High Prevalence and Clinical Impact of Malnutrition in Older Patients with a Hematological Malignancy—Basis for Patient Orientated Guidelines and Healthcare Interventions

Abstract Intro Malnutrition represents a frequent problem in cancer patients. However, data on the prevalence and the clinical impact of malnutrition in older patients with hematological malignancies are so far rare. Objectives Objective of this study was to investigate prospectively the nutritional status at baseline in older patients with blood cancer and to analyze the impact of malnutrition on clinical performance and outcome. Goal was to form a rational basis for interventions and practice guidelines in this continuously growing group of patients. Methods In 149 newly diagnosed patients with a hematological malignancy aged ≥ 70 years from the Department of Internal Medicine V (Haematology and Oncology), Innsbruck Medical University, different nutritional parameters including loss of appetite, recent weight loss, Mini Nutritional Assessment (MNA), body mass index, serum albumin and the inflammation marker C-reactive protein (CRP) were assessed and compared with status in multidimensional geriatric assessment and with overall survival (OS). SPSS (IBM Corporation, Armonk, NY, USA) was used for all statistical analyses. Two-year overall survival was analyzed with Kaplan-Meier methods and the log rank test. Hazard ratios were first analyzed in a univariate Cox proportional hazard regression. Parameters statistically significant in the univariate analyses were then included in the multivariate Cox regressions, additionally assessing the significance of the parameters with a bootstrapped model. Canoco 5.10 was used for principal component analyses (PCA). Results A moderate or severe decrease of appetite was reported by 23 % and 40% of patients. Moreover, a recent weight loss of 1-3 or >3kg was present in 19 and 31% and a BMI <23kg/m2 was found in 29% of patients. Based on MNA-evaluation, 44% revealed a risk of malnutrition and 14% of manifest malnutrition. Prevalence of lowered serum albumin <3.5 g/dL was detected in 14% of patients. Geriatric impairments >3 were detected in about one third of the patients (36%). PCA demonstrated clustering of impairments in performance status and in IADL as well as of low appetite, low serum albumin, fatigue and depression in the first principal component accounting for a variability of 24%. Loss of appetite, recent weight loss, impaired MNA, low serum albumin and elevated CRP were significantly associated with shortened OS. Recent weight loss >3kg and low BMI remained significant predictive parameters for OS in a Cox regression analysis (HR: 2.01 (1.19-3.38), p=0.009 and HR: 2.46 (1.53-3.96), p<0.001, respectively). Conclusion These analyses reveal malnutrition at initial diagnosis in a relevant proportion of older patients with a hematological malignancy. Importantly, impaired nutritional status is associated with shortened overall survival. The correlation between malnutrition, fatigue, impaired performance and functional capacities, and inflammation might suggest an underlying common pathway. Thus, assessment of nutritional status is essential in studies and in daily practice and forms the basis for interventions to improve nutritional status. More robust data on the clinical impact of malnutrition in hematological malignancies and the effect of geriatric interventions on essential oncologic and non-oncologic outcomes such as survival and quality of life are needed. Disclosures Stauder: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Teva: Research Funding.

Download Full-text

Does nutritional status affect treatment tolerability, chemotherapy response and survival in metastatic gastric cancer patients? Results of a prospective multicenter study in Turkey

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155220987291 ◽

2021 ◽

pp. 107815522098729

Author(s):

Senem Karabulut ◽

Izzet Dogan ◽

Cigdem Usul Afsar ◽

Mehmet Karabulut ◽

Naziye Ak ◽

...

Keyword(s):

Overall Survival ◽

Weight Loss ◽

Nutritional Status ◽

Multicenter Study ◽

Risk Index ◽

Tumor Resection ◽

Severe Malnutrition ◽

Chemotherapy Response ◽

Prospective Multicenter Study ◽

Nutritional Risk Index

Background The possible impact of malnutrition on the efficacy and tolerability of modern chemotherapy for metastatic gastic adenocarcinoma (mGC) patients is unclear. With this study, we aimed to represent the possible impact of malnutrition on the efficacy and tolerability of chemotherapy, and also on the overall survival of mGC patients. Methods In this prospective multicenter study, we collected demographic, oncological and nutritional data of our mGC patients. The nutritional status of patients were assessed with the Nutritional Risk Index (NRI), Body Mass Index (BMI) and weight loss percentage within 21-day period, between the chemotherapy cycles. All of these parameters along with toxicity assessment were evaluated after each courses of chemotherapy in order to determine inter-treatment weight loss. NRIs were calculated with a formula as follows; [1.519 × serum albumin level(g/L) + 41.7 × current weight/basic weight]. Patients were classified as having ‘no malnutrition’ (NRI > 97.5), ‘moderate malnutrition’ (97.5 ≥ NRI ≥ 83.5) or ‘severe malnutrition’ (NRI < 83.5). Drug-induced toxicities and treatment responses were evaluated via National Cancer Institute CTCAE version 4.0 and RECIST Criteria 1.1, respectively. Results One hundred and sixteen mGC patients were enrolled into the study. Median age was 60 years with range 32–83. Primary location of the tumor was antrum in 40% of the patients and of which 24% had undergone primary tumor resection. Ninety-eight percent of the patients had WHO performance status 0 or 1. Malnutrition was diagnosed in 67% of the patients and was severe in 31% of them. All patients received chemotherapy as first-line setting. Severe malnutrition was not associated with chemotherapy responses (p = 0.57). Moderate/severe malnutrition was associated with more cytopenia, nausea/vomiting, diarrhea, neuropathy, (p < 0.05 for all parameters). Moderate/severe malnutrition is associated with worser non-hematological toxicities (p = 0.038). Forty-one percent of patients died during the follow up period (Median: 138 days, range: 21–378). Malnutritional level was associated with significantly reduced overall survival. Severe malnutrition was associated with shorter median overall survival (74 days (95% CI, 20.7–111.0) vs. 237 (95% CI, 148.4-325.6) in none/moderate groups, p = 0.007). Conclusions In mGC patients, moderate/severe malnutrition is associated with worse non-hematological toxicities. Severe malnutrition is also associated with reduced overall survival.

