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Rituximab: A viable treatment option for epoetin-induced pure red cell aplasia.

Mahajan SA, Nandagopal N, Soni M, Annigeri RA - Indian J Nephrol (2015 Nov-Dec)

Bottom Line: He presented with severe transfusion-dependent anemia and was initially treated with prednisolone and oral cyclophosphamide.However, within 2 weeks the immunosuppressive drugs had to be stopped due to complications, following which he remained transfusion dependent.Subsequently, he was given two doses 700 mg each of rituximab following which there were hematological recovery and resolution of anti-epoetin antibodies.

View Article: PubMed Central - PubMed

Affiliation: Department of Nephrology, Apollo Hopsitals, Chennai, Tamil Nadu, India.

ABSTRACT
Pure red cell aplasia (PRCA) due to neutralizing antibodies can rarely develop following treatment with epoetin. The treatment of this condition is generally unsatisfactory and immunosuppression is often recommended, which improves chances of hematological recovery. We describe a case of PRCA due to neutralizing anti-epoetin antibodies following therapy with epoetin-α in a 68-year-old man on hemodialysis. He presented with severe transfusion-dependent anemia and was initially treated with prednisolone and oral cyclophosphamide. However, within 2 weeks the immunosuppressive drugs had to be stopped due to complications, following which he remained transfusion dependent. Subsequently, he was given two doses 700 mg each of rituximab following which there were hematological recovery and resolution of anti-epoetin antibodies.

No MeSH data available.


Related in: MedlinePlus

Bone marrow biopsy showing absence of erythroblasts and normal myeloid series and platelet precursors
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Figure 1: Bone marrow biopsy showing absence of erythroblasts and normal myeloid series and platelet precursors

Mentions: A 68-year-old man was diagnosed to have end-stage renal disease due to hypertensive nephropathy and was initiated on hemodialysis (HD) in March 2012. He received HD three times a week for 5 h each time. He received epoetin-α 4000 IU twice a week intravenously initially and later switched to subcutaneous administration in August 2013. He responded well to epoetin till November 2013, when Hb was 11.6 g/dl. Between November 2013 and January 2014, he had a precipitous drop in Hb (11.6 to 6.4 g/dl) for no obvious reason. Iron deficiency, external bleeding, gastrointestinal blood loss or hemolysis was excluded by appropriate investigations. Anemia worsened rapidly over next few days and he was hospitalized with significant anemic symptoms and received 4 units of blood during the hospital stay. Erythropoietin treatment was withdrawn as epoetin related PRCA was suspected since reticulocyte count was low at 0.7%. Bone marrow aspiration and biopsy were done, which confirmed the presence of PRCA. Bone marrow showed normocellular marrow, with severe suppression of erythroid series and normal myeloid and megakaryocyte series [Figure 1]. The presence of neutralizing anti-epoetin antibodies was confirmed by immunoprecipitation test [Table 1]. The neutralizing anti-epoetin antibody was positive at a dilution of 1:10,000 at the time of diagnosis. Serum level of endogenous erythropoietin levels was low [Table 1]. Renal transplantation was not a viable option for him in view of advanced age and comorbidities. In an effort to reduce the anti-epoetin antibodies, he was commenced on oral cyclophosphamide (1.5 mg/kg/day) and oral prednisolone 0.5 mg/kg/day. Two weeks into the treatment, he developed massive gastrointestinal bleed due to duodenal ulcer, requiring blood transfusions, following which steroid was withdrawn. He was admitted to Critical Care Unit where he developed right upper zone pneumonia requiring mechanical ventilation. In addition, he developed low white cell count, necessitating withdrawal of cyclophosphamide. He was given 8 units of transfusions during 10 days of hospitalization. Subsequently he remained transfusion dependent and required approximately one unit of red cells per week to maintain Hb above 6 g/dl [Figure 2]. In view of advanced age and intolerance to conventional immunosuppressive agents such as steroid and cyclophosphamide, he was treated with rituximab, 2 doses of 700 mg (approximately 500 mg/m2) in the month of April 2014, given 2 weeks apart. Meanwhile, he was also treated with 3 doses of androgenic steroid (nandrolone 25 mg) at 15 days interval, in order to support the recovery of the bone marrow. With the treatment, his Hb remained in the range of 6.1–6.4 g/dl for 2–3 weeks without blood transfusion and subsequently improved to above 7 g/dl. Currently, the patient maintains his Hb above 7 g/dl without any need for blood transfusion for more than 6 months after the last dose of rituximab. Serial measurement of neutralizing anti-epoetin antibody titer showed a decline and reached nonsignificant levels by 6 months, demonstrating success with therapy [Table 1]. We did not repeat the bone marrow study since there was clear clinical evidence of hematological recovery in the form of sustained increment in Hb, freedom from a blood transfusion and an increase in the reticulocyte count. He was not rechallenged with any other preparation of epoetin since he was symptom-free and did not require any further blood transfusions to maintain stable Hb.


