losartan-potassium and Anemia--Refractory

Topics: Acetamides; Aged; Anemia, Refractory; Anemia, Sideroblastic; Anti-Bacterial Agents; Arthroplasty; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Combined Modality Therapy; Comorbidity; Diabetes Mellitus, Type 2; Diagnosis, Differential; Erythrocyte Transfusion; Erythropoietin; Female; Humans; Linezolid; Methicillin-Resistant Staphylococcus aureus; Obesity, Morbid; Oxazolidinones; Polypharmacy; Postoperative Complications; Prosthesis-Related Infections; Reoperation

The present meta-analysis was undertaken to (1) assess erythroid response rates in myelodysplastic syndromes (MDS) patients treated with epoetin alfa as a monotherapy, (2) gain further insights into predictors of response rates, and (3) compare the erythroid response rates observed with epoetin alfa and darbepoetin alfa. A systematic review of studies from 1990 to 2006 in MDS patients treated with epoetin alfa or darbepoetin alfa was performed and yielded 30 studies evaluating a total of 1,314 patients (epoetin alfa: 22 studies, 925 patients; darbepoetin alfa: eight studies, 389 patients). Pooled estimates of erythroid response rates, stratified by the International Working Group criteria (IWGc) and treatment group, were calculated using random-effects meta-analysis methods. Univariate meta-regression analyses were further conducted to identify study characteristics associated with erythroid response rate. The pooled estimate of erythroid response rate was significantly higher for epoetin alfa IWGc studies (57.6%) as compared to non-IWGc studies (31.6%; p < 0.001). Study factors predictive of higher response rate in the epoetin alfa IWGc studies included higher proportion of patients with RA/RARS (p < 0.001), lower mean baseline serum erythropoietin level (p = 0.007), and fixed dosing regimen (p < 0.001). There was no significant difference in the pooled erythroid response rates between the two agents (epoetin alfa: 57.6% vs. darbepoetin alfa: 59.4%; p = 0.828). The current study reported significantly higher erythroid response rates predominantly in the more recent studies that primarily utilized IWGc to define response. With the use of standardized patient selection and response evaluation methods, epoetin alfa and darbepoetin alfa yielded comparable erythroid response rates in MDS patients.

Topics: Aged; Anemia; Anemia, Refractory; Anemia, Sideroblastic; Blood Transfusion; Darbepoetin alfa; Dose-Response Relationship, Drug; Drug Evaluation; Epoetin Alfa; Erythropoiesis; Erythropoietin; Female; Hematocrit; Hemoglobins; Humans; Male; Myelodysplastic Syndromes; Recombinant Proteins; Treatment Outcome

Erythropoietin (epo) can be used to improve the anaemia of patients with myelodysplastic syndromes (MDS), but the efficacy is relatively low and the treatment is expensive. So far, no individual clinical trial has been sufficiently extensive to provide a basis for a decision model for the use of epo in MDS. This meta-analysis included 17 original articles with a total of 205 patients with MDS who had been treated with epo. 33 patients (16%) showed a significant response to treatment. Patients with refractory anaemia with ring sideroblasts (RAS) showed a lower response rate than all other patients (7.5% v 21%, P = 0.010). The difference in response rate between patients with and without transfusion need was also highly significant (10% v 44%, P < 0.001). The serum level of epo was significantly lower in the responding patients, but this parameter on its own could not be used to identify patients with a favourable response. FAB group (RAS versus others), transfusion need and s-epo (>/< 200 U/l) were combined in a model to provide information about the probability of response in different groups of patients. Patients with no transfusion requirement and MDS other than RAS showed a response rate of > or = 50%, irrespective of their serum level of epo. In patients with RAS and s-epo > 200 U/l, no response was observed. In the remaining groups the response rates varied between 9% and 33%. This meta-analysis shows that the efficacy of epo in MDS in general was low, but that groups of patients with an acceptable response rate could be identified.

Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; Anemia, Refractory; Anemia, Sideroblastic; Blood Transfusion; Erythropoietin; Female; Humans; Male; Middle Aged; Myelodysplastic Syndromes; Prognosis; Recombinant Proteins

Topics: Anemia; Anemia, Refractory; Erythroid Precursor Cells; Erythropoiesis; Erythropoietin; Humans; Hypoxia; Kidney Failure, Chronic; Polycythemia; Recombinant Proteins

Topics: Anemia, Refractory; Erythropoietin; Humans; Kidney Failure, Chronic; Recombinant Proteins

We previously reported a 60% erythroid response rate with recombinant erythropoietin + 13-cis retinoic acid + dihydroxylated vitamin D3 in 63 elderly myelodysplastic patients (median age 75 years) with unfavourable features for response to erythropoietin alone [70% transfusion-dependent, 35% refractory anaemia with ring sideroblasts/refractory anaemia with excess of blasts type 1 (RAEB1), 70% with International Prognostic Scoring System (IPSS) Intermediate-1 or -2]. This report updates that case study at a 7-year follow-up, and compared the impact on overall survival of erythroid response to known prognostic factors. The erythroid response duration (median 17 months; 22 in non-RAEB patients, with 20% patients in response after 6 years of therapy) was longer than in most studies with erythropoietin alone. Overall survival (median 55 months in non-RAEB, 15 in RAEB1 patients) was negatively affected by RAEB1 diagnosis, IPSS and WPSS intermediate scores and transfusion-dependence. In the multivariate analysis, erythroid response maintained an independent positive impact on survival, particularly in non-RAEB patients in the first 3 years from diagnosis (90% survival compared to 50% of non-responders). In conclusion, the long-term follow-up confirmed the achievement, by our combined treatment, of fairly long-lasting erythroid response in the majority of MDS patients with unfavourable prognostic features for response to erythropoietin: this translated in a survival benefit that was independent from other prognostic features.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Refractory; Calcitriol; Drug Administration Schedule; Drug Therapy, Combination; Erythropoietin; Female; Humans; Isotretinoin; Male; Middle Aged; Myelodysplastic Syndromes; Prognosis; Recombinant Proteins; Survival Analysis; Treatment Outcome

Hemodialysis (HD) patients with functional iron deficiency (FID) often develop resistance to recombinant human erythropoietin (Epo). The contributory role of chronic inflammation and oxidative stress in its pathogenesis is poorly understood. We assessed the effect of vitamin C, an antioxidant, on Epo-hyporesponsive anemia in hemodialysis patients with un-explained hyperferritinemia levels. Thirty-one of 132 with Hb 15 patients received standard care and 300 mg of intravenous vitamin C with each dialysis session (group 1) and 15 patients received standard care (group 2). After 3 months, Hb and transferrin saturation levels significantly increased in group 1 but not in group 2 (p < 0.05%). Hemoglobin content in reticulocyte and serum ferritin decreased significantly in group 1 but not in control group. In conclusion, hemodialysis patients with refractory anemia and adequate iron stores, vitamin C improved responsiveness to Epo by augmenting iron mobilization and possibly via antioxidant effect.

Topics: Anemia, Refractory; Antioxidants; Ascorbic Acid; Erythropoietin; Female; Ferritins; Humans; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Renal Dialysis; Reticulocytes

Five, repeatedly transfused, patients with refractory anemia (RA) or RA with ringed sideroblast (RARS) subtypes of myelodysplastic syndrome (MDS), with serum ferritin (SF) levels of > 2,000 microg/L, and one female with Hb E [beta26(B8)Glu --> Lys]/beta0-thalassemia (thal) with an SF level of 1,760 microg/ L, were treated with deferiprone (L1) at the dose of 4-6 g per day for at least 26 months. Beginning in the second month, all patients received recombinant human erythropoietin (rHuEPO) at the dose of 150 IU/kg thrice weekly, subcutaneously for 24 months. A significant increase in iron excretion after combined administration of L1 and rHuEPO compared to treatment with L1 as a single agent, was observed in all patients. The amount of excreted iron in urine ranged from 7.5 to almost 20 mg per day. In one patient, a response to rHuEPO resulted in transfusion independence and her SF decreased from 2086 to 879 microg/L. In four MDS patients, who remained dependent on red blood cell (RBC) transfusions, simultaneous administration of L1 and rHuEPO enabled the stabilization of SF levels, despite continuing iron load from the transfusions. Combined administration of rHuEPO and oral iron chelators may potentiate mobilization of storage iron and maintain iron balance in transfusion-dependent iron overloaded early MDS patients.

Topics: Administration, Oral; Anemia, Refractory; Deferiprone; Drug Administration Schedule; Drug Therapy, Combination; Erythropoietin; Female; Ferritins; Humans; Injections, Subcutaneous; Iron; Iron Chelating Agents; Myelodysplastic Syndromes; Pyridones; Recombinant Proteins

Treatment with recombinant human erythropoietin (rHuEpo) improves anaemia in approximately 20% of patients with myelodysplastic syndromes (MDS). We investigated the potential advantage of a prolonged administration of rHuEpo to achieve higher erythroid response rates (RR) in 281 MDS patients: 118 with refractory anaemia (RA), 77 with refractory anaemia and ringed sideroblasts (RARS), 59 with refractory anaemia with excess of blasts and blast count < 10% (RAEB-I), and 27 with RAEB and blast count between 11-20% (RAEB-II). rHuEpo was given subcutaneously at a dose of 150 U/kg thrice weekly, for a minimum of 26 weeks. Response to treatment was evaluated after 12 and 26 weeks of therapy. The overall RR was 45.1%; the RR for RA, RARS, RAEB-I and RAEB-II were 48.3%, 58.4%, 33.8% and 13% respectively. A significant increase in RR was observed at week 26 in RA, RARS and RAEB-I patients, as the response probability increased with treatment duration. The RR was higher in the good cytogenetic prognostic group and serum Epo level of > 150 U/l at baseline predicted for non-response. The median duration of response was 68 weeks and the overall risk of leukaemic transformation was 21.7%. These results suggest that prolonged administration of rHuEpo produces high and long-lasting erythroid RR in MDS patients with low blast counts, particularly in those with pretreatment serum Epo levels of < 150 U/l and good cytogenetic prognosis.

