Kenneth F. Mangan

Effect of different modes of dialysis on serum erythropoietin levels in pediatric patients: a report of the southwest pediatric nephrology study group

The relative importance of erythropoietin (Ep) and inhibitors of erythropoiesis in the development of anemia in pediatric patients with end-stage renal disease (ESRD) was assessed in 82 patients: 41 treated with peritoneal dialysis (PD) and 41 with hemodialysis (HD). Serum Ep was determined with a sensitive radioimmunoassay. Potential serum inhibition of erythroid (CFU-E) and granulocytic (CFU-GM) progenitor cell growth was assessed using human bone marrow cell cultures. The mean Ep level for all 82 patients was 33.1±3.1 mU/ml, which was significantly higher (P<0.05) than the values obtained in 29 normal children (26.2±2.4 mU/ml). Serum Ep in the PD group (41.6±5.6 mU/ml) was significantly higher (P=0.007) than that of the HD group (24.6±2.1 mU/ml). The mean hematocrit in the PD group (25.2±0.8%) was also significantly higher (P<0.002) than that of the HD group (22.2±0.5%). The mean serum parathyroid hormone (PTH) level as measured by a mid-terminal radioimmunoassay was not significantly different (P=0.79) in the HD group (17,298±3,998 pg/ml) from that of the PD group (15,747±4,227 pg/ml). Neither serum Ep nor PTH concentration correlated with hematocrit or degree of inhibition of erythroid progenitor cell colony (CFU-E) formation in either group of dialysis patients, nor did the hematocrit correlate, with the degree of serum inhibition of CFU-E formation. The higher level of Ep in the PD group may indicate more effective removal by PD of some enzymatic substance which reduces the immunologic and biologic activities of Ep. The higher hematocrit in the PD group may be due to the higher serum level of biologically active Ep in the PD patients. The lack of any difference in PTH level in the HD and PD groups suggests that differences in PTH activity are not responsible for the higher hematocrit in PD patients.

Hematologic and cytogenetic remission of 5q- refractory anemia after syngeneic bone marrow transplantation

Refractory macrocytic anemia with hypolobulated megakaryocytic nuclei and partial deletion of the long arm of chromosome 5 has been termed the 5q- syndrome. Although long survival has been reported in a few cases of 5q- refractory anemia, accumulating evidence suggests that this syndrome is a preleukemic state with risk of transformation to acute nonlymphocytic leukemia as well as complications of bone marrow failure. This report describes the first apparently successful therapy for this disorder in a young man who originally presented with a clinical picture consistent with pure red cell aplasia and normal marrow chromosomes but with hypolobulated megakaryocytic nuclei. He was treated with vitamins, androgens, and sequential trials of immunosuppressive therapy, all without response. Two years after diagnosis, repeated marrow cytogenetic studies showed a 5q- abnormality in 70 percent and later in 100 percent of marrow metaphases. Because of transfusion-induced hemosiderosis and the availability of a cytogenetically normal monozygotic twin, bone marrow transplantation was undertaken. In light of the clonal (and suspected preleukemic) nature of the 5q- syndrome, the patients marrow was ablated with a busulfan plus cyclophosphamide regimen used for patients with nonlymphocytic leukemia. Sustained engraftment of cytogenetically normal marrow ensued. Two years after transplantation, and following six months of regular phlebotomy, the patient was hematologically normal with a normal serum ferritin level.