Development, Prediction, and Treatment of Anemia in Patients (pts) with Lymphoma/Multiple Myeloma (L/M): Findings of Two European Surveys (ECAS and BEPOS).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3133-3133
Author(s):  
Heinz Ludwig ◽  
Simon Van Belle ◽  
Pere Gascón

Abstract Quality of life (QOL) in cancer pts is adversely affected by several factors, including disease- or treatment-related anemia. Between January 2001 and February 2002, the European Cancer Anaemia Survey (ECAS) was conducted to provide information on pervasiveness of cancer-related anemia, impact of anemia on WHO performance status, risk factors for its development, and anemia treatment practices in Europe. Briefly, a total of 15,370 pts were enrolled, of whom 2,360 had L/M. Data analysis showed 53% of L/M pts were anemic (hemoglobin [Hb] <12 g/dL) at enrollment and 73% were anemic at some time during the survey. Low Hb levels correlated significantly with WHO performance scores of 3 or 4 (P <0.001, R =.352). The ECAS data were additionally analyzed to determine patient and disease characteristics that predicted anemia development and to construct a model for identifying pts at risk. Using logistic regression on the L/M incidence group (pts who were not anemic and not being treated for cancer at enrollment, started chemotherapy [CT] during ECAS, and had at least 2 CT cycles during the survey), 4 variables were found to significantly predict anemia development. Initial Hb, persistent/recurrent disease, female gender, and intent to treat or treatment with platinum-based CT were found to independently predict anemia (P <0.001), with an area under the ROC curve of 0.821 (95% CI; 0.763–0.878), indicating acceptable predictive accuracy of the model. Three levels of risk (low [24%], moderate [51%], and high [72%]) for developing anemia were calculated from the model (χ2(2) = 112.6, P <0.001). Mean time required for anemia development was 9.0 wks to reach Hb of <12 g/dL, 11.1 wks to reach Hb of <11 g/dL, and 13.3 wks to reach Hb of <10 g/dL. Notably, only 46% of anemic L/M pts received anemia treatment. Subsequently, a recent (2003) survey, the Belgian Erythropoietin Survey (BEPOS), extended the information gained through ECAS by examining use of recombinant human erythropoietin (rHuEPO) in pts receiving CT. Specifically, BEPOS documented when rHuEPO treatment was started, dosing schedules and dosage adjustments, length of treatment, impact of iron supplementation on rHuEPO treatment, and outcomes. Patients enrolled had either solid tumors (non-small-cell lung cancer, breast cancer) or hematologic malignancies (multiple myeloma [MM], Hodgkin’s disease [HD], non-Hodgkin’s lymphoma [NHL]). Interim results suggest that 72% of BEPOS pts began rHuEPO during the first 2 CT cycles, with an overall median Hb value of 10.1 g/dL at treatment initiation. For hematologic malignancy pts, the median Hb at treatment initiation was ~10 g/dL for HD; in NHL and MM, the median Hb was >9 to <10 g/dL. Mean time for all pts to achieve a 2-g/dL increase in Hb in the absence of transfusion was 6.4 wks; mean time for NHL pts (6.3 wks) was similar, while mean time for MM pts (9.1 wks) was longer, more in line with that seen in clinical trials. Achievement of the 2-g/dL increase in Hb after 6.4 wks determined in BEPOS is consistent with increases of ~1 g/dL after 4 wks and ~2 g/dL after 8 wks noted in studies of epoetin alfa (Demetri 1998, Gabrilove 2001, Littlewood 2001). Using the large ECAS database, an anemia risk model has been established that should help identify pts at risk for anemia, so that administration of rHuEPO can be initiated expeditiously, before Hb declines to considerably lower levels and/or anemia symptoms, including impaired QOL, develop.

