Kostova Gabriela, Siljanovski Nikola
Prilozi. 2004;25(1-2):53-66.
Anaemia is the most common haematological complication in patients with malignant diseases. It is found in 60%-90% of cases with multiple myeloma. The pathogenesis of this hypoproliferative, normochromic, normocytic anaemia is complex. Results from clinical studies which evaluate the efficacy of recombinant human erythropoietin (rHuEpo) refer to the possibility that patients with multiple myeloma independently of renal function could have Epo deficiency. Based on this finding, the aim of the study was to evaluate the erythropoietin production in patients with multiple myeloma in order to define clinical conditions of Epo deficiency and thereby enable rational use of this expensive drug. 42 patients with multiple myeloma were examined. The control group consisted of 25 patients with iron deficiency anaemia. 14 healthy volunteers represented the so-called "normal" control. The adequacy of Epo production was estimated from the graphic representation of the linear regression between Epo and haemoglobin (Hb) in the control group, as well as from O/PEpo ratio as a measure of the degree of adequacy of Epo production (O -- observed Epo value, P -- predicted Epo value from the regression equation of the control group). The erythropoietic activity was estimated from the graphic representation of the linear regression between soluble transferin receptors (sTfR) and Hb in the control group, as well as from O/PsTfR ratio, as a measure of the degree of adequacy of erythropoietic activity (O -- observed sTfR value, P -- predicted sTfR value from the regression equation of the control group). Significant inverse correlation between Epo and Hb was found in patients with multiple myeloma but preserved renal function, which was not the case in patients with renal insufficiency. 43% of patients without renal insufficiency and 85% of patients with renal insufficiency had inadequate Epo response to anaemia. In both patient groups (with and without renal insufficiency) instead of the expected inverse relationship between Hb and sTfR as in the control group, a positive correlation was found. 76% of patients had inadequate sTfR response to anaemia. There is a positive correlation between O/PEpo and O/PsTfR which is in favour of Epo driven erythropoiesis. O/PEpo and O/PsTfR in patients with multiple myeloma are significantly lower in comparison to the control group, which also points to the inadequacy of erythropoietin production, respectively erythropoietic activity. In conclusion, the results from this study show unambiguously that anaemia in patients with multiple myeloma appears because of decreased erythropoiesis as a consequence of bone marrow infiltration with malignant plasma cells as well as inadequate Epo production. Most probably, there are two forms of inadequate Epo production: one because of the renal insufficiency and the other that found in patients with anaemia of chronic diseases the mechanism of which is not clear.
贫血是恶性疾病患者中最常见的血液学并发症。在60%-90%的多发性骨髓瘤病例中可发现贫血。这种增生低下、正色素性、正细胞性贫血的发病机制较为复杂。评估重组人促红细胞生成素(rHuEpo)疗效的临床研究结果表明,多发性骨髓瘤患者无论肾功能如何都可能存在促红细胞生成素缺乏。基于这一发现,本研究的目的是评估多发性骨髓瘤患者的促红细胞生成素产生情况,以确定促红细胞生成素缺乏的临床状况,从而合理使用这种昂贵的药物。对42例多发性骨髓瘤患者进行了检查。对照组由25例缺铁性贫血患者组成。14名健康志愿者作为所谓的“正常”对照。根据对照组中促红细胞生成素与血红蛋白(Hb)之间线性回归的图形表示,以及O/PEpo比值(作为促红细胞生成素产生充足程度的指标,O——观察到的促红细胞生成素值,P——根据对照组回归方程预测的促红细胞生成素值)来评估促红细胞生成素产生的充足性。根据对照组中可溶性转铁蛋白受体(sTfR)与Hb之间线性回归的图形表示,以及O/PsTfR比值(作为红细胞生成活性充足程度的指标,O——观察到的sTfR值,P——根据对照组回归方程预测的sTfR值)来评估红细胞生成活性。在肾功能正常的多发性骨髓瘤患者中发现促红细胞生成素与血红蛋白之间存在显著负相关,而肾功能不全患者则并非如此。43%的肾功能正常患者和85%的肾功能不全患者对贫血的促红细胞生成素反应不足。在两组患者(有和无肾功能不全)中,与对照组中血红蛋白和sTfR之间预期的负相关关系不同,发现了正相关。76%的患者对贫血的sTfR反应不足。O/PEpo与O/PsTfR之间存在正相关,这支持促红细胞生成素驱动的红细胞生成。与对照组相比,多发性骨髓瘤患者的O/PEpo和O/PsTfR显著更低,这也分别表明促红细胞生成素产生不足和红细胞生成活性不足。总之,本研究结果明确表明,多发性骨髓瘤患者的贫血是由于恶性浆细胞浸润骨髓导致红细胞生成减少以及促红细胞生成素产生不足所致。很可能存在两种促红细胞生成素产生不足的形式:一种是由于肾功能不全,另一种是在慢性病贫血患者中发现的,其机制尚不清楚。