losartan-potassium and Lymphoproliferative-Disorders

Rituximab, a monoclonal antibody directed against the CD20 molecule found on pre-B cells and mature B cells (but not on plasma cells), was introduced in the late 1990s for the treatment of non-Hodgkin's lymphoma. Recently, this antibody has been used to treat autoimmune diseases, especially those associated with a prominent humoral component and with potentially pathogenic autoantibodies. Small cohort studies have indicated that rituximab could have an important role in the management of these disorders. Rituximab has also been utilized in the transplant setting, to diminish levels of alloreactive antibodies in highly sensitized patients, to manage ABO-incompatible transplants, and to treat rejection associated with B cells and antibodies. The exact mechanism by which rituximab exerts its effects in autoimmunity and transplantation remains unclear, as specific autoantibody or alloantibody levels often seem not to diminish in parallel with clinical improvement. A role for rituximab in depleting B cells and compromising their antigen-presenting function seems likely; rituximab might also inhibit T-cell activation. A synergistic effect has been noted in vitro following administration of corticosteroids to B-cell lines, with accentuation of B-cell cytotoxicity; this observation might be relevant to certain studies, as some regimens have utilized both agents simultaneously. This article reviews the current use of rituximab in renal disease and transplantation, and includes discussion of the drug's potential role in novel therapeutic protocols.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Autoimmune Diseases; Autoimmunity; B-Lymphocytes; Erythropoietin; Glomerulonephritis, Membranous; Glomerulosclerosis, Focal Segmental; Graft Rejection; Humans; Immunologic Factors; Kidney Diseases; Kidney Transplantation; Lupus Erythematosus, Systemic; Lymphoproliferative Disorders; Recombinant Proteins; Red-Cell Aplasia, Pure; Rituximab; Vasculitis

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 common finding in patients with hematologic malignancies and most commonly can be attributed to the anemia of chronic disease compounded by the myelotoxic effects of chemotherapy. Symptoms of anemia include fatigue, and the patient's quality of life may be impaired. Possible treatments for the anemia are to do nothing, to transfuse with red cells, or to treat with recombinant human erythropoietin (rhEPO). rhEPO has become standard treatment for the anemia in chronic renal failure and has been successfully used in anemia secondary to malignancy. In patients with lymphoproliferative diseases, rhEPO increases the hemoglobin concentration, decreases the need for transfusion, and improves the patients' quality of life. Disadvantages of rhEPO include its cost, efficacy in only around 60% of patients, and delay of 4 to 8 weeks before maximum benefit is achieved. The anemia in patients with myelodysplasia responds less well to rhEPO. Misuse of rhEPO is common in the clinical setting but usually not of clinical importance. Misuse to enhance sporting prowess is probably rare but has potentially serious consequences.

Topics: Anemia; Doping in Sports; Erythropoietin; Humans; Lymphoproliferative Disorders; Medication Errors; Myelodysplastic Syndromes; Primary Myelofibrosis; Treatment Outcome

Anemia is a frequent clinical feature with adverse prognostic effects in patients with chronic lymphocytic leukemia (CLL). It may complicate CLL at any time during the course of the disease. Different factors concur to the occurrence of anemia in CLL, as in other lymphoproliferative diseases: leukemic bone marrow infiltration, the myelosuppressive effect of chemotherapy and inhibiting cytokines, autoimmune phenomena, hypersplenism, a poor nutritional status that leads to folic acid, vitamin B12 and iron deficiency. In addition, a defective endogenous erythropoietin (EPO) production has also been described in patients with lymphoproliferative diseases. The severity of anemia, which may be worsened by an impaired cardiopulmonary function, may profoundly compromise the patients' quality of life and, indirectly, the outcome of cancer bearing patients. Several Authors have reported the clinical activity of recombinant human (rHu)EPO in anemic patients with lymphoproliferative diseases, including CLL. Low serum EPO levels at baseline and EPO levels inappropriately low for the degree of anemia help to identify patients who are likely to respond to EPO. A clear dose-dependent response to EPO has been reported by different Authors and it has been suggested that 5,000 IU should be considered as an appropriate initial dose for the majority of patients. rHuEPO represents a potentially effective and safe therapy for the management of anemia associated with lymphoproliferative diseases. The reduction of red blood cell transfusion requirement, the improvement of quality of life through the remission of fatigue-related anemia are two important results that should be considered in the management of patients with CLL. In prospect, the availability of new rHuEPO molecules with a more prolonged half-life may open new therapeutic avenues.

