Pediatr Nephrol (2004) 19:1059–1061 DOI 10.1007/s00467-004-1489-x BRIEF REPORT Angel Alonso Melgar · Marta Melgosa Hijosa · Rafael Pardo de la Vega · Carmen García Meseguer · Mercedes Navarro Torres Antierythropoietin antibody-induced pure red cell aplasia: posttransplant evolution Received: 28 October 2003 / Revised: 9 March 2004 / Accepted: 9 March 2004 / Published online: 7 May 2004  IPNA 2004 Abstract Pure red cell aplasia is a rare complication of recombinant human erythropoietin (rHuEPO) treatment, which physicians should consider once the more frequent causes of hyporegenerative anemia have been excluded. To our knowledge, no pediatric cases have been described. In our patient, cyclosporin A treatment enabled a reduc- tion in the number of transfusions and the risk of hyper- immunization. After transplantation, our patient’s hemo- globin level has remained normal and stable. Keywords Pure red cell aplasia · Antierythropoietin antibodies · Cyclosporin A · Transplantation Introduction Production of human erythropoietin (rHuEPO) by re- combinant DNA technology and its application in clini- cal practice since the late 1980s has resulted in a break- through in the treatment of anemia in patients with chronic renal insufficiency. During the 1st decade of us- age, only three cases of pure red cell aplasia induced by erythropoietin administration were published [1, 2, 3]. However, since 1998 there has been a significant increase in the number of patients developing this complication, the total number of cases reported worldwide being 200 [4]. To our knowledge, no pediatric cases have been re- ported to date. Case report A 17-year-old male patient with end-stage renal disease secondary to obstructive uropathy had received his first renal cadaver-donor transplant at the age of 10 years. Three years later a native kidney bilateral nephrectomy was performed due to arterial hypertension. The patient evolved a progressive loss of renal function because of graft chronic nephropathy. Erythropoietin alpha (Eprex) treatment was initiated in April 1998 at the age of 15 years. In August 1999, a transplantectomy was performed and peritoneal dialysis was start- ed. In November 2000, progressive anemia with maintained retic- ulocytopenia was detected, which did not respond to intravenous iron treatment or to a gradual increase of the rHuEPO dose [max- imum dose 5,000 IU 5 times per week (416 IU/kg per week)]. Ferropenia, hemolytic anemia, hyperparathyroidism, drug toxicity, viral infections, hidden losses due to digestive hemorrhage, and non-compliance were ruled out. Anemia worsened and transfusions were required monthly at first, and then every 15 days. In February 2001, a bone marrow biopsy was performed, showing red series hypoplasia with normal megakaryocytic and granulocytic series. Six months after the onset of that clinical picture, in May 2001, antierythropoietin antibodies with neutralizing activity were de- tected on three separate determinations. The study was performed by the Department of Pharmacovigilance of Jansen-Cylag. Samples were analyzed with a cell-based assay for antierythropoietin neu- tralizing antibody (Johnson and Johnson Pharmaceuticals) at MDS Pharma Services in Montreal, Canada. Erythropoietin treatment was interrupted. Prednisone at 1 mg/kg per day was given, and 4 months later azathioprine (50 mg/day, 0.8 mg/kg per day) was added. This regimen was maintained for 6 months without im- provement. In November 2001, because of the worsening of his condition and to prevent hyperimmunization, cyclosporin A treat- ment at 5 mg/kg per day was initiated, with trough levels oscillating between 60 and 100 mg/ml. Two months after the start of this treatment the antibodies were no longer detectable and the patient did not require transfusions. At 20 months, 6 months after the antibodies were no longer detectable, the patient received a trans- plant from a living donor, his mother. Induction therapy with basiliximab was employed. After transplantation the patient was managed with corticosteroids, mycophenolate, and tacrolimus. The hemoglobin response has been excellent, with a level of 7.4 g/dl immediately post transplant, increasing to 9.3 g/dl 15 days later, and becoming normal (>12 g/dl) 2 months later. At present, 2 years after the transplant, the patient maintains a stable hemo- globin level, around 12–13 g/dl, with a normal glomerular filtration rate. Figure 1 summarizes the hemoglobin levels and transfusion needs, as well as the treatments used. A. Alonso Melgar · M. Melgosa Hijosa · R. Pardo de la Vega · C. García Meseguer · M. Navarro Torres Pediatric Nephrology Unit, Hospital “La Paz”, Madrid, Spain M. Melgosa Hijosa ( ) ) Servicio de Nefrología Infantil, Hospital “La Paz”, Paseo de la Castellana 261, 28046 Madrid, Spain e-mail: mmelgosa.hulp@salud.madrid.org Tel.: +34-91-7277131 Fax: +34-91-7277534