: 2059859-2

In: American Journal of Hematology, Wiley, Vol. 94, No. 10 ( 2019-10), p. 1132-1140

Abstract: The current study assesses the characteristics and outcomes of multiple myeloma (MM) patients, treated with novel agents for hematogenous extramedullary (HEMM) relapse. Consecutive patients diagnosed with HEMM between 2010‐2018 were included. Patients' characteristics at diagnosis and at HEMM presentation, response to treatment, survival and factors predicting survival were recorded and analyzed. A group of 127 patients, all diagnosed with HEMM by imaging (87.3%) and/or biopsy (79%), were included. Of those, 44% were initially diagnosed with ISS3, 57% presented with plasmacytomas, and 30% had high‐risk cytogenetics. Median time to HEMM was 32 months. In multivariate analysis, ISS3 and bone plasmacytoma predicted shorter time to HEMM ( P = .005 and P = .008, respectively). Upfront autograft was associated with longer time to HEMM ( P = .002). At HEMM, 32% of patients had no BM plasmacytosis, 20% had non‐secretory disease and 43% had light‐chain disease. Multiple HEMM sites were reported in 52% of patients, mostly involving soft tissue, skin (29%), and pleura/lung (25%). First treatment for HEMM included proteasome inhibitors (50%), immunomodulatory drugs (IMiDs) (39%), monoclonal antibodies (10%), and chemotherapy (53%). Overall response rate (ORR) was 57%. IMiDs were associated with higher ORR (HR 2.2, 95% CI 1.02‐4.7, P = .04). Median survival from HEMM was 6 months (CI 95% 4.8‐7.2). Failure to achieve ≥VGPR was the only significant factor for worse OS in multivariate analyses (HR = 9.87, CI 95% 2.35 ‐ 39, P = .001). In conclusion, HEMM occurs within 3 years of initial myeloma diagnosis and is associated with dismal outcome. The IMiDs might provide a higher response rate, and achievement of ≥VGPR predicts longer survival.

Type of Medium: Online Resource

ISSN: 0361-8609 , 1096-8652

URL: Issue

URL: Article

DOI: 10.1002/ajh.v94.10

DOI: 10.1002/ajh.25579

Language: English

Publisher: Wiley

Publication Date: 2019

detail.hit.zdb_id: 1492749-4

In: Acta Haematologica Polonica, VM Media Group sp. z o.o, Vol. 51, No. 4 ( 2020-12-01), p. 193-202

Abstract: Monoclonal gammopathy of undetermined significance (MGUS) is a clonal plasma cell disorder implicated as a precursor of multiple myeloma (MM), while smoldering multiple myeloma (SMM) is a malignant plasma cell disorder without evidence of a myeloma-defining event(s) (MDE). This is a review article of both disorders outlining their current definition and management according to the current standard of care. We focus on the pathogenesis of MM and the role of MGUS and SMM in the development of active MM. MGUS is a benign disorder and, subsequently, is followed by observation. In contrast, for SMM, although the current standard of care is “watch and wait”, this paper will explore the circumstances in which treatment should be considered to prevent MDE.

Type of Medium: Online Resource

ISSN: 2300-7117

URL: Article

DOI: 10.2478/ahp-2020-0035

Language: Unknown

Publisher: VM Media Group sp. z o.o

Publication Date: 2020

detail.hit.zdb_id: 2704533-X

In: Journal of Clinical Medicine, MDPI AG, Vol. 10, No. 15 ( 2021-07-23), p. 3255-

Abstract: Background: The COVID-19 pandemic has, by necessity, contributed to rapid advancements in medicine. Owing to the necessity of following strict anti-epidemic sanitary measures when taking care of infected patients, the accessibility of standard diagnostic methods may be limited. Consequently, the significance and potential of bedside diagnostic modalities increase, including lung ultrasound (LUS). Method: Multicenter registry study involving adult patients with confirmed COVID-19, for whom LUS was performed. Results: A total of 228 patients (61% males) qualified for the study. The average age was 60 years (±14), 40% were older than 65 years of age. In 130 from 173 hospitalized patients, HRCT (high-resolution computed tomography) was performed. In 80% of patients, LUS findings indicated interstitial pneumonia. In hospitalized patients multifocally located single B-lines, symmetrical B-lines, and areas of white lung were significantly more frequent as compared to ambulatory patients. LUS findings, both those indicating interstitial syndrome and consolidations, were positively correlated with HRCT images. As compared to HRCT, the sensitivity and specificity of LUS in detecting interstitial pneumonia were 97% and 100%, respectively. Conclusions: As compared to HRCT, LUS is characterized by a very high sensitivity and specificity in detecting interstitial pneumonia in COVID-19 patients. Potentially, LUS can be a particularly useful diagnostic modality for COVID-19 patients pneumonia.