Topics: Aged; Aged, 80 and over; Anemia, Refractory; Anemia, Refractory, with Excess of Blasts; Anemia, Sideroblastic; Erythropoietin; Female; Humans; Male; Middle Aged; Myelodysplastic Syndromes; Prospective Studies; Treatment Outcome

The outcome of continued EPO therapy was studied in 18 responding MDS patients. The EPO dose was reduced in a stepwise fashion to find the lowest possible maintenance dose. Relapses of anemia were associated with either progressive disease or reduction of the administered EPO dose. In the latter group second responses to renewed EPO therapy were readily achieved. Long-term responses were seen in about a third of the patients. Thus, it seems safe to reduce the EPO dose among responding patients. This approach may have advantages both from a medical and a socio-economic perspective.

Topics: Aged; Aged, 80 and over; Anemia, Refractory; Dose-Response Relationship, Drug; Erythropoietin; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myelodysplastic Syndromes; Recombinant Proteins; Survival Rate; Treatment Outcome

Amifostine is a cytoprotective agent mainly used in cancer therapies, in order to ameliorate the toxic effects of anticancer chemotherapy and radiotherapy. In the past years an intriguing number of applications of amifostine have been identified; one of these is bone marrow cells protection and stimulation. Amifostine was administered in seven patients with myelodysplastic syndromes, four males and 3 females aged between 67 and 78 years old, in order to estimate its efficacy in reducing the need for red blood cells transfusions. Two patients had RAEB, four RA and one RARS. The drug was administered in an outpatient basis in a dose of 300 mgr/m2, three times weekly for at least four weeks. We administered at the same time erythropoietin 10.000 U subcutaneously. All patients received daily supplementation of oral ferrum sulfate and folic acid. Three patients, a woman with RA and two men, one with RA and another with RAEB improved the levels of Hb beyond 12,0 gr/dl and did not receive blood transfusions after the second week of treatment. The drug was well tollerated without any side effects in all of the patients.

Topics: Aged; Amifostine; Anemia, Refractory; Anemia, Refractory, with Excess of Blasts; Blood Transfusion; Bone Marrow Cells; Cytoprotection; Erythropoietin; Female; Humans; Male; Myelodysplastic Syndromes; Outpatients; Recombinant Proteins

Severe forms of epidermolysis bullosa result in a transfusion-dependent chronic anemia and are fatal. The cause of the anemia is unknown. We evaluated five children whose anemia failed to respond to oral iron but who became transfusion independent after treatment with intravenous iron and human recombinant erythropoietin.

Topics: Adolescent; Anemia, Refractory; Blood Transfusion; Child; Child, Preschool; Chronic Disease; Drug Therapy, Combination; Epidermolysis Bullosa; Erythropoietin; Humans; Infant; Infusions, Intravenous; Iron; Iron Deficiencies; Recombinant Proteins

Patients with myelodysplastic syndromes (MDS) have refractory cytopenias leading to transfusion requirements and infectious complications. In vitro marrow culture data have indicated that granulocyte colony stimulating factor (G-CSF) synergizes with erythropoietin (EPO) for the production of erythroid precursors. In an effort to treat the anemia and neutropenia in this disorder, MDS patients were treated with a combination of recombinant human EPO and recombinant human G-CSF. Fifty-five patients were enrolled in the study of which 53 (96%) had a neutrophil response. Forty-four patients were evaluable for an erythroid response of which 21 (48%) responded. An erythroid response was significantly more likely in those patients with relatively low serum EPO levels, higher absolute basal reticulocyte counts and normal cytogenetics at study entry. Seventeen (81%) of the patients who responded to combined G-CSF plus EPO therapy continued to respond during an 8-week maintenance phase. G-CSF was then discontinued and all patients' neutrophil responses were diminished, whereas 8 continued to have an erythroid response to EPO alone. In 7 of the remaining 9 patients, resumption of G-CSF was required for recurrent erythroid responses. The median duration of erythroid responses to these cytokines was 11 months, with 6 patients having relatively prolonged and durable responses for 15 to 36 months. Our results also indicate that approximately one half of responding patients require both G-CSF and EPO to maintain an effective erythroid response, suggesting that synergy between G-CSF and EPO exists in vivo for the production of red blood cells in MDS.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Refractory; Anemia, Refractory, with Excess of Blasts; Drug Synergism; Drug Therapy, Combination; Erythropoietin; Female; Follow-Up Studies; Granulocyte Colony-Stimulating Factor; Humans; Life Tables; Male; Middle Aged; Recombinant Proteins; Treatment Outcome

Ten patients with aplastic anemia (AA) and seven patients with refractory anemia (RA) were treated with recombinant human granulocyte colony-stimulating factor (rhG-CSF) and erythropoietin (rhEpo) in combination. rhG-CSF (5-20 micrograms/kg) and rhEpo (120-720 U/kg) were administered by s.c. injection three times a week for at least six months, and the administration was continued as maintenance therapy for as long as possible when hematological responses were observed. Six (60%) of the ten AA patients and four (58%) of the seven RA patients showed multilineage responses. Of these responders, six patients achieved trilineage recovery. While all of the responders were dependent on red blood cell transfusions and eight of them required platelet transfusions before treatment, they now no longer need transfusions of either red blood cells or platelets. A median treatment duration of 9 (range 1 to 28) months was required to achieve multilineage recovery. The responders showed an ability to maintain the multilineage recovery for 9+ to 47+ months and to tolerate long-term treatment. These results indicate that the long-term treatment with rhG-CSF and rhEpo may benefit a substantial percentage of patients with AA and RA and provide an optional therapy for these patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia, Aplastic; Anemia, Refractory; Drug Therapy, Combination; Erythrocyte Transfusion; Erythropoietin; Female; Granulocyte Colony-Stimulating Factor; Humans; Male; Middle Aged; Platelet Transfusion; Recombinant Proteins; Time Factors

Sixteen patients (ages 53 to 85) with myelodysplastic syndrome (MDS) were treated with recombinant human erythropoietin (rHuEPO) to observe its effects on hematopoiesis. All were transfusion dependent and had Hb levels less than 9.0 g/dl and less than 10% marrow blasts. Eight patients had refractory anemia (RA), one had refractory anemia with excess blasts (RAEB), and seven had refractory anemia with ringed sideroblasts (RARS). A response was defined as an increase in Hb by greater than 2 g/dl and/or a decrease in transfusion requirement by greater than 50%. Patients were considered to be evaluable if on study greater than two months. Three of thirteen evaluable patients had a response. One patient with RA had a sustained trilineage hematologic response with no evidence of disease progression. None of the patients had trouble with hypertension or with thrombotic events. This suggests than an occasional patient with MDS will respond to rHuEPO. In some patients, this may be beneficial clinically.

Topics: Aged; Aged, 80 and over; Anemia, Refractory; Anemia, Refractory, with Excess of Blasts; Bone Marrow; Drug Tolerance; Erythropoietin; Hematopoiesis; Humans; Middle Aged; Myelodysplastic Syndromes

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

Twenty patients with myelodysplastic syndromes (MDS) entered a randomized, placebo-controlled, double-blind trial designed to evaluate the efficacy and toxicity of high doses of recombinant human erythropoietin (rhEPO). Patients completing the trial were eligible to receive rhEPO as part of an open-label study. Eighteen patients were transfusion dependent; 10 had refractory anemia (RA), and 10 had refractory anemia with ringed sideroblasts (RARS). A response to rhEPO was defined as an increase in hematocrit of 4 percentage points or more over baseline, or the elimination of all transfusions with the hematocrit stable at the baseline level. In the double-blind trial, 1 patient (12.5%) receiving rhEPO responded, as compared with no responses in the placebo group. Overall, responses occurred in 4 of 17 patients (24%) receiving rhEPO at a dose of 1,200 to 1,600 U/kg intravenously (IV) twice weekly. Changes in granulocyte or platelet counts were not observed. Despite the administration of high doses of rhEPO, toxicity attributable to rhEPO was not observed in either the double-blind or open-label study. Response to rhEPO was not significantly related to age, gender, type of MDS, time since diagnosis, time since initiation of transfusion therapy, or baseline serum EPO. These studies indicate that rhEPO can be administered safely in very high doses to patients with MDS and that 24% of these patients will respond with increased erythropoiesis.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Refractory; Double-Blind Method; Erythropoietin; Female; Hematocrit; Humans; Male; Middle Aged; Myelodysplastic Syndromes; Placebos; Recombinant Proteins