Download Full-text

307 A Survey of Nutritional Status of Older Patients Attending Medicine for Older Person Clinics

Age and Ageing ◽

10.1093/ageing/afz103.197 ◽

2019 ◽

Vol 48 (Supplement_3) ◽

pp. iii17-iii65

Author(s):

Keneilwe Malomo ◽

Josephine Soh ◽

Eamon Dolan ◽

Marie O'Connor

Keyword(s):

Weight Loss ◽

Nutritional Status ◽

Older Patients ◽

Healthcare Professionals ◽

Nutritional Assessment ◽

Clinical Information ◽

Nutritional Supplement ◽

Community Dwelling ◽

Factors Affecting ◽

Clinical Complications

Abstract Background Nutritional assessment is an important but frequently overlooked aspect of comprehensive geriatric assessment. Malnutrition is common and associated with clinical complications. Our study aimed to assess older patients’ perceptions of their nutritional status and to investigate clinical factors affecting it. Methods All patients attending our clinics over a 2 week period were invited to complete a self-administered questionnaire. Further clinical information including diagnosis and weight collected by review of medical notes. Results A total of 43 patients completed the questionnaire; median age 82.5 years (67-102). Of these, 69.8%(n=30) were female and 27.9% (n=12) lived alone. Majority reported good appetite (83.7%, n=36) and eating 3 meals a day (79.1%,n=34). 25.6%(n=11) prepared meals themselves and 34.9%(n=15) had received nutritional advise from healthcare professionals. 17 patients (39.5%) self-reported weight loss over the past year, and of these 76.5% (n=13) had objective weight loss documented. Only 2.3% (n=1) were concerned and seek advice from healthcare professionals. 50% (n=12) of the remaining 24 patients who self-reported no weight loss had objective weight loss in clinic. 26 (60.5%) patients had objective weight loss. A higher proportion of the weight loss cohort lived alone (30.8% vs 23.5%), had no home care packages(HCP) (65.4% vs 47.1%), did not take nutritional supplement (76.9% vs 58.8%), had no dentures ( 42.5% vs 23.5%) and had no diagnosis of dementia (57.7% vs 47.1%). Of those who lost weight, 34.6% (n=9) lost significant amount (>5%) of weight, including 4 (15.4%) who lost >10%. Conclusion 2 out of 3 of our community dwelling, older patients lost weight, with one third having lost significant amount. Awareness is poor with 50% not recognising their weight loss and only one third ever sought nutritional advice. Patients who lost weight were more likely to be living alone with no formal community supports.

Download Full-text

PS02.179: NUTRITIONAL STATUS DIFFERENCES BETWEEN YOUNG AND ELDERLY PATIENTS UNDERGOING SURGERY FOR ESOPHAGEAL AND GASTROESOPHAGEAL JUNCTION CANCER

Diseases of the Esophagus ◽

10.1093/dote/doy089.ps02.179 ◽

2018 ◽

Vol 31 (Supplement_1) ◽

pp. 172-173

Author(s):

Irene Lidoriki ◽

Dimitrios Schizas ◽

Efstratia Mpaili ◽

Adamantios Michalinos ◽

Maria Mpoura ◽

...

Keyword(s):

Weight Loss ◽

Nutritional Status ◽

Elderly Patients ◽

Older Patients ◽

Laboratory Tests ◽

Handgrip Strength ◽

Gastroesophageal Junction ◽

Anthropometric Measurements ◽

Unintentional Weight Loss ◽

Gastroesophageal Junction Cancer

Abstract Background Esophageal cancer patients often suffer from malnutrition. Older people constitute a group of patients more susceptible to nutritional status deterioration. The aim of this study is to investigate the differences in nutritional status between elderly patients and patients younger than 65 years of age with esophageal and gastroesophageal junction cancer. Methods The study sample consisted of 73 patients with esophageal (n = 11) and gastroesophageal junction cancer (n = 62) who were admitted for surgery in the First Department of Surgery, Laikon General Hospital, Athens, Greece, between September 2015 and December 2017. Patients were divided into 2 groups according to their age, those younger than 65 years (n = 39) and those older than 65 years (n = 34). The preoperative assessment of nutritional status was based on Patient Generated Subjective Global Assessment (PG-SGA), laboratory tests, anthropometric measurements, handgrip strength, unintentional weight loss during the last six months and Skeletal Muscle Index (SMI) derived from analysis of CT scans. Results Malnutrition and sarcopenia were more prevalent in the group of older patients compared to the group of younger ones (73.5% vs 41%, P < 0.05 and 60% vs 35.3%, P < 0.05). PG-SGA was significantly higher in elderly patients (12.35 vs 8.23, P < 0.05), while SMI and handgrip strength were significantly lower in elderly patients (48.47 cm2/m2 vs 55.5 cm2/m2, P < 0.05 and 31 kg vs 39.1 kg, P < 0.05 respectively). Among the laboratory tests, albumin, hemoglobin and hematocrit were lower in the group of older patients (3.86 g/dL vs 4.15 g/dL, P < 0.05, 12.25 g/dL vs 13.17 g/dL, P < 0.05 and 36.5 vs 39.5, P < 0.05, respectively), whereas platelet-to-lymphocyte ratio was higher (205.4 vs 156.2, P < 0.05). Concerning anthropometric measurements, corrected mid arm muscle area and calf circumference were lower in older patients (42.15 cm2 vs 49.26 cm2, P < 0.05 and 34.86 cm vs 36.89 cm, P < 0.05, respectively), whereas no significant differences were observed in Body Mass Index values and unintentional weight loss between the two groups. Conclusion Geriatric patients with esophageal and gastroesophageal junction cancer have more compromised nutritional status compared to their younger counterparts. Preoperative nutritional assessment should be performed in all such patients in order to detect those who will benefit from perioperative nutritional support. Disclosure All authors have declared no conflicts of interest.

