Responsiveness of bone marrow erythroid progenitors (CFU‐E and BFU‐E) to recombinant human erythropoietin (rh‐Ep) <i>in vitro</i> in multiple myeloma

Aoki, I; Nishijima, Kosuke; Hòmori, Masashi; Nakahara, Kazuhiko; Higashi, Katsumi; Ishikawa, Kinya

doi:10.1111/j.1365-2141.1992.tb02976.x

Cited by 15 publications

(1 citation statement)

References 23 publications

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“…ACD is characterized by decreased RBC survival and defective iron reutilization due to cytokines, like tumor necrosis factor and IL-1, which are produced by tumor and normal host cells and suppress erythropoiesis [6,17,22], In MM, IL-6 is also important [ 16,22], Ariad et al [23] suggested that the anemia is caused not by low serum Epo levels, but by inadequate response to Epo at the level of the target cell. Aoki et al [24] conclud ed that rHuEpo increases the number of erythroid progen itors. Even if these patients have relatively normal serum Epo levels, therapeutic doses of Epo may correct the ane mia by a pharmacological rather than a physiological effect.…”

Section: Discussionmentioning

confidence: 99%

Recombinant Human Erythropoietin in the Treatment of Multiple Myeloma-Associated Anemia

Mittelman¹,

Zeidman²,

Fradin³

et al. 1997

Acta Haematol

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Multiple myeloma (MM) is commonly associated with anemia. Several causes have been implicated but inadequate erythropoietin (Epo) production appears to be important. This single-institute open-label, non-comparative clinical trial was undertaken in order to evaluate serum Epo levels in patients with MM and to study the efficacy and toxicity of recombinant human Epo (rHuEpo) in the treatment of MM-associated anemia. MM patients with a baseline hemoglobin (Hb) level of < 11 g/dl received rHuEpo 150 U/kg 3 times/week subcutaneously, with a possible dose increase to 300 U/kg if no response was observed after 4 weeks. The study was designed for 12 weeks, although some responders continued rHuEpo. The study endpoints were determined by an increase in Hb and a decrease in blood transfusion requirements (BTR). Seventeen patients were enrolled in the study. The median serum Epo level was 150 mU/ml (range 11-232). Four patients did not complete the study for reasons unrelated to rHuEpo, but to their underlying MM. Twelve patients (70.6%) responded with an increase in their Hb levels. One patient (5.9%) responded partially. The median Hb level rose from 9.4 g/dl (range 7.3-10.7) at study commencement to 12.5 g/dl (range 9.0-15.2). Six of the 11 patients who were transfusion dependent enjoyed a complete abolition of BTR. The response was also interpreted as an improved quality of life: 3 patients reported a decrease of 1 level in their WHO performance status (PS) score; in 8 patients, the PS declined by 2 grades and 1 patient enjoyed PS reduction by 4 scores. Six patients continue to receive rHuEpo up to 18 months, with a good response and a smaller maintenance dose. Four patients reported flu-like symptoms, 2 suffered from a local irritation and 1 experienced a transient controlled elevation of blood pressure. Summmary: (1) Pretreatment endogenous serum Epo levels were relatively low in all patients studied with MM-associated anemia; (2) rHuEpo was well tolerated in these patients; (3) rHuEpo was highly effective in the treatment of anemia in MM, and (4) the response to rHuEpo is characterized by an increase in Hb levels, a reduction in BTR and an improvement in the WHO PS score.

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Section: Discussionmentioning

confidence: 99%

Recombinant Human Erythropoietin in the Treatment of Multiple Myeloma-Associated Anemia

Mittelman¹,

Zeidman²,

Fradin³

et al. 1997

Acta Haematol

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Recombinant human erythropoietin for the correction of cancer associated anemia with and without concomitant cytotoxic chemotherapy