As anemia is frequently the main problem in myelodysplastic syndromes (MDS), we studied the efficacy of human erythropoietin (rhEpo) in stimulating the erythroid lineage in 14 patients, starting with 40 U/kg three times a week and doubling the dose every 6 weeks until a response was observed. The highest doses administered were 80 (n = 1), 160 (n = 4), 320 (n = 8) and 640 U/kg (n = 1). One patient (refractory anemia with an excess of blasts, RAEB) showed an increase of hemoglobin, white blood cells and platelets with 80 U/kg rhEpo. However, this patient developed acute leukemia while on therapy. Two other patients (RAEB and RAEB in transformation) also transformed to acute leukemia. In the other 11 patients no response was observed. There was no correlation between in vitro culture data and in vivo responsiveness. The treatment was well tolerated and no nonhematological side effects were observed. From this study we conclude that rhEpo, even when given at high doses, has a low response rate in patients with MDS. Further investigation is needed in order to clarify whether rhEpo increases the potential risk of transformation to acute leukemia.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Refractory; Anemia, Refractory, with Excess of Blasts; Anemia, Sideroblastic; Blood Platelets; Bone Marrow; Drug Evaluation; Erythrocytes; Erythropoietin; Female; Hemoglobins; Humans; Leukocytes; Male; Middle Aged; Myelodysplastic Syndromes; Recombinant Proteins

Refractory anaemia (RA) among myelodysplastic syndrome (MDS) is associated with a partial functional iron deficit and may require transfusions. In low-risk lymphoma and solid tumour patients, iron support improves erythropoietin (EPO) cost-effectiveness in treating anaemia. The aim of this study is to see if oral sucrosomial iron support improves the cost-effectiveness of EPO treatment in MDS patients affected by low-risk RA. We treated patients with EPO only or with EPO plus oral sucrosomial iron or intravenous (i.v.) iron. The need for transfusions was lowest in the group taking oral iron (p = 0.016) or not receiving supplementation at all (p = 0.022). We compared costs of EPO with i.v. ferric gluconate or oral sucrosomial iron supplementation or no iron supplementation. The oral iron group had fewer side effects, fewer patient medical visits in the out-patient setting, and fewer transfusions; this led to higher savings on direct hospital costs and indirect patient costs (lost days at work) and translated into a 50% abatement of overall expenditures. EPO treatment-related expenditures in MDS-RA patients were lowest with oral sucrosomial iron supplementation (Sideral®), with a longer interval between EPO administration in maintenance treatment, quicker hemoglobin recovery, lower ferritin increase and fewer blood transfusions.

Topics: Aged; Aged, 80 and over; Anemia, Refractory; Dietary Supplements; Disease Progression; Erythropoietin; Female; Ferric Compounds; Ferritins; Health Care Costs; Humans; Iron; Italy; Male; Myelodysplastic Syndromes; Treatment Outcome

Topics: Anemia, Refractory; Autoantibodies; Bone Marrow; Erythropoietin; Female; Glycine; Humans; Hypoxia-Inducible Factor-Proline Dioxygenases; Isoquinolines; Middle Aged; Renal Insufficiency, Chronic; Treatment Outcome

Myelodysplastic syndrome (MDS) is a heterogeneous malignant hematologic disease with median overall survival ranging from six months to more than ten years. Solid tumor rarely occurs in combination with MDS and the underlying pathogenesis and prognostic significance still remain controversial.. Here we report a relative low risk myelodysplastic syndrome-refractory cytopenia with multilineage dysplasia (MDS-RCMD) patient, with a rare t(1; 19)chromosome translocation. This patient also suffered from gastric carcinoma.. Gastric carcinoma, Myelodysplastic syndrome with t (1; 19) chromosome translocation.. This patient received radical operation for gastric carcinoma and erythropoietin infusion.. The patient took follow up visits every 2 to 3 months in past years and now he is in stable disease without further treatment.. We reviewed the mechanism of MDS complicated by solid tumor and concluded the potential mechanisms of this patient. The interactions between potential factors may play a role in oncogenesis which, however, need an in-depth study of its operating mechanism.

Topics: Anemia, Refractory; Bone Marrow; Carcinoma; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 19; Cytogenetic Analysis; Erythropoietin; Gastrectomy; Hematinics; Humans; Male; Middle Aged; Myelodysplastic Syndromes; Stomach Neoplasms; Translocation, Genetic; Treatment Outcome

Topics: Aged; Anemia, Refractory; Bone Marrow; Chromosome Deletion; Chromosomes, Human, Pair 20; Clone Cells; Epoetin Alfa; Erythropoietin; Hemoglobins; Humans; Male; Recombinant Proteins; Remission Induction; Withholding Treatment

To describe our 15-year experience on the patients' response and safety to the use of EPO in IBD patients with refractory anemia.. Single center retrospective chart analysis of all IBD patients receiving EPO for the period 1994-2009. Patients with resistant anemia not responding to I.V. iron therapy were enrolled. Concommitant medication, medical and laboratory data on short and long-term patients' responses and safety were recorded.. In total 820 IBD files were reviewed and among 78 patients treated with I.V. iron we identified 26 patients who received EPO in concordance to our inclusion criteria. Azathioprine or methotrexate was administered in 17 patients and 7 patients received concomitant Infliximab. After EPO, 22/26 patients (84.6%) responded and peripheral blood parameters were significantly improved and blood transfusions were significantly decreased (p<0.001). Erythropoietin dose was increased in three non-responders while two patients required emergency transfusions. No adverse events were recorded.. In anemic IBD patients who are refractory to I.V. iron monotherapy, administration of EPO significantly improved peripheral blood parameters with safety. Prospective controlled trials are needed to confirm positive patients' response to EPO and identify those patients who are more likely to benefit.

Topics: Adult; Aged; Anemia, Refractory; Erythropoietin; Female; Humans; Inflammatory Bowel Diseases; Male; Middle Aged; Recombinant Proteins; Retrospective Studies; Treatment Outcome

Topics: Anemia, Refractory; Antimicrobial Cationic Peptides; Erythropoietin; Female; Heart Valve Prosthesis Implantation; Hepcidins; Humans; Iron; Middle Aged; Mitral Valve; Recombinant Proteins; Tricuspid Valve; Tricuspid Valve Insufficiency

Patients with refractory anemia with ring sideroblasts and thrombocytosis (RARS-T) are difficult to treat because the cytoreductive treatment might be beneficial for the thrombocytosis component but harmful for the RARS component. As lenalidomide has shown to be efficacious in both myelodysplastic syndromes and myeloproliferative neoplasms, we have treated 2 RARS-T patients, who were transfusion dependent, with lenalidomide. We report the results of lenalidomide treatment in these patients and show that lenalidomide has clinical activity in this rare disorder. Both patients became transfusion independent, and 1 of the patients attained indeed a complete molecular remission.

Topics: Aged, 80 and over; Anabolic Agents; Anemia, Refractory; Anemia, Sideroblastic; Antineoplastic Agents; Erythropoietin; Humans; Hypertension, Pulmonary; Janus Kinase 2; Lenalidomide; Male; Middle Aged; Mutation; Pulmonary Embolism; Pyridoxine; Reverse Transcriptase Polymerase Chain Reaction; Thalidomide; Thrombocytosis; Vitamin B Complex

The combination of intravenous iron and recombinant human erythropoietin has been proved to be effective in the treatment of refractory anaemia in patients with inflammatory bowel disease (IBD). Darbepoetin-alpha (DPO) has a three-fold longer terminal half-life than erythropoietin. The purpose of this pilot study was to determine whether darbepoetin-alpha is also effective for the treatment of refractory anaemia in IBD.. Twenty IBD patients (nine ulcerative colitis and 11 Crohn's disease) and refractory anaemia received intravenous iron sucrose (total iron dose 1.3+/-0.5 g, range 0.7-1.9) and darbepoetin-alfa at the single, weekly dose of 0.9 microg/kg subcutaneously for 4 weeks. Serum erythropoietin, ferritin, transferrin, soluble transferrin receptor, C-reactive protein and interleukin-6 were measured at baseline and after treatment.. Haematopoietic response (increase of haemoglobin > or = 2.0 g/dl) was observed in 15 out of the 20 patients (75%). The mean haemoglobin concentrations increased from 9.48+/-0.82 g/dl at baseline to 12.71+/-1.12 g/dl after treatment (P<0.0001). Mean corpuscular volume and serum ferritin levels were also significantly increased whereas mean C-reactive protein levels and endogenous erythropoietin levels significantly decreased after treatment.. In IBD patients with refractory anaemia the administration of darbepoetin in combination with intravenous iron sucrose can raise haemoglobin levels.