Topics: Anemia; Anemia, Hemolytic, Autoimmune; Antineoplastic Agents; Bone Marrow; Cytokines; Dose-Response Relationship, Drug; Erythropoiesis; Erythropoietin; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Hypersplenism; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoproliferative Disorders; Multicenter Studies as Topic; Nutrition Disorders; Radiotherapy; Randomized Controlled Trials as Topic; Recombinant Proteins; Red-Cell Aplasia, Pure; Treatment Outcome

T gamma lymphocytes are those lymphocytes that express receptors for both the Fc portion of IgG and sheep erythrocytes. A very high proportion of normal T gamma lymphocytes are large granular lymphocytes (LGL), the cell responsible for most, if not all, natural killer (NK) and antibody-dependent cell-mediated cytotoxicity (ADCC) in humans, rats, and mice. In general, these cells are large lymphocytes with prominent azurophilic granules in the cytoplasm. Recently, a group of lymphoproliferative disorders made up predominantly of T gamma lymphocytes has been described. The most common and best studied of these disorders we refer to as "chronic T gamma-lymphoproliferative disease" (T gamma-LPD). In most cases, this disease represents the abnormal expansion of LGL, which is reflected by an increase in functionally active NK or ADCC effector cells. The chronic T gamma-LPD lymphocytes are generally characterized as E- and EA-rosette positive, acid-phosphatase, and beta-glucuronidase positive and express the pan-T antigens OKT3/Leu-4, OKT11/Leu-5, the suppressor-associated antigens OKT5,8/Leu-2, and the NK-associated antigens Leu-7/HNK-1. Typically, the patients are older, predominantly males and characteristically have a lymphocytosis of predominantly T gamma lymphocytes with lymphocyte infiltration of the bone marrow and often the spleen. While chronic T gamma-LPD is not usually an aggressive disease, the patients are often neutropenic and have recurrent bacterial infections requiring antibiotic therapy. Some patients have benefited from cytotoxic chemotherapy., but most patients have not required chemotherapy. An experimental LGL leukemia in F344 rats appears morphologically, functionally, and clinically similar to the human chronic T gamma-LPD and serves as an experimental model for further examining the ontogeny and function of LGL and may be applicable for exploring new and more effective means for the treatment of patients with chronic T gamma-LPD.

Topics: Adult; Aged; Alkylating Agents; Anemia; Animals; Antibody-Dependent Cell Cytotoxicity; Antigens, Surface; Erythrocytes; Erythropoietin; Female; Humans; Immunologic Surveillance; Killer Cells, Natural; Lymphocyte Activation; Lymphoma; Lymphoproliferative Disorders; Male; Middle Aged; Phagocytosis; Rats; Receptors, Fc; Rosette Formation; Skin Neoplasms; Splenectomy; T-Lymphocytes; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory

Functional iron deficiency is one reason for lack of response to erythropoietin treatment. Concomitant intravenous (IV) iron supplementation has the potential to improve response to erythropoietin, allowing a decrease in erythropoietin dose requirements. In a recent study of anaemic, iron-replete patients with lymphoproliferative malignancies (Leukemia, 21, 2007, 627), the haemoglobin (Hb) increase and response rate were significantly greater in patients receiving epoetin beta with concomitant IV iron compared with patients receiving epoetin beta without IV iron (P < 0.05). The present analysis aimed to investigate whether a combination of epoetin beta and IV iron is cost-effective compared with epoetin beta without IV iron.. This analysis was performed from a Swedish societal perspective as a within-trial evaluation of overall costs (based on differences in drug costs and resource use between groups) and effect (differences in Hb increases) during 16 weeks' treatment with epoetin beta with or without concomitant IV iron.. There was an improved response to epoetin beta with IV iron therapy and an almost 2-fold greater increase in Hb levels. Overall mean cost per patient in the epoetin beta with IV iron group was euro5558 and in the epoetin beta without IV iron group was euro6228. Thus, treatment with epoetin beta with IV iron resulted in overall cost savings of about 11% compared with epoetin beta without iron, mainly due to reduced erythropoietin dosages.. Epoetin beta with concomitant IV iron in anaemic patients with lymphoproliferative malignancies not receiving chemotherapy resulted in better outcomes at lower cost compared with epoetin beta without iron. This suggests that epoetin beta with IV iron is a dominant therapy from a Swedish perspective.