Type of Medium: Online Resource

ISSN: 2077-0383

URL: Article

DOI: 10.3390/jcm10153255

Language: English

Publisher: MDPI AG

Publication Date: 2021

detail.hit.zdb_id: 2662592-1

In: American Journal of Hematology, Wiley, Vol. 95, No. 5 ( 2020-05), p. 503-509

Abstract: The t(14;16) translocation, found in 3%‐5% of newly diagnosed (ND) multiple myeloma (MM), has been associated with adverse outcomes. However, the studies establishing the characteristics of t(14;16) included solely small cohorts. The goal of the current international, multicenter (n = 25 centers), retrospective study was to describe the characteristics and outcomes of t(14;16) patients in a large, real‐world cohort (n = 223). A substantial fraction of patients had renal impairment (24%) and hemoglobin 〈 10 g/dL (56%) on initial presentation. Combined therapy of both immunomodulatory drug and proteasome inhibitor (PI) in the first line was used in 35% of patients. Autologous stem cell transplantation was performed in 42% of patients. With a median follow up of 4.1 years (95% CI 3.7‐18.7), the median progression‐free survival (PFS) and overall survival (OS) from first line therapy were 2.1 years (95% CI 1.5‐2.4) and 4.1 years (95% CI 3.3‐5.5), respectively. Worse OS was predicted by age  〉  60 years (HR = 1.65, 95% CI [1.05‐2.58]), as well as revised International Scoring System (R‐ISS) 3 (vs R‐ISS 2; HR = 2.59, 95% CI [1.59‐4.24] ). In conclusion, based on the largest reported cohort of t(14;16) patients, quarter of this subset of MM patients initially presents with renal failure, while older age and the R‐ISS 3 predict poor survival.

Type of Medium: Online Resource

ISSN: 0361-8609 , 1096-8652

URL: Issue

URL: Article

DOI: 10.1002/ajh.v95.5

DOI: 10.1002/ajh.25758

Language: English

Publisher: Wiley

Publication Date: 2020

detail.hit.zdb_id: 1492749-4

In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 4452-4452

Abstract: Introduction One of the strongest predictors of outcome in multiple myeloma (MM) patients are the intrinsic genetic abnormalities in the malignant plasma cells. t(14;16)(q32;q23) deregulates the c-musculoaponeurotic fibrosarcoma (c-MAF) oncogene. Due to the relative rarity of t(14;16) [ 〈 5% of newly diagnosed MM], there are no large databases which provide the natural history of this abnormality (the largest reported by Palumbo et al, R-ISS for MM: An IMWG Report included 84 patients). Methods We retrospectively analyzed 213 patients with t(14;16) from 24 clinical centers in Germany, Italy, Spain, Israel, Poland, Romania, Czech Republic and the United States. Diagnosis and clinical responses were based on the International Myeloma Working Group criteria. The t(14;16) was detected by double color fluorescence in situ hybridization using bone marrow samples. Baseline characteristics at diagnosis, patient treatment and clinical outcomes were collected using unified forms. Overall survival (OS) was defined as the period between the date of diagnosis and the date of death or last observation. Progression-free survival (PFS) was defined as the period between the date of diagnosis and either the date of the first relapse, of the last observation or death of any causes. Cox proportional hazard regression analysis was applied to assess risk factors of death. Survival curves were plotted by the Kaplan-Meier method and compared using log-rank and Breslow-Gehan-Wilcoxon tests. Results We analyzed a total of 213 patients, mean age 62.1 years (range 32 to 90), including 91 (42.7%) males. Immunoglobulin isotype included IgG (n=98, 46.0%), IgA (n=60, 28.2%) and IgM (n=1, 0.5%), light chain only in 47 cases (22.1%). ISS stage at diagnosis included: stage III (n=78, 36.6%), stage II (n=81, 38.0%) and stage I (n=47, 22.1%); for R-ISS: stage III (n=79, 37.1%), stage II (n=71, 33.3%), stage I (n=10, 4.7%). For stage is unknown for the remaining patients. Hypercalcemia was present in 38 cases (17.8%), anemia ( 〈 10g/dl) in 109 (51.2%) and impaired renal function (creatinine clearance 〈 40 mL per minute or serum creatinine 〉 2 mg/dl) in 54 (25.4%) patients. In 104 (48.8%) cases osteolytic lesions were present. The t(14;16) was associated with other aberrations in 134 (62.9%), in 35 (16.4%) patients with del17p. First line treatment for MM with t(14;16) included PIs + chemotherapy in 72 patients (36%), PIs + IMIDs in 39 patients (20%) or chemotherapy + PIs + IMIDs in 25 patients (13%). Overall response rate was 67%. Median PFS was 31 months (CI 95% 28-40.3 months; Figure 1, panel A). Median OS was 88 months (CI 95% 49-177 months; Figure 1, panel B). 5-year OS from MM diagnosis was 55% (46-63%), whereas 10-year OS reached 44% (31-56%). Median OS for stage I was not reached, for stage II was 62 months (95%CI 38-177 months) and for stage III was 32 months (95% CI 18-88 months). Patients in ISS stage I had better OS than stage III patients (p 〈 0.001; Figure 2, panel A). A total of 74 (34.7%) patients died. The causes of death included mostly disease progression in 28 cases (37.8%; 16 patients received ≥4 treatment lines) and infection in patients with progression in 21 cases (28.4%). Patients treated with combined therapy of IMIDs, PIs ± chemotherapy had better survival than patients treated with IMIDs or PIs alone or chemotherapy alone (p=0.044; Figure 3, panel A). Patients after auto-PBSCT (median OS not reached, n=62, 29.1%), especially tandem auto-PBSCT (median OS not reached, n=18, 8.5%) performed better OS than patients without transplant (median OS: 42.1 months [95%CI 27- 62 months], p 〈 0.0001, Figure 3, panel B). Patients with additional del17p exhibited worse OS than patient with single t(14;16) mutation (median OS 42 vs 107 months, p=0.043; Figure 2, panel B). Conclusion This is the largest report of myeloma patients with t(14;16). Patients with t(14;16) and del17p had a worse prognosis than patients with t(14;16) alone. The use of auto-PBSCT, especially in the subgroup who received planned tandem auto-PBSCT, is associated with better survival. Combined therapy with PIs and IMIDs improved the overall survival in t(14;16) patients, which may suggests, that this high-risk prognostic feature might be partially overcome by the use of new-drug therapies. This study of 213 patients indicates that t(14;16) is not as severe adverse factor as compared to the original IMWG R-ISS analysis (n= 84), which suggests that the revised ISS may require updating. Disclosures Castillo: Genentech: Consultancy; Abbvie: Consultancy, Research Funding; Millennium: Research Funding; Pharmacyclics: Consultancy, Research Funding; Beigene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. Niesvizky:Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Amgen Inc.: Consultancy, Research Funding. Rosinol Dachs:Janssen: Honoraria; Celgene: Honoraria; Amgen: Honoraria. Cohen:Janssen: Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Neopharm Israel: Consultancy, Honoraria; Medisson Israel: Consultancy, Honoraria, Research Funding. Hari:Spectrum: Consultancy, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Kite Pharma: Consultancy, Honoraria; Sanofi: Honoraria, Research Funding; Janssen: Honoraria; Amgen Inc.: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Takeda: Consultancy, Honoraria, Research Funding. Goldberg:COTA Inc.: Employment, Equity Ownership.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2018-99-115971