Author(s):  
Yan-Hua Zheng ◽  
Hong-Yuan Shen ◽  
Xiang Chen ◽  
Juan Feng ◽  
Guang-Xun Gao

IntroductionAutophagy functions as a prosurvival mechanism in multiple myeloma (MM).The objective of this research was to establish an autophagy-related gene (ARG) signature for predicting the survival outcomes of MM patients with TP53 mutations.Material and methodsInformation about MM patients with TP53 mutations was downloaded from Gene Expression Omnibus (GEO) database. Cox proportional hazard regression was employed to determine the independent prognostic ARG and construct a risk signature. Time-dependent receiver-operating characteristic (t ROC) curve was used to explore the predictive accuracy of the prognostic model. A nomogram was constructed to give a more precise prediction of the probability of 5-year, 8-year and 10-year overall survival (OS). In addition, we utilized the CIBERSORT algorithm to explore the distribution difference of 22 immune-infiltrating cells.ResultsThree differentially expressed ARGs (CASP8, MAPK8, RB1CC1) were finally incorporated to construct the risk model. Area under the curve (AUC) of corresponding tROC curve for 5-year,8-year and 10-year OS were 0.735, 0.686 and 0.662, respectively. MM patients were categorized into high and low-risk group in accordance with the median threshold value (-1.724549). ARG-based risk score model was an independent prognostic element correlated with OS, giving an hazard ratio (HR) of 3.29 (95%CI 2.35-4.60, P<0.001). 13 immune infiltrating cells were found to have distribution differences between the two groups.ConclusionsWe established a three-ARGs risk signature which manifested an independent prognostic factor. The nomogram was testified to perform well in forecasting the long-term survival of TP53-mutated MM patients.


2017 ◽  
Vol 22 (01) ◽  
pp. 033-037 ◽  
Author(s):  
Suphi Bulğurcu ◽  
Behçet Şahin ◽  
Gökhan Akgül ◽  
İlker Arslan ◽  
İbrahim Çukurova

Introduction Sudden hearing loss is one of the otologic emergencies. The treatment of this disease is affected negatively by some prognostic factors. Objective In this study, the effects of early treatment initiation in patients with idiopathic sudden hearing loss and of prognostic factors in early treated patients were investigated. Methods Out of the 216 patients admitted between September 2007 and September 2015, 154 were identified as having idiopathic sudden hearing loss; they were followed-up for a mean time of 7.4 months, and evaluated retrospectively. The effects of several parameters on the success of the treatment were statistically evaluated, such as the time the treatment was initiated, being of the female gender, the severity of the hearing loss, having descending type audiogram patterns, being older than 60 years old, and the co-presence of vertigo. Results Success rates were found to be significantly higher in idiopathic hearing loss patients that were admitted within the first week (p < 0.05) of the onset of the hearing loss. However, the outcomes were found to be similar when patients admitted within the first 3 days and 4–7 days after the occurrence of the hearing loss were compared (p > 0.05). Parameters such as female gender, severe hearing loss, descending type audiogram, being older than 60 years old, and co-presence of vertigo didn't reveal statistically significant effects on the outcome (p >0.05). Conclusion The aforementioned prognostic factors, which are well-known in the literature, did not have significant effects when the idiopathic sudden hearing loss treatment was initiated within the first 7 days of the onset of the hearing loss.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e20544-e20544
Author(s):  
Joshua Ryan Richter ◽  
Jason Yeaw ◽  
Drishti Shah ◽  
Ruthwik Anupindi ◽  
Suneel Kudaravalli ◽  
...  

e20544 Background: Multiple Myeloma (MM) is a hematologic malignancy with an estimated 5-year survival rate of just over 50%. Evolving paradigms arising from numerous FDA approvals continue to shape the treatment landscape for relapsed and refractory MM (RRMM) patients. As the number of approved drugs/regimens increases, the efficacy as well as toxicity profiles for the more heavily refractory patient change. The objective of this study was to evaluate adverse event rates and associated outcome patterns among RRMM patients treated with pomalidomide (poma) or daratumumab (dara). Methods: Adult patients with ≥1 claim of poma or dara (index) were identified between Jan 1, 2012 and Feb 28, 2018 using IQVIA’s Real-World Adjudicated US claims database. Patients were required to be continuously enrolled in the health plan ≥180 days prior and ≥360 days post index date, have a diagnosis or treatment claim for MM and a claim of any immunomodulatory drugs and proteasome inhibitors before index date. Mean time to new therapy and mean time to readmission were evaluated over the 1-year post-index period among RRMM patients. Overall survival (OS) was measured using Kaplan-Meier curves. Occurrences of adverse events (AEs) and mean length of stay for AE-related hospitalization were also reported. Results: There were 289 patients in the RRMM cohort with 67.8% of patients treated with combination therapy in the baseline period. Of index therapies, 81% of patients used poma and 40% used dara in post-index period. Overall, 42% of patients had a Charlson Comorbidity Score of ≥3. Among 258 patients with a new treatment post-index, mean (SD) time to a new treatment was 4.7(5.3) months. Median OS was 14.6 months. Post-index hematological AE were frequent such as anemia (72.0%), febrile neutropenia (52.6%), neutropenia (30.1%) and thrombocytopenia (36.0%, Table). Mean length of stay for AE-related hospitalizations was 10.1 days and mean time to readmission was 63.3 days. Conclusions: Low OS, high frequency of AEs and longer LOS for AE-related hospitalizations suggest that outcomes of these patients remain poor despite availability of newer treatment options. Further study is warranted to better manage the individual and system-wide toxicity in this clinical setting. [Table: see text]


