losartan-potassium and Hematologic-Neoplasms

Anemia has and will continue to be a central theme in medicine particularly as clinicians are treating a burgeoning population of complex multi-organ system processes. As a result of multiple randomized controlled trials (RCTs), meta-analyses, and societal recommendations overly restrictive paradigms and under-administration of erythropoiesis stimulating agents (ESAs) have likely been followed by clinicians among all specialties.. A review of anemia in the context of chronic kidney disease, hematologic malignancies, and cancer is presented with focus on the establishment of ESAs as integral in the treatment of anemia. Multiple RCTs and meta-analyses studying the use of ESAs are presented with focus upon their application to clinical practice. A 'compendium' is proffered describing the evolution, establishment, and implications of ESA administration initially among those with CKD with rapid subsequent application to the Hematology-Oncology population of patients. Literature search methodologies have included MEDLINE (1985-2020), PubMed (1996-2020), Cochrane Central Trials (1985-2020), EMBASE (2000-2020), and ClinicalTrials.gov (2000-2020).. Upon evaluation of risks and benefits of ESAs focused opinion and commentary is made supporting more liberal use of these agents and strongly suggesting that the current underlying treatment 'pendulum' has perhaps shifted too far to the 'under-treatment' side in many cases.

Topics: Anemia; Blood Transfusion; Combined Modality Therapy; COVID-19; Epoetin Alfa; Erythropoietin; Expert Testimony; Forecasting; Guideline Adherence; Hematinics; Hematologic Neoplasms; Hematopoiesis; Humans; Iron; Medicine; Meta-Analysis as Topic; Multicenter Studies as Topic; Myocardial Ischemia; Neoplasms; Observational Studies as Topic; Pandemics; Practice Guidelines as Topic; Practice Patterns, Physicians'; Randomized Controlled Trials as Topic; Receptors, Erythropoietin; Renal Dialysis; Renal Insufficiency, Chronic; SARS-CoV-2; Venous Thromboembolism

Topics: Anemia, Hypochromic; Antineoplastic Agents; Breast Neoplasms; Carcinoma, Small Cell; Clinical Protocols; Darbepoetin alfa; Data Interpretation, Statistical; Erythropoietin; Female; Filgrastim; Follow-Up Studies; Graft vs Host Disease; Granulocyte Colony-Stimulating Factor; Granulocytes; Hematinics; Hematologic Neoplasms; Hematopoietic Cell Growth Factors; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulins, Intravenous; Lung Neoplasms; Lymphoma; Lymphoma, Non-Hodgkin; Male; Multicenter Studies as Topic; Neoplasms; Neutropenia; Platelet Aggregation Inhibitors; Polycythemia Vera; Polyethylene Glycols; Randomized Controlled Trials as Topic; Recombinant Proteins; Research Design; Survival Analysis; Thrombocythemia, Essential; Treatment Outcome

Erythropoiesis-stimulating agents (ESA) improve the hemoglobin level of roughly half the patients receiving chemotherapy for solid tumors or for blood diseases. These figures vary highly between studies. On average, 6 of these patients must be treated with ESA to prevent a transfusion for one patient. The impact of ESA prescription on quality of life is difficult to assess in the studies available today. The medicoeconomic analyses are on the whole unfavorable to the prescription of ESA for chemotherapy-induced anemia. This analysis might change if there were a way to select the patients highly likely to respond to ESA. Concern also exists about the potential negative impact of ESA prescription on patient survival when the objective of the prescription is to normalize hemoglobin. International guidelines must be followed to ensure that under treatment hemoglobin is always less than 12 g/dL.

Topics: Anemia; Erythropoietin; Hematologic Neoplasms; Humans; Neural Tube Defects; Practice Guidelines as Topic

Anemia is highly prevalent in patients with cancer and its impact on quality of life and long-term outcome in these patients is well documented. Recombinant human erythropoietins, or epoetins, have been used to treat cancer-related or antitumor therapy-induced anemia for many years. Through a combination of clinical studies and extensive experience in the real-life clinical setting, epoetin beta has been shown to be efficacious and well tolerated, increasing hemoglobin levels, reducing the need for transfusion and improving quality of life. This favorable efficacy and safety profile has been demonstrated across a broad range of malignancy types, irrespective of the treatment used (platinum or non-platinum based). The effect of treatment with epoetin beta is rapid, with mean hemoglobin increases of 1 g/dl seen as early as 4 weeks following the start of therapy. Furthermore, there is no evidence that epoetin beta negatively affects overall survival or tumor progression in anemic patients with cancer. The approved 30,000 IU once-weekly dosing regimen (as opposed to the 10,000 IU three-times weekly regimen) provides greater convenience and may result in improved treatment compliance.

Topics: Epoetin Alfa; Erythropoietin; Hematologic Neoplasms; Hemoglobins; Humans; Medical Oncology; Neoplasms; Recombinant Proteins

Anemia is common in patients with hematologic malignancies, and it has negative effects on their quality of life. The current clinical practice guidelines recommend erythropoietic therapy in patients with cancer- or chemotherapy-related anemia, but anemia is often undertreated in patients with hematologic malignancies. Several randomized controlled trials have shown that treatment with erythropoiesis-stimulating proteins such as epoetin alfa (Procrit), epoetin beta, and darbepoetin alfa (Aranesp) increases hemoglobin levels, reduces the need for red blood cell transfusions, and improves quality of life in patients with hematologic malignancies and anemia receiving chemotherapy. Furthermore, preliminary data from a recent open-label study suggest that early treatment of mild anemia in patients with hematologic malignancies treated with chemotherapy produces marked improvements in quality of life and productivity. Increasing patients' hemoglobin levels may also improve their cognitive function. These findings support the use of erythropoietic therapy to manage anemia in patients with hematologic malignancies who are treated with chemotherapy.

Topics: Anemia; Darbepoetin alfa; Epoetin Alfa; Erythropoiesis; Erythropoietin; Hematologic Neoplasms; Humans; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins

Comparison of the efficacies of erythropoiesis-stimulating agents (ESAs) between different clinical trials is becoming increasingly common, although differences in study design and populations evaluated can have a considerable effect on results. A comparison of two seemingly similar trials of ESAs, one of epoetin alfa and the other of epoetin beta, showed that only 27% of the 115 patients with hematologic malignancies who received epoetin alfa in the epoetin alfa trial met the inclusion criteria for the epoetin beta trial. The mean hemoglobin increase from baseline to week 16 of epoetin alfa therapy in the patients who met these inclusion criteria was 3.3 g/dl. This is substantially higher than the mean hemoglobin increase of 2.2 g/dl from baseline to week 16 of epoetin alfa therapy in the patients who did not meet the epoetin beta study inclusion criteria. These results demonstrate the considerable effects that exclusion criteria can have on trial results and highlight the value of scrutinizing the study design details of clinical trials before comparing outcome data between trials.

Topics: Epoetin Alfa; Erythropoietin; Hematinics; Hematologic Neoplasms; Humans; Outcome Assessment, Health Care; Patient Selection; Randomized Controlled Trials as Topic; Recombinant Proteins; Research Design

The role of erythropoietin in the development of anemia in patients with oncohematological diseases has been discussed. Efficacy of use of erythropoietin in patients with oncohematological diseases was analyzed. Features of use, contraindication and adverse reactions have been discussed. Erythropoietins-beta have proved to be more effective than erythropoietins-alpha.

