Defective Erythropoiesis in Bone Marrow is a Mechanism of Anemia in Children with Cancer

Abstract

Evaluation of the mechanism of anemia in cancer patients might help to select patients for the more efficient use of erythropoietin (EPO, a growth factor for erythroid precursor cells). For this, we investigated whether the production of EPO responds to anemia and the bone marrow responds to EPO appropriately, and whether chronic inflammation is inhibitory to erythropoiesis in anemic cancer children. Serum levels of EPO, soluble transferrin receptor (sTfR), tumor necrosis factor (TNF)-, and erythrocyte sedimentation rate (ESR) in anemic cancer children were measured by enzyme-linked immunosorbent assay and then the correlation coefficients between those parameters and hemoglobin (Hb) were determined. Both in leukemia and in solid tumor patients, there were significant inverse correlations between Hb and EPO (leukemia: tau=-0.547, p<0.0001; solid tumor: tau=-0.591, p<0.0001), and between sTfR and EPO (leukemia: tau=-0.223, p< 0.05; solid tumor: tau=-0.401, p<0.05). In contrast, sTfR showed a correlation with Hb in leukemia (tau=0.216, p<0.05) but not in solid tumor patients. sTfR was suppressed in 53% of anemic episodes of leukemia and 78% of those of solid tumor patients. Our results suggest that in cancer children, the EPO production is not defective and chronic inflammation is not inhibitory to erythropoiesis. Rather, the defective erythropoiesis itself is thought to be responsible for the anemia.

Hubungan Laju Filtrasi Glomerulus dengan Derajat Anemia pada Penderita Penyakit Ginjal Kronik

“…Pada penderita keganasan terjadi interaksi antara sel tumor dengan sistem imun pejamu yang akan mengganggu metabolisme besi, dan mengurangi produksi eritropoietin (EPO) dan perdarahan pada tumor. 13 Hemoglobinopati ditandai dengan adanya suatu produksi atau struktur yang abnormal pada molekul hemoglobin. 15 Kejadian anemia sebesar 18% pada penderita HIV asimtomatik seropositif, 50% pada penderita HIV simtomatik stadium ringan, dan 75% pada penderita AIDS.…”

The Role of Recombinant Erythropoietin in Childhood Cancer

“…Defective erythroid progenitor activity secondary to the presence of soluble inhibitory factors associated with cancer has been postulated as causative for CAA in children [10,11]. Furthermore, increased circulating levels of cytokines in blood, such as interleukin 1, tumor necrosis factor ␣, and transforming growth factor ␤, have been shown in both hematological and solid tumor malignancies in adults [12][13][14][15].…”

“…Patients randomized to the EPO group received epoetin alfa at a dose of 150 IU/kg s.c. three times a week for 16 weeks. Epoetin alfa was commenced after a mean of 4.7 courses of chemotherapy (range, [1][2][3][4][5][6][7][8][9][10][11][12][13][14]. Patients in the EPO group had a significantly lower rate of RBC and platelet transfusion (18%) than patients in the control group (45%) (p Ͻ .05).…”