Topics: Anemia, Refractory; C-Reactive Protein; Darbepoetin alfa; Drug Therapy, Combination; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Ferritins; Glucaric Acid; Hematinics; Hemoglobins; Humans; Inflammatory Bowel Diseases; Injections, Intravenous; Interleukin-6; Male; Pilot Projects; Receptors, Transferrin; Transferrin; Treatment Outcome

Topics: Administration, Oral; Anemia, Refractory; Blood Pressure; Blood Transfusion; Erythropoietin; Female; Follow-Up Studies; Hemoglobins; Humans; Injections, Intravenous; Iron; Iron Deficiencies; Iron-Dextran Complex; Kidney Failure, Chronic; Middle Aged; Recombinant Proteins; Time Factors; Treatment Outcome

Topics: Acute Disease; Anemia, Refractory; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Cytarabine; Erythropoietin; Etoposide; Follow-Up Studies; Granulocyte Colony-Stimulating Factor; Humans; Leukemia, Myeloid; Male; Methotrexate; Middle Aged; Mitoxantrone; Peripheral Blood Stem Cell Transplantation; Postoperative Complications; Primary Myelofibrosis; Recombinant Proteins; Transplantation Conditioning; Transplantation, Autologous; Whole-Body Irradiation

Erythroid apoptosis in low-risk myelodysplastic syndrome (MDS) maybe mediated via mitochondrial release of cytochrome c and subsequent caspase activation. In the present study, we compared the in vitro and in vivo effects of proerythroid treatment with erythropoietin + granulocyte colony-stimulating factor (G-CSF) on myelodysplastic erythropoiesis regarding apoptosis and preferential growth of clones with cytogenetic abnormalities.. We enrolled 15 refractory anemia (RA) and 11 refractory anemia with ringed sideroblasts (RARS), including 5q- aberration, monosomy 7, and trisomy 8, before initiation of treatment and followed nine patients after successful treatment. The effects of G-CSF and erythropoietin were assessed. The expression of G-CSF receptor (G-CSFR) was explored during erythroid maturation. The relative growth of erythroid progenitors with cytogenetic aberrations in presence of erythropoietin was investigated.. Significant redistribution of cytochrome c was seen before treatment at all stages of erythroid differentiation. This release was blocked by G-CSF during the whole culture period and by erythropoietin during the latter phase. Both freshly isolated glycophorin A+ bone marrow cells and intermediate erythroblasts during cultivation retained their expression of G-CSFR. Cytochrome c release and caspase activation were significantly less pronounced in progenitors obtained from successfully treated nonanemic patients and showed no further response to G-CSF in vitro. Moreover, erythropoietin significantly promoted growth of cytogenetically normal cells from 5q- patients, whereas no such effect was observed on erythroblasts from monosomy 7 or trisomy 8 patients.. We conclude that growth factors such as erythropoietin and G-CSF can act both via inhibition of apoptosis of myelodysplastic erythroid precursors and via selection of cytogenetically normal progenitors.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Refractory; Anemia, Sideroblastic; Apoptosis; Bone Marrow Cells; Caspases; Cytochromes c; Enzyme Activation; Erythroid Precursor Cells; Erythropoietin; Glycophorins; Granulocyte Colony-Stimulating Factor; Humans; In Vitro Techniques; Middle Aged; Monosomy; Receptors, Granulocyte Colony-Stimulating Factor; Recombinant Proteins; Trisomy

To determine the efficacy and tolerance to cyclosporine A (CsA) based therapy in patients with myelodysplastic syndrome (MDS), 16 patients with MDS consisting of 10 refractory anemia (RA) and 6 refractory anemia with accessory blasts less than 10% (RAEB-1) were analyzed. Five patients had hypocellular bone marrows and 11 patients had normocellular or hypercellular marrows. The dose of CsA was 2.5-5.5 mg/(kg.d) for 2 weeks to 2 years (mean 8 months). Two out of 16 patients were treated with CsA alone, 14 patients were treated with CsA, recombinant human erythropoietin, androgens, 1, 25 dihydroxy vitamin D(3) or two or three of them combination with CsA. Treatment responses were classified according to the International Working Group (IWG) criteria as complete remission (CR), partial remission (PR), hematological improvement (HI) and no response (NR). Patients who obtained CR, PR or HI were defined as responders. The results showed that HI was observed in 12 patients, PR in 2 patients and NR in 2 patients. Total response rate was 87.5%. Response rates shown in neutrophil lineage, platelet and erythroid lineage were 83.3%, 66.7% and 60%, respectively; their shortest time required to obtain some hematologic improvement after initiation of CsA therapy was 2 weeks, 1 month and 1 month, respectively. Of 13 patients being transfusion-dependent before treatment, 3 patients did not need transfusion any more and 5 showed the reduced transfusion requirements after CsA therapy. In 10 patients with RA, 9 responded to CsA. Of 6 patients with RAEB, 1 patient had no response and died of RAEB-t and 5 patients had transient responses. One of the latter transformed to CMML and two relapsed. The total response rate decreased to 50% in the patients with CsA therapy lasting more than 3 months at the end of following-up. The adverse effects included hirsutism, hyperplastic gingiva, reversible hepatic and renal dysfunction. In conclusion, the usefulness of CsA based therapy for MDS-RA and RAEB-1 with any marrow cellularity is useful, the CsA dose of 3-5 mg/(kg.d) is safe and efficacious.

Topics: Adolescent; Adult; Aged; Androgens; Anemia, Refractory; Anemia, Refractory, with Excess of Blasts; Calcitriol; Cyclosporine; Drug Therapy, Combination; Erythropoietin; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Myelodysplastic Syndromes; Recombinant Proteins; Treatment Outcome

Topics: Aged; Anemia, Refractory; Erythropoietin; Humans; Male; Recombinant Proteins; Red-Cell Aplasia, Pure

Myelodysplastic syndromes (MDS) are a heterogenous group of hematological clonal malignancies. Patients belonging to the refractory anemia (RA) subtype are usually treated with recombinant human erythropoietin (EPO). Not all patients respond to EPO administration and they are strictly dependent on supportive therapy with red cell blood (RBC) transfusions. The aim of this study was to investigate the efficacy of an alternative combination regimen containing EPO, low-dose methylprednisolone and nandrolone decanoate, in patients with RA unresponsive to EPO administration alone. Ten patients, 4 women and 6 men, median age: 70 years (range: 55-78 years) with refractory anemia unresponsive to EPO administration and RBC transfusion-dependent were included in the study. Median hematological data at baseline were Hb: 8.7 g/dl, (range 6.2-9.8), WBC: 3.35x10(9)/l (range 2.1-4), PLT: 82.5x10(9)/l (range 59-110). EPO 150 U/Kg three times/week subcutaneously, low-dose methylprednisolone 8 mg/day orally and nandrolone decanoate (Decadurabolin) 50 mg two-times/week intramuscularly were administered. As complete response (CR) to treatment was considered the normalization of the peripheral blood and bone marrow smears and biopsy. As partial response (PR) was considered increase in Hb level > or = 2 g/dl, or up to 10 g/dl and discontinuation of RBC transfusions. The response to therapy was evaluated on the 4th week after the initiation of the combination treatment. Bone marrow smear evaluation was carried out at baseline and every six months afterwards. After a 4-week treatment all patients achieved PR and discontinued RBC transfusions. Median and range hematological values on the 4th week after treatment initiation were Hb: 11.2 g/dl, (range: 9.8-12.8), WBC: 4.4x10(9)/l (3.5-6.6), PLT: 130x10(9)/l (95-160). The increase observed in hematological values was significant (p = 0.0001, 0.0004 and < 0.0001, respectively, for Hb, WBC and PLT counts). Treatment was well tolerated. Furthermore, two women, on treatment with the combination regimen, achieved CR one after six months and the second after 12 months. They are alive after 5 years from initiation of the combination treatment. After a median period of 18 months (range 12 to 20 months) in PR three men developed acute leukemia; they received intensive antileukemic chemotherapy without any response and died during the phase of pancytopenia. Three other men achieved CR, one after 6 and two after 12 months of therapy and they ar

Topics: Aged; Androgens; Anemia; Anemia, Refractory; Anti-Inflammatory Agents; Blood Transfusion; Bone Marrow Cells; Drug Therapy, Combination; Erythrocytes; Erythropoietin; Female; Humans; Male; Methylprednisolone; Middle Aged; Myelodysplastic Syndromes; Nandrolone; Recombinant Proteins; Time Factors

The anemia of low-risk myelodysplastic syndromes (MDS), refractory anemia (RA) and RA with ringed sideroblasts (RARS), may respond to treatment with hematopoietic growth factors (GF)); erythropoietin (Epo) +/- granulocyte colony-stimulating factor (G-CSF). The present study was designed to assess whether functional iron deficiency may develop in MDS patients receiving these treatments.. Erythrocyte scattergrams from 34 patients with RA and RARS (untreated, transfused, or GF-treated with partial or complete erythroid response) were analyzed with Bayer-Advia equipment.. In untreated RARS, the proportion of hypochromic erythrocytes (Hypo-e, median 6.2%, range 1.1-8%) and hypochromic reticulocytes (Hypo-r, median 45%, range 22-48%), as well as mean corpuscular volume (MCV, median 101 fL) were significantly elevated compared to corresponding values in controls. These values increased further after GF-treatment (median 11%, 57%, and 105 fL, respectively), in spite of improved hemoglobin values and adequate body iron stores. The values observed in untreated RA patients largely fell within the normal range, and there was no significant influence of GF treatment. Notably, the hemoglobin content of reticulocytes (MCHr) did not differ between MDS and controls, and was not influenced by GF treatment.. The red cell population in RARS shows morphological abnormalities in terms of varying but overall increased size, and reduced hemoglobin concentration. The proportion of abnormal cells increases after successful pro-erythroid GF treatment, indicating that GF promote erythroblast survival, and maturation into erythrocytes. Hence, the finding of hypochromic red cells should not routinely be interpreted as a marker for Epo-induced functional iron deficiency in MDS.