Download Full-text

Impact of Gene Mutations on Overall Survival in Older Patients with Acute Myeloid Leukemia (AML) Treated with Azacitidine (AZA) or Conventional Care Regimens (CCR)

Blood ◽

10.1182/blood.v128.22.2859.2859 ◽

2016 ◽

Vol 128 (22) ◽

pp. 2859-2859 ◽

Cited By ~ 4

Author(s):

Lin Tang ◽

Anna Dolnik ◽

Kyle J. MacBeth ◽

Hervé Dombret ◽

John F. Seymour ◽

...

Keyword(s):

Dna Methylation ◽

Overall Survival ◽

Board Of Directors ◽

Older Patients ◽

Research Funding ◽

Gene Mutations ◽

Molecular Heterogeneity ◽

Employment Equity ◽

Advisory Committees ◽

Equity Ownership

Abstract Background: AML is characterized by molecular heterogeneity and specific mutations are prognostically important (Papaemmanuil, Gerstung et al, NEJM,2016). Mutational analysis of NPM1, CEBPA, and FLT3 is included in the 2010 European LeukemiaNet recommendations for AML (Döhner et al, Blood, 2010). Additional recurrently mutated genes have since been identified with potential value for prognosis and prediction of treatment (Tx) response. The phase 3 AZA-AML-001 study showed AZA prolonged median overall survival (OS) vs CCR (10.4 vs 6.5 months [mos]; P=0.101) and improved 1-year survival (46.5% vs 34.2%) in older patients (pts) with AML (Dombret et al, Blood, 2015). Aim: To investigate relationships between gene mutations and OS in the subpopulation of AZA-AML-001 pts with available baseline bone marrow (BM) for molecular analyses ("biomarker" cohort). Methods: Eligible pts were age ≥65 years with newly diagnosed AML (>30% BM blasts), ECOG performance status (PS) score 0-2, WBC count ≤15x109/L, and NCCN-defined intermediate- or poor-risk cytogenetics. Pts received AZA (75 mg/m2/day [d] x 7d/28d cycle) or a preselected CCR: intensive chemotherapy (7 + 3 regimen), low-dose ara-C, or best supportive care only. DNA was isolated from BM mononuclear cells and targeted sequencing of 39 genes was performed with Haloplex target enrichment (Agilent) on Illumina HiSeq 2500 using 2x100bp read lengths. FLT3 tyrosine kinase domain (TKD) mutations were determined by next-generation sequencing (NGS) and internal tandem duplications (ITD) were determined by capillary electrophoresis sizing of PCR amplicons. Target regions varied by gene from all exons to hot-spots. Log-rank test, stratified by ECOG PS score (0-1 vs 2) and cytogenetic risk (intermediate vs poor) at baseline, was used to assess OS of pts with mutations (mut) in genes detected in ≥5 pts vs OS in pts with wild-type (wt) genes within the AZA and CCR arms. Median OS was estimated using Kaplan-Meier methods. Results: The biomarker cohort comprised 156 of all 488 pts in AZA-AML-001 (32%; AZA n=83, CCR n=73). Baseline characteristics and hematologic response rates were well-matched between biomarker and non-biomarker pts. Mutations were detected in 33 of 39 sequenced genes. The most frequently mutated genes were DNMT3A (27%), TET2 (25%), IDH2 (23% [R140 15%, R172 8%]), TP53 (21%), RUNX1 (18%), NPM1 (16%), NRAS (12%), FLT3 (12% [-ITD 10%, -TKD 5%]), ASXL1 (11%), and STAG2 (10%). Stratified log-rank tests showed that median OS was significantly reduced for CCR pts with TP53mut (2.4 vs 12.5 mos with TP53wt; P=0.026) and with NRASmut (4.3 vs 10.3 mos with NRASwt; P=0.020). In the AZA arm, median OS was not significantly different between pts with TP53mutor TP53wt (7.2 vs 12 mos; P=0.40) or between pts with NRASmut or NRASwt (11.8 vs 8.9 mos; P=0.95), but was reduced in pts with FLT3mut (5.4 vs 12.0 mos with FLT3wt; P=0.017). Compared with similar pts treated with CCR, pts with TP53mut and/or NRASmut treated with AZA had nominally better median OS (7.2 vs 2.4 mos for TP53mut; 11.8 vs 4.3 mos for NRASmut), and pts with FLT3mut had nominally worse OS (5.4 vs 6.4 mos) (Table). Median OS was similar for pts with or without mutations in each of the genes known to influence DNA methylation (DNMT3A, IDH1, IDH2, and TET2); however, there was a statistical difference in OS within the AZA arm for pts with TET2mut (P=0.005) despite similar median OS for pts with TET2mut vs TET2wt (9.6 vs 9.5 mos) that was not observed within the CCR arm (P=0.45). Median OS for pts with a mutation in any 1 of the DNA methylation genes listed above was similar in the AZA and CCR arms (Table). Conclusion: These exploratory analyses suggest older AML pts with TP53 or NRAS mutations have a better prognosis when treated with AZA than with CCR. Mutations in genes that regulate DNA methylation did not impact median OS with AZA Tx, although the potential negative effects of TET2mut and FLT3mut warrant further evaluation. Prognostic implications of isolated gene mutations can vary due to co-mutations; larger pt cohorts are needed to establish the influence of recurring co-mutational patterns in AZA-treated pts. Disclosures Tang: Celgene: Employment, Equity Ownership. MacBeth:Celgene Corporation: Employment, Equity Ownership, Patents & Royalties, Research Funding. Dombret:Agios: Honoraria; Sunesis: Honoraria; Ambit (Daiichi Sankyo): Honoraria; Karyopharm: Honoraria; Kite Pharma.: Honoraria, Research Funding; Menarini: Honoraria; Menarini: Honoraria; Astellas: Honoraria; Janssen: Honoraria; Servier: Honoraria; Seattle Genetics: Honoraria; Roche/Genentech: Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Pfizer: Honoraria; Ariad: Honoraria, Research Funding; Novartis: Honoraria; Celgene: Consultancy, Honoraria; Jazz Pharma: Honoraria, Research Funding. Seymour:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding, Speakers Bureau; Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Stone:Pfizer: Consultancy; Sunesis Pharmaceuticals: Consultancy; Karyopharm: Consultancy; ONO: Consultancy; Jansen: Consultancy; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celator: Consultancy; Roche: Consultancy; Agios: Consultancy; Amgen: Consultancy; Novartis: Consultancy; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Juno Therapeutics: Consultancy; Merck: Consultancy; Seattle Genetics: Consultancy; Xenetic Biosciences: Consultancy. Beach:Celgene Corporation: Employment, Equity Ownership.