Topics: Aged; Aged, 80 and over; Anemia; Cost-Benefit Analysis; Dose-Response Relationship, Drug; Drug Costs; Drug Therapy, Combination; Erythropoietin; Female; Hemoglobins; Humans; Injections, Intravenous; Iron Compounds; Lymphoproliferative Disorders; Male; Middle Aged; Neoplasms; Recombinant Proteins; Sweden

The purpose of this study is to investigate the efficacy and safety of recombinant erythropoietin-beta in the treatment of anemic patients with multiple myeloma (MM), low-grade non-Hodgkin's lymphoma (NHL), and chronic lymphocytic leukemia (CLL). From December 2005 to November 2006, the patients with MM, low-grade NHL, and CLL were enrolled in this study, male or female, aged > or = 18 years, transfusion-dependant, and receiving anti-neoplasia chemotherapy. Recombinant human erythropoietin-beta was used in this study with the dose initiated at 150 IU/kg, thrice a week, subcutaneously. The total treatment duration was 12 weeks. The primary endpoint of the study is response rate (RR), which is defined as hemoglobin increasing > or = 2 g/dL comparing to baseline level, or returning to normal range, without any transfusion within 6 weeks of evaluation. Fifty out of 82 (64.6%) patients enrolled in this study responded to the treatment and 29 patients had no response. Hypertension (12.2%) is the most common adverse effect; however, all the adverse events were mild, categorized in NCI grade I or II. We conclude that recombinant erythropoietin-beta was effective in the treatment of anemia of the patients with MM, NHL, and CLL, as well as it is well-tolerated.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Asian People; Erythropoietin; Female; Ferritins; Humans; Iron; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Non-Hodgkin; Lymphoproliferative Disorders; Male; Middle Aged; Multiple Myeloma; Recombinant Proteins; Treatment Outcome

This randomized study assessed if intravenous iron improves hemoglobin (Hb) response and permits decreased epoetin dose in anemic (Hb 9-11 g/dl), transfusion-independent patients with stainable iron in the bone marrow and lymphoproliferative malignancies not receiving chemotherapy. Patients (n=67) were randomized to subcutaneous epoetin beta 30 000 IU once weekly for 16 weeks with or without concomitant intravenous iron supplementation. There was a significantly (P<0.05) greater increase in mean Hb from week 8 onwards in the iron group and the percentage of patients with Hb increase >or=2 g/dl was significantly higher in the iron group (93%) than in the no-iron group (53%) (per-protocol population; P=0.001). Higher serum ferritin and transferrin saturation in the iron group indicated that iron availability accounted for the Hb response difference. The mean weekly patient epoetin dose was significantly lower after 13 weeks of therapy (P=0.029) and after 15 weeks approximately 10 000 IU (>25%) lower in the iron group, as was the total epoetin dose (P=0.051). In conclusion, the Hb increase and response rate were significantly greater with the addition of intravenous iron to epoetin treatment in iron-replete patients and a lower dose of epoetin was required.

