Deficiency In Cancer Patients Research Articles

ONCOLOGY NURSING CARE CONFERENCE: Osteoporosis and Vitamin D Deficiency in Cancer Patients

ONCOLOGY NURSING CARE CONFERENCE: Osteoporosis and Vitamin D Deficiency in Cancer Patients

Current Practice In Diagnosis and Treatment of Chemotherapy-Induced Anemia In Five European Countries – A Patient Record Study

AbstractAbstract 1512 Introduction:The most comprehensive study on the prevalence and treatment of anemia in cancer patients in Europe (ECAS) dates from 2004. A reevaluation of treatment patterns for anemia in cancer patients (ACT, 2009) focused on patients treated with erythropoiesis-stimulating agents (ESAs). The study reported here aimed to assess current practice in the diagnosis and treatment of chemotherapy-induced anemia (CIA) as well as the role of iron therapy. Methods:Onco-hematologists in 5 European countries (France, Germany, UK, Spain, Switzerland; Jun - Oct 2009) completed forms asking for patient demographics, TNM stage of cancer, status of anemia, tests for diagnosis or confirmation of anemia, treatment, and if applicable details of iron therapy (used product, dosing regimen, reasons for prescription). Records of the last 5 CIA patients treated for anemia within the last 6 months were analyzed. Results are presented as mean [range] across countries. Results:244 physicians (194 hospital-, 50 office-based) reported 1209 cases. Lymphoma (23%), myeloma (13%), lung (14%) and breast (12%) cancer were the most frequent cancer types. Metastatic disease was present in 66% of 662 patients with solid tumors. Tests to confirm anemia comprised mainly hemoglobin (Hb; 89% [85-95%]) and serum ferritin (48% [32-56%]). Transferrin saturation (TSAT) was only tested in 13% [9-23%] of patients. In 11% of patients, Hb was the only test performed. At diagnosis, 71% [62-82%] presented with Hb ≤ 10 g/dL, the EMA/FDA recommended cut-off level for ESA treatment initiation. Ferritin ≤ 30 ng/mL, commonly used as an indicator of absolute iron deficiency, was seen in 17% [8-21%] of patients. However, 29% [18-80%] of patients tested for TSAT had levels ≤ 20%, indicating insufficient available iron for effective erythropoiesis. Anemia treatment included an ESA in 48% [13-81%] of patients. Although only 15% [9-22%] of patients had a Hb ≤ 8 g/dL at diagnosis, 54% [27-80%] received at least one blood transfusion in the 6 months prior to the survey. Iron treatment (oral or i.v.) was given in 23% [8-56%] of patients of whom, 62% received iron in combination with an ESA, 31% received iron in combination with red blood cell transfusion and 23% received iron alone; 35% in these three groups received i.v. iron. ‘Quick onset of action’ was stated as main reason for the use of i.v. iron in 35% of cases. Interestingly, the decision for oral iron treatment was justified by ‘Effective when used in combination’ in 31% of cases although clinical trials have shown that oral iron in contrast to i.v. iron does not add to the benefit of ESA therapy. Discussion:Despite pivotal trials showing the efficacy of i.v. iron supplementation in ESA-treated cancer patients and the potential to reduce required ESA doses or blood transfusions, the majority of anemic cancer patients are still treated with ESAs or blood transfusions alone. Only 23% receive iron therapy in routine practice. Compared to the patients who received anemia treatment in the 2004 ECAS study, this study reveals only moderately higher rates of iron treated patients (23 vs. 17%) whereas the frequency of blood transfusions is substantially higher (54 vs. 38%). Furthermore, only one third of iron treated patients receive i.v. iron despite of international guidelines recommending i.v. iron for the treatment of absolute and functional iron deficiency in cancer patients and oral iron has not been proven effective in these patients. This gap in the awareness about iron metabolism in specific patient populations is also reflected in the underuse of TSAT determination, a reliable and widely available marker of absolute and functional iron deficiency. Diagnosis of iron deficiency is still mainly based on ferritin although NCCN guidelines consider patients with ferritin levels up to 800 ng/mL as functionally iron deficient if TSAT is <20%. This study confirms the need to increase awareness about the impact of cancer on iron metabolism and about evidence-based recommendations for i.v. iron supplementation. Disclosures:Beguin:Vifor Pharma: Honoraria, Membership on an Advisory Board. Aapro:Vifor Pharma: Honoraria, Membership on an Advisory Board. Bokemeyer:Vifor Pharma: Membership on an Advisory Board. Glaspy:Vifor Pharma: Membership on an Advisory Board. Hedenus:Vifor Pharma: Honoraria, Membership on an Advisory Board. Littlewood:Vifor Pharma: Honoraria, Membership on an Advisory Board. Ludwig:Vifor Pharma: Honoraria, Membership on an Advisory Board. Österborg:Vifor Pharma: Honoraria, Membership on an Advisory Board. Mitchell:Vifor Pharma: Employment.

