Bray G L, Reaman G H
Department of Hematology/Oncology, Children's National Medical Center, Washington, DC 20010.
Am J Pediatr Hematol Oncol. 1991 Winter;13(4):426-30. doi: 10.1097/00043426-199124000-00006.
Cisplatin (CDDP) has been implicated in the development of anemia via several mechanisms of action, including shortening of red cell (RBC) survival and direct toxicity of the drug on RBC bone marrow precursors. Recent studies and case reports suggest an association between CDDP and the development of hyporegenerative anemia as a consequence of relative erythropoietin (EPO) deficiency. To study the effects of CDDP on the relationship between serum EPO and hemoglobin (Hb) concentration, we measured levels of EPO in 12 patients (1-21 years of age) who were treated with cumulative doses of CDDP ranging from 300 to 720 mg/m2 for a variety of pediatric malignancies. Post-CDDP glomerular filtration rates (GFR) varied from 29 to 143 ml/min/1.73 m2 for 11 of the 12 patients studied. At the completion of CDDP therapy, an inverse linear relationship between log(10) serum EPO and Hb was noted among those patients who retained at least 40-50% of their pre-CDDP therapy GFR. One patient with chronic renal failure at the completion of CDDP therapy (GFR 25-35 ml/min/1.73 m2) exhibited a chronic transfusion-dependent, hyporegenerative anemia that was due to persistently low levels of EPO. Institution of recombinant human (r-Hu) EPO therapy resulted in an abrupt cessation of this patient's RBC transfusion dependency. Additional studies are needed to further characterize the effects of CDDP on EPO production and secretion and to determine optimal dosing schedules for r-Hu EPO in pediatric patients who receive CDDP and other myelosuppressive chemotherapy.
顺铂（CDDP）通过多种作用机制与贫血的发生有关，包括缩短红细胞（RBC）生存期以及药物对RBC骨髓前体细胞的直接毒性。最近的研究和病例报告表明，CDDP与因相对促红细胞生成素（EPO）缺乏导致的低再生性贫血的发生之间存在关联。为了研究CDDP对血清EPO与血红蛋白（Hb）浓度之间关系的影响，我们测量了12例患者（年龄1 - 21岁）的EPO水平，这些患者因各种儿科恶性肿瘤接受了累积剂量为300至720 mg/m²的CDDP治疗。在研究的12例患者中，有11例患者在接受CDDP治疗后的肾小球滤过率（GFR）在29至143 ml/min/1.73 m²之间。在CDDP治疗结束时，在那些保留了至少40 - 50% CDDP治疗前GFR的患者中，观察到log(10)血清EPO与Hb之间呈负线性关系。1例在CDDP治疗结束时患有慢性肾衰竭（GFR 25 - 35 ml/min/1.73 m²）的患者表现出慢性输血依赖的低再生性贫血，这是由于EPO水平持续较低所致。重组人（r - Hu）EPO治疗的实施导致该患者对RBC输血的依赖突然停止。需要进一步的研究来进一步描述CDDP对EPO产生和分泌的影响，并确定接受CDDP和其他骨髓抑制性化疗的儿科患者中r - Hu EPO的最佳给药方案。