Language: English

Publisher: American Society of Hematology

Publication Date: 2018

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood Cancer Journal, Springer Science and Business Media LLC, Vol. 11, No. 4 ( 2021-04-14)

Abstract: Telomeres are involved in processes like cellular growth, chromosomal stability, and proper segregation to daughter cells. Telomere length measured in leukocytes (LTL) has been investigated in different cancer types, including multiple myeloma (MM). However, LTL measurement is prone to heterogeneity due to sample handling and study design (retrospective vs. prospective). LTL is genetically determined; genome-wide association studies identified 11 SNPs that, combined in a score, can be used as a genetic instrument to measure LTL and evaluate its association with MM risk. This approach has been already successfully attempted in various cancer types but never in MM. We tested the “teloscore” in 2407 MM patients and 1741 controls from the International Multiple Myeloma rESEarch (IMMeNSE) consortium. We observed an increased risk for longer genetically determined telomere length (gdTL) (OR = 1.69; 95% CI 1.36–2.11; P  = 2.97 × 10 −6 for highest vs. lowest quintile of the score). Furthermore, in a subset of 1376 MM patients we tested the relationship between the teloscore and MM patients survival, observing a better prognosis for longer gdTL compared with shorter gdTL (HR = 0.93; 95% CI 0.86–0.99; P  = 0.049). In conclusion, we report convincing evidence that longer gdTL is a risk marker for MM risk, and that it is potentially involved in increasing MM survival.

Type of Medium: Online Resource

ISSN: 2044-5385

URL: Article

DOI: 10.1038/s41408-021-00462-y

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2021

detail.hit.zdb_id: 2600560-8

In: BMC Primary Care, Springer Science and Business Media LLC, Vol. 24, No. 1 ( 2023-01-03)

Abstract: Home blood pressure monitoring (HBPM) is an increasingly important tool in managing hypertension (HTN); however, its efficacy depends on its accuracy. This study aimed to explore the differences between blood pressure (BP) measurements conducted by patients and medical professionals and the patient demographic factors correlating with inaccurate self-measured BP levels. Methods One hundred hypertensive patients completed a questionnaire inquiring about their health status and HBPM procedures and were filmed while measuring their BP using their own devices. A researcher then measured the patients' BP using a calibrated sphygmomanometer to assess the accuracy of patient-performed readings. This cross-sectional study was conducted in five primary healthcare centers in Kraków, Poland. Results The mean differences in systolic and diastolic BP readings by patients and researchers were 8.36 mmHg (SD = 10.90 mmHg) and 2.16 mmHg (SD = 9.12 mmHg), respectively. Inaccuracies in patient BP measurements were associated with a less than high school education level, patients’ age, and a family history of HTN. Conclusion Patient self-measured BP levels were higher than researcher values, likely due to a higher patient error rate. Healthcare providers must increase training regarding correct HBPM techniques offered to patients; such efforts should be directed at all hypertensive patients, emphasizing the most error-prone demographics.

Type of Medium: Online Resource

ISSN: 2731-4553

URL: Article

DOI: 10.1186/s12875-022-01962-x

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2023

detail.hit.zdb_id: 3107315-3