Response to recombinant human erythropoietin (rHu-Epo) in a patient with chronic renal failure and myelomonocytic leukaemia

Filippo Salvati1, Mario Liani2 and Mario Bonomini3

1 Renal Unit, Dept Internal Medicine, SS Immacolata Hospital, Chieti-Guardiagrele Hospital 2 Renal Unit, Dept Internal Medicine, San Massimo Hospital, Penne, Pescara 3 Institute of Nephrology, G.D'Annunzio University, Chieti, Italy

Sir,

We describe here the case of a patient affected by chronic myelomonocytic leukaemia, which is a subtype of myelodysplastic syndromes (MDS) [1], and chronic renal failure requiring haemodialysis, who presented a complete and stable response to rHu-Epo therapy.

Case.

In May 1998, a 71-year-old Caucasian male was admitted for adynamic ileus and advanced renal failure. He had a past medical history of dysuria for 5 years and mentioned a mild renal failure due to the chronic lythiasic pyelonepritis associated with a moderate degree of anaemia. However, no laboratory value of the 3 years before admission was available. Initial laboratory investigations revealed serum creatinine 8.89 mg/dl, BUN 160 mg/dl, white blood cells 6200 (differential leukocyte count showing 57% neutrophils, 11.5% lymphocytes, 28.5% monocytes, 2.5% basophils), haemoglobin 7.8 g/dl, haematocrit 23.8%, platelets 79 000, erythrocyte sedimentation rate 89 mm/h, uric acid 8.28 mg/dl, serum ferritin 466 ng/ml, iron 36 mg/dl. Blood values for AST, ALT, albumin, electrolytes, folic acid, vitamin B12, tryglicerides, and cholesterol were within normal range. Urine analysis showed 4–8 erythrocytes and 2–4 leukocytes per high power field, specific gravity=1007. An abdominal ultrasound showed marked hypoplasia of the left kidney and caliceal lythiasis with hydronephrosis of the right kidney. Lytothripsia of the right kidney was unsuccessful and a stent was positioned. The clinical course was characterized by a rapid decline in renal function (creatinine 9.98 mg/dl, May 30th 1998). After arteriovenous fistula was fashioned, the patient was started on chronic haemodialytic treatment three times weekly (June 1998).

Besides monocytosis, peripheral blood smear revealed the presence of atypical monocytic cells. The patient underwent bone marrow aspiration that revealed a hypercellular marrow with dysplasia of all three lineages and 7% blasts (Figure 1Go). The results for immunochemistry of both bone marrow and peripheral blood are shown in Table 1Go. Taken together, these results are compatible with a diagnosis of MDS of myelo-monocytic chronic leukaemia subtype, according to the French-American-British classification [2]. The differentiation from the other types of MDS (refractory anaemia, RA; refractory anaemia with ringed sideroblasts, RARS; refractory anaemia with excess of blasts=RAEB, refractory anaemia with excess of blasts in transformation, RAEB-T) was based on four points: (i) monocytes over 10009/l in the peripheral blood; (ii) atypical monocytes in the peripheral blood smears; (iii) absence of ringed sideroblasts in the bone marrow; and (iv) elevated CD11b expression (expression of monocyte phenotype) over 50% in the peripheral blood and bone marrow.



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Fig. 1. Bone marrow smear of the patient showing hypoplastic erythropoiesis, dysplastic myelopoiesis and excess myelo-monoblasts.

 

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Table 1. Immunochemistry of bone marrow and peripheral blood

 
The patient was affected by a marked, symptomatic anaemia requiring intermittent blood transfusions. In November 1998, haemoglobin value was still 7.1 g/dl. Therefore, in an attempt to improve the patient's anaemia, we decided to start therapy with rHu-Epo (8000 UI i.v. three times weekly). In January 1999, haemoglobin values rose to 12.3 g/dl and thereafter stabilized between 12 and 13 g/dl. The patient is progressing well under a thrice-weekly dialytic treatment with a complete remission of symptoms related to anaemia. No adverse effect attributable to rHu-Epo was observed. A 1 year peripheral blood immunochemistry control showed results comparable with those reported in Table 1Go.

Comment.

In several published trials the effect of rHu-Epo has been studied in MDS patients with normal renal function, suffering from RA and RAEB [3,4]. With these types of MDS the response rate is generally low and a combination with cytokines such as recombinant G-CSF [5] has been tested with uncertain results. In myelomonocytic leukaemia, anaemia is not a typical complication, but can be found in some patients. In the present case it was probably due to the combination with chronic renal failure. The erythrocytes were microcytic (mean cell volume (MCV)=71 before treatment, MCV=84 during rHu-Epo and i.v. iron therapy), which is more compatible with the renal origin of anaemia rather than a haematological cause. On the other hand the relatively high dose requirement for rHu-Epo of 150 IU/kg three times weekly, which is intermediate between the usual dose required in renal anaemia and the higher dosage in haematological malignancies (200–300 IU/kg), points to an additional haematological cause of anaemia.

Acknowledgments

We thank Prof. G. Fioritoni, Head of the Department of Haematology, Regional Hospital of PESCARA, Chair of Haematology University of Chieti, for providing immunochemistry and clear diagnostic accuracy in the case under examination.

References

  1. Galton DAG. The myelodysplastic syndromes. Clin Lab Haematol1984; 6: 99–112[ISI][Medline]
  2. Bennett JM, Catovsky D, Daniel MT et al. Proposal for the classification of the myelodysplastic syndromes. Br J Haematol1992; 51: 189–199
  3. Dowen D, Culligan D, Jacobs A. The treatment of anaemia in the myelodysplastic syndromes with recombinant human erythropoietin. Br J Haematol1991; 77: 419–423[ISI][Medline]
  4. Casadevall N, Belanger C, Goy A, Varet B, Lang J, Poisson D. High-dose recombinant human Erythropoietin administered intravenously for the treatment of anaemia in myelodysplastic syndrome. Acta Haematol1992; 87 [Suppl. 1]: 25–27[ISI][Medline]
  5. Negrin R, Haeuber D, Nagler A et al. Maintenance treatment of patients with myelodysplastic syndromes using recombinant human granulocyte colony-stimulating factor. Blood1990; 76: 36–43[Abstract]




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