Topics: Anemia; Dose-Response Relationship, Drug; Drug Administration Schedule; Erythropoietin; Female; Hemoglobins; Humans; Infusions, Intravenous; Iron; Leukemia, Lymphoid; Lymphoma, Non-Hodgkin; Lymphoproliferative Disorders; Male

Epoetin beta, three-times weekly (t.i.w.), is effective in reversing anaemia in lymphoproliferative disorders. The current study investigated whether an epoetin beta dose of 30,000 IU given subcutaneously once weekly (q.w.) was at least as effective as 10,000 t.i.w. administration in anaemic patients with lymphoproliferative malignancy and defective endogenous erythropoietin (Epo) production. Overall, 241 anaemic patients with multiple myeloma, low-grade non-Hodgkin's lymphoma or chronic lymphocytic leukaemia, all with serum Epo values

Topics: Adult; Aged; Aged, 80 and over; Anemia; Area Under Curve; Blood Transfusion; Disease-Free Survival; Drug Administration Schedule; Erythropoietin; Female; Hemoglobins; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Non-Hodgkin; Lymphoproliferative Disorders; Male; Middle Aged; Multiple Myeloma; Proportional Hazards Models; Recombinant Proteins; Time

This phase 3, randomized, double-blind, placebo-controlled study was designed to evaluate the efficacy and safety of darbepoetin alfa in anaemic patients with lymphoproliferative malignancies. Patients (n = 344) with lymphoma or myeloma received darbepoetin alfa 2.25 microg/kg or placebo s.c., once weekly for 12 weeks. The percentage of patients achieving a haemoglobin response was significantly higher in the darbepoetin alfa group (60%) than in the placebo group (18%) (P < 0.001), regardless of baseline endogenous erythropoietin level. However, increased responsiveness was observed in patients with lower baseline erythropoietin levels. Darbepoetin alfa also resulted in higher mean changes in haemoglobin than placebo from baseline to the last value during the treatment phase (1.80 g/dl vs 0.19 g/dl) and after 12 weeks of treatment (2.66 g/dl vs 0.69 g/dl). A significantly lower percentage of patients in the darbepoetin alfa group received red blood cell transfusions than in the placebo group (P < 0.001). The efficacy of darbepoetin alfa was consistent for patients with lymphoma or myeloma. Improvements in quality of life were also observed with darbepoetin alfa. The overall safety profile of darbepoetin alfa was consistent with that expected for this patient population. Darbepoetin alfa significantly increased haemoglobin and reduced red blood cell transfusions in patients with lymphoproliferative malignancies receiving chemotherapy.

Topics: Aged; Analysis of Variance; Anemia; Blood Transfusion; Darbepoetin alfa; Diarrhea; Double-Blind Method; Erythropoietin; Fatigue; Female; Fever; Follow-Up Studies; Humans; Linear Models; Lymphoma; Lymphoproliferative Disorders; Male; Middle Aged; Multiple Myeloma; Nausea; Quality of Life

Darbepoetin alfa is a novel erythropoiesis-stimulating protein with a prolonged serum half-life. This randomized, double-blind, placebo-controlled, dose-finding study investigated the efficacy and safety of darbepoetin alfa in anaemic patients with lymphoproliferative malignancies who were receiving chemotherapy. Patients were randomized in a 1:2:2:1 ratio to receive darbepoetin alfa 1.0 microg/kg (n = 11), 2.25 microg/kg (n = 22), 4.5 microg/kg (n = 22) or placebo (n = 11), administered subcutaneously once weekly for 12 weeks. No dose increases were allowed during the study. A higher proportion of patients achieved a haemoglobin response (defined as a >/= 2.0 g/dl increase from baseline) in the darbepoetin alfa 1.0 microg/kg (45%), 2.25 microg/kg (55%) and 4.5 microg/kg (62%) groups than in the placebo group (10%; P < 0.01). The mean change in haemoglobin from baseline to week 13 was 1.56 g/dl in the 1.0 microg/kg group, 1.64 g/dl in the 2.25 microg/kg group and 2.46 g/dl in the 4.5 microg/kg group, compared with a mean change of 1.00 g/dl in the placebo group. The overall safety profile of darbepoetin alfa in this study was similar to that of placebo. These results show that darbepoetin alfa effectively and safely increased haemoglobin concentrations in patients with lymphoproliferative malignancies. Confirmative studies at doses of 2.25 and/or 4.5 microg/kg/week in this population are warranted.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Darbepoetin alfa; Dose-Response Relationship, Drug; Double-Blind Method; Erythrocyte Transfusion; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Lymphoproliferative Disorders; Male; Middle Aged