Download Full-text

Azacitidine (AZA) Prolongs Overall Survival in Older Patients with Acute Myeloid Leukemia (AML) with Poor Prognostic Karyotypes Compared with Conventional Care Regimens (CCR)

Blood ◽

10.1182/blood.v128.22.1638.1638 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1638-1638 ◽

Cited By ~ 2

Author(s):

Hartmut Döhner ◽

Paresh Vyas ◽

John F. Seymour ◽

Valeria Santini ◽

Richard M. Stone ◽

...

Keyword(s):

Overall Survival ◽

Board Of Directors ◽

Older Patients ◽

Research Funding ◽

Complex Karyotype ◽

Employment Equity ◽

Advisory Committees ◽

Cytogenetic Abnormalities ◽

Poor Risk ◽

Equity Ownership

Abstract Background: Karyotype is the strongest independent prognostic factor for survival in AML. The randomized phase 3 AZA-AML-001 study of older patients with AML showed AZA prolonged overall survival (OS) compared with CCR (10.4 vs 6.5 months, respectively; P=0.101) (Dombret et al, Blood, 2015). In a prospective subanalysis of the study, AZA was shown to meaningfully prolong OS by 3.2 months compared with CCR (P=0.0185) in the subgroup of patients with NCCN-defined poor-risk cytogenetics (Döhner et al, Blood, 2014: Abstract 621). Aim: This analysis evaluates treatment effects of AZA vs CCR on OS in subgroups of patients with specific cytogenetic abnormalities as well as in patient subgroups defined by cytogenetic risk per modified European LeukemiaNet (ELN) recommendations (not considering molecular markers) (Döhner et al, Blood, 2010). Methods: Patients aged ≥65 years with newly diagnosed AML (>30% bone marrow [BM] blasts), ECOG performance status score ≤2, intermediate- or poor-risk cytogenetics per NCCN 2009 criteria, and WBC count ≤15x109/L were randomized to receive AZA (75 mg/m2/day [d] x7d/28d) or CCR: intensive chemotherapy (cytarabine 100-200mg/m2IV x7d + anthracycline IV x3d induction), low-dose ara-C (20mg SC BID x10d/28d), or best supportive care only. Karyotypes obtained from BM were reviewed centrally by an independent cytogeneticist. OS was evaluated in subgroups of patients with frequent specific abnormalities, including -5/del(5q), -7, -7/del(7q), abnormal (17p) or complex karyotype (based on specific abnormalities, patients may have been evaluated in more than one category). OS was also assessed for patients in ELN-defined karyotype risk subgroups: Intermediate (Int)-I (normal karyotype), Int-II (all abnormalities not classified as Favorable or Adverse), and Adverse karyotype. OS was assessed using Kaplan-Meier methods and compared using a weighted log-rank test. Results: Centrally reviewed cytogenetic data were available for 485/488 patients (99.4%). In all, 220 patients (45.4%; AZA n=114, CCR n=106) had Int-I karyotype, 111 patients (22.9%; AZA n=53, CCR n=58) had Int-II karyotype, and 154 patients (31.8%, AZA n=73, CCR n=81) had Adverse karyotype (Figure 1). OS was comparable between AZA and CCR in patients with Int-I karyotype (14.1 vs 10.1 months, respectively; hazard ratio [HR] 0.83, 95%CI 0.60, 1.1; P=0.44) and patients with Int-II karyotype (8.9 vs 9.6 months; HR 1.19, 95%CI 0.79, 1.8; P=0.78). There was a significant 2.4-month median OS difference in favor of AZA in patients with Adverse karyotype (5.3 vs 2.9 months with CCR; HR 0.71, 95%CI 0.51, 0.99; P=0.046; Figure 2), with 1-year survival rates of 29.1% vs 14.7% for AZA and CCR, respectively. AZA was associated with longer median OS and higher 1-year survival compared with CCR for all subgroups of patients with the specific cytogenetic abnormalities under study: -5/del(5q), -7, -7/del(7q), abnormal (17p), and complex karyotype, with HRs ranging from 0.54 to 0.69(Table). Median OS in the CCR arm was less than 3 months for each of these subgroups. Similar to what has been reported in MDS (Ravandi et al, Cancer, 2009), AML patients with chromosome 7 abnormalities responded particularly well to AZA, with an improvement in median OS of 4.1 months over CCR. Patients with complex karyotypes also had meaningful improvements in OS, with ~15% more AZA-treated patients alive at 1 year than CCR patients. Conclusions: Prognosis is dismal for older AML patients with adverse karyotypes, and is especially poor for patients with complex karyotypes. Median OS and 1-year survival in patients with ELN-defined Adverse karyotype treated with AZA were almost double those of patients treated with CCR. AZA-treated patients with the specific cytogenetic abnormalities and/or complex karyotype in this analysis had a 31-46% reduction in risk of death vs CCR, and proportions of patients alive at 1 year were 11-22% greater with AZA. These data suggest AZA should be the preferred treatment for older patients with AML and adverse karyotypes. Disclosures Seymour: Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding, Speakers Bureau; Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Santini:Astex: Consultancy; Amgen: Consultancy; Onconova: Consultancy; Novartis: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding. Stone:Celator: Consultancy; Novartis: Consultancy; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Xenetic Biosciences: Consultancy; Agios: Consultancy; Amgen: Consultancy; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy; Jansen: Consultancy; Pfizer: Consultancy; ONO: Consultancy; Juno Therapeutics: Consultancy; Merck: Consultancy; Roche: Consultancy; Seattle Genetics: Consultancy; Sunesis Pharmaceuticals: Consultancy. Al-Ali:Celgene: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Morrill:Celgene: Employment, Equity Ownership. Songer:Celgene: Employment, Equity Ownership. Weaver:Celgene Corporation: Employment, Equity Ownership. Skikne:Celgene: Employment, Equity Ownership. Beach:Celgene Corporation: Employment, Equity Ownership. Dombret:Agios: Honoraria; Ambit (Daiichi Sankyo): Honoraria; Menarini: Honoraria; Menarini: Honoraria; Servier: Honoraria; Sunesis: Honoraria; Karyopharm: Honoraria; Kite Pharma.: Honoraria, Research Funding; Astellas: Honoraria; Janssen: Honoraria; Seattle Genetics: Honoraria; Roche/Genentech: Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Pfizer: Honoraria; Ariad: Honoraria, Research Funding; Novartis: Honoraria; Celgene: Consultancy, Honoraria; Jazz Pharma: Honoraria, Research Funding.

