Yoshida Takuhiro, Matsuda Masayuki, Katoh Nagaaki, Tazawa Ko-ichi, Shimojima Yasuhiro, Gono Takahisa, Ishii Wataru, Nakazawa Yozo, Sakashita Kazuo, Koike Kenichi, Yamada Toshiyuki, Ikeda Shu-Ichi
Department of Internal Medicine (Neurology and Rheumatology), Shinshu University School of Medicine, Matsumoto.
Intern Med. 2008;47(20):1783-90. doi: 10.2169/internalmedicine.47.0966. Epub 2008 Oct 15.
Primary systemic AL amyloidosis arises from immunoglobulin light chains produced by plasma cell dyscrasia. To prospectively investigate the production of M-protein and plasma cells in bone marrow before and after chemotherapy, we performed flow cytometry and analysis of serum free light chains (FLCs).
Fifty-nine patients with primary systemic AL amyloidosis (mean age, 59.9+/-8.8 years) were enrolled in this study, and of these 31 were serially studied before and after chemotherapy. Complete hematological remission was defined as normalization of the FLC kappa/lambda ratio.
MPC-1(-)CD45(-) (p<0.05) and MPC-1(+)CD45(-)CD49e(-) (p<0.005) were significantly higher, and MPC-1(-)-CD45(+) (p<0.05), MPC-1(+)CD45(+)CD49e(-) (p<0.0001) and MPC-1(+)CD45(+)CD49e(+) (p<0.0005) were significantly lower in the patients with AL amyloidosis than in controls. There was a significantly positive correlation between the serum predominant FLC/serum creatinine ratio and MPC-1(+)CD45(-)CD49e(-) (p<0.05). After chemotherapies, such as high-dose melphalan with autologous stem cell support, 20 of 31 patients with AL amyloidosis achieved complete hematological remission. There were no significant differences in any subtype of plasma cells before treatment between the remission and non-remission groups, but in the former group MPC-1(+)CD45(-)CD49e(-) and MPC-1(-)CD45(+) were significantly decreased and increased after chemotherapy compared with before, respectively.
Abnormal plasma cells in the bone marrow, particularly the MPC-1(+)CD45(-)CD49e(-) subset, may be important as a follow-up marker before and after chemotherapy in primary systemic AL amyloidosis. These cells maintain low levels as long as no relapse occurs.
原发性系统性AL淀粉样变性由浆细胞异常增殖产生的免疫球蛋白轻链引起。为前瞻性研究化疗前后骨髓中M蛋白和浆细胞的产生情况，我们进行了流式细胞术检测及血清游离轻链（FLC）分析。
59例原发性系统性AL淀粉样变性患者（平均年龄59.9±8.8岁）纳入本研究，其中31例在化疗前后进行了系列研究。完全血液学缓解定义为FLC κ/λ比值正常化。
与对照组相比，AL淀粉样变性患者中MPC-1(-)CD45(-)（p<0.05）和MPC-1(+)CD45(-)CD49e(-)（p<0.005）显著升高，而MPC-1(-)-CD45(+)（p<0.05）、MPC-1(+)CD45(+)CD49e(-)（p<0.0001）和MPC-!1(+)CD45(+)CD49e(+)（p<0.0005）显著降低。血清主要FLC/血清肌酐比值与MPC-1(+)CD45(-)CD49e(-)之间存在显著正相关（p<0.05）。经高剂量美法仑联合自体干细胞支持等化疗后，31例AL淀粉样变性患者中有20例实现了完全血液学缓解。缓解组和未缓解组治疗前任何浆细胞亚群均无显著差异，但化疗后，缓解组中MPC-1(+)CD45(-)CD49e(-)和MPC-1(-)CD45(+)分别较化疗前显著降低和升高。
骨髓中的异常浆细胞，尤其是MPC-1(+)CD45(-)CD49e(-)亚群，可能作为原发性系统性AL淀粉样变性化疗前后随访的重要标志物。只要不复发，这些细胞水平维持较低状态。