Topics: Anemia; Erythropoietin; Hematologic Neoplasms; Humans; Recombinant Proteins

Anaemia has a detrimental impact on quality of life and it is important that this condition is recognised and treated in patients with cancer. Epoetin beta is an effective and well-tolerated treatment of anaemia in patients with a wide range of solid and haematological malignancies. A study in patients with lymphoid malignancies confirms that epoetin beta is equally effective at the same overall weekly dose (30,000 IU weekly) when given once-weekly or three-times weekly. This once-weekly regimen has also proved effective in patients with solid tumours. Once-weekly treatment is more convenient for the patient, potentially improving compliance and is associated with reduced hospital administration costs. The majority of patients with cancer will respond to epoetin therapy with an increase in haemoglobin levels. However, it is of value to identify those patients who are likely to respond, so that cost-effectiveness can be improved. Despite much research into potential predictive factors, follow-up studies are required and clinical judgement remains key to managing the anaemia of cancer. In addition, studies suggest that intravenous iron supplementation can improve response to epoetin therapy in patients with functional iron deficiency. Epoetin beta offers an effective, safe and convenient therapy for the management of anaemia in patients with cancer. Ongoing studies are expected to lead to a greater understanding of the optimal use of epoetins in cancer-related anaemia.

Topics: Anemia, Iron-Deficiency; Antineoplastic Combined Chemotherapy Protocols; Drug Therapy, Combination; Erythropoietin; Hematologic Neoplasms; Humans; Iron Compounds; Multivariate Analysis; Neoplasms; Predictive Value of Tests; Quality of Life; Recombinant Proteins; Treatment Outcome

Anemia in cancer patients undergoing treatment is common and can cause debilitating symptoms such as fatigue and reduced exercise tolerance. The introduction of recombinant human erythropoietin represents a potential improvement in the treatment of this condition. Clinical studies in patients with solid tumors and nonmyeloid hematologic malignancies have convincingly shown an improvement in mean hemoglobin concentration, a reduction in transfusion requirement along with an improvement in quality of life scores, although an effect on survival is less clear. In myeloid disorders such as myelodysplasia, response to single-agent recombinant human erythropoietin is disappointing but significant synergism with granulocyte colony stimulating factor has been demonstrated and different dosing regimens may also improve response. Unfortunately, a significant proportion of patients remain refractory to treatment. Efforts have been made to identify treatable causes of erythropoietin refractoriness, such as functional iron deficiency, and concomitant intravenous iron supplementation does appear to improve response rates. The search for pretreatment factors that predict response has been largely disappointing, although a promising model for myelodysplasia has been developed that awaits large-scale evaluation. Recombinant human erythropoietin is well tolerated, although there were concerns in the late 1990s due to a rising incidence of pure red cell aplasia in chronic renal failure patients treated with subcutaneous Eprex (Ortho Biologics) in Europe. Since potentially contributory manufacturing processes have been identified and corrected, the incidence of this complication has been falling.

Topics: Anemia; Clinical Trials as Topic; Epoetin Alfa; Erythropoietin; Granulocyte Colony-Stimulating Factor; Hematologic Neoplasms; Hemoglobins; Humans; Neoplasms; Prognosis; Quality of Life; Recombinant Proteins

Topics: Anemia; Blood Transfusion; Clinical Trials as Topic; Erythropoietin; Hematologic Neoplasms; Humans; Lymphoproliferative Disorders; Myelodysplastic Syndromes; Prognosis; Quality of Life; Recombinant Proteins; Red-Cell Aplasia, Pure; Treatment Outcome

Anemia is a frequent symptom encountered in hematological malignancies at diagnosis or in the course of the disease. Allogeneic transfusions were, until recently, the only treatment available and used only for severe anemia. Erythropoietin is currently an important alternative especially for treatment and even to prevent severe anemia. It has been assessed for the treatment of chemotherapy related anemia in NHL, myeloma and CLL with a significant reduction of blood transfusions and prevention of grade 3-4 anemia in 51% of patients. In myelodysplasia, the more effective regimen is the association of G-CSF and Epo. In the setting of allogeneic bone marrow transplantation, it reduces the time to red cell engraftment and probably the number of blood cell unit per patient in contrast with autologous stem cell transplant. All these studies assessed the efficacy of Epo in hematological malignancies but needs further trials including the assessment of the quality of life and economical parameters.

Topics: Anemia; Erythropoietin; Hematologic Diseases; Hematologic Neoplasms; Hematopoietic Cell Growth Factors; Hematopoietic Stem Cell Transplantation; Humans; Myelodysplastic Syndromes; Recombinant Proteins

Anemia has been reported in approximately 40%-70% of patients with hematologic malignancies, with severity depending on the type and stage of disease and whether the patient has received myelosuppressive chemotherapy. Growing evidence supports the role of epoetin alfa in correcting anemia and improving quality of life (QOL) in patients with hematologic malignancies. Clinical practice guidelines recommend the use of epoetin alfa in patients with cancer-related anemia (including patients with hematologic malignancies) and hemoglobin levels < or =10 g/dL. Epoetin alfa treatment is optional for patients with cancer-related anemia and hemoglobin levels>10 g/dL and <12 g/dL, depending on clinical circumstances. A prospective, open-label, randomized trial evaluating hematologic response, transfusion use, and QOL after immediate or delayed epoetin alfa treatment in mildly anemic patients (hemoglobin< or =12 g/dL) undergoing chemotherapy for chronic lymphocytic leukemia, multiple myeloma, or lymphoma was recently completed. Study objectives included determining any correlation between changes in hemoglobin level and QOL and assessing any correlation between QOL measures and health care resource use. Interim results suggest that epoetin alfa treatment in patients with hematologic cancers and hemoglobin< or =12 g/dL who are receiving chemotherapy increases hemoglobin, functional capacity, well-being, work and productivity, and health resource use. Further evaluation of alternative epoetin alfa dosing schedules and use of epoetin alfa in treating anemia in patients with specific hematologic malignancies is ongoing.

Topics: Anemia; Clinical Trials as Topic; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Hematinics; Hematologic Neoplasms; Hemoglobins; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Linear Models; Multiple Myeloma; Myelodysplastic Syndromes; Quality of Life; Random Allocation; Recombinant Proteins

Anemia is prevalent among cancer patients with hematologic malignancies, with fatigue and weakness, major symptoms of anemia, contributing to diminished quality of life (QOL). Data from several randomized, placebo-controlled clinical trials and three large community-based studies in patients with hematologic malignancies indicate that recombinant human erythropoietin (r-HuEPO, epoetin alfa) can correct anemia, reduce transfusion requirements, and improve QOL. Moreover, a positive relationship has been found between increased hemoglobin (Hb) levels and improvements in QOL assessments, regardless of disease state, with the greatest incremental improvement occurring when Hb increases from 11 g/dL to 12 g/dL (range, 11 to 13 g/dL). This suggests that patients with mild-to-moderate anemia may achieve the greatest QOL benefit from epoetin alfa therapy. Evidence from community-based studies suggests that epoetin alfa administered once weekly has a similar safety and efficacy profile as three-times-weekly administration. Further research is ongoing with less frequent dosing regimens. The beneficial effects of epoetin alfa therapy have been reported in studies involving patients with chronic lymphocytic leukemia (CLL), multiple myeloma, and lymphomas. Evidence also exists that epoetin alfa can benefit patients with myelodysplastic syndromes (MDS), although these results have not been as impressive. Combining epoetin alfa with other cytokine growth factors may confer some additional benefit in these patients, but more rigorous investigation is required.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematologic Neoplasms; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Multiple Myeloma; Recombinant Proteins; Treatment Outcome