Download Full-text

Serum Albumin Is an Independent Factor Predicting Survival in Patients with Peripheral T Cell Lymphoma: A Multi-Institutional Study from the Latin American Working Group for Lymphomas (GELL)

Blood ◽

10.1182/blood-2019-123588 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4047-4047

Author(s):

Henry Idrobo ◽

Brady E. Beltrán ◽

Luis Villela M ◽

Marialejandra Torres Viera ◽

Victoria Otero ◽

...

Keyword(s):

Overall Survival ◽

Prognostic Factors ◽

Serum Albumin ◽

Board Of Directors ◽

Latin American ◽

Research Funding ◽

Prognostic Index ◽

Advisory Committees ◽

Cox Proportional Hazard ◽

Cox Proportional Hazard Regression

Introduction: Peripheral T cell lymphoma (PTCL) is a very heterogenous disease and corresponds to approximately 15% of all non-Hodgkin lymphoma cases. PTCL is divided into several subtypes, however, PTCL not otherwise specified (PTCL-NOS) is the most frequent, with a proportion of 26% of all PTCL cases. There is a lack of demographic and clinical data about PTCL-NOS in middle- and low-income countries, where patients' access to early diagnosis and otherwise standard care might be suboptimal. The objective of this study is to describe the population of PTCL-NOS patients in Latin America, specifically from the countries conforming the "Grupo Latinoamericano de Linfomas" (GELL), in order to better understand clinical behavior and find possible prognostic factors that might prognosticate overall survival (OS). We specifically evaluated the neutrophil/lymphocyte ratio (NLR) and serum albumin as potential prognostic factors. Methods: An observational, retrospective and analytical study was conducted during the period from January 2000 through January 2018. A total of 200 Latin American patients with a pathological diagnosis of PTCL-NOS were included. Clinical data were gathered from clinical records. NLR ≥4 and serum albumin ≤3.5 g/dl were considered adverse prognostic factors. Median Overall Survival (mOS) and 5-year Overall Survival (5y-OS) rates were estimated using the Kaplan-Meier method. Univariate and multivariate Cox proportional-hazard regression analyses were performed to identify adverse prognostic factors for OS. Data were analyzed and interpreted using STATA 15. Results: A total of 200 patients with a diagnosis of PTCL-NOS were included. 50% of patients were ≥60 years, 57% were male, 50% had ECOG ≥2, 40% had elevated serum Lactate Dehydrogenase (LDH) level, 70% showed stage III/IV disease, bone marrow involvement was present in 37% of patients, B symptoms in 65%, 33% presented with hemoglobin levels <10 g/dL. The International Prognostic Index (IPI) score was high-intermediate in 33% and high in 14% of cases. The Prognostic Index for PTCL-U (PIT) risk score was high-intermediate in 32% and high in 26% of cases. Serum albumin <3.5 mg/dl was seen in 58%, and NLR ≥4 in 37% of patients. Median OS (mOS) for the entire cohort was 0.83 years (95% CI 0.58-1.75) and 5-year OS rate was 31% (95% CI 23-40%). Patients with serum albumin levels <3.5 g/dL had mOS of 0.42 years (95% CI 0.25-0.75) and 5-year OS rate of 20% (95% CI 9-33%), while patients with albumin ≥3.5 g/dL had mOS of 5.1 years (95% CI 0.83-not reached) and 5-year OS rate of 51% (95% CI 36-65%) (log-rank p<0.001). The mOS for NLR <4 was 1.67 years (95% CI 0.75-4.92) with 5-year OS rate of 37% (95% CI 25-48%) while for NLR ≥4, the mOS was 0.58 years (95% CI 0.25-1.00) and 5-year OS rate was 23% (95% CI 12-36%) (log-rank p=0.02). Cox proportional Hazard regression multivariate analyses found serum albumin <3.5 g/dL (HR 1.83, 95% CI 1.10-3.05; p=0.02) and ECOG ≥2 (HR 1.95, 95% CI 1.15-3.30; p=0,01) were associated with a worse OS. Serum albumin remained an adverse prognostic factor for OS after adjustment for the IPI and the PIT scores (HR 1.66, 95% CI 1.01-2.75; p=0.047, and HR 1.70, 95% CI 1.03-2.80; p=0.038, respectively). Conclusion: This multi-institutional Latin American study showed that serum albumin level <3.5 g/dL was an adverse prognostic factor for OS, independent from the IPI and the PIT scores, in Latin American patients with a diagnosis of PTCL-NOS. The survival rates of Latin American patients with PTCL-NOS appear lower than in developed countries. Disclosures M: Merck-Sharp-Dome: Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Roche-Mexico: Consultancy, Speakers Bureau. Peña:Novartis: Other: Congress inscription and flights; Tecnofarma: Other: Congress inscription and flights; Roche: Other: Congress inscription and flights; Biotoscana: Other: Congress inscription and flights; Janssen: Other: Congress inscription and flights; Pfizer: Membership on an entity's Board of Directors or advisory committees. Paredes:Tecnofarma: Honoraria. Rojas:ROCHE: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; NOVARTIS: Membership on an entity's Board of Directors or advisory committees; ABBVIE: Membership on an entity's Board of Directors or advisory committees. Abello:Takeda: Other: Participation in advisory board meeting. Castillo:Abbvie: Research Funding; Janssen: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Beigene: Consultancy, Research Funding; TG Therapeutics: Research Funding.

Download Full-text

Older Adults with Chronic Myelogenous Leukemia (CML), During the Tyrosine Kinase Inhibitor (TKI) Era, Can Be Successfully Treated with Reduced Intensity Conditioning (RIC) Hematopoietic Cell Transplant (HCT) Using Sibling or Unrelated Donors: A Center for International Blood and Marrow Transplant Research (CIBMTR) Analysis

Blood ◽

10.1182/blood.v118.21.494.494 ◽

2011 ◽

Vol 118 (21) ◽

pp. 494-494

Author(s):

Erica D Warlick ◽

Brian McClune ◽

Tanya L. Pedersen ◽

Kwang W Awn ◽

Joseph H. Antin ◽

...

Keyword(s):