Our objective was to evaluate the effects of darbepoetin alfa (Aranesp) on hemoglobin and transfusions in anemic patients with cancer undergoing chemotherapy, and the impact of age, sex, baseline hemoglobin, chemotherapy type, and tumor type. Patients were randomized to one of three darbepoetin alfa groups based on average weekly dose (< 1.5 microg/kg, 1.5 to 2.25 microg/kg, and > 2.25 microg/kg) or to placebo. Dose response was evaluated for change in hemoglobin, hemoglobin and hematopoietic responses, and red blood cell transfusion rates. Hazard ratios for the incidence of hemoglobin response and transfusions were calculated. Adverse events and antibody formation were assessed. Treatment effects were observedfor all hemoglobin end points and incidence of transfusion. The incidence of hematopoietic response among the darbepoetin alfa dose groups ranged from 46% (95% confidence interval [CI] = 33%-60%) to 74% (95% CI = 66%-81%) and increased with higher darbepoetin alfa dose. Patients receiving darbepoetin alfa were more likely to exhibit a hemoglobin response and less likely to require a transfusion, compared with placebo, irrespective of the patient characteristics examined. No increased risk of adverse events and no development of neutralizing antibodies were observed with darbepoetin alfa use. Darbepoetin alfa increased the likelihood of a hemoglobin response and decreased the need for transfusions in cancer patients with chemotherapy-induced anemia.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Anemia; Darbepoetin alfa; Double-Blind Method; Drug Administration Schedule; Erythrocyte Transfusion; Erythropoietin; Female; Hemoglobins; Humans; Lung Neoplasms; Lymphoproliferative Disorders; Male; Middle Aged; Platinum; Population Surveillance; Sex Factors; Treatment Outcome

We have used recombinant human erythropoietin (rHuEPO) in a phase I/II clinical trial to evaluate its ability to reverse refractory anemia in hematologic disorders. rHuEPO was administered subcutaneously 5 days per week at escalating doses (50 to 150 U/kg per day). The aim of treatment was a hemoglobin (Hb) level greater than or equal to 10 g/dL without blood transfusion. Of 25 patients treated, 17 were evaluable, most of them with a regular need for transfusion. Eight of these had lymphoproliferative disorders (three cases of malignant lymphoma and five of monoclonal gammopathy) and were exposed to cytotoxic therapy. The other nine patients had hematopoietic stem cell disorders (four cases of myelodysplastic syndrome, three of idiopathic myelofibrosis, and two of chronic myelogenous leukemia). All patients with lymphoproliferative disorder had serum EPO levels inappropriately low for the degree of anemia, while patients with stem cell disorder showed variable values. Erythroid marrow activity was inadequate in all cases. Seven of eight patients with lymphoproliferative disorder responded to treatment maintaining Hb above 10 g/dL without transfusion. The median dose of rHuEPO required for correction of anemia was 75 U/kg. In four cases response was maintained with 50 U/kg, three times per week. There was no complete response among patients with hematopoietic stem cell disorder, although transfusion requirement was eliminated or reduced in four cases. Four patients developed functional iron deficiency during rHuEPO treatment and required iron supplementation to obtain response. Aggravation of splenomegaly was observed in two cases of myeloproliferative disorder. We conclude that: (1) subcutaneous administration of rHuEPO can be effective and safe in patients with lymphoproliferative disorder exposed to chemotherapy and showing inappropriate EPO response to anemia; (2) this is less likely in hematopoietic stem cell disorders, although favorable responses may be observed in occasional patients; and (3) functional iron deficiency as a cause of nonresponse to rHuEPO is frequent also in nonrenal anemia.