Topics: Anemia, Refractory; Anemia, Sideroblastic; Blood Cell Count; Drug Therapy, Combination; Erythrocyte Indices; Erythrocyte Transfusion; Erythrocytes; Erythropoietin; Ferritins; Granulocyte Colony-Stimulating Factor; Hemoglobins; Humans; Iron; Iron Deficiencies; Methylmalonic Acid; Reticulocytes; Risk; Transferrin

We have published previously a prototype of a decision model for anaemic patients with myelodysplastic syndromes (MDS), in which transfusion need and serum erythropoietin (S-Epo) were used to define three groups with different probabilities of erythroid response to treatment with granulocyte colony-stimulating factor (G-CSF) + Epo. S-Epo 500 U/l and >/= 2 units/month for a poor response, whereas the presence of only one negative prognostic marker predicted an intermediate response. A total of 53 patients from a prospective study were included in our evaluation sample. Patients with good or intermediate probability of response were treated with G-CSF + Epo. The overall response rate was 42% with 28.3% achieving a complete and 13.2% a partial response to treatment. The response rates were 61% and 14% in the good and intermediate predictive groups respectively. The model retained a significant predictive value in the evaluation sample (P < 0.001). Median duration of response was 23 months. Scores for global health and quality of life (QOL) were significantly lower in MDS patients than in a reference population, and fatigue and dyspnoea was significantly more prominent. Global QOL improved in patients responding to treatment (P = 0.01). The validated decision model defined a subgroup of patients with a response rate of 61% (95% confidence interval 48-74%) to treatment with G-CSF + Epo. The majority of these patients have shown complete and durable responses.

Topics: Aged; Anemia; Anemia, Refractory; Anemia, Refractory, with Excess of Blasts; Anemia, Sideroblastic; Blood Transfusion; Decision Support Techniques; Erythropoietin; Female; Granulocyte Colony-Stimulating Factor; Humans; Male; Middle Aged; Myelodysplastic Syndromes; Prognosis; Prospective Studies; Quality of Life; Treatment Outcome

Topics: Aged; Anemia, Refractory; Anemia, Refractory, with Excess of Blasts; Carcinoma, Hepatocellular; Cell Differentiation; Erythroid Precursor Cells; Erythropoiesis; Erythropoietin; Female; Humans; Hypersplenism; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged; Myelodysplastic Syndromes; Pancytopenia; Reticulocyte Count; Reticulocytes

In our previous study, approximately 60% of aplastic anemia (AA) and refractory anemia (RA) patients treated with recombinant human granulocyte colony-stimulating factor (rhG-CSF) and recombinant human erythropoietin (rhEpo) showed a multilineage response. In this study, we analyzed the long-term follow-up of the multilineage responders (multi-R). In the follow-up analysis of 11 multi-R (6 AA and 5 RA), 10 patients (5 AA and 5 RA) were evaluable. The range of time from the start of treatment to the final contact was 50 to 125 months. Analysis of survival times revealed a significant difference between multi-R and non-multi-R among AA patients given this treatment (P = .016). One AA and 1 RA patient among the multi-R developed acute leukemia. Of 7 living multi-R, 3 AA and 2 RA patients did not need transfusion at final contact. Four of them maintained the target hemoglobin concentration of more than 11 g/dL for quality-of-life benefit. The findings suggested that this result is an important advantage of this treatment.

Topics: Acute Disease; Adolescent; Adult; Aged; Anemia, Aplastic; Anemia, Refractory; Blood Transfusion; Erythropoietin; Female; Follow-Up Studies; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Leukemia, Myeloid; Male; Middle Aged; Survival Analysis

Treatment with recombinant erythropoietin (EPO) can alleviate anaemia in patients with myelodysplastic syndromes (MDS). The present study, based on a long-term follow-up of 68 MDS patients (26RA, 16 RAS, 26 RAEB) treated with EPO alone, pinpoints pre-treatment variables associated with response induction, response duration and overall survival. Response, defined as an increase in haemoglobin >15gL1 or eliminated erythrocyte transfusion requirements, was observed in 22 of 66 (33%) evaluable patients. The median response duration was 15 (range 3-64+) months. Using univariate logistic regression models, responders displayed significantly lower baseline serum EPO levels (S-EPO), more often normal bone marrow blast cell content (RA/RAS vs. RAEB), normal cytogenetics and no need for erythrocyte transfusion. In a multiple logistic regression model, S-EPO (P=0.009), marrow blast content (P=0.031) and erythrocyte transfusion need (P=0.024) remained associated with response induction. The probability of response for a patient with S-EPO >50UL1, RA/RAS and no transfusion need was 0.79 (0.53-0.93, 95% CI). The median overall survival time from start of EPO treatment was 26 months, significantly longer for responders than for non-responders (49 vs. 18 months, P=0.018). Survival was also predicted by baseline S-EPO; patients with S-EPO >50UL1 (n=50) had a median survival of 17 months, as compared to 65 months for those with S-EPO >50UL1 (n=14, P=0.024). The international prognostic scoring system (IPSS) for MDS predicted survival (P=0.003) and progression to acute leukemia (P<0.001) but not response to EPO treatment. Furthermore, in a logistic regression model with S-EPO and IPSS, S-EPO (but not IPSS) was again a significant predictor for response (P=0.007). Our data facilitate the optimal selection of MDS patients suitable for EPO treatment and pinpoint S-EPO as a powerful predictor of response and overall survival in MDS.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Refractory; Anemia, Refractory, with Excess of Blasts; Bone Marrow Cells; Erythrocyte Transfusion; Erythropoietin; Female; Hemoglobins; Humans; Logistic Models; Male; Middle Aged; Myelodysplastic Syndromes; Prognosis; Recombinant Proteins; Survival Rate

Topics: Anemia, Refractory; Anemia, Refractory, with Excess of Blasts; Erythrocyte Transfusion; Erythropoietin; Humans; Recombinant Proteins

Recombinant human erythropoietin (rHuEpo) improves anemia in 25% of patients with myelodysplastic syndromes (MDS). The variable and sometimes low response rate to rHuEpo treatment raises the question whether the existence of autoantibodies against erythropoietin (epo) is partially responsible. In the present study we investigated the presence of anti-epo autoantibodies in MDS patients.. Forty-three patients with MDS were studied. Sixteen patients had refractory anemia (RA), 13 had RA with ringed sideroblasts, 3 had RA with excess of blasts (RAEB), 9 had RAEB in transformation and 2 patients had chronic myelomonocytic leukemia. They were divided in 3 groups according to rHuEpo treatment. Group A consisted of 10 patients who did not receive rHuEpo treatment. Group B included 13 patients who were on rHuEpo treatment (150 IU/kg subcutaneously, 3 times weekly) showing an increase of hemoglobin (Hb) values or reduction of transfusion requirements and Group C consisted of 20 patients who did not respond or stopped responding to rHuEpo treatment. Laboratory studies consisted of a complete blood cell count, measurement of serum epo and determination of anti-epo antibodies using ELISA.. There were no significant differences with regard to age and sex among the three groups. No autoantibodies against epo were found in the examined sera, apart from a female patient from group A who showed a low positive titer.. We suggest that anti-epo autoantibodies do not contribute to the development of MDS-related anemia and are not responsible for the modest response to rHuEpo treatment. Further investigation is needed to identify possible reasons for the low response rate to rHuEpo treatment.

Topics: Aged; Aged, 80 and over; Anemia, Refractory; Anemia, Refractory, with Excess of Blasts; Antibody Specificity; Autoantibodies; Autoantigens; Blood Cell Count; Blood Transfusion; Combined Modality Therapy; Erythropoietin; Female; Hemoglobins; Humans; Isoantibodies; Isoantigens; Leukemia, Myelomonocytic, Chronic; Male; Middle Aged; Myelodysplastic Syndromes; Recombinant Proteins; Treatment Failure

In refractory anemia (RA) and refractory anemia with ringed sideroblasts (RARS) a discrepancy is observed between the decreased in vitro erythroid colony formation and the normal or increased number of normoblasts in the bone marrow. To study the in vivo and in vitro erythropoiesis in more detail erythron transferrin uptake (ETU), soluble transferrin receptor (sTfR) and erythroid in vitro colony formation were performed in 24 patients with RA and five patients with RARS. These results were correlated with bone marrow morphology and transfusion dependency. Increased (mean, 124.9; range, 74-225 micromol/l blood/day) and normal (mean, 60.6; range, 50-71) ETU values were observed in 51% and 28% of the cases, whereas 21% of the cases demonstrated a diminished ETU value (mean, 35.8; range, 28-46), which correlated significantly with sTfR in cases with RA (P < 0.05, r = 0.64). A significant difference in ETU values was observed between RA (mean, 77.6; range, 28-189) and RARS (mean, 144.0; range, 59-225, P < 0.05). Most of the cases (73%) with increased ETU values showed an augmented percentage of erythroblasts in the bone marrow, which was inversely related with the serum Epo levels (P < 0.05, r = 0.51). However no correlation was found between the ETU values and the in vitro erythroid colony formation. Transfusion dependency was associated with normal to increased ETU levels (P < 0.05) and cytogenetic abnormalities (P < 0.05). These observations demonstrate that different patterns of defects can be observed in the erythropoiesis of RA and RARS patients whereby normal to increased ETU levels and the presence of cytogenetic abnormalities differentiate between cases of RA with ineffective erythropoiesis associated with regular transfusions and cases who are relatively transfusion independent.