Anemia is a common complication in patients with hematologic malignancies, with incidence rates ranging up to 63%. In myelodysplastic syndromes, anemia is an essential feature of the disease. The decrease in hemoglobin may lead to several symptoms such as fatigue, exhaustion, and impaired quality of life, and it may worsen prognosis. Before the introduction of recombinant human erythropoietin (rHuEPO, epoetin alfa), red blood cell transfusions were the traditional treatment for improvement of Hb levels. Transfusions, however, are associated with several adverse events and risks, have only transient effects, and have a limited capacity to ameliorate the symptoms of anemia. Epoetin alfa represents a physiologic treatment option, especially in the long-term treatment of cancer- and cancer treatment-associated anemia, and is well tolerated, with response rates as high as 80%. Epoetin alfa is less effective in the treatment of the anemia of myelodysplastic syndrome, but appears to be synergistic with granulocyte-colony stimulating factor. However, not every patient responds to epoetin alfa; to avoid unnecessary interventions and costs, predictors of response have been proposed. This article outlines the advantages and disadvantages of the two major treatment forms of anemia: transfusions and epoetin alfa. Representative studies on the efficacy of epoetin alfa in anemic patients with hematologic malignancies as well as models to predict response to epoetin alfa treatment are summarized.

Topics: Anemia; Blood Transfusion; Epoetin Alfa; Erythropoietin; Hematinics; Hematologic Neoplasms; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Multiple Myeloma; Myelodysplastic Syndromes; Prevalence; Recombinant Proteins

Anemia is common in patients with hematological malignancy. Most patients will have their anemia attributed to the anemia of chronic disease. The anemia of chronic disease is caused by cytokine mediated suppression of erythropoiesis and low serum erythropoietin levels are found in the majority of patients with cancer. Many of these anemic patients will be symptomatic with fatigue. Data from many studies indicates that treatment of anemic patients with erythropoietin will increase their hemoglobin concentration, decrease transfusion need and also improve their quality of life. A recent study also suggests that improving the hemoglobin level may improve the patients' prognosis but this finding needs to be confirmed.

Topics: Anemia; Erythropoietin; Hematologic Neoplasms; Hemoglobins; Humans; Quality of Life; Recombinant Proteins

It remains to be elucidate whether measurements of cytokines in serum have any clinical significance. In this article, the clinical uses of cytokines are reviewed. The purposes of clinical use of cytokines are: 1) for the immunological treatment of malignancy; and 2) as hematopoietic growth factors. During the clinical use of cytokine, measurements of cytokine in serum might be important to estimate clinical efficacy and the clinical course.

Topics: Cytokines; Erythropoietin; Granulocyte-Macrophage Colony-Stimulating Factor; Hematologic Neoplasms; Humans; Interferons

Patients with malignant diseases frequently develop anemia. An alternative to blood transfusions is the application of recombinant human erythropoietin. Several nonrandomized and prospective, placebo-controlled studies have demonstrated the effect and safety of erythropoietin in patients with hematological malignancies, particularly in patients with multiple myeloma and low- to intermediate-grade non-Hodgkin's lymphoma. However, in patients with myelodysplastic syndromes, the rather low response rate of erythropoietin is overcome by the combination of erythropoietin with granulocyte colony-stimulating factor. A significant acceleration of the reconstitution of erythropoiesis has been reported in allogeneic, but not in autologous bone marrow transplantation. Especially in large open-label, multicenter studies, a statistically and clinically significant improvement in quality of life independent from chemotherapeutic response or tumor type has been demonstrated. A number of simple algorithms have been proposed using the pretreatment serum erythropoietin level, transfusion requirements, and early changes in hematological parameters.

Topics: Anemia; Clinical Trials as Topic; Erythropoietin; Hematologic Neoplasms; Humans; Recombinant Proteins

Topics: Angiogenesis Inhibitors; Antimetabolites, Antineoplastic; Azacitidine; DNA, Neoplasm; Erythropoietin; Hematologic Neoplasms; Humans; Recombinant Proteins; Thrombocytopenia

Topics: Anemia; Cell Hypoxia; Erythropoietin; Hematologic Neoplasms; Humans; Prognosis; Radiotherapy; Recombinant Proteins; Treatment Outcome

Anemia is a frequent complication in hematologic malignancies. In advanced stages of chronic lymphocytic leukemia, non-Hodgkin's lymphoma, and myeloma, anemia usually develops in parallel with marrow involvement. However, anemia may occur in the absence of overt infiltration of bone marrow by malignant cells. When all other causes of anemia (such as chronic bleeding, vitamin deficiency, hemolysis, and pure red blood cell aplasia) are eliminated, anemia can be related to "anemia of chronic disorders." Myelodysplastic syndromes are characterized by cytopenias. Anemia is very frequent, and nearly 90% of patients present with anemia during the evolution of the disease. In this disorder, erythroid progenitors are defective for their proliferation and maturation, as shown by in vitro culture techniques. Moreover, these patients often have a high endogenous serum erythropoietin level. The rationale for treating these patients with epoetin alfa is the possibility of overcoming the defective proliferation by pharmacologic doses of epoetin alfa. The response rate was rather low with epoetin alfa alone. Combinations with earlier-acting cytokines, such as recombinant human granulocyte colony-stimulating factor, have been tested in an attempt to improve response rates.

Topics: Epoetin Alfa; Erythropoietin; Hematinics; Hematologic Neoplasms; Humans; Myelodysplastic Syndromes; Recombinant Proteins

The use of cytokines following bone marrow transplantation has become an area of increasing controversy with specific regard to indication, efficacy and cost. This review will attempt to summarize cytokine data in both adult and pediatric transplantation. Indications for cytokines following transplantation will be presented, as well as suggestions for specific issues that should be addressed in future clinical trials.

Topics: Adult; Bone Marrow Transplantation; Child; Clinical Trials, Phase III as Topic; Drug Administration Schedule; Erythropoietin; Graft Survival; Granulocyte-Macrophage Colony-Stimulating Factor; Hematologic Neoplasms; Hematopoiesis; Hematopoietic Cell Growth Factors; Humans; Interleukin-3; Neoplasms; Recombinant Fusion Proteins

Topics: Anemia; Darbepoetin alfa; Drug Therapy, Combination; Erythropoietin; Ferric Compounds; Ferric Oxide, Saccharated; Follow-Up Studies; Glucaric Acid; Hematinics; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Injections, Intravenous; Sucrose; Survival Analysis; Transplantation, Autologous

Topics: Antineoplastic Agents; Erythropoietin; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Opportunistic Infections; Survival Analysis; Transplantation Conditioning; Transplantation, Homologous; Treatment Outcome