Topics: Adult; Aged; Anemia, Refractory; Bone Marrow; Drug Evaluation; Erythroid Precursor Cells; Erythropoietin; Female; Ferritins; Hematologic Diseases; Humans; Iron; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Lymphoproliferative Disorders; Male; Middle Aged; Myelodysplastic Syndromes; Primary Myelofibrosis; Receptors, Transferrin; Recombinant Proteins

To clarify the prognostic value of the baseline blood levels of endogenous erythropoietin (EE) and tumor necrosis factor-a (TNF-a) involved in the key components of the pathogenesis of anemia in lymphoproliferative diseases (LPD), the counts of reticulocytes and platelets (hematopoietic preservation indicators) in the use of erythropoiesis-stimulating agents (ESAs) to correct anemia syndrome (AS) in patients with LPD.. The results of AS treatment with ESAs were analyzed in 48 patients with LPD. A study group comprised patients with chronic lymphocytic leukemia (n=1 3), indolent lymphomas (n=14), and multiple myeloma (n=21). Their hemograms (hemoglobin concentration, red blood cells, packed cell volume, reticulocytes, and platelets) and blood EE and TNF-alpha levels were examined before using ESAs. The hemogram was monitored during treatment. ESAs (eralfon (epoietin alpha) in 21 patients and epres in 27) were subcutaneously injected in a dose of 150 IU/kg thrice weekly (for not more than 16 weeks). A control group included 21 anemic patients with multiple myeloma who did not receive ESAs. Increasing hemoglobin concentrations up to 120 g/l was regarded as a positive response to ESA treatment.. By and large, the efficacy of epoietin alpha was 62.5% (61.9% for eralfon and 63.0% for epres), which was significantly higher than that in the control group (23.4%; p<0.05). A number of blood laboratory parameters were found to be of value in predicting the efficacy of ESAs. The patients with the decreased baseline concentrations o EE ( <130 mlU/ml) and TNF- alfa (,15 pg/ml) were ascertained to show a positive response more frequently (80 and 92.9%, respectively; p<0.05) than those with thepredicting the efficacy of ESAs. The patients with the decreased baseline concentrations of EE (<130 mlU/ml) and TNF-a (<15 elevated concentrations of the enzymes in question. In addition, a positive response was more often recorded in patients with reticulocyte counts of more than 1% (77.4%; p<0.05) and platelets of 100-10(9)/1 (70%; p=0.05).. Estimating the baseline blood levels of EE and TNF-a and the counts of reticulocytes and platelets prior to the use of ESAs enables prediction of the efficiency of erythropoiesis-stimulating therapy in anemic patients with LPD.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Erythropoietin; Female; Hematinics; Hematologic Tests; Humans; Lymphoproliferative Disorders; Male; Middle Aged; Predictive Value of Tests; Severity of Illness Index; Treatment Outcome; Tumor Necrosis Factor-alpha; Young Adult

Recent studies have suggested that epoetin treatment of anaemia may influence the survival of patients with cancer. We conducted an analysis of long-term survival in patients with lymphoproliferative malignancies treated with epoetin-beta or placebo in a large-scale study. This was a randomized, double-blind trial in which patients with transfusion-dependent anaemia and lymphoproliferative malignancy received epoetin-beta 150 IU/kg or placebo three times weekly for 16 weeks. Long-term survival data were analysed by standard Kaplan-Meier methods and differences between groups were assessed using a log-rank test. The intention-to-treat population consisted of 343 patients (epoetin-beta, n = 170; placebo, n = 173). There were no major differences between the two treatment groups in demographic or clinical characteristics/prognostic factors. A total of 110 (65%) patients died in the epoetin-beta group (censored, n = 60) and 109 (63%) died in the placebo group (censored, n = 64) up to the end of long-term follow up. Kaplan-Meier curves for survival were similar in both groups. Median survival was 17 months with epoetin-beta and 18 months with placebo. A log-rank test indicated no significant difference in survival (P = 0.76). This long-term follow up indicated that epoetin-beta has no significant effect on survival compared to placebo in anaemic patients with lymphoproliferative malignancies.