Topics: Adult; Aged; Anemia, Refractory; Anemia, Refractory, with Excess of Blasts; Blood Transfusion; Bone Marrow Cells; Cells, Cultured; Colony-Forming Units Assay; Erythropoiesis; Erythropoietin; Hematocrit; Hematopoietic Stem Cells; Humans; Leukocyte Count; Middle Aged; Platelet Count; Receptors, Transferrin; Reticulocyte Count; Transferrin

We present a case report of a 55-year-old male patient with hypoplastic myelodysplastic syndrome (MDS, refractory anemia) in which a good response to recombinant human erythropoietin (rhEPO) has been maintained for more than 60 months. There is with no evidence of progression to high risk MDS or acute leukemia, although he was predicted to be a low-responder to rhEPO therapy because of very high serum EPO levels (5,260 mU/ml), a history of multiple transfusions, chromosomal abnormalities (47,XY,+8) and severe thrombocytopenia. Since he received rhEPO with no adverse effects, it may be valuable to try rhEPO treatment at least one time for low-risk MDS patients, depending on red cell transfusion requirements.

Topics: Anemia, Refractory; Biopsy, Needle; Bone Marrow; Chromosome Aberrations; Chromosome Disorders; Chromosomes, Human, Pair 8; Erythropoietin; Follow-Up Studies; Humans; Karyotyping; Male; Middle Aged; Recombinant Proteins; Thrombocytopenia

Myelodysplasia (MDS) is mostly characterized by a normal or increased number of normoblasts in the bone marrow and an impaired in vitro colony formation. In the present study we analyzed whether this might be due to a disconnection between proliferation and differentiation. CD34+/CD36- sorted bone marrow cells of 18 MDS patients were cultured in a clonogenic and suspension culture assay in the presence of erythropoietin (Epo) and mast cell growth factor (MGF). Burst-forming units erythroid (BFU-E, 75 +/- 88/10(4) CD34+ cells, X +/- s.d.) and colony-forming units E (CFU-E) were observed in eight of the 13 cases (62%) with refractory anemia with or without ring sideroblasts (RA and RARS) and one of the five cases with RA with excess of blasts or in transformation (RAEB and RAEB-T). Suspension cultures with CD34+/CD36- sorted cells with Epo plus MGF demonstrated an 8.9 +/- 6.5-fold expansion after 7 days in cases with >10 BFU-E/10(4) CD34+/CD36- cells while cases with <10 BFU-E/10(4) CD34+/CD36- cells demonstrated 1.0 +/- 0.8-fold expansion especially in cases with RAEB/RAEB-T. FACS and morphology analysis after 7 days of suspension culture demonstrated partial differentiation along the erythroid lineage in cases with RA/RARS (75%) and RAEB/RAEB-T (66%) reflected by the presence of erythroblasts and normoblasts with variable expression of CD34, CD36 and Glycophorin A. In cases with erythroid colony formation 69 +/- 24% of the cells were CD34-/CD36+ and in cases with <10 BFU-E/10(4) CD34+ cells 18 +/- 16% of cells were CD34-/CD36+. Iron staining showed the presence of ring sideroblasts in two cases with RARS indicating that the cells originate from the abnormal erythroid clone. Finally, it was shown that cases with an impaired proliferative response demonstrate an enhanced binding of Annexin-V on CD34+ cells during the first days of the cell suspension culture phase. These results suggest that a defect in the proliferative response is most pronouncedly expressed in MDS whereas a subpopulation of cells retain the capacity to differentiate between transition to a terminated stage.

Topics: Anemia, Refractory; Antigens, CD34; Bone Marrow Cells; CD36 Antigens; Cell Differentiation; Cell Division; Erythroid Precursor Cells; Erythropoietin; Humans; Stem Cell Factor

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

In order to reduce anaemia in patients with myelodysplastic syndromes (MDS) a stepwise treatment protocol including erythropoietin (EP) and granulocyte-macrophage colony-stimulating factor (GM-CSF) was designed. Thirty-seven MDS patients (stages I-III) with symptomatic anaemia were first given EPO 10,000 U s.c. 3 times weekly for 6 weeks. Those not responding, i.e. increased their haemoglobin levels > 15 g/l, proceeded into the second phase of the study where GM-CSF (200 micrograms/d. s.c. on weeks 1-6) was combined with EPO (10,000 U s.c. 3 times weekly on weeks 5-14). Following the initial EPO treatment phase, 14 of the 37 patients (38%) responded with increased haemoglobin levels. Responders were significantly different from non-responders in that their pre-treatment values of s-EPO, s-LDH and bone marrow blast cell counts were lower, their baseline haemoglobin levels higher and their transfusion dependency less pronounced. Eighteen of the 23 non-responders proceeded into the second phase, 13 of those were evaluable having completed the entire schedule. Three of the 13 initially EPO resistant patients (23%) responded to the GM-CSF/EPO combination with increased haemoglobin levels, suggesting a positive synergy between the two cytokines. Thus, the overall response rate to the present protocol was 46% (17 of 37 cases), but only a limited subset of the patients did clearly benefit from the combined GM-CSF/EPO administration. Therefore, we believe this step-wise approach to multiple growth factor treatment in MDS, starting with EPO alone and reserving the combination for refractory cases, has considerable advantages, taking into account both medical and socio-economical aspects.

Topics: Aged; Aged, 80 and over; Anemia, Refractory; Anemia, Refractory, with Excess of Blasts; Anemia, Sideroblastic; Drug Administration Schedule; Drug Synergism; Drug Therapy, Combination; Erythropoietin; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Male; Middle Aged

Initial treatment with androgen (metenolone acetate) alone for 19 weeks had no effect in a 45-year-old Japanese female with refractory anemia (RA). The patient achieved trilineage hematologic recovery after addition of recombinant human granulocyte colony-stimulating factor (G-CSF) and recombinant human erythropoietin (Epo) to the androgen therapy. Anemia progressed after the cessation of metanolone acetate, but was effectively treated by the readministration of metenolone acetate. Thus, the androgen therapy in combination with hematopoietic growth factors such as G-CSF and/or Epo may be effective in patients with RA.

Topics: Anemia, Refractory; Drug Therapy, Combination; Erythropoietin; Female; Granulocyte Colony-Stimulating Factor; Humans; Methenolone; Middle Aged; Recombinant Proteins

Topics: Anemia, Refractory; Blood Transfusion; Chronic Disease; Combined Modality Therapy; Erythropoietin; Hepatitis C; Humans; Male; Middle Aged; Pancytopenia; Recombinant Proteins; Recurrence; Remission Induction; Splenectomy

Topics: Aged; Anemia, Refractory; Erythropoietin; Heart Valve Diseases; Hemolysis; Humans; Kidney Failure, Chronic; Male; Renal Dialysis

The in vitro colony-forming capacities of marrow CD34-positive (CD34+) cells from 25 patients with myelodysplastic syndromes (MDS) were studied. In all patients this purified cell population showed erythroid (burst-forming unit erythroid; BFU-E) or non-erythroid colony growth, both of which were more restricted than non-purified mononuclear cell population under stimulation with erythropoietin (EPO) or granulocyte/macrophage colony-stimulating factor (GM-CSF) alone. MDS patients examined were put into two groups; refractory anemia (RA) or RA with ringed sideroblasts (RA/RARS) and RA with excess of blasts (RAEB) or RAEB in transformation (RAEB/RAEB-t). The CD34+ cells of both RA/RARS and RAEB/RAEB-t exhibited a similarity to the cells of normal individuals in their responsiveness to the addition of interleukin 6 (IL-6), IL-3 or stem cell factor (SCF). SCF caused powerful but highly variable responses in both erythroid and nonerythroid colony formation as compared with IL-6 or IL-3. We demonstrated that MDS marrow hematopoietic progenitor cells reactive to GM-CSF or EPO were additionally stimulated with early-acting hematopoietic growth factors including IL-6, IL-3 and SCF in a fashion similar to those of normal individuals.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Refractory; Anemia, Refractory, with Excess of Blasts; Antigens, CD; Antigens, CD34; Bone Marrow; Cell Division; Colony-Forming Units Assay; Erythroid Precursor Cells; Erythropoietin; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoietic Cell Growth Factors; Hematopoietic Stem Cells; Humans; Male; Middle Aged; Myelodysplastic Syndromes

Topics: Anemia, Refractory; Anemia, Sideroblastic; Blood Transfusion; Drug Therapy, Combination; Erythropoietin; Granulocyte Colony-Stimulating Factor; Hemoglobins; Humans; Leukocyte Count; Myelodysplastic Syndromes

Different response patterns to recombinant human erythropoietin (rHuEpo) administration to anemic patients with myelodysplastic syndromes (MDS) are described. The biology of rHuEpo effect on erythropoiesis in patients with MDS has not been elucidated. However, until more biological information is obtained, it could be prudent to consider these response patterns as guidelines in the treatment of MDS. In the small but interesting series of nine patients with MDS only one responded to rHuEpo within the treatment period of eight weeks. Two additional patients continued the treatment on their own, and after 16 weeks a response was noted for the first time. A third patient was treated for only six weeks and a delayed response was recorded while off treatment for ten weeks. This response was also recorded 16 weeks from treatment initiation-as in the other two patients. A fourth patient with MDS developed transfusion related hemosiderosis and during iron chelation therapy the RBC transfusion rate dropped to a rate lower than the rate needed before the rHuEpo treatment. It is emphasized that in non responders, non-routine approaches should be considered.