The approval of epoetin biosimilars in the European Union requires extensive scientific evaluation and stringent regulatory procedures, including post-marketing studies. The ORHEO (place of biOsimilaRs in the therapeutic management of anaemia secondary to chemotherapy in HaEmatology and Oncology) study was an observational, longitudinal, multicentre study performed in France to evaluate the efficacy and safety of biosimilar epoetins for the treatment of chemotherapy-induced anaemia (CIA) in the clinical setting.. Patients >18 years with CIA (haemoglobin [Hb] <11 g/dL) in association with solid tumours, lymphoma or myeloma and eligible for treatment with an epoetin biosimilar were included in this study. Patient characteristics were recorded at baseline along with anaemia-related information, such as observed and target Hb (as chosen by the treating clinician), brand and dose of epoetin biosimilar prescribed, and details of any other treatments. Patients were then followed-up at 3 and 6 months. The primary endpoint was Hb response (defined as Hb reaching ≥10 g/dL, an increase of Hb ≥1 g/dL since inclusion visit or reaching physician-defined target Hb, with no blood transfusions in the 3 weeks prior to measurement). Other endpoints included adverse events, achievement of target Hb and associated treatments.. Overall, 2333 patients >18 years (mean age 66.5 years) with CIA (haemoglobin [Hb] <11 g/dL) in association with solid tumours, lymphoma or myeloma and eligible for biosimilar epoetin treatment were included. 99.9% of patients received epoetin zeta (median dose 30,000 IU/week). Mean baseline Hb was 9.61 g/dL, with 35.6% of patients having moderate anaemia (Hb 8-9.5 g/dL). Hb response was achieved in 81.6% and 86.5% of patients at 3 and 6 months, respectively. Overall mean change in Hb level was 1.52 ± 1.61 and 1.72 ± 1.61 g/dL at 3 and 6 months, respectively. Transfusion and thromboembolic event rates were 9.4% and 2.4% at 3 months, and 5.8% and 1.5% at 6 months, respectively.. Epoetin zeta was effective and well tolerated in the management of CIA in patients with solid tumours, lymphoma and myeloma.. NCT02140736 (date of registration: 14 May 2014).

Topics: Adult; Aged; Anemia; Biosimilar Pharmaceuticals; Erythropoietin; Female; France; Hematologic Neoplasms; Humans; Longitudinal Studies; Male; Middle Aged; Recombinant Proteins

The objective of this study was to examine whether treatment with recombinant human erythropoietin (rHuEPO), previously found to be associated with a positive effect on cell-mediated immunity and humoral immunity (hepatitis B vaccine), is associated with an improved response to the seasonal influenza (flu) vaccine. Three groups received flu vaccine: healthy controls, hematologic patients not treated with rHuEPO ("No EPO" group), and hematologic patients receiving rHuEPO for their anemia ("EPO" group). Anti-flu Ab titer was measured (complement fixation test) from blood samples drawn before and approximately 3-4 weeks, 7-8 weeks and 4 months after vaccination. Nineteen healthy subjects were compared with 17 No EPO and 17 EPO patients. Mean ages were 59.5, 61.3, and 73.1 years, respectively (EPO patients were older; p = 0.005). In the healthy group, the percentage of those sustaining only a partial (twofold) response, a strong (fourfold or greater) response, and an overall response (combined partial and strong responses) were 31.6%, 57.9%, and 89.5%, respectively. In the No EPO group, values were 35.3%, 17.6%, and 52.9%, respectively. EPO group results were similar to those of the healthy controls: 23.5%, 58.8%, and 82.4% (p = 0.016, EPO vs. No EPO). In conclusion, hematologic patients (NoEPO group) respond poorly to the flu vaccine, compared with healthy subjects, and rHuEPO treatment is associated with an improved immune response to the flu vaccine in hematologic patients, with titers similar to those of healthy subjects.

Topics: Aged; Anemia; Antibodies, Viral; Erythropoietin; Female; Hematinics; Hematologic Neoplasms; Hemoglobins; Humans; Immunocompromised Host; Influenza A virus; Influenza Vaccines; Male; Middle Aged; Myelodysplastic Syndromes; Recombinant Proteins; Vaccination

Evaluate efficacy and safety of epoetin beta in anaemic patients receiving chemotherapy for a non-myeloid malignancy.. This open-label, multicentric, clinical trial was conducted in France among 691 anaemic patients (haemoglobin < or = 12 g/dL) with a solid or haematological malignancy to evaluate the benefit of epoetin beta 30,000 IU/week subcutaneously for 16 weeks. The primary endpoint was the rate of therapeutic response.. The overall response rate was 60.4% (CI 95%: [56.6%-64.1]). According to initial haemoglobin level < 11 g/dL or between 11 and 12 g/dL, it was 61.2% and 57.5% respectively. Response rates by tumour type (solid and haematological) were similar. The mean haemoglobin level increases were respectively 1.1 g/dL, approximately 2 and 2.2 g/dL at 4, 9, and 12 weeks after treatment initiation. In patients with haemoglobin level < 11 g/dL at inclusion the mean increases in haemoglobin level were respectively 1.17, 2.03 and 2.45 g/dL at 4, 9 and 12 weeks. During study period, 23% of patients required red blood cell transfusion. Overall treatment with epoetin beta was well-tolerated and 7.1% of patients only experienced thromboembolic events.. For treating chemotherapy-induced anaemia in patients with solid or haematological malignancy (especially if haemoglobin level < 11 g/dL), epoetin beta 30.000 IU subcutaneously once-weekly (450 IU/kg/week) is rapidly effective and overall well-tolerated.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Drug Administration Schedule; Erythropoietin; Female; France; Hematinics; Hematologic Neoplasms; Hemoglobin A; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; Recombinant Proteins; Young Adult

This study aimed to provide further clinical evidence for the efficacy and safety of epoetin beta once weekly across a wide range of cancer types.. This was a multicenter, open-label, prospective, single-arm study in patients with either a solid tumor or non-myeloid hematological malignancy, receiving or scheduled to receive further chemotherapy. Patients received epoetin beta 30,000 IU subcutaneously once weekly for 16 weeks. The primary efficacy endpoint was the change in hemoglobin (Hb) level according to the patient's baseline Hb level.. A total of 691 patients were included in the intent-to-treat population. Epoetin beta effectively increased Hb levels (a mean increase from baseline of 1.1 g/dl by week 4 and 2.2 g/dl by week 12). Hb response was achieved in 60.4% of all patients and 61.2% of those with baseline Hb <11 g/dl. Hb response was similar in patients with solid tumors (60.5%) and non-myeloid hematological malignancies (60.2%). Type of chemotherapy and baseline platelet count were independent predictive factors for response. Epoetin beta treatment was well tolerated.. Epoetin beta 30,000 IU once weekly effectively increases Hb levels, is well tolerated and has similar efficacy in anemic patients with solid tumors or non-myeloid hematological malignancies.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Erythropoietin; Female; Hematinics; Hematologic Neoplasms; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; Recombinant Proteins