Deficiency of Mannose-Binding Lectin Is a Risk Factor for Invasive Pulmonary Aspergillosis in Patients with Multiple Myeloma: An Analysis of 482 Patients

Invasive pulmonary aspergillosis (IPA) is a major cause of morbidity and mortality in neutropenic cancer patients. Mannose-binding lectin (MBL) is a circulating pattern-recognition molecule that recognizes microbial carbohydrate motifs, leading to complement activation, opsonization, phagocytosis, and cell lysis and is considered an important component of innate immunity. Deficiency of MBL is common due to genetic polymorphisms and has been identified as a risk factor for severe infections among myeloma patients undergoing autologous stem cell transplantation (ASCT). MBL deficiency has also been reported as a predisposing factor for chronic necrotizing pulmonary aspergillosis, a locally invasive infection typically seen in patients with chronic lung disease. The association between MBL deficiency in cancer patients and susceptibility to IPA has never been evaluated.This study investigated whether MBL deficiency, as measured by serum MBL levels, is associated with the development of IPA in patients with multiple myeloma undergoing multiple cycles of antineoplastic chemotherapy including tandem ASCT and post-transplant consolidation chemotherapy. Baseline serum MBL level was measured using ELISA. The frequency of IPA was assessed retrospectively in 482 adult myeloma patients (2007–2008), 50 of whom developed IPA.Association between MBL levels and IPA was analyzed using logistic regression analysis (table 1). Patients with normal serum MBL levels (≥ 1000 ng/mL) had significantly fewer episodes of IPA [(21 in 303 patients; 6.9%); Odds ratio, 0.385; 95% CI (0.212–0.699); P = 0.0017] than patients with low (100–999 ng/mL; 18 episodes in 125 patients (14.4%)) and very low (<100 ng/mL) MBL levels (11 episodes in 54 patients; 20.4%) (Table 1). We conclude that MBL deficiency is associated with more frequent episodes of IPA among patients with myeloma undergoing intensive antineoplastic therapy including ASCT and should be added to the list of risk factors for chemotherapy-related IPA. Baseline MBL level may serve as a predictor for the risk of IPA among such patients. This novel finding may have important therapeutic implications because recombinant Human MBL replacement therapy is now available and could therefore be applied prophylactically to decrease the risk of IPA in MBL-deficient patients receiving chemotherapy.Table 1. Association between serum MBL level and risk of invasive pulmonary aspergillosis (482 pts)AspergillosisMBL (ng/mL)No (n=432)Yes (n=50)RateOdds ratio (95%C.I.)P-value<10043 (10%)11 (22%)11/54 (20% )ReferenceReference100–1000107 (25%)18 (36%)18/125 (14%)0.658 (0.287–1.507)0.32181000282 (65%)21 (42%)21/303 (7%)0.291 (0.131–0.646)0.0024MBL <1000150 (35%)29 (58%)29/179 (16%)Reference

