Baron Frédéric, Frère Pascale, Fillet Georges, Beguin Yves
Department of Medicine, Division of Hematology, University of Liège, 4000 Liège, Belgium.
Clin Cancer Res. 2003 Nov 15;9(15):5566-72.
Previous trials of recombinant human erythropoietin (rHuEpo) therapy after autologous hematopoietic stem cell transplantation have administered very high doses of i.v. rHuEpo starting on day 1 and continuing for 1-2 months until erythroid engraftment and have shown no benefit of rHuEpo therapy. We sought to establish a more effective use of rHuEpo in this setting.
In this report, we show in a first cohort of 45 lymphoma or myeloma patients undergoing peripheral blood stem cell transplant (control group) that endogenous erythropoietin levels are high for the degree of anemia during the first 3 weeks after transplant but become adequate or slightly decreased thereafter. We thus enrolled 41 consecutive similar patients in a trial of rHuEpo therapy at a dose of 500 units/kg/week started on day 30 after the transplant.
The 12-week probability of achieving hemoglobin (Hb) levels of 13 g/dl was 87% in rHuEpo-treated patients versus 14% in controls (P = 0.0001). Mean Hb levels were significantly higher in the rHuEpo group than in the control group from day 42 through day 150 after transplant (Ps of <0.05 to <0.001). Two of 41 patients in the rHuEpo group versus 12 of 45 patients in the control group had Hb levels of <9 g/dl between day 42 and day 100 after the transplant (P = 0.0078).
Anemia after autologous peripheral blood stem cell transplant is exquisitely sensitive to rHuEpo when therapy is started soon after engraftment. This is the first convincing report showing that rHuEpo is effective in this setting. Our data set the stage for a more rational use of rHuEpo after autologous hematopoietic stem cell transplantation and should renew interest in erythropoietin therapy in this setting. Prospective, randomized trials should investigate the impact of rHuEpo therapy on transfusion requirements and quality of life.
既往自体造血干细胞移植后重组人促红细胞生成素(rHuEpo)治疗的试验,从第1天开始静脉注射非常高剂量的rHuEpo,并持续1 - 2个月直至红系植入,结果显示rHuEpo治疗并无益处。我们试图在此情况下建立一种更有效的rHuEpo使用方法。
在本报告中,我们在首批45例接受外周血干细胞移植的淋巴瘤或骨髓瘤患者(对照组)中发现,移植后前3周内,内源性促红细胞生成素水平对于贫血程度而言较高,但此后变得充足或略有下降。因此,我们招募了41例连续的类似患者进行rHuEpo治疗试验,剂量为500单位/千克/周,于移植后第30天开始。
接受rHuEpo治疗的患者在12周时血红蛋白(Hb)水平达到13 g/dl的概率为87%,而对照组为14%(P = 0.0001)。移植后第42天至第150天,rHuEpo组的平均Hb水平显著高于对照组(P值<0.05至<0.001)。rHuEpo组41例患者中有2例,而对照组45例患者中有12例在移植后第42天至第100天之间Hb水平<9 g/dl(P = 0.0078)。
自体外周血干细胞移植后的贫血在植入后不久开始治疗时对rHuEpo极为敏感。这是第一份令人信服的报告,表明rHuEpo在此情况下有效。我们的数据为自体造血干细胞移植后更合理地使用rHuEpo奠定了基础,并应重新激发对此情况下促红细胞生成素治疗的兴趣。前瞻性随机试验应研究rHuEpo治疗对输血需求和生活质量的影响。