Topics: Anemia; Double-Blind Method; Epoetin Alfa; Erythropoietin; Follow-Up Studies; Hematinics; Humans; Lymphoproliferative Disorders; Proportional Hazards Models; Randomized Controlled Trials as Topic; Recombinant Proteins; Survival Rate; Treatment Failure

Topics: Animals; Cell Line, Tumor; Disease Models, Animal; Epoetin Alfa; Erythropoietin; Female; Leukemia, B-Cell; Lymphoma, B-Cell; Lymphoproliferative Disorders; Mice; Mice, Inbred BALB C; Plasmacytoma; Recombinant Proteins

Topics: Anemia; Drug Administration Schedule; Erythropoietin; Humans; Lymphoproliferative Disorders; Recombinant Proteins

Topics: Anemia; Drug Administration Schedule; Erythropoietin; Humans; Lymphoproliferative Disorders; Recombinant Proteins

We compared the use of G-CSF plus EPO in a group of 32 multiple myeloma and lymphoma patients with historical controls receiving G-CSF alone. Haemopoietic reconstitution was significantly faster in patients receiving G-CSF+EPO (group B), with a median time of 10 days to achieve an ANC count >0.5 x 10(9)/l, compared to 11 days in the historical group (A). The median duration of severe neutropenia (ANC count <100/ml) was significantly shorter in group B compared to group A; platelet counts >20 x 10(9) and >50 x 10(9)/l were achieved at days + 13 and + 17, respectively in group B, compared to days + 14 and + 24, respectively, in group A (P = 0.015, 0.002) patients. The transfusion requirement was reduced in group B, with 0 (0-6) RBC units and 1 (0-5) platelet unit transfused in group B vs 2 RBC (0-9) and 2 platelet units (0-8) in group A. Median days of fever, antibiotic therapy and hospital stay were reduced in group B (9.5 days vs 22). The mean cost of autotransplantation per group A patient was 23,988 Euro, compared with 18,394 Euro for a group B patient. Our study suggests that the EPO + G-CSF combination not only accelerates engraftment kinetics, but can also improve the clinical course of ASCT.

Topics: Adult; Aged; Blood Transfusion; Cost-Benefit Analysis; Erythropoietin; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Humans; Kinetics; Lymphoproliferative Disorders; Male; Middle Aged; Multiple Myeloma; Multivariate Analysis; Platelet Count; Recombinant Proteins; Stem Cell Transplantation; Time Factors; Treatment Outcome

Thirty three B-chronic lymphoproliferative disorder (B-CLD) patients [22 with B-chronic lymphocytic leukemia (B-CLL), 5 with small lymphocytic lymphoma (SLL) and 6 with lymphoplasmacytic lymphoma (LPL)] with anaemia (Ht <32%) of no other cause but their disease, received recombinant human erythropoietin (r-HuEPO). The treatment protocol provided r-HuEPO in a dose of 150 U/kg s.c. thrice weekly for 3 mo. After 1.5 mo of r-HuEPO administration, if response was not satisfactory, r-HuEPO dose escalation was utilised by giving incremental doses of 50 U/kg more than the previous dose up to a maximum dose of 300 U/kg tiw. After maximal response, half of the responding patients discontinued therapy, while the other half received maintenance therapy at a dose of 150 U/kg s.c./w. Oral iron was given throughout the study. Pretreatment EPO levels were determined in all patients. A complete response (CR) was defined when Ht was >38% and a partial response (PR) when there was an increase of the Ht >6% from the initial value was achieved. Sixteen of the 22 B-CLL patients had Rai stage III disease and 6 stage IV, with a median duration of anaemia 27 months (6-38); twelve of them were receiving chlorambucil while the rest were on no treatment. Of the SLL and LPL group, 4 patients had Ann Arbor stage III disease and 7 stage IV with a median duration of anaemia 24 months (5-36); 8 patients were on chlorambucil. Complete response was achieved in 50% of the B-CLL group and 54% of the SLL and LPL group, with an overall response rate of 77% and 81% respectively. All patients on maintenance therapy had a continuous response, while all patients, in whom rHuEPO was discontinued, relapsed. No correlation was found between patients: with low or high pretreatment serum EPO levels; those receiving concomitant therapy or not; those with B-symptoms or not; those with a non-diffuse or diffuse bone marrow infiltration pattern; and with splenomegaly or not. Life quality was significantly improved and no major side effects were encountered. We conclude from our study that r-HuEPO is very effective in correcting disease-related anaemia in B-CLD, resulting in down-staging of Rai stage III patients and that maintenance therapy is necessary. Whether the correction of anaemia improves patients' overall survival, still remains to be seen.