Evaluation of Vitamin D Deficiency in Breast Cancer Patients on Bisphosphonates

Bisphosphonates are very effective in treating osteoporosis and metastatic bone disease; however, unfavorable outcomes can occur when they are given to patients with occult vitamin D deficiency. No clear consensus exists on the assessment of vitamin D status in cancer patients undergoing bisphosphonate therapy. This study examines the prevalence of vitamin D deficiency among breast cancer patients treated with bisphosphonates for osteoporosis or metastatic bone disease, and observes the use of calcium and vitamin D supplementation in these patients. This retrospective study reviewed the electronic records of 321 breast cancer patients treated with bisphosphonates. Information on age, race, and serum levels of 25-hydroxyvitamin D (25-OHD), parathyroid hormone, and calcium were collected, and intakes of calcium and vitamin D supplements were queried in an outpatient pharmacy database. Of the 321 patients treated with bisphosphonates, 209 (65.1%) had their 25-OHD levels checked at least once. Of these patients, 57 (27.3%) had a serum 25-OHD level <20 ng/ml. Of the 209 patients with a known 25-OHD level, only eight (3.8%) received >600 IU of vitamin D per day, and 41 (19.6%) patients received 400-600 IU of vitamin D daily. Especially in the setting of metastatic bone disease in breast cancer patients, we advocate routine 25-OHD concentration screening for vitamin D deficiency in general. Clear guidelines for the diagnosis of vitamin D deficiency in cancer patients would be extremely beneficial to have, as would identification of the proper dose of vitamin D supplementation. We recommend 1,000 IU daily to our metastatic cancer patients.

Investigation of the relationship between serum hepcidin and prohepcidin in anemia of cancer (AoC) patients with the anemia of inflammation (AI)

20644 Background: The anemia observed in cancer patients is complex and may result from a combination of causes; iron deficiency, inflammation (AI), toxicity related to therapy, marrow infiltration, dyserythropoiesis and others. Determining effective anemia treatment can therefore be complex, requiring a combination of diagnostic tests. Algorithms exist to quantify the contribution of iron deficiency versus AI but are complex and as yet unvalidated. Hepcidin, a peptide reducing iron availability for erythropoiesis is induced by inflammation, and elevated hepcidin levels may underlie functional iron deficiency in cancer patients. Hepcidin levels have been suggested as an appropriate marker of AI but in the absence of a readily available serum hepcidin assay, a commercial assay to detect prohepcidin (DRG ELISA) has been used. Several studies have attempted to establish a relationship between prohepcidin and inflammation. Here we have contrasted the quantification of prohepcidin with mature hepcidin to defin...

Hyperhomocysteinaemia and immune activation in patients with cancer

Recently, homocysteine production was observed in tumour cell lines and homocysteine was proposed as a tumour marker. Furthermore, homocysteine production by activated immunocompetent cells was demonstrated. In this study, homocysteine metabolism and immune activation status were investigated in 128 patients suffering from various types of cancer (haematological disorders, lung cancer, gastrointestinal tumours, gynaecological cancer and tumours of other localisation) and healthy age-matched controls. A high percentage of patients (39.1%) showed moderate hyperhomocysteinaemia, while cysteine, folate and vitamin B(12) concentrations were within reference ranges. Most patients were found to have elevated concentrations of the immune activation and inflammation markers neopterin and C-reactive protein (CRP), as well as a higher erythrocyte sedimentation rate (ESR). Patients of different cancer groups differed significantly regarding vitamin B(12) and neopterin concentrations; higher B(12) levels were also associated with tumour progression. Univariate regression analysis showed that CRP, ESR and neopterin were suited best to predict death. In multivariate analysis, neopterin was best suited to predicting death, while homocysteine and B vitamins were not associated with patient outcome. Homocysteine concentrations were correlated with folate and cysteine levels. Higher neopterin concentrations coincided with lower folate concentrations, but higher vitamin B(12) concentrations. Associations between neopterin and folate concentrations may indicate that cellular immune activation might partly contribute to the development of folate deficiency in cancer patients, thus possibly also impairing homocysteine remethylation.

