Owen Roger G, Hillmen Peter, Rawstron Andy C
Haematological Malignancy Diagnostic Service Laboratory, The Leeds Teaching Hospitals NHS Trust, General Infirmary at Leeds, Great George Street, Leeds LS1 3EX, UK.
Clin Lymphoma. 2005 Mar;5(4):278-81. doi: 10.3816/clm.2005.n.016.
The efficacy of monoclonal antibody therapy is determined, at least in part, by the extent to which the target antigen is expressed. This is a complex issue in Waldenstrom's macroglobulinemia (WM) as it is a disorder characterized by plasma cell differentiation and therefore target antigen expression may differ between the B-cell and plasma cell compartments of the disease. In order to assess this in the context of alemtuzumab therapy, the authors used multiparameter flow cytometry to determine CD52 expression in the B-cells and plasma cells of patients with WM. CD52 expression was demonstrable in the B-cells of all cases, with a median of 99% of cells (range, 81%-100%) expressing the antigen compared with the isotype control (n = 47). Antigen density was very similar to that seen in chronic lymphocytic leukemia (median mean fluorescence intensity [MFI], 1249; range, 175-3170). Antigen expression was, however, significantly lower in the plasma cells (median MFI, 235; range, 31-1814) in all but 1 of the cases assessed (n = 21). The clinical significance of this was assessed by examining serial bone marrow samples from patients receiving alemtuzumab as part of an ongoing clinical trial. In 4 of 5 patients, alemtuzumab therapy successfully eradicated clonal B-cells from the bone marrow, but residual plasma cells remained evident in 2 of these patients. The implications of these findings for monoclonal antibody therapy in WM are discussed.
单克隆抗体治疗的疗效至少部分取决于靶抗原的表达程度。在华氏巨球蛋白血症（WM）中，这是一个复杂的问题，因为它是一种以浆细胞分化为特征的疾病，因此该疾病的B细胞和浆细胞区室中的靶抗原表达可能不同。为了在阿仑单抗治疗的背景下评估这一点，作者使用多参数流式细胞术来确定WM患者B细胞和浆细胞中的CD52表达。在所有病例的B细胞中均证实有CD52表达，与同型对照相比（n = 47），中位有99%的细胞（范围为81%-100%）表达该抗原。抗原密度与慢性淋巴细胞白血病中所见非常相似（中位平均荧光强度[MFI]，1249；范围为175-3170）。然而，在除1例评估病例外的所有病例（n = 21）中，浆细胞中的抗原表达显著较低（中位MFI，235；范围为31-1814）。通过检查正在进行的一项临床试验中接受阿仑单抗治疗患者的系列骨髓样本，评估了这一现象的临床意义。在5例患者中的4例中，阿仑单抗治疗成功地从骨髓中清除了克隆性B细胞，但其中2例患者的残留浆细胞仍然明显。讨论了这些发现对WM单克隆抗体治疗的意义。