Ludwig

Sundal

Pecherstorfer

et al. 1995

Cancer

119

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Background. Chronic anemia is a common complication in patients with cancer, especially in those with advanced disease or who are under intensive chemotherapy. Because homologous blood transfusions involve some hazards, the safety and efficacy of recombinant human erythropoietin (r‐HuEPO) in the treatment of anemic patients with cancer with and without concomitant chemotherapy were studied. Methods. One‐hundred two cancer patients with hemoglobin less than 11 g/dl, ferritin greater than 30 μg/l, and creatinine < 220 μmol/l were enrolled in the study, 94 were eligible for efficacy evaluation. Sixty‐eight patients received chemotherapy (CT group) and 26 had no cytotoxic cancer treatment (NT group). Recombinant human erythropoietin was administered subcutaneously at a dose of 150 U/kg three times per week for 6 weeks; in nonresponders the dose was doubled for the subsequent 6 weeks. Response was defined as the achievement of a hemoglobin increase of 2 g/dl. Clinical and laboratory parameters, including serum erythropoietin (EPO) levels, performance status, and quality of life, were investigated at baseline and monitored at regular intervals thereafter. Results. Response was achieved by 52% and 62% of CT and NT patients, respectively. The highest response rates were observed in patients with lung cancer or with a histology of squamous cell carcinoma (both 80%). In responding patients, the symptoms of anemia subsided. They no longer needed blood transfusions after 4 weeks of therapy; and both their performance status and quality of life improved significantly. The NT patients achieved slightly more favorable results on lower weekly doses: 450 U/kg/week in NT versus 570 U/kg/week in CT patients. Serum EPO levels were higher in nonresponders at baseline and further increased during the course of treatment. Recombinant human erythropoietin was well tolerated by all patients. Conclusion. This multicenter study in a large patient collective shows that r‐HuEPO treatment represents a safe and effective means to increase the red cell mass and eliminate the need for blood transfusions in approximately 50% of the patients with chronic anemia of cancer. Responding patients not only have increased levels of hemoglobin, but their performance status also improves significantly, and they enjoy a significantly enhanced quality of life. Cancer 1995; 76:2319–29.

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Recombinant human erythropoietin for the treatment of chronic anemia in multiple myeloma and squamous cell carcinoma

Ludwig¹,

Pecherstorfer²,

Leitgeb³

et al. 1993

STEM CELLS

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Recombinant human erythropoietin (rHuEPO) improves chronic anemia of cancer, but the proportion of patients who respond favorably to the treatment varies depending on the type of neoplasia. Preliminary data of the two malignancies with the highest response rates, namely, multiple myeloma and squamous cell carcinoma, are reported. Twenty patients with multiple myeloma and 14 with squamous cell carcinoma, who had presented with hemoglobin levels < 11 g/dl, were treated with rHuEPO, 150 U/kg, three times/week. Response, defined as an increase of at least 2 g/dl hemoglobin within 12 weeks, was achieved by 15 myeloma patients (75%) and 11 patients with squamous cell carcinoma (79%). Tolerance of the treatment was excellent. The WHO performance status and quality of life improved in responders. The remarkably low levels of endogenous EPO in our patients with squamous cell carcinoma, most of whom had been treated with cisplatin-or carboplatin-containing regimens, suggest that anemia in these cases had been at least partly chemotherapy induced. In myeloma patients, the blunted EPO response to the anemic condition may have been partly caused by subclinical tubular insufficiency induced by toxic paraproteins. Future studies should aim to elucidate factors which are responsible for the inability of some patients to respond to rHuEPO treatment, even though in multiple myeloma and squamous cell carcinoma these non-responders are a small minority.

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Responsiveness of bone marrow erythroid progenitors (CFU‐E and BFU‐E) to recombinant human erythropoietin (rh‐Ep) in vitro in multiple myeloma

Cited by 15 publications

References 23 publications

Recombinant Human Erythropoietin in the Treatment of Multiple Myeloma-Associated Anemia

Recombinant Human Erythropoietin in the Treatment of Multiple Myeloma-Associated Anemia

Recombinant human erythropoietin for the correction of cancer associated anemia with and without concomitant cytotoxic chemotherapy

Recombinant human erythropoietin for the treatment of chronic anemia in multiple myeloma and squamous cell carcinoma

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