Frequency of Combined Deficiencies of Vitamin D and Holotranscobalamin in Cancer Patients

: Vitamin D and holotranscobalamin (HTCII) deficiencies have been seen to demonstrate an association with various types of cancers. The objective of this study is to determine the frequency of vitamin D and HTCII deficiency in cancer patients. Our study investigated vitamin D, total B12, and HTCII levels in 70 cancer patients. Vitamin D status was measured as serum 25-hydroxyvitamin D [25(OH)D, Nichols Advantage assay], and serum B12 was measured as both total B12 and as the metabolically active HTCII (Immulite B12 assay followed by glass adsorption). Insufficiency of serum 25(OH)D levels for this study is defined based on differing literature standards of insufficiency and was selected to be either <50 or <75 nmol/l. When 25(OH)D insufficiency is defined as serum level of <75 nmol/l, 43 of 60 (72%) of cancer patients were found to be insufficient. At the lower definition of insufficiency, <50 nmol/l, 24 of 60 patients (40%) were insufficient. Of 52 patients, only 3 (6%) were found to have insufficient serum levels of total B12 (normal = >300 pg/ml), whereas 17 of 52 (34%) were found to be HTCII insufficient (normal = >69 pg/ml). Of these 17 patients, 14 (84.4%) had normal total B12 levels. Low serum levels of 25(OH)D strongly correlated with low serum HTCII. All 12 HTCII-deficient patients were vitamin D insufficient at the <75-nmol/l standard. Six of 12 HTCII-deficient patients (50%) were vitamin D deficient at the <50-nmol/l cutoff. The standard measurement of total serum B12 alone is inadequate for identifying patients with insufficient levels of metabolically active B12. Deficiency of vitamin D (72%) and HTCII (34%) is prevalent among newly diagnosed patients with cancer and could play a role in cancer development and host response to tumor and therapy. Possible explanations for combined HTCII and 25(OH)D deficiencies include patient age, presence of atrophic gastritis, and lack of sun exposure.

Rapid gas chromatographic–mass spectrometric diagnosis of dihydropyrimidine dehydrogenase deficiency and dihydropyrimidinase deficiency

A rapid yet reliable chemical diagnosis for dihydropyrimidine dehydrogenase (DHPD) deficiency, and possibly dihydropyrimidinase (DHP) deficiency in cancer patients, prior to therapy with pyrimidine analogues such as 5-fluorouracil, is desired for prevention of severe side-effects by these drugs. We have reported the basic separation and quantitation technology for pyrimidine metabolites using gas chromatography–mass spectrometry. A proposal to use the number ( n) of standard deviations (SD) above the normal mean, as the index of the excessive urinary excretion of the metabolites appears not to be commonly used. When used, the values were too small, such as two or three, even in genetic disorders. Here, we applied the method to 11 urine specimens from proven cases including two DHP carriers and proved how specific the method is, because “ n”-values were markedly large for thymine (T), uracil (U) and/or dihydrothymine (DHT) and dihydrouracil (DHU). In three cases with DHPD deficiency, two were siblings, one with symptoms and the other without, n was 12 for T and 5.9 for U, and 5-hydroxymethyluracil was distinctly detected. These values indicate that the nature of genetic mutation relates closely to the degree of metabolite accumulation in pyrimidine disorders. In six patients with DHP deficiency, n was 8.4–12 for DHT and 7.2–11 for DHU. Many mutations are known for both genes and the assay of residual enzyme activity may be time-consuming or invasive especially for those with DHP deficiency. Thus, this noninvasive yet comprehensive urinalysis has great value for those without a family history, as the first trial, before DNA or the enzyme assay. Our findings again raise the question whether the metabolic block really causes the symptoms found in pyrimidine disorders.