Chemotherapy-related anemia is prevalent among patients with hematologic malignancies. A randomized, open-label, multicenter trial of early versus late epoetin alfa in this population was conducted, focusing on quality of life (QOL).. Patients with non-Hodgkin lymphoma, Hodgkin lymphoma, chronic lymphocytic leukemia, or multiple myeloma and baseline hemoglobin of 10 to 12 g/dL who were scheduled for > or = 4 months of myelosuppressive chemotherapy were randomized to receive < or = 16 weeks of epoetin alfa at a dose of 40,000 U once weekly immediately (early) or to wait and only receive epoetin alfa if hemoglobin decreased to < 9 g/dL (late). Those patients with a hemoglobin level > 12 g/dL after 3 chemotherapy cycles were not randomized. The primary endpoint was a mean change in the Functional Assessment of Cancer Therapy-Anemia (FACT-An) total.. In all, 269 patients with a hemoglobin level < or = 12 g/dL were randomized. The mean total FACT-An increased 3.84 (95% confidence interval [95% CI], 0.21-7.46) in early patients and decreased 4.37 (95% CI, -7.99 to -0.74) in late patients (P = .003). Early patients had significantly (P < .05) higher mean scores for total FACT-General; FACT-General physical and functional well-being subscales, total anemia scale, and fatigue subscale; and daily activity, energy, and important activity Linear Analog Scale Assessment scales, as well as reduced bedrest days and restricted activity days. The mean hemoglobin increased 1.2 g/dL (95% CI, 0.98-1.46) in early patients but decreased 0.2 g/dL (95% CI, -0.32-0.12) in late patients (P < .0001). Adverse events were similar between groups (with fatigue being the most prevalent); clinically relevant thromboembolic events were more common in early patients.. Treating mild anemia immediately with epoetin alfa during chemotherapy for hematologic malignancy significantly improved QOL, productivity, and hemoglobin compared with delaying treatment until the hemoglobin level decreases to < 9.0 g/dL.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Epoetin Alfa; Erythropoietin; Fatigue; Female; Hematologic Neoplasms; Hemoglobins; Humans; Male; Middle Aged; Quality of Life; Recombinant Proteins; Work Capacity Evaluation

The use of recombinant human erythropoietin (rHuEPO) has been controversial after myeloablative allogeneic Stem cell transplantation (allo-SCT). Reduced intensity conditioning regimens (RIC) offer a novel approach that might translate into a different profile of erythropoietic recovery. We treated 20 consecutive patients with rHuEPO early after matched sibling RIC allo-SCT. Conditioning included fludarabine, busulfan and antithymocyte globulin. EPO treatment was analyzed in terms of toxicity, impact on the frequency of Red blood cell transfusions (RBCT) and kinetics of Hemoglobin recovery within the 60 days post-allo-SCT. Results were compared with 27 matched patients who did not receive rHuEPO. In the first 2 months after allo-SCT all patients receiving rHuEPO (100%) achieved an Hb level > 11 g/dl at a median of 30 (15-35) days post-allo-SCT, as compared to only 63% of the patients not receiving rHuEPO (P = 0.007) at a median of 35 (20-55) days (P = 0.03). A total of 70% (95% CI, 50-90) of rHuEPO patients maintained an Hb over 11 g/dl in the second month as compared to only 19% (95% CI, 4-34) in the other group (P = 0.0004). For patients receiving RBCT, the use of rHuEPO was associated with a trend towards reduced RBCT requirements. This pilot study suggests a potential benefit of early administration of rHuEPO after RIC allo-SCT on early erythropoietic recovery.

Topics: Adult; Aged; Erythropoiesis; Erythropoietin; Female; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Hemoglobins; Humans; Male; Middle Aged; Myeloablative Agonists; Pilot Projects; Recombinant Proteins; Transplantation Conditioning; Transplantation, Homologous

The communication is summarizing results of study aimed to ascertain the efficacy of treatment with epoetin alpha in patients with different hematological disorders and, at the same time to evaluate the impact of this treatment on quality of their lives. Treatment efficacy in separate patients of the monitored population has been evaluated not only according to hemoglobin level increase, but also according to its effect on erythrocyte products consumption needed to control anemic syndrome. Overall 134 patients with different lymphoproliferative disorders were included in the evaluation. Full-extended monitoring, i.e. at least 3-month treatment with epoetin alpha, was passed by 127 (94.8%) patients. Favorable effect of epoetin alpha administration was most often reported in patients with multiple myeloma (85.7%), Waldenstrom s macroglobulinemia (80%) and chronic lymphatic leukemia (76.7%). Conversely the lowest efficacy was reported in the group of patients with myelodysplastic syndrome. Administration of epoetin alpha within treatment of underlying anemia in numerous hematological disorders represents suitable alternative to the substitution therapy via erythrocyte transfusions. Approximately 75% of monitored patients showed improvement of life quality, in some cases irrespective of results of treatment of their underlying disorder.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hematologic Neoplasms; Humans; Male; Quality of Life; Recombinant Proteins; Treatment Outcome

Anemia has been reported in approximately 40%-70% of patients with hematologic malignancies, with severity depending on the type and stage of disease and whether the patient has received myelosuppressive chemotherapy. Growing evidence supports the role of epoetin alfa in correcting anemia and improving quality of life (QOL) in patients with hematologic malignancies. Clinical practice guidelines recommend the use of epoetin alfa in patients with cancer-related anemia (including patients with hematologic malignancies) and hemoglobin levels < or =10 g/dL. Epoetin alfa treatment is optional for patients with cancer-related anemia and hemoglobin levels>10 g/dL and <12 g/dL, depending on clinical circumstances. A prospective, open-label, randomized trial evaluating hematologic response, transfusion use, and QOL after immediate or delayed epoetin alfa treatment in mildly anemic patients (hemoglobin< or =12 g/dL) undergoing chemotherapy for chronic lymphocytic leukemia, multiple myeloma, or lymphoma was recently completed. Study objectives included determining any correlation between changes in hemoglobin level and QOL and assessing any correlation between QOL measures and health care resource use. Interim results suggest that epoetin alfa treatment in patients with hematologic cancers and hemoglobin< or =12 g/dL who are receiving chemotherapy increases hemoglobin, functional capacity, well-being, work and productivity, and health resource use. Further evaluation of alternative epoetin alfa dosing schedules and use of epoetin alfa in treating anemia in patients with specific hematologic malignancies is ongoing.

Topics: Anemia; Clinical Trials as Topic; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Hematinics; Hematologic Neoplasms; Hemoglobins; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Linear Models; Multiple Myeloma; Myelodysplastic Syndromes; Quality of Life; Random Allocation; Recombinant Proteins

Anemia, a commonly occurring morbidity in patients with cancer, often leads to diminished quality of life (QOL). Numerous clinical trials have shown that epoetin alfa treatment improves hematologic and QOL variables in cancer patients. The clinical trial analysis reported here was performed to assess response to epoetin alfa in patients with hematologic malignancies. Cancer patients with anemia undergoing non-platinum-based chemotherapy who were enrolled in a multinational, randomized (2:1), double-blind, placebo-controlled trial were prospectively stratified by tumor type (hematologic, solid). Efficacy endpoints included proportion of patients transfused after day 28; change in hemoglobin (Hb) level from baseline to last assessment; proportion of treatment responders (increase in Hb > or =2 g/dl unrelated to transfusion) and correctors (patients whose Hb levels reached > or =12 g/dl during the study); and QOL. The protocol was amended before unblinding to prospectively collect and assess survival data 12 months after the last patient completed the study, and survival for the full study cohort was estimated using Kaplan-Meier techniques. Efficacy analyses of hematologic and QOL variables, as well as Kaplan-Meier estimates of survival, were performed post hoc for the hematologic tumor stratum. Among patients with hematologic malignancies, the mean increase in Hb levels was greater with epoetin alfa than with placebo treatment (2.2 vs. 0.3 g/dl). Transfusion requirements were lower in patients who received epoetin alfa versus placebo (25.2 vs. 43.1%), and the proportion of responders and correctors was higher with epoetin alfa than with placebo (75.2 vs. 16.7% and 72.6 vs. 14.8%, respectively). Patients who received epoetin alfa had improved QOL while patients who received placebo had decreased QOL. These results are similar to those seen in the full study cohort, where differences between epoetin alfa and placebo were significant (P<0.05) for all five primary cancer- and anemia-specific QOL domains evaluated. Although the study was not powered for survival, Kaplan-Meier estimates showed a trend in overall survival favoring epoetin alfa in both the full study cohort and the hematologic subgroup. Epoetin alfa treatment was well tolerated. Epoetin alfa therapy increased Hb levels, reduced transfusion requirements, and improved QOL in patients with anemia undergoing non-platinum chemotherapy for hematologic malignancies.

