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Saudi Journal of Kidney Diseases and Transplantation
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Year : 1994  |  Volume : 5  |  Issue : 3  |  Page : 371-373
Is erythropoietin safe in haemodialysis patients with multiple myeloma ?

Department of Nephrology and Dialysis Al Hada Armed Forces Hospital, Taif, Saudi Arabia

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The use of recombinant human erythropoietin (rHuEpo) for the treatment of anemia of end-stage renal disease (ESRD) is now well established. There have also been reports about its use in treating the anemia of other diseases including multiple myeloma (MM). Some concern about the usage of rHuEpo in patients with MM has been raised by studies reporting worsening of myeloma activity after starting this drug. However, other studies have reported its safety in patients with MM. We report here a patient on maintenance haemodialysis, not known to have MM who developed symptoms related to this disease four months after starting rHuEpo. Although we might speculate that the onset of symptoms was coincidental and not causally related to rHuEpo, we recommend close monitoring of the disease activity in patients with MM receiving rHuEpo.

Keywords: rHuEpo, Haemodialysis, Multiple myeloma, ESRD

How to cite this article:
Hussein M, Mooij J, Roujouleh H. Is erythropoietin safe in haemodialysis patients with multiple myeloma ?. Saudi J Kidney Dis Transpl 1994;5:371-3

How to cite this URL:
Hussein M, Mooij J, Roujouleh H. Is erythropoietin safe in haemodialysis patients with multiple myeloma ?. Saudi J Kidney Dis Transpl [serial online] 1994 [cited 2021 Jan 19];5:371-3. Available from: https://www.sjkdt.org/text.asp?1994/5/3/371/41163

   Introduction Top
Recombitant human erythropoietin(r-HuEpo) is now widely used for the treatment of anemia of end-stage renal disease(ESRD) and has markedly improved the well-being of the dialysis patients [1] .It has also been used in the treatment of anemia associated with other diseases including multiple myeloma(MM)[2] . Although most of the theoretical and experimental data suggest that erythropoietin selectively promotes the growth of the erythroid precursor cells, there are some reports of stimulation of non-erythroid hematopoietic progenitor cells during rHuEpo treatment, with increased numbers of megakaryocytic and myeloid progenitors in the bone marrow as well as peripheral blood [3],[4],[5] . Also, a r-HuEpo receptor has been detected on a human myeloma cell line [6] . Therefore, there is some concern about the safety of this drug in patients with MM.

Ruedin et al [7] described four patients with ESRD due to MM in which there was good efficacy and no adverse effects of this treatment. However, recently Caillette et al [8] reported a relapse of MM in a hemodia. lysis patient one month after the start of rHuEpo. A similar event was reported earlier in a patient with MM without renal failure [9] . We describe here, one of our patients who developed MM while on rHuEpo, and this report might add to the discussion on this subject.

   Case Report Top

A female patient, born in 1939, was known since 1991 to have ESRD of uncertain etiology (shrunken kidneys). Initially, she was treated with haemodialysis in another hospital and in July 1992 she was transferred to our department. Since the patient had symptomatic anemia with a hemoglobin level of 7.6 g/dl and a hematocrit of 23%, requiring repeated blood transfusions, treatment with rHuEpo was started (Eprex, Cilag). The initial dosage used was 120 U/ kg body weight (BW) per week, divided in 3 doses given intravenously post-dialysis. Gradually, the dosage was increased to 210 U/kg BW per week, resulting in hemoglobin of 9.3 g/dl and a hematocrit of 28%. A routine metabolic bone survey performed in August 1992 showed multiple lytic bone lesions, which were initially interpreted as due to secondary hyperparathyroidism, although the serum parathormone (PTH) level was only slightly elevated (177 pg/ml) and the alkaline phosphatase level was in the normal range.

In December 1992, the patient started to complain about severe rib pain. X-rays were repeated which showed an increase in the size of the lytic lesions, now very suggestive of MM.

Laboratory investigations showed a Lambda light chain paraproteinemia with a serum M-component of 23 g/1. A bone marrow aspirate showed a plasmacytosis of more than 30%. Bence-Jones protein (Lambda light-chain paraprotein) was detectable in the urine. The diagnosis of MM stage III-B was made although the renal insufficiency was possibly not related to this disease.

The patient was treated with monthly melphalan-prednisone courses and local radiotherapy, after which she became pain free with a concomitant reduction of the serum M-component level. After one year, the patient's myeloma activity is still in remission and she remains on weekly erythropoietin in a dose of 210 U/kg resulting in a hemoglobin level of 8.9 g/dl and a hematocrit of 27%.