Topics: Aged; Aged, 80 and over; Anemia, Refractory; Anemia, Sideroblastic; Blood Transfusion; Chelation Therapy; Combined Modality Therapy; Deferoxamine; Erythrocyte Count; Erythropoietin; Female; Follow-Up Studies; Hemochromatosis; Humans; Male; Myelodysplastic Syndromes; Primary Myelofibrosis; Recombinant Proteins; Remission Induction; Transfusion Reaction; Treatment Outcome

A 3-year-old girl was admitted with a one-month history of a tendency to bleed to Jikei Kashiwa hospital in May, 1992. She developed pancytopenia as follows; hemoglobin: 8.6 g/dl, red blood cell: 316 x 10(4)/microliters, reticulocyte: 9,480/microliters, white blood cell: 2,500/microliters (neutrophil: 400/microliters) and platelet count: 2.7 x 10(4)/microliters. Her bone marrow was hypoplastic, but was so dysplastic in 3 cell-lines as to be diagnosed as hypoplastic refractory anemia. After two courses of methylprednisolone pulse therapy followed by oral prednisolone therapy which were not effective and were supplemented by blood transfusions, the treatment of 20mg/day oral Cepharanthin, a biscoclaurine alkaloid, and intravenous recombinant human erythropoietin (rhEPO) twice a week at dose of 6,000 U/week was initiated in January, 1993. About 3 months later she showed a steady rise in hemoglobin concentration (from 4.1 to 11.9 g/dl) and platelet count (from 4,000 to 39,000/microliters). Although the rhEPO was tapered and ceased in September, 1993, her hemoglobin concentration has ranged from 11.0 to 11.9 g/dl and her platelet count from 30,000 to 40,000/microliters by giving her Cepharanthin and low dose prednisolone.

Topics: Alkaloids; Anemia, Aplastic; Anemia, Refractory; Anti-Inflammatory Agents, Non-Steroidal; Benzylisoquinolines; Child, Preschool; Drug Synergism; Drug Therapy, Combination; Erythropoietin; Female; Humans; Recombinant Proteins

In an attempt to obtain a synergistic effect on the hemoglobin levels in anaemic patients with myelodysplastic syndromes (MDS), granulocyte colony-stimulating factor (G-CSF) and erythropoietin (epo) were combined in a clinical phase II trial. Twenty-two patients with MDS were included in the study. G-CSF was given alone for six weeks and then in combination with epo for the following twelve weeks. Eight (38%) of 21 evaluable patients showed a significant increase in hemoglobin. One patient with a previous response and subsequent failure to epo alone improved after the addition of G-CSF. Responses were more frequent in patients with less advanced pancytopenia, lower endogenous levels of serum-epo and in those with ring sideroblasts in the bone marrow. The response frequency of 38% is higher than in any study of epo as monotherapy. Moreover, patients with ring sideroblasts, who respond poorly to epo alone, showed a response rate of 60%. Our findings suggest a synergistic in vivo effect of granulocyte-CSF and erythropoietin in patients with myelodysplastic syndromes.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Refractory; Anemia, Refractory, with Excess of Blasts; Drug Synergism; Drug Therapy, Combination; Erythropoietin; Female; Granulocyte Colony-Stimulating Factor; Humans; Male; Middle Aged

Topics: Anemia; Anemia, Refractory; Blood Preservation; Blood Transfusion, Autologous; Erythropoiesis; Erythropoietin; Hematologic Diseases; Humans; Inflammation; Neoplasms; Receptors, Erythropoietin; Recombinant Proteins; Renal Dialysis

Topics: Aged; Anemia, Refractory; Anemia, Sideroblastic; Child; Drug Evaluation; Erythropoietin; Female; Humans; Immunologic Factors; Male; Recombinant Proteins

Because GM-CSF possesses burst-promoting activity (BPA) and megakaryocyte colony-stimulating activity (Meg-CSF) as well as stimulating activity on granulocyte-macrophage progenitors, and erythropoietin (Epo) has thrombopoietin-like activity, the combination therapy of GM-CSF and Epo seems to be more effective for stimulating erythropoiesis and thrombocytopoiesis in patients with pancytopenia. For this reason, the combination therapy of recombinant human GM-CSF (rhGM-CSF) and rhEpo was performed in two patients with refractory anemia (RA) and aplastic anemia (AA). Epo-unresponsive anemia was remarkably improved by adding rhGM-CSF to Epo and the effect lasted for 1 1/2 months in a patient with RA, but severe anemia occurred again immediately after the discontinuation of Epo. The neutralizing antibodies against GM-CSF were not demonstrated at the phase when anemia re-progressed in this patient. In a patient with AA, anemia and thrombocytopenia, which were refractory to previous administration of rhGM-CSF, responded to the combined administration of GM-CSF and Epo. Although the effects were maintained for 3 1/2 months, the anemia and thrombocytopenia became worse again after the administration of rhGM-CSF was changed from daily to every other day. These findings suggest the usefulness of combination therapy of GM-CSF and Epo for patients with pancytopenia.

Topics: Adult; Anemia, Aplastic; Anemia, Refractory; Drug Therapy, Combination; Erythropoietin; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Male; Recombinant Proteins

In a dose titration study we tested the efficacy and tolerance of recombinant human erythropoietin (rhEPO) in 10 patients with myelodysplasia (MDS) and 2 patients with idiopathic myelofibrosis. Patients with a haemoglobin level < 100 g/l were treated as out-patients for 12 weeks with daily doses ranging from 30 U/kg body weight (BW) up to 240 U/kg BW in non-responders. Of the 10 patients with MDS, 6 were suffering from refractory anaemia with sideroblasts (RAS) and 4 from refractory anaemia with an excess of blasts. The median age was 73 years (range 41-81). Two patients with RAS responded with a rise in haemoglobin concentration to > 130 g/l. They had not been transfusion-dependent prior to treatment. Both patients had relatively low serum concentrations of immunoreactive EPO. There was neither a rise in haemoglobin nor a reduction in transfusion dependence in any of the other patients. It may be concluded that rhEPO is possibly effective in a subgroup of MDS patients where the disease is less advanced. None of the transfusion-dependent patients benefited.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Refractory; Anemia, Refractory, with Excess of Blasts; Blood Transfusion; Erythropoietin; Female; Hemoglobins; Humans; Male; Middle Aged; Myelodysplastic Syndromes; Primary Myelofibrosis; Recombinant Proteins

Patients with hemosiderosis who also suffer from coexistent anemia may be unable to tolerate frequent phlebotomies needed for depletion of body iron stores. Chelation therapy, an alternative approach, may be unsuitable for some patients due to allergic reactions, poor response or intolerance of long-duration subcutaneous administration. The use of recombinant human erythropoietin in such patients could increase the hematocrit and improve exercise tolerance allowing for more frequent phlebotomies. We report the successful use of this combined approach in two such patients.

Topics: Aged; Anemia, Refractory; Bloodletting; Combined Modality Therapy; Erythropoietin; Female; Hemosiderosis; Humans; Male; Middle Aged; Recombinant Proteins

The effect of human recombinant erythropoietin (rhEPO) was investigated in 29 anemic patients with myelodysplastic syndromes (MDS). A rhEPO dosage of 150 U/kg was administered subcutaneously three times weekly for a minimum of 6 weeks. Seven out of 27 evaluable patients (26%) had an effective clinical response to therapy by increasing hemoglobin concentrations by more than 15 g/l (reaching at least 105 g/l) or by eliminating transfusion requirements. Six out of the seven patients responded within four weeks. Three of the responders successfully continued rhEPO treatment 15 months or more. To determine whether it may be possible to predict response to rhEPO, various clinical parameters were examined. Responders were found to be significantly different from non-responders in five aspects: They had less elevated baseline serum EPO levels (92 +/- 33 versus 515 +/- 108 U/l, mean +/- SEM; p = 0.023) and were more often transfusion-independent (71% versus 20% of non-responders; p = 0.022). Furthermore, responders were more often females (71% versus 40% in the non-responding group; p = 0.025), of subtype RA rather than RAEB (four patients and one patient, respectively, compared to seven and nine patients in the non-responding group; p = 0.025), and they predominantly displayed normal karyotypes or a 5q- aberration (86% versus 47%; p = 0.005). We conclude, that rhEPO treatment can reduce anemia in MDS and that certain pre-treatment clinical parameters may be used to predict response.