Topics: Adult; Anemia; Blood Transfusion; Double-Blind Method; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hematologic Neoplasms; Hemoglobins; Humans; Male; Middle Aged; Placebos; Quality of Life; Recombinant Proteins; Survival Analysis

Data from two large, community-based clinical trials that evaluated the efficacy of epoetin alfa in anemic cancer patients receiving chemotherapy were retrospectively analyzed to determine if clinical outcomes were different depending on whether chemotherapy was platinum- or nonplatinum-based.. Patients received epoetin alfa 150-300 IU/kg (Glaspy: Study 1; n = 2,342) or 10,000-20,000 IU (Demetri: Study 2; n = 2,370) s.c. three times each week for 4 months. Efficacy end points were changes in transfusion requirements, hemoglobin (Hb) levels, and quality of life (QOL). A total of 4,298 out of 4,712 patients (platinum-based, n = 1,601; nonplatinum-based, n = 2,697), who both received chemotherapy and had available data, were eligible for this retrospective analysis.. Baseline characteristics across groups were comparable with few exceptions, which were anticipated in view of the characteristics of the two different chemotherapy types. Decreases in transfusion requirements after 2, 3, and 4 months were significant, regardless of chemotherapy type. Mean increases in Hb level from baseline to final evaluation ranged from 1.6 g/dl to 2.0 g/dl across study groups and were significant, regardless of chemotherapy type. QOL, as measured by the Linear Analog Scale Assessment (LASA), improved significantly by 20%-43%, regardless of chemotherapy type, and improvements were associated with increases in Hb. Epoetin alfa was well tolerated in both studies, regardless of chemotherapy type.. Treatment of anemic cancer patients with epoetin alfa results in significant reduction in transfusion requirements, increase in Hb levels, and improvements in QOL, regardless of whether the chemotherapy is platinum- or nonplatinum-based.

Topics: Anemia; Blood Transfusion; Disease Progression; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Female; Follow-Up Studies; Hematinics; Hematologic Neoplasms; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Platinum; Predictive Value of Tests; Prognosis; Quality of Life; Recombinant Proteins; Retrospective Studies; Sensitivity and Specificity; Time Factors; Treatment Outcome

This experiment aimed to detect serum erythropoietin (EPO) levels in patients with haematological tumours and to investigate its clinical significance. For this purpose, 110 patients with haematological tumours admitted to our hospital between January 2019 and December 2020 were selected as the study population according to the inclusion and exclusion criteria, and they were included in the case group, and the clinical data of the patients were retrospectively analysed. 90 cases of people without hematological tumors who underwent physical examination during the same period were also included as a control group. The serum EPO levels of the two study groups were compared, and the clinical diagnostic value of EPO was analysed using the subject operating characteristic curve (ROC). Results indicated that of the 110 patients, 56 were leukaemia patients, 24 were multiple myeloma patients and 30 were malignant lymphoma patients. The differences in gender, age, disease history, alcohol consumption and smoking history between the two groups were not significant (P>0.05), while the EPO levels in the control group were significantly lower than those in the case group, with a statistical significant difference of P<0.05. The EPO levels in patients with leukaemia, multiple myeloma and malignant lymphoma were (165.43± 20.46) mU/mL, ( 28.14± 4.51) mU/mL and (86.25±10.33) mU/mL significantly higher than the control group, with a significant difference of P<0.05. Using the absence of haematological tumours as a control, the analysis yielded an area under the ROC curve of 0.995 for EPO diagnosis in patients with leukaemia, a 95% confidence interval of 0.987 to 1.000, a sensitivity of 97.80%, with a sensitivity of 98.2 %; the area under the ROC curve for patients with multiple myeloma was 0.910, with a 95% confidence interval of 0.818 to 1.000, with a sensitivity of 98.90% and specificity of 87.50%; the area under the ROC curve for patients with malignant lymphoma was 0.992, with a 95% confidence interval of 0.978 to 1.000, with a sensitivity of 96.70% and specificity of 96.70%. In conclusion, the serum EPO levels of patients with haematological tumours are significantly higher than those of the normal population, and the detection of serum EPO levels is valuable for the diagnosis of clinical haematological tumours.

Topics: Clinical Relevance; Erythropoietin; Hematologic Neoplasms; Humans; Leukemia; Multiple Myeloma; Retrospective Studies

Autologous stem-cell transplantation (ASCT) has shown to provide curative benefit in patients with relapsed lymphoma and multiple myeloma (MM), often requiring hematopoietic support until marrow engraftment. Because of Jehovah's Witnesses' (JW) refusal of blood products, treatment challenges arise. This study represents 125 JWs with lymphoma (n = 55), MM (n = 68), or amyloidosis (n = 2), treated with high-dose chemotherapy (HDC) and ASCT without transfusions.. Priming with intravenous iron and erythropoietin occurred to increase hemoglobin (Hb) pretransplantation. Cytokine mobilization of stem-cells was used. Delay to HDC was done to allow Hb and platelets to approach 11 g/dL and 100 × 10(3)/μL, respectively. Patients with MM received a standard dose of melphalan 200 mg/m(2), with dose reduction for severe kidney dysfunction. Patients with lymphoma received carmustine 300 mg/m(2), cyclophosphamide 1,500 mg/m(2) on days 2 through 5 (total 6 g/m(2)), and etoposide 700 mg/m(2) per day on days 2 through 4 (total 2,100 mg/m(2)). Post-transplantation, a combination of granulocyte colony-stimulating factor, erythropoietin, aminocaproic acid, and phytonadione was administered.. There were two major and 15 minor bleeding complications, none occurring at platelets less than 5.0 × 10(3)/μL, with six (4.8%) treatment-related mortalities. The median decrease in Hb was 5.0 g/dL, with median Hb nadir of 7.0 g/dL. The median number of days with platelet count less than 10 × 10(3)/μL was 3, with median platelet nadir of 5.0 × 10(3)/μL. Cardiac complications occurred in 40 patients (32%).. ASCT can safely be performed without transfusion support. A platelet transfusion trigger of ≤ 5 × 10(3)/μL may be appropriate in select patients. Pharmacotherapy and cardiac monitoring are effective in the management of cardiac complications.