2020 ◽  
Vol 27 (2) ◽  
pp. 187-215 ◽  
Author(s):  
Lavinia Raimondi ◽  
Angela De Luca ◽  
Gianluca Giavaresi ◽  
Agnese Barone ◽  
Pierosandro Tagliaferri ◽  
...  

: Chemoprevention is based on the use of non-toxic, pharmacologically active agents to prevent tumor progression. In this regard, natural dietary agents have been described by the most recent literature as promising tools for controlling onset and progression of malignancies. Extensive research has been so far performed to shed light on the effects of natural products on tumor growth and survival, disclosing the most relevant signal transduction pathways targeted by such compounds. Overall, anti-inflammatory, anti-oxidant and cytotoxic effects of dietary agents on tumor cells are supported either by results from epidemiological or animal studies and even by clinical trials. : Multiple myeloma is a hematologic malignancy characterized by abnormal proliferation of bone marrow plasma cells and subsequent hypercalcemia, renal dysfunction, anemia, or bone disease, which remains incurable despite novel emerging therapeutic strategies. Notably, increasing evidence supports the capability of dietary natural compounds to antagonize multiple myeloma growth in preclinical models of the disease, underscoring their potential as candidate anti-cancer agents. : In this review, we aim at summarizing findings on the anti-tumor activity of dietary natural products, focusing on their molecular mechanisms, which include inhibition of oncogenic signal transduction pathways and/or epigenetic modulating effects, along with their potential clinical applications against multiple myeloma and its related bone disease.


Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 375
Author(s):  
Manish Kohli ◽  
Winston Tan ◽  
Bérengère Vire ◽  
Pierre Liaud ◽  
Mélina Blairvacq ◽  
...  

Precise management of kidney cancer requires the identification of prognostic factors. hPG80 (circulating progastrin) is a tumor promoting peptide present in the blood of patients with various cancers, including renal cell carcinoma (RCC). In this study, we evaluated the prognostic value of plasma hPG80 in 143 prospectively collected patients with metastatic RCC (mRCC). The prognostic impact of hPG80 levels on overall survival (OS) in mRCC patients after controlling for hPG80 levels in non-cancer age matched controls was determined and compared to the International Metastatic Database Consortium (IMDC) risk model (good, intermediate, poor). ROC curves were used to evaluate the diagnostic accuracy of hPG80 using the area under the curve (AUC). Our results showed that plasma hPG80 was detected in 94% of mRCC patients. hPG80 levels displayed high predictive accuracy with an AUC of 0.93 and 0.84 when compared to 18–25 year old controls and 50–80 year old controls, respectively. mRCC patients with high hPG80 levels (>4.5 pM) had significantly lower OS compared to patients with low hPG80 levels (<4.5 pM) (12 versus 31.2 months, respectively; p = 0.0031). Adding hPG80 levels (score of 1 for patients having hPG80 levels > 4.5 pM) to the six variables of the IMDC risk model showed a greater and significant difference in OS between the newly defined good-, intermediate- and poor-risk groups (p = 0.0003 compared to p = 0.0076). Finally, when patients with IMDC intermediate-risk group were further divided into two groups based on hPG80 levels within these subgroups, increased OS were observed in patients with low hPG80 levels (<4.5 pM). In conclusion, our data suggest that hPG80 could be used for prognosticating survival in mRCC alone or integrated to the IMDC score (by adding a variable to the IMDC score or by substratifying the IMDC risk groups), be a prognostic biomarker in mRCC patients.