Rituximab: A viable treatment option for epoetin-induced pure red cell aplasia.

Mahajan SA, Nandagopal N, Soni M, Annigeri RA - Indian J Nephrol (2015 Nov-Dec)

Bone marrow biopsy showing absence of erythroblasts and normal myeloid series and platelet precursors
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4663775&req=5

Figure 1: Bone marrow biopsy showing absence of erythroblasts and normal myeloid series and platelet precursors
Mentions: A 68-year-old man was diagnosed to have end-stage renal disease due to hypertensive nephropathy and was initiated on hemodialysis (HD) in March 2012. He received HD three times a week for 5 h each time. He received epoetin-α 4000 IU twice a week intravenously initially and later switched to subcutaneous administration in August 2013. He responded well to epoetin till November 2013, when Hb was 11.6 g/dl. Between November 2013 and January 2014, he had a precipitous drop in Hb (11.6 to 6.4 g/dl) for no obvious reason. Iron deficiency, external bleeding, gastrointestinal blood loss or hemolysis was excluded by appropriate investigations. Anemia worsened rapidly over next few days and he was hospitalized with significant anemic symptoms and received 4 units of blood during the hospital stay. Erythropoietin treatment was withdrawn as epoetin related PRCA was suspected since reticulocyte count was low at 0.7%. Bone marrow aspiration and biopsy were done, which confirmed the presence of PRCA. Bone marrow showed normocellular marrow, with severe suppression of erythroid series and normal myeloid and megakaryocyte series [Figure 1]. The presence of neutralizing anti-epoetin antibodies was confirmed by immunoprecipitation test [Table 1]. The neutralizing anti-epoetin antibody was positive at a dilution of 1:10,000 at the time of diagnosis. Serum level of endogenous erythropoietin levels was low [Table 1]. Renal transplantation was not a viable option for him in view of advanced age and comorbidities. In an effort to reduce the anti-epoetin antibodies, he was commenced on oral cyclophosphamide (1.5 mg/kg/day) and oral prednisolone 0.5 mg/kg/day. Two weeks into the treatment, he developed massive gastrointestinal bleed due to duodenal ulcer, requiring blood transfusions, following which steroid was withdrawn. He was admitted to Critical Care Unit where he developed right upper zone pneumonia requiring mechanical ventilation. In addition, he developed low white cell count, necessitating withdrawal of cyclophosphamide. He was given 8 units of transfusions during 10 days of hospitalization. Subsequently he remained transfusion dependent and required approximately one unit of red cells per week to maintain Hb above 6 g/dl [Figure 2]. In view of advanced age and intolerance to conventional immunosuppressive agents such as steroid and cyclophosphamide, he was treated with rituximab, 2 doses of 700 mg (approximately 500 mg/m2) in the month of April 2014, given 2 weeks apart. Meanwhile, he was also treated with 3 doses of androgenic steroid (nandrolone 25 mg) at 15 days interval, in order to support the recovery of the bone marrow. With the treatment, his Hb remained in the range of 6.1–6.4 g/dl for 2–3 weeks without blood transfusion and subsequently improved to above 7 g/dl. Currently, the patient maintains his Hb above 7 g/dl without any need for blood transfusion for more than 6 months after the last dose of rituximab. Serial measurement of neutralizing anti-epoetin antibody titer showed a decline and reached nonsignificant levels by 6 months, demonstrating success with therapy [Table 1]. We did not repeat the bone marrow study since there was clear clinical evidence of hematological recovery in the form of sustained increment in Hb, freedom from a blood transfusion and an increase in the reticulocyte count. He was not rechallenged with any other preparation of epoetin since he was symptom-free and did not require any further blood transfusions to maintain stable Hb.

Bottom Line: He presented with severe transfusion-dependent anemia and was initially treated with prednisolone and oral cyclophosphamide.However, within 2 weeks the immunosuppressive drugs had to be stopped due to complications, following which he remained transfusion dependent.Subsequently, he was given two doses 700 mg each of rituximab following which there were hematological recovery and resolution of anti-epoetin antibodies.

View Article: PubMed Central - PubMed

Affiliation: Department of Nephrology, Apollo Hopsitals, Chennai, Tamil Nadu, India.

ABSTRACT
Pure red cell aplasia (PRCA) due to neutralizing antibodies can rarely develop following treatment with epoetin. The treatment of this condition is generally unsatisfactory and immunosuppression is often recommended, which improves chances of hematological recovery. We describe a case of PRCA due to neutralizing anti-epoetin antibodies following therapy with epoetin-α in a 68-year-old man on hemodialysis. He presented with severe transfusion-dependent anemia and was initially treated with prednisolone and oral cyclophosphamide. However, within 2 weeks the immunosuppressive drugs had to be stopped due to complications, following which he remained transfusion dependent. Subsequently, he was given two doses 700 mg each of rituximab following which there were hematological recovery and resolution of anti-epoetin antibodies.

No MeSH data available.


Related in: MedlinePlus