Topics: Adult; Aged; Aminocaproic Acid; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Carmustine; Combined Modality Therapy; Cyclophosphamide; Erythropoietin; Etoposide; Female; Granulocyte Colony-Stimulating Factor; Hematologic Neoplasms; Hemoglobins; Humans; Iron; Jehovah's Witnesses; Lymphoma; Male; Melphalan; Middle Aged; Multiple Myeloma; Recurrence; Stem Cell Transplantation; Transplantation, Autologous; Vitamin K 1; Young Adult

Topics: Bipolar Disorder; Epoetin Alfa; Erythropoietin; Female; Hematologic Neoplasms; Humans; Kidney Transplantation; Lithium; Medical Oncology; Physician-Patient Relations; Recombinant Proteins; Renal Insufficiency, Chronic; Spouses

Clinical significance of the JAK2V617F mutation in patients with a myeloproliferative neoplasm has been the target of intensive research in recent years. However, there is considerably uncertainty about prognosis in JAK2V617F positive individuals without overt signs of myeloproliferative disease. In this study, we tested the hypothesis that increased JAK2V617F somatic mutation burden is associated with myeloproliferative neoplasm progression rate in the general population. Among 49,488 individuals from the Copenhagen General Population Study, 63 (0.1%) tested positive for the JAK2V617F mutation in the time period 2003-2008. Of these, 48 were available for re-examination in 2012. Level of JAK2V617F mutation burden was associated with myeloproliferative neoplasm progression rate, consistent with a biological continuum of increasing JAK2V617F mutation burden across increasing severity of myeloproliferative neoplasm from no disease (n=8 at re-examination) through essential thrombocythemia (n=20) and polycythemia vera (n=13) to primary myelofibrosis (n=7). Among those diagnosed with a myeloproliferative neoplasm only at re-examination in 2012, in the preceding years JAK2V617F mutation burden increased by 0.55% per year, erythrocyte volume fraction increased by 1.19% per year, and erythrocyte mean corpuscular volume increased by 1.25% per year, while there was no change in platelet count or erythropoietin levels. Furthermore, we established a JAK2V617F mutation burden cut-off point of 2% indicative of disease versus no disease; however, individuals with a mutation burden below 2% may suffer from a latent form of myeloproliferative disease revealed by a slightly larger spleen and/or slightly higher lactic acid dehydrogenase concentration compared to controls. Of all 63 JAK2V617F positive individuals, 48 were eventually diagnosed with a myeloproliferative neoplasm.

Topics: Aged; Aged, 80 and over; Blood Platelets; Denmark; Disease Progression; Erythrocyte Indices; Erythropoietin; Female; Genetic Testing; Hematologic Neoplasms; Humans; Janus Kinase 2; Male; Middle Aged; Mutation; Myeloproliferative Disorders; Platelet Count; Prospective Studies; Registries; Severity of Illness Index

This 12th biannual report of the Cochrane Haematological Malignancies Group highlights recently published randomized controlled trials in the field of hemato-oncology, covering the publication period from September 1, 2009, through June 30, 2010. Implication for clinical practice and methodological aspects are the main principles used to select trials for this report. Studies on tyrosine kinase inhibitors for patients with chronic myeloid leukemia were identified through electronic search of MEDLINE with a broad search filter that covered all topics in hemato-oncology combined with a highly sensitive search filter for randomized studies as described in the Cochrane Handbook for Systematic Reviews of Interventions.

Topics: Adrenal Cortex Hormones; Aminoglycosides; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Benzamides; Cyclophosphamide; Dasatinib; Diphosphonates; Disease-Free Survival; Epoetin Alfa; Erythropoietin; Evidence-Based Medicine; Gemtuzumab; Graft vs Host Disease; Hematologic Neoplasms; Hodgkin Disease; Humans; Imatinib Mesylate; Interferon-alpha; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Methotrexate; Piperazines; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Pyrimidines; Randomized Controlled Trials as Topic; Recombinant Proteins; Rituximab; Stem Cell Transplantation; Thiazoles; Treatment Outcome; Vidarabine

To accurately determine the causes of anemia and proportion of unexplained anemia in a racially diverse cohort of older adults after a comprehensive and standardized evaluation.. We evaluated results from a single-institutional university anemia clinic. Patients with anemia, defined as a hemoglobin less than 13.0 g/dL for men and less than 12.0 g/dL for women, underwent a prospective standardized history, physical examination, and laboratory measures, with additional studies including bone marrow examination as indicated. Empiric treatment trials were given for identified deficiencies.. One hundred and seventy-four primarily community-dwelling adults aged 65 years and older were evaluable. African Americans accounted for 69% of patients and whites were 27%. Anemia etiologies included iron deficiency anemia at 25.3%, anemia of chronic inflammation at 9.8%, and hematologic malignancy in 7.5%. Unexplained anemia in the elderly accounted for 43.7% and predominated in both African Americans and whites. The prevalence of iron deficiency anemia and hematologic malignancies did not differ by race. Unexplained anemia in the elderly showed a consistent phenotype composed of a hypoproliferative mild-to-moderate anemia with suppressed serum erythropoietin. Specifically, erythropoietin levels showed no correlation with hemoglobin concentration in unexplained anemia in the elderly (r = -.15, p = .19) as opposed to iron deficiency anemia (r = -.63, p < .0001).. In summary, an intensive hematologic evaluation reveals a wide number of anemia etiologies among older adults, including 7.5% with hematologic malignancies; nevertheless, unexplained anemia in the elderly prevails as the most common category in whites and African Americans.

Topics: Aged; Aging; Anemia; Anemia, Iron-Deficiency; Black or African American; Chronic Disease; Cohort Studies; Erythropoietin; Female; Hematologic Neoplasms; Hemoglobins; Humans; Inflammation; Male; Outpatient Clinics, Hospital; Prevalence; Prospective Studies; Referral and Consultation; White People

Dual specificity protein tyrosine phosphatase PRL-2 is overexpressed in pediatric acute myeloid leukemia (AML) and is located at human chromosome 1p35, a region often rearranged or amplified in malignant lymphoma and B-cell chronic lymphocytic leukemia (B-CLL). Little is known of the significance of PRL-2 expression in hematopoietic malignancies. Herein we demonstrated that ectopic expression of PRL-2 in murine pre-B-cell line Baf3ER and mouse bone marrow cells induced key features associated with malignant progression and metastasis. PRL-2-transfected Baf3ER cells had augmented growth responses to hematopoietic growth factors Epo or IL-3 with shortened cell cycle, reduced requirement (5x) for Epo in cell survival, increased cell migration (3x), reduced cell adhesion (5x), and conversion to an immature cell morphology in association with increased expression (3x) of stem cell marker Bmi-1. When transduced into mouse bone marrow cells, PRL-2 increased Epo-induced colony formation (4x) and gave rise to larger colonies. These observations provide evidences implicating PRL-2 as a pathogenic molecule in hematopoietic malignancies and suggest its potential as a novel therapeutic target.

Topics: Animals; Bone Marrow Cells; Cell Adhesion; Cell Dedifferentiation; Cell Division; Cell Line; Cell Movement; Cell Survival; Colony-Forming Units Assay; Epoetin Alfa; Erythropoietin; Hematologic Neoplasms; Humans; Interleukin-3; Mice; Mice, Inbred C57BL; Precursor Cells, B-Lymphoid; Protein Tyrosine Phosphatases; Recombinant Fusion Proteins; Recombinant Proteins; STAT5 Transcription Factor; Transduction, Genetic

Topics: Animals; Carrier Proteins; Cytokines; Darbepoetin alfa; Erythropoietin; Fibroblast Growth Factor 7; Filgrastim; Granulocyte Colony-Stimulating Factor; Hematologic Neoplasms; Hematopoietic Cell Growth Factors; Humans; Polyethylene Glycols; Receptors, Fc; Recombinant Fusion Proteins; Recombinant Proteins; Thrombopoietin

To study whether hematologic malignancy patients with anemia have a lower erythropoietin (EPO) response.. Serum EPO levels were detected by ELISA in patients with hematologic malignancies and with iron deficiency anemia (IDA). Eighty patients with hematologic malignancies, including 13 multiple myeloma (MM), 7 chronic lymphocytic leukemia (CLL) and 60 non-Hodgkin's lymphoma (NHL) were studied. Thirty of them had anemia(21 NHL,6 MM and 3 CLL). Twenty patients with IDA were studied as the control.. Hematologic malignancy patients with anemia had higher EPO levels [(97.8 +/- 183.9) IU/L] than those with normal Hb values [(27.8 +/- 85.4) IU/L; P <0.01]. In patients with IDA, serum EPO response was inversely correlated with Hb level (r= -0.5, P <0.05) , but no such inverse correlation was found in the hematologic malignancy patients with anemia (r = -0.14). After corrected for Hb level, the serum EPO levels were significantly lower in anemic patients with hematologic malignancies than in IDA patients (P = 0.032) , indicating a decreased EPO response in the former group.. Anemia associated with hematologic malignancy might result from an inappropriately low EPO response. EPO treatment for these patients may be beneficial.