Overall Survival ◽

Board Of Directors ◽

Older Patients ◽

Age Groups ◽

Advisory Committees ◽

Age Cohorts ◽

Gvhd Prophylaxis ◽

Age Cohort ◽

Unrelated Donors ◽

Conditioning Intensity

Abstract Abstract 494 The introduction of tyrosine kinase inhibitors (TKI) and advent of RIC and non-myeloablative (NMA) conditioning hematopoietic cell transplants (HCT) have changed and the therapeutic strategy for patients with CML. We analyzed the post HCT outcomes of CML patients aged 40 and older undergoing RIC/NMA HCT in 2001–2007. Detailed information regarding pre HCT TKI use or rationale for timing of transplant was not available; however, the analysis time period captures the entry of TKIs into clinical practice. Outcomes were compared between age cohorts of 40–49, 50–59, and ≥ 60 years. Overall survival (OS), Day +100 acute graft versus host disease (aGVHD) grades II-IV, chronic (cGVHD), transplant-related mortality (TRM), relapse, and disease-free survival (DFS) were analyzed with multivariate analysis testing the impact of age, gender, disease status at HCT (CP1vs. CP2/accelerated phase (AP) vs. blast phase (BP), sex match, HLA match, GVHD prophylaxis, and conditioning intensity (RIC versus NMA as described by Bacigalupo et all 2009) on outcomes. A total of 306 CML patients underwent HCT at 125 centers: 117 (38%) aged 40–49; 119 (39%) aged 50–59; and 70 (23%) aged ≥ 60. At HCT most patients in the 40–49 age cohort were in CP1 (72%), while only 44% of patients aged 50–59 and 31% aged ≤ 60 were in CP1. Interval from diagnosis to HCT for CP1 patients was similar across age groups with a large percentage of each age cohort undergoing HCT ≥ 2 years (32%, 40%, and 45%, respectively). Sibling donors were the stem cell source for 56% of those aged 40–49; older cohorts had a higher percentage of unrelated donors (58 and 60%, respectively). Primarily peripheral blood grafts (78%, 80% and 90%) and RIC (78%, 76% and 70%) were used across age groups, respectively. GVHD prophylaxis was similar. Three year OS and cGVHD, Day +100 grade II-IV acute GVHD, and 1 year TRM were similar in all age cohorts. Three year relapse incidence increased and DFS decreased with age. Importantly in analysis of CP1 patients only, relapse and DFS were similar in each age cohort.Table 1:Univariate AnalysisOutcomeAge 40–49 Probability (95% CI)Age 50–59 Probability (95% CI)Age ≥ 60 Probability (95% CI)P-valueEntire CohortOSA54% (44–64)52% (42–61)41% (30–54)0.26aGVHDB II-IV26% (18–34)32% (24–40)32% (21–43)0.53cGVHDA58% (47–68)51% (41–61)43% (33–55)0.19TRMC18% (11–26)20% (13–27)13% (6–22)0.43RelapseA36% (27–46)43% (34–52)66% (53–77)0.001DFSA35% (26–45)32% (24–41)16% (7–27)0.01CP1 OnlyRelapseA34% (23–46)42% (28–56)51% (29–72)0.40DFSA43% (31–55)36% (23–51)39% (19–61)0.81A=3 year; B=Day +100; C=1 year Multivariate analysis confirmed the significant adverse impact of advanced CML (AP/CP2+ and BP) at HCT, NMA conditioning intensity, male gender, and older age on relapse and DFS. Overall survival was not impacted by age, but was significantly worse with advanced CML at HCT. (Table 2)Table 2:Multivariate AnalysisOutcomeRR95% CIP valueRelapse:Age:10.69–1.6420.000340–491.0641.441–3.60750–592.28≥60Disease Status:10.1319–0.9170.01CP11.3350.0036–1.403AP/CP2+2.823BPConditioning Intensity10.222–0.469<0.0001NMA0.323RICGender10.397–0.830.0032Male0.574FemaleOverall SurvivalAge:10.55–1.2260.4240–490.8210.683–1.61850–591.051≥60Disease Status:11.206–2.47<0.0001CP11.7263.199–10.0740.42AP/CP2+5.677BPGender:10.0189–0.4810.019Male0.671Female These data indicate that HCT is safe in older patients with CML with equivalent acute and chronic GVHD, TRM, and OS across age cohorts. Relapse increased in patients receiving NMA conditioning and in those aged 60 and above; most of whom had advanced disease. However, for HCT during CP1 relapse risks and DFS were similar, regardless of age. Allogeneic HCT using RIC conditioning for older patients with CP1 CML can control relapse with acceptable toxicity and survival. Comparison of outcomes with second line TKI versus HCT are as yet unreported but these favorable findings indicate appropriate consideration of HCT for older patients with CML. Disclosures: Gupta: Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

Download Full-text

The Relationship Between Cytokine Levels and Symptoms in Patients (Pts) With Myelofibrosis (MF) From COMFORT-II, a Phase 3 Study of Ruxolitinib (RUX) Vs Best Available Therapy (BAT)

Blood ◽

10.1182/blood.v122.21.4070.4070 ◽

2013 ◽

Vol 122 (21) ◽

pp. 4070-4070 ◽

Cited By ~ 11

Author(s):

Matthew Squires ◽

Claire N Harrison ◽

Giovanni Barosi ◽

Alessandro M Vannucchi ◽

Tiziano Barbui ◽

...

Keyword(s):

