Rawstron Andy C, Davies Faith E, DasGupta Ranjit, Ashcroft A John, Patmore Russell, Drayson Mark T, Owen Roger G, Jack Andrew S, Child J Anthony, Morgan Gareth J
Academic Unit of Haematology and Oncology, Algernon Firth Building, University of Leeds, Leeds LS1 3EX, UK.
Blood. 2002 Nov 1;100(9):3095-100. doi: 10.1182/blood-2001-12-0297.
Conventional monitoring strategies for myeloma are not sufficiently sensitive to identify patients likely to benefit from further therapy immediately after transplantation. We have used a sensitive flow cytometry assay that quantitates normal and neoplastic plasma cells to monitor the bone marrow of 45 patients undergoing high-dose chemotherapy. Neoplastic plasma cells were detectable at 3 months after transplantation in 42% of patients. Once detected, neoplastic cell levels increased steadily until clinical progression: these patients had a significantly shorter progression-free survival (PFS) (median, 20 months) than those with no detectable disease (median, longer than 35 months; P =.003). Neoplastic plasma cells were detectable in 27% (9 of 33) of immunofixation-negative complete-remission patients. These patients had a significantly shorter PFS than immunofixation-negative patients with no detectable neoplastic plasma cells (P =.04). Normal plasma cells were present in 89% of patients immediately after transplantation, but were not sustained in most cases. Patients with only normal phenotype plasma cells present at 3 months after transplantation and also at second assessment had a low risk of disease progression. Patients with neoplastic plasma cells present at 3 months after transplantation, or with only normal plasma cells present at first assessment and only neoplastic plasma cells at second assessment, had a significantly higher risk of early disease progression (P <.0001) with a 5-year survival of 54% for the high-risk group, compared with 100% in the low-risk group (P =.036). Analysis of normal and neoplastic plasma cell levels is more sensitive than immunofixation and can identify which patients may benefit from additional treatment strategies at an early stage after transplantation.
骨髓瘤的传统监测策略不够敏感，无法立即识别出可能从移植后进一步治疗中获益的患者。我们使用了一种灵敏的流式细胞术检测方法，对正常和肿瘤性浆细胞进行定量，以监测45例接受大剂量化疗患者的骨髓情况。42%的患者在移植后3个月可检测到肿瘤性浆细胞。一旦检测到，肿瘤细胞水平会持续稳定上升直至临床进展：这些患者的无进展生存期（PFS）显著缩短（中位数为20个月），而未检测到疾病的患者PFS更长（中位数超过35个月；P = 0.003）。在免疫固定阴性的完全缓解患者中，27%（33例中的9例）可检测到肿瘤性浆细胞。这些患者的PFS显著短于未检测到肿瘤性浆细胞的免疫固定阴性患者（P = 0.04）。89%的患者在移植后即刻存在正常浆细胞，但在大多数情况下未能持续存在。移植后3个月及第二次评估时仅存在正常表型浆细胞的患者疾病进展风险较低。移植后3个月出现肿瘤性浆细胞的患者，或首次评估时仅存在正常浆细胞而第二次评估时仅存在肿瘤性浆细胞的患者，疾病早期进展风险显著更高（P < 0.0001），高危组的5年生存率为54%，而低危组为100%（P = 0.036）。对正常和肿瘤性浆细胞水平的分析比免疫固定更敏感，能够在移植后早期识别出哪些患者可能从额外的治疗策略中获益。