Topics: Adolescent; Adult; Aged; Anemia, Iron-Deficiency; Enzyme-Linked Immunosorbent Assay; Erythropoietin; Female; Hematologic Neoplasms; Hemoglobins; Humans; Male; Middle Aged; Prospective Studies

Blood transfusions are frequently required for several weeks after allogeneic transplantation due to inadequate erythropoiesis and defective erythropoietin production. Because red cell transfusion is not without complications in this setting, we sought to avoid them using recombinant human erythropoietin (rhEpo) therapy. We treated 53 patients following allogeneic transplantation for haematological malignancy, using rhEpo at a dose of 10 000 units subcutaneously twice weekly. The median time of commencement of rhEpo was 61 days post-transplant (range 19-465 days), and the median haemoglobin (Hb) concentration was 9.4 g dL(-1) (range 7.0-10.7 g dL(-1)). Thirty patients responded to rhEpo and required no further transfusion with a median rise in Hb after 2 weeks of therapy of 1.5 g (0.7-4.1 g dL(-1)). Erythropoietin (Epo) was discontinued at a median of 5 weeks (range 2-36), when the median Hb concentration was 12.3 g dL(-1) (range 10.0-14.3 g dL(-1)). Those patients who failed to respond to rhEpo frequently had additional reasons for anaemia including cytomegalovirus (CMV) reactivation and treatment, major ABO incompatibility, disease relapse, graft rejection or other transplant-related complications. We conclude that a short course of rhEpo is an effective treatment for anaemia arising following allogeneic hematopoietic cell transplantation, and can avoid the need for transfusion in this setting.

Topics: Anemia; Blood Transfusion; Drug Evaluation; Erythropoietin; Female; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Hemoglobins; Humans; Male; Recombinant Proteins; Retrospective Studies; Risk Factors; Transplantation, Homologous; Treatment Outcome

Topics: Erythropoietin; Hematologic Neoplasms; Humans; Myelodysplastic Syndromes; Neovascularization, Pathologic; Receptors, Erythropoietin

This study analyses the factors affecting mobilisation and engraftment in autologous peripheral blood progenitor cell transplantation according to the number of CD34(+) re-infused.. A total of 190 patients underwent mobilisation with G-CSF alone (n=113) or in combination with chemotherapy (n=77). A total of 116 patients (61%) were autografted with <2 x 10(6) CD34(+) cells/kg and 74 patients were transplanted with >2 x 10(6) CD34(+) cells/kg. Rates of granulocyte and platelet recovery were estimated using the product-limit method of Kaplan-Meier and compared using a log-rank test. The Cox regression model was used for the multivariate analysis of factors influencing engraftment. Differences between cohorts were evaluated by one-way ANOVA or Mann-Whitney tests, and multivariate analysis was performed using a stepwise lineal regression.. Neutrophil and platelet engraftment was significantly longer with <2 x 10(6)/CD34(+)/kg (12 vs 10 days, P=0.014 and 16 vs 13 days, P=0.0001 respectively). Platelet recovery was affected by exposure to alkylating agents (P=0.04), refractory disease (P=0.02) and AML (P=0.0001), but only the last two variables remained significant in Cox regression (P<0.01). Granulocyte engraftment was longer in CML (univariate, P=0.04) and in refractory disease (multivariate, P=0.02). In patients re-infused with >2 x 10(6)/CD34(+)/kg, the Cox model did not identify prognostic factors for haematopoietic recovery.. Although mobilisation schedules and disease status influenced not only the yield of progenitor cells, but also the engraftment kinetics, the number of CD34(+) re-infused was the main predictor of haematopoietic recovery. While engraftment succeeded in most of the cases, the re-infusion of >2 x 10(6)/CD34(+)/kg resulted in significantly shorter recovery times.

Topics: Adolescent; Adult; Aged; Antigens, CD34; Antineoplastic Combined Chemotherapy Protocols; Blood Cell Count; Caspase 14; Caspases; Cerebral Hemorrhage; Cohort Studies; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Erythropoietin; Etoposide; Female; Graft Survival; Granulocyte Colony-Stimulating Factor; Hematologic Neoplasms; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Humans; Hydroxyurea; Infections; Leukapheresis; Life Tables; Male; Middle Aged; Neoplasms; Proportional Hazards Models; Transplantation Conditioning; Transplantation, Autologous

Serum erythropoietin (sEpo) concentration depends primarily on the rate of renal production in response to hypoxia. However, sEpo levels increase inappropriately after conditioning for autologous stem cell transplantation (ASCT) before progressively returning to adequate levels. We investigated the possible influence of erythropoietic activity on these observations.. Forty patients undergoing an ASCT, 8 with bone marrow (BMT) and 32 with peripheral blood stem cells (PBSC), were separated into 3 groups. Group 1 was formed of the 8 BMT patients (median time to 1% reticulocytes: 39 days), group 2 of 16 PBSC patients with relatively slow erythroid engraftment (> or = 15 days to 1% reticulocytes, median 19 days) and group 3 of 16 PBSC patients with prompt erythroid recovery (< 15 days to 1% reticulocytes, median 13 days). Marrow erythroid activity was assessed by serum transferrin receptor levels (sTfR). Serum Epo (sEpo) levels were expressed in relation to the degree of anemia as observed/predicted (O/P) ratios of (O/P) log (sEpo).. Serum sTfR levels decreased by more than 50% in all 3 groups after conditioning, reaching their nadir on day 7. Nadir values doubled by day 28 in group 3, day 60 in group 2, but not within 100 days in group 1. O/P sEpo ratios increased inappropriately in all 3 groups after conditioning but then declined at very differing speeds in the 3 groups. In group 1, ratios remained above 1.10 through to day 28 and above 1.00 through to day 42, before leveling off at around 1.00 thereafter. In group 2, ratios remained above 1.00 through to day 14, than decreased to a minimum of 0.89 by day 42 before returning to 1.00 by day 100. In group 3, ratios decreased to 0.84 by day 21 and remained below 0.90 thereafter.. We conclude that sEpo levels are not only influenced by tissue oxygenation but also depend on the mass of erythroid precursors in the bone marrow. This may be the main explanation for the observed changes in sEpo levels during ASCT.

Topics: Adolescent; Adult; Bone Marrow Transplantation; Child; Erythropoiesis; Erythropoietin; Female; Hematologic Neoplasms; Humans; Male; Middle Aged; Transplantation, Autologous