Weight Loss ◽

Board Of Directors ◽

Symptom Score ◽

Research Funding ◽

Advisory Board ◽

Advisory Committees ◽

Cytokine Levels ◽

Night Sweats ◽

Loss Of Appetite ◽

Over Time

Abstract Background RUX is a JAK1/ JAK 2 inhibitor that has demonstrated improvements in splenomegaly, MF-related symptoms, and quality of life measures in the 2 phase 3 COMFORT studies. We recently demonstrated possible prognostic/predictive relationships between baseline (BL) cytokine levels and changes in spleen volume. Here, we evaluated the associations between cytokine levels and symptoms in COMFORT-II. Methods Ten symptoms, (fever, weight loss, easily tired, loss of appetite, pain, itching, sleeping well, lack of energy, night sweats, and trouble sleeping) were assessed at BL and weeks 8, 24, and 48 using the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) instrument (0 to 4 scale). In this exploratory analysis, reverse coding of symptoms (except sleeping well) was performed. A high score reflects low symptom burden, and a positive change indicates improvement. Plasma samples were analyzed using Rules-Based Medicine's HumanMAP v1.6, measuring 89 cytokines at weeks 4, 24 and 48. Cytokines with ≥ 30% of values below lower limit of quantification were excluded. Two binary (0/1) variables were defined; Symptom Present = 1 when symptom score ² 2 and Improvement = 1 when change from BL symptom score > 0. Associations between Symptom Present and BL cytokine level were evaluated using univariate logistic regression (adjusted for IPSS risk and JAK2 mutation status), and for those associated at BL, the relationship between the fold-change in cytokine level (log2) and the Improvement over time was evaluated. Improvement and fold-change in a cytokine were considered as a bivariate response vector, and if the components of the response vector correlated it implied that the change in symptom score and change in cytokine were correlated over time. Results Of the 10 symptoms analyzed, 9 had BL associations with cytokines (Figure). Table shows cytokines and symptoms for which changes from BL were associated over time. At BL, lower ferritin levels were associated with itching and night sweats, lower leptin levels with weight loss, higher IL 1 receptor-α (IL1RA) levels with loss of appetite and higher CD40L, Pal1, and RANTES levels with not sleeping well. RUX-treated pts were more likely to have improvements in itching and night sweats than BAT-treated pts and had larger increases in ferritin levels over time. Larger changes in leptin levels with RUX treatment positively correlated with improvements in weight loss. IL1RA decreased significantly with time in the RUX arm and negatively correlated with loss of appetite, which improved over time. Conclusions Both BL levels and changes over time of various cytokines significantly correlated with MF-related symptoms. Ferritin levels appeared to be an important component of itching and night sweats. Additional analyses are required to explore the relationships between changes in cytokine levels and quality of life measures. These observations suggest a link between individual cytokines and symptoms in MF enhancing our understanding of the disease and providing a potential basis for future patient management tools. Disclosures: Squires: Novartis Phama AG: Employment. Harrison:Novartis: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; YM Bioscience: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Celgene: Honoraria; Shire: Speakers Bureau; S Bio: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Vannucchi:Novartis: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Gisslinger:AOP Orphan Pharmaceuticals: Advisory Board Other, Honoraria; Novartis: Advisory Board, Advisory Board Other, Research Funding; Sanofi-Aventis: Advisory Board, Advisory Board Other, Honoraria; Shire: Advisory Board, Advisory Board Other, Honoraria; Celgene: Advisory Board Other, Honoraria; Janseen: Advisory Board, Advisory Board Other, Honoraria. Passamonti:Sanofi: Honoraria; Novartis: Honoraria. Al-Ali:Novartis: Consultancy, Honoraria; Celgene: Honoraria, Research Funding. Kiladjian:Novartis: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Celgene: Research Funding; Sanofi: Honoraria, Membership on an entity’s Board of Directors or advisory committees; AOP Orphan: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding. Marker:Novartis: Employment. Mendelson:Novartis: Employment. Stalbovskaya:Novartis: Employment, Equity Ownership. Cervantes:Novartis: Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Sanofi Aventis: Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau. Knoops:Novartis: Consultancy; BMS: Consultancy.