Topics: Aged; Aged, 80 and over; Anemia; B-Lymphocytes; Erythropoietin; Female; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoproliferative Disorders; Male; Middle Aged; Prognosis; Quality of Life; Recombinant Proteins; Severity of Illness Index; Splenomegaly; Treatment Outcome

Topics: Aged; Anemia, Refractory; Erythropoietin; Female; Humans; Leukemia; Lymphoproliferative Disorders; Male; Middle Aged; Recombinant Proteins; Waldenstrom Macroglobulinemia

Topics: Adolescent; Adult; Blood Donors; Busulfan; Child; Child, Preschool; Cyclosporine; Erythropoietin; Female; Graft vs Host Disease; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Histocompatibility Testing; Humans; Leukemia; Lymphoma; Lymphoproliferative Disorders; Male; Methotrexate; Middle Aged; Prednisolone; Whole-Body Irradiation

A 54-year-old man was admitted with fatigue. The peripheral blood count showed leukocytosis (9, 600/microliters), including 76% granular lymphocytes (GLs), which expressed CD2, 3, 8, 16 and HLA-DR, and anemia (hemoglobin 8.1 g/dl). He was diagnosed as having T cell type-granular lymphocyte proliferative disorder with anemia. Bone marrow examination revealed the involvement of 4.6% of GL and erythroblastopenia. A clonogenic assay of bone marrow cells revealed the decrease in erythroid colony formation in both CFU-E and BFU-E, but the number of erythroid colonies increased when CD8-positive cells were depleted from bone marrow cells and the number of erythroid colonies decreased again when CD8-positive GLs were added. The supernatant of cultured CD8-positive GLs had no inhibitory effect on CFU-E and BFU-E colony formation. These suggested that CD8-positive GLs suppressed the erythroid colony formation in this case. Treatment with 6,000 U/body of recombinant human erythropoietin (rh-Epo) subcutaneously three times a week was started and increased dose of 12,000 U/body of rh-Epo led to an increase in the hemoglobin level to 10.5 g/dl two months later. He has been treated with rh-Epo only.

Topics: Anemia; Erythropoietin; Humans; Lymphoproliferative Disorders; Male; Middle Aged; Recombinant Proteins

Pathogenesis of anemia in patients with myeloma, low grade lymphoma and acute leukaemia was the aim of the study. Erythropoietin (Epo) serum level was detected according to ELISA test. Significant increase of Epo serum level in 13 myeloma and 30 low grade lymphoma patients was found. In 21 acute leukemia cases the Epo serum level was significantly increased (disproportional to Hb concentration).. in the studied myeloma and low grade lymphoma patients anemia did not depend on defective Epo secretion. Significant increase of Epo serum level in acute leukaemia, strongly suggested additional stimulation mechanism for hormone synthesis. Further studies of this mechanism are needed.

Topics: Adult; Aged; Anemia; Enzyme-Linked Immunosorbent Assay; Erythropoietin; Humans; Lymphoproliferative Disorders; Middle Aged

Immunoreactive erythropoietin levels were measured in 42 patients with lymphoid malignancies with anaemia and bone marrow involvement. Results were compared to a control group of 16 patients suffering from anaemia due to other causes. Significant inverse correlations between serum erythropoietin level and haemoglobin concentration were shown for the patients with lymphoid malignancies and also for the control subjects. Overall, the erythropoietin levels of patients with lymphoid malignancies with bone marrow infiltration and with normal renal function did not differ significantly from erythropoietin levels of the anaemic controls. We conclude that anaemia in patients with lymphoproliferative disorders with bone marrow infiltration and normal renal function is caused primarily by a diminished/inadequate response to erythropoietin at the level of the target cell.

Topics: Anemia; Bone Marrow Diseases; Erythropoietin; Female; Hematocrit; Hemoglobins; Humans; Lymphoma; Lymphoproliferative Disorders; Male; Multiple Myeloma; Neoplasm Metastasis