   Discussion Top

The complaints of this patient developed and the bone lesions became worse after the initiation of rHuEpo treatment. Therefore, it was questioned if this therapy could have stimulated the myeloma growth. Ludwig et al treated 13 patients with myeloma associated anemia without renal failure by administering rHuEpo for six months and did not observe any apparent interaction between the underlying disease and the erythropoietin therapy [2] . Ruedin et al studied four patients with ESRD due to MM and found no apparent worsening of myeloma activity during treatment with rHuEpo for 5 to 34 months [7] . Both studies concluded that rHuEpo is safe and effective in treating anemia associated with MM. However, some concern regarding this was raised by Caillette et al who observed a relapse of myeloma activity in a haemodialysis patient one month after starting rHuEpo [8] . Earlier, Rogers et al had found an increase of myeloma activity in a patient without renal failure during rHuEpo therapy, which reversed to the previous level when this treatment was discontinued [9] .

Most of the patients with MM and receiving rHuEpo therapy who are described in the literature had received chemotherapy prior to the rHuEpo treatment [2],[7],[8] . The history of our patient was different in that she was diagnosed and started treatment for MM four months after commencement of rHuEpo therapy. One of the patients of Ruedin et al [7] had also not received chemotherapy prior to starting rHuEpo treatment, and is therefore possibly comparable with our patient. In that patient, there was no relapse or worsening of myeloma activity during rHuEpo therapy.

After the initiation of treatment for the myeloma, the pain our patient complained of subsided. There was also a concomitant decrease of the serum-M component, indicating reduction of tumor mass. During this whole course, the rHuEpo treatment was continued, resulting in the maintenance of acceptable hemoglobin and hematocrit levels.

From the observations of Ruedin et al [7] as well as the course in our patient, we would speculate that the onset of symptoms due to MM in our patient was probably not causally related to the rHuEpo therapy but coincidental.

In conclusion, we would agree with the findings of Ludwig et al [2] and Ruedin et al [7] that rHuEpo can be used safely in treating anemia of patients with MM on dialysis. However, as also indicated by Caillette et al [8] we would strongly recommend close monitoring of myeloma activity in such patients while on treatment with rHuEpo.[10]

   References Top

1.Ersley AJ. Erythropoietin. New Engl J 1991;324:1339-44.   Back to cited text no. 1    
2.Ludwig H, Fritz E, Kotzmann H, Hocker P, Gisslinger H, Barnas U. Erythropoietin treatment of anemia associated with multiple myeloma. N   Back to cited text no. 2    
3.Engl J Med 1990;322:1693-9.   Back to cited text no. 3    
4.Krantz SB. Erythropoietin. Blood 1991;77:419-34.  Back to cited text no. 4  [PUBMED]  [FULLTEXT]
5.Dessypris EN, Graber SE, Kiantz SB, Stone WJ. Effects of recombinant erythropoietin on the concentration and cycling status of human marrow hematopoietic progenitor cells in vivo. Blood 1988;72:2060-2.  Back to cited text no. 5    
6.Geissler K, Stockenhuber F, Kabrna E, Hinterberger W, Balke P, Lechner K. Recombinant human erythropoietin and hematopoietic progenitor cells in vivo. Blood 1989;73:2229.  Back to cited text no. 6    
7.Okuno Y, Takahashi T, Suzuki A, et al. Expression of the erythropoietin receptor on a human myeloma cell line. Biochem Biophys Res Commun 1990;170:1128-34.  Back to cited text no. 7  [PUBMED]  [FULLTEXT]
8.Ruedin P, Pechere-Bertschi A, Chapuis B, Benedet P, Leski M. Safety and efficacy of recombinant human erythropoietin treatment of anaemia associated with multiple myeloma in haemodialysed patients. Nephrol Dial Transplant 1993;8:315-8.  Back to cited text no. 8    
9.Caillette A, Barreto S, Gimenez E, Labeeuw M, Zech P. Is erythropoietin treatment safe and effective in myeloma patients receiving hemodialysis? Clin Nephrol 1993;40:176-8.   Back to cited text no. 9  [PUBMED]  
10.Rogers S, Russell NH, Morgan AG. Effect of erythropoietin in patients with myeloma. BMJ 1990;301:667.  Back to cited text no. 10    

Correspondence Address:
Magdi Hussein
Department of Nephrology and Dialysis, Al Hada Armed Forces Hospital, P.O. Box 1347, Taif
Saudi Arabia
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PMID: 18583767

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