Download Full-text

Does nutritional status affect treatment tolarability, response and survival in metastatic colorectal cancer patients? Results of a prospective multicenter study

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155220959427 ◽

2020 ◽

pp. 107815522095942

Author(s):

Senem Karabulut ◽

Izzet Dogan ◽

Cigdem Usul Afsar ◽

Mehmet Karabulut ◽

Sule Karaman ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Weight Loss ◽

Nutritional Status ◽

Metastatic Colorectal Cancer ◽

Multicenter Study ◽

Cytotoxic Chemotherapy ◽

World Health ◽

Severe Malnutrition ◽

Chemotherapy Response

Background The efficacy and tolerability of modern cytotoxic chemotherapy regimens used in malnourished metastatic colorectal cancer (mCRC) patients is uncertain. The aim of this study was to investigate the effect of malnutrition on efficacy and tolerability of cytotoxic chemotherapy and overall survival in mCRC patients. Methods In this multicenter study, demographic, oncologic and nutritional data were collected prospectively from mCRC patients. Nutritional status of the patients were evaluated on the basis of NRI (Nutritional Risk Assessment), BMI (Body Mass Index) and WL (Weight Loss) before the first chemotherapy, after the first and second chemotherapy during 2 cycles of chemotherapy every 15 days. To determine the inter-treatment weight loss toxicity assessment was included to theese parameters after each chemotherapy. NRI calculation was performed as [1.51xserum albumin level (g/L)+41.7xcurrent weight/basic weight]. NRIs were examined in 3 categories as ‘no malnutrition’ (NRI >97.5), ‘moderate malnutrition’ (97.5 ≥NRI ≥83.5) or ‘severe malnutrition’ (NRI <83.5). Response to treatment and drug-induced toxicities were assessed based on Criteria in Solid Tumors (RECIST) 1.1 and National Cancer Institute CTCAE version 4.0 respectively. Results One-hundred and thirty-seven mCRC patients were prospectively included. Median age was 48 (range 18-83). Primary location was colon in 66% of patients and 84% of their primary source was left colon. Malnutrition was detected in 39% of the cases. Response rate to treatment was twenty four percent. While there was no significant relationship between chemotherapy response and moderate/severe malnutrition (p = 0.24), moderate/severe malnutrition was associated with multipl site of metastases, WHO PS (World Health Organization Performance Status) of 1, over the median value of CEA/CA 19-9 (carcinoembryonic antigen/carbohydate antigen 19-9) levels (p = 0.003, p = 0.03, p < 0.001, and p = 0.02; respectively). Hypoalbuminemia and moderate/severe malnutrition were associated with all types of toxicity (p < 0.001 and p < 0.001). Moderate/severe malnutrition was associated with thrombocytopenia, and diarrhea following chemotherapy predominately, (p = 0.02 and p = 0.04; respectively). In moderate/severe malnutrition group median overall survival was prominently shorter than those with no malnutrition [6.6 moths (95%CI, 5.6-7.6) vs 11.9 moths (95% CI, 11.1-12.7) respectively, p < 0.001]. Conclusions Our study showed that moderate/severe malnutrition in mCRC patients was associated with decreased overall survival and increased chemotherapy toxicity.

Download Full-text

Loss of Appetite

Pediatric Care Online ◽

10.1542/aap.ppcqr.396092 ◽

2014 ◽

Keyword(s):

Weight Loss ◽

Weight Gain ◽

Nutritional Status ◽

Caloric Intake ◽

Acute Illness ◽

Key Points ◽

Transient Loss ◽

Loss Of Appetite ◽

Poor Weight Gain

Key Points Transient loss of appetite often accompanies acute illness and self-resolves.Prolonged loss of appetite, particularly when associated with poor weight gain or weight loss, may signify a serious illness.Serial assessments of weight and intake are the cornerstone of evaluation.Evaluation must accurately assess nutritional status, both caloric intake and caloric output.

Download Full-text