2021 ◽  
Vol 28 (1) ◽  
pp. 640-660
Author(s):  
Grace Lassiter ◽  
Cole Bergeron ◽  
Ryan Guedry ◽  
Julia Cucarola ◽  
Adam M. Kaye ◽  
...  

Multiple myeloma (MM) is a hematologic malignancy characterized by excessive clonal proliferation of plasma cells. The treatment of multiple myeloma presents a variety of unique challenges due to the complex molecular pathophysiology and incurable status of the disease at this time. Given that MM is the second most common blood cancer with a characteristic and unavoidable relapse/refractory state during the course of the disease, the development of new therapeutic modalities is crucial. Belantamab mafodotin (belamaf, GSK2857916) is a first-in-class therapeutic, indicated for patients who have previously attempted four other treatments, including an anti-CD38 monoclonal antibody, a proteosome inhibitor, and an immunomodulatory agent. In November 2017, the FDA designated belamaf as a breakthrough therapy for heavily pretreated patients with relapsed/refractory multiple myeloma. In August 2020, the FDA granted accelerated approval as a monotherapy for relapsed or treatment-refractory multiple myeloma. The drug was also approved in the EU for this indication in late August 2020. Of note, belamaf is associated with the following adverse events: decreased platelets, corneal disease, decreased or blurred vision, anemia, infusion-related reactions, pyrexia, and fetal risk, among others. Further studies are necessary to evaluate efficacy in comparison to other standard treatment modalities and as future drugs in this class are developed.


1999 ◽  
Vol 26 (1) ◽  
pp. 125-140 ◽  
Author(s):  
ANN WARD ◽  
JOHN DOCKERILL

Current methods for screening violent offenders for program eligibility are expensive and time consuming. Developers of the Violent Offender Treatment Program (VOTP) have designed a brief and economical instrument to screen offenders for program eligibility. The present study was undertaken to assess the reliability and predictive accuracy of the VOTP Risk Assessment Scale (RAS). An interrater reliability of 20 court histories attained a mean kappa of .81. The RAS was applied to court histories of 202 violent offenders released between 1985 and 1987. A 10-year follow-up of convictions for violent behavior yielded a 47% base rate. Receiver Operating Characteristic curves showed that for varying time-at-risk periods, the predictive accuracy remained between .72 and .76. The recommended cutoff score for all time-at-risk periods was 11. The relatively high accuracy rate of the VOTP RAS indicated that it was accurate enough to aid program eligibility decisions.


Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Clare T Garrard ◽  
Mahesh Amin ◽  
Abdul H Hakki

The widely used CHADS2 score has been validated to predict the annual stroke risk (SR) in patients with non-valvular atrial fibrillation (AF). The CHA2DS2-VASc score incorporates 5 more risk factors including female gender, age 65 to 74 years, and peripheral arterial disease (PAD), prior myocardial infarct or aortic plaque. The two schemes have different SR and require separate tables to calculate SR (Table 1) . Table 1 An acronym (AFIB)2S4 + PaF2 (Table 2) is presented to predict SR that increases with higher scores, simplifies memorization of the score, incorporates all known risk factors and more accurately predicts SR without the use of tables. Table 2 The SR per 100 patient-years is calculated by adding (AFIB)2S4 + PaF2 scores. For example if all are positive including age 75 years then the SR is 15%, while if all are negative, including age <65 and male gender, then the SR is 0. To determine the predictive accuracy of the three scores, we reviewed the records of 100 consecutive patients admitted with acute cerebrovascular events and AF. The results showed 83% would have been classified as moderate to high risk (score>1) by CHADS2 , 95% by CHA2DS2-VASc , and 99% by (AFIB)2S4 + PaF2. (P <0.012). Conclusion: Compared to the CHADS2 , and CHA2DS2-VASc , (AFIB)2S4 + PaF2 more accurately predicts risk of acute cerebrovascular events in patients with AF. It is easy to remember and does not require the use of tables to assess SR in AF. Further studies are needed for validation. PEN ©


2016 ◽  
Vol 451 ◽  
pp. 113-122 ◽  
Author(s):  
Hojin Lee ◽  
Jae Wook Song ◽  
Woojin Chang
Keyword(s):  
At Risk ◽  

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