Topics: Aged; Aged, 80 and over; Anemia, Refractory; Blood Transfusion; Chromosome Deletion; Chromosomes, Human, Pair 5; Erythropoietin; Female; Humans; Male; Middle Aged; Myelodysplastic Syndromes; Predictive Value of Tests; Prognosis; Recombinant Proteins; Sex Factors

We studied the efficacy of high doses (100,000 IU intravenously (IV)/twice a week) of human recombinant erythropoietin (rHuEpo) in patients with transfusion dependent myelodysplastic syndromes (MDS). Rationale for such dose of IV Epo was the poor in vitro response of MDS erythroid progenitors (CFU-E) to physiological concentrations of Epo, and the usual high endogenous serum Epo levels of MDS patients. Seventeen patients (nine males, eight females) were included, five refractory anaemia (RA), six RA with blasts excess (RAEB), five RA with ringed sideroblasts (RARS). Tolerance was good, except in three patients who experienced severe flu-like syndrome after Epo injection. None of the patients showed hypertension or developed anti rHuEpo antibodies. Three patients (17.6%) with RAEB had 35-60% reduction of transfusion requirements. No progression of disease occurred. Percentage of erythroblasts, endogenous baseline Epo level and in vitro cultures of erythroid progenitors did not correlate with response to Epo treatment. This study shows that very high IV doses induce only seldom and partial improvement in the status of transfusion dependent MDS. This rate of response, not higher than described with lower dosage, probably represents the maximum expectable response to rHuEpo in this category of patients.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Refractory; Anemia, Sideroblastic; Bone Marrow; Erythrocyte Transfusion; Erythroid Precursor Cells; Erythropoietin; Female; Humans; Injections, Intravenous; Male; Middle Aged; Myelodysplastic Syndromes; Recombinant Proteins

Topics: Adult; Anemia, Refractory; Cyclosporine; Erythropoietin; Humans; Male; Prednisolone; Recombinant Proteins

Recombinant human erythropoietin (rhEpo) was administered to 14 patients with myelodysplastic syndrome (MDS) and seven patients with aplastic anemia (AA). In 19 patients, doses of 6000 units were given intravenously three times a week (t.i.w.) with the dose being doubled up to 24,000 units every 8 weeks until a response was obtained. RhEpo was given subcutaneously in two patients. Seven patients, four with MDS and three with AA, showed a significant response with an increase of hemoglobin concentration during therapy. The response occurred at doses of 12,000 units in five and 24,000 units in two patients. Responding patients with both MDS and AA had a relatively low serum Epo (s-Epo) level prior to Epo therapy. MDS responders had either refractory anemia (RA) or RA with ring sideroblasts (RARS), while two of the Epo responders in AA had a severe form of the disease. However, since some of the Epo responders had a high initial s-Epo concentration, a high s-Epo level does not preclude the use of rhEpo. Serial determination of s-Epo levels showed a progressive decline in six of the seven responders even when they were on rhEpo therapy, while the s-Epo levels remained elevated or further increased with time in most nonresponders. RhEpo was well tolerated by all patients. The results suggest that rhEpo is a safe and effective treatment for a certain proportion of patients with MDS and AA. Moreover, serial determination of s-Epo during therapy may be useful in monitoring and predicting the therapeutic effect of rhEpo.

Topics: Adolescent; Adult; Aged; Anemia, Aplastic; Anemia, Refractory; Anemia, Refractory, with Excess of Blasts; Erythropoietin; Female; Humans; Male; Middle Aged; Prognosis; Recombinant Proteins

Inflammatory bowel disease (IBD) is often associated with anemia. Of 85 patients with IBD, 28 were anemic and had an inadequately low plasma erythropoietin (EPO) concentration. Three patients with a long-standing history of IBD and refractory chronic anemia (hemoglobin values < 10 g/dL, plasma EPO concentrations below 100 mU/mL) were treated with recombinant human EPO, which was administered subcutaneously three times per week at a dose of 200-300 U/kg of body weight. Bone marrow biopsy specimens taken before therapy showed slightly decreased erythropoiesis with a shift of erythroid precursors toward more immature stages. EPO treatment resulted in a marked increase in hemoglobin values in all 3 patients. Bone marrow biopsies after EPO therapy showed quantitatively and qualitatively normal erythropoiesis in all of them. Correction of anemia was followed by improved well-being, and all patients were able to cope much better with their IBD. In all three patients, there was an increase in body weight and their Karnofsky index improved. After a complete workup and exclusion of any other cause for anemia, erythropoietin treatment, although expensive, should be considered in patients with IBD and refractory anemia.

Topics: Anemia, Refractory; Bone Marrow; Colitis, Ulcerative; Crohn Disease; Erythropoietin; Female; Humans; Male; Recombinant Proteins

In myeloproliferative disorders, aggravation of splenomegaly was reported as an adverse effect of erythropoietin (EPO). Recently, we experienced the adverse effect of EPO in myelodysplastic syndrome (MDS). A 65-year-old male was admitted to our hospital for scrutiny of pancytopenia in July 8, 1991. He was diagnosed as having MDS (refractory anemia: RA). After discharge, daily subcutaneous administration of EPO (3,000U) was started on August 1 because his Hb concentration had decreased to 9.2 g/dl. After the daily dose of EPO was increased up to 6,000U in August 15, left hypochondralgia gradually developed. EPO administration was haltedon August 22. His splenomegaly was aggravated from 2 finger breadths below the left costal margin before EPO administration to 4.5 finger breadths. Bone marrow examination revealed a change to extremely hypercellular marrow from slightly hypocellular marrow before EPO administration. The peripheral blood cell count was not altered. We concluded that he was a rare case of MDS in which aggravation of splenomegaly was observed, probably as a result of extramedullary hematopoiesis induced by administration of EPO.

Topics: Aged; Anemia, Refractory; Bone Marrow; Erythropoietin; Hematopoiesis, Extramedullary; Humans; Male; Splenomegaly

We studied the feasibility of treating refractory anemia and post-transfusional serious hemochromatosis in a patient undergoing hemodialysis (3x4 h weekly) for fourteen years, with recombinant human erythropoietin (r-HuEPO) associated with blood-letting. Blood transfusion previously received by the patient at a rate of two units of packed red cells every month for nine years was stopped and r-HuEPO (80 U/kg b.w.) was administered i.v. at the end of each hemodialysis. When Hct increased over 30%, approximately 40 ml of blood was removed per hemodialysis session in an attempt to accelerate iron loss. Excellent control of anemia and hemochromatosis was achieved after seven months of treatment. The patient's general condition and skin pigmentation were significantly improved.

Topics: Adult; Anemia, Refractory; Blood Transfusion; Bloodletting; Combined Modality Therapy; Erythropoietin; Female; Hemochromatosis; Humans; Kidney Failure, Chronic; Recombinant Proteins; Renal Dialysis; Time Factors

Topics: Anemia, Refractory; Erythrocytes; Erythrocytes, Abnormal; Erythroid Precursor Cells; Erythropoiesis; Erythropoietin; Ferritins; Humans; Iron; Myelodysplastic Syndromes

A chronic hemodialysis case, a 46-year-old woman with secondary hemosiderosis induced by parenteral iron and blood transfusion due to a refractory anemia, was effectively treated with recombinant human erythropoietin and the removal of red blood cells. The cumulative dose of the iron removed was 5,712 mg. Plasma ferritin decreased from 8,290 to 2,203 micrograms/l during 18 months. Concomitantly, liver histology performed before and after the therapy revealed a prominent regression of the deposited iron.

Topics: Anemia, Refractory; Biopsy; Blood Transfusion; Erythrocyte Count; Erythropoietin; Female; Ferritins; Follow-Up Studies; Hemosiderosis; Humans; Iron; Liver; Middle Aged; Recombinant Proteins; Renal Dialysis

Recombinant human erythropoietin was administered to an anemic patient with multiple myeloma (IgD, lambda type) and renal dysfunction who had been dependent on blood transfusions. Three thousand units of the recombinant human erythropoietin was given intravenously three times a week. Thereafter transfusion requirements, hemoglobin level, and reticulocyte responses have been monitored. An increase in hemoglobin level and reticulocyte counts was observed within 10 days and then further blood transfusion was not necessary. Neither organ dysfunction nor toxic effects were observed. The administration of recombinant human erythropoietin can be a new method to treat anemia associated with multiple myeloma and renal dysfunction.

Topics: Anemia, Refractory; Erythropoietin; Female; Humans; Kidney Diseases; Middle Aged; Multiple Myeloma; Recombinant Proteins

Responsiveness of bone marrow erythropoietic stem cells (CFU-E and BFU-E) to recombinant human erythropoietin (rh-Ep) was examined in vitro in 23 patients with aplastic anemia and 14 with myelodysplastic syndrome (MDS) to investigate the clinical use of rh-Ep for these diseases. Bone marrow mononuclear cells were cultured by methylcellulose methods for CFU-E and BFU-E assays. In normals, the CFU-E numbers reached a plateau of increase at Ep doses of almost 2-5 units, and no further increase was observed with the addition of larger Ep doses. In aplastic anemia, the responses of CFU-E to Ep were relatively good in nonsevere type and generally poor in severe type. However, the CFU-E numbers increased with increasing doses of Ep in some of the patients with aplastic anemia. Among the patients with MDS, the responses of CFU-E to Ep were relatively good in primary acquired refractory anemia (PARA) and primary acquired sideroblastic anemia. On the other hand, the responses of CFU-E to Ep were poor in refractory anemia with an excess of blasts (RAEB) and RAEB in transformation among the MDS patients. BFU-E responses to Ep were poor in severe aplastic anemia, RAEB, and RAEB-T. However, there are Ep responsive patients in some of aplastic anemia and PARA. High titers of rh-Ep were suggested to be effective clinically in some patients with aplastic anemia and those with PARA.

Topics: Anemia, Aplastic; Anemia, Refractory; Anemia, Refractory, with Excess of Blasts; Anemia, Sideroblastic; Bone Marrow; Cells, Cultured; Dose-Response Relationship, Drug; Erythroid Precursor Cells; Erythropoietin; Humans; Myelodysplastic Syndromes; Recombinant Proteins; Reference Values

A short review is presented of the primary and the secondary types of therapy-refractory anemia. Special emphasis is placed on the newest results obtained with therapeutic plasmapheresis and with recombinant human erythropoietin.

Topics: Anemia, Refractory; Anemia, Sideroblastic; Erythropoietin; Humans; Plasmapheresis; Red-Cell Aplasia, Pure