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抗CD20抗体作为高剂量治疗和自体干细胞移植后原发性浆细胞白血病患者的巩固治疗。

Anti-CD20 antibody as consolidation therapy in a patient with primary plasma cell leukemia after high-dose therapy and autologous stem cell transplantation.

作者信息

Gemmel C, Cremer F W, Weis M, Witzens M, Moldenhauer G, Koniczek K-H, Imbach U, Ho A D, Moos M, Goldschmidt H

机构信息

Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.

出版信息

Ann Hematol. 2002 Feb;81(2):119-23. doi: 10.1007/s00277-001-0397-4. Epub 2001 Dec 22.

Abstract

In multiple myeloma (MM), circulating malignant B cells are proposed as the proliferative compartment of the disease. In view of the close relationship between multiple myeloma and primary plasma cell leukemia (PCL), an anti-CD20 antibody treatment might also be considered as consolidation for patients with PCL. A 55-year-old patient diagnosed with PCL achieved complete remission after autologous transplantation. A total of four weekly courses of rituximab (375 mg/m(2)) were administered. Prior to antibody therapy, CD20+ cells comprised 22.6% of the mononuclear cells in peripheral blood (PB) assessed by flow cytometry and were enriched by magnetic activated cell sorting (MACS). In the enriched CD20+ fraction, 0.093% clonotypic cells were detected using a quantitative polymerase chain reaction (PCR) assay based on limiting dilutions. The proportion of clonotypic cells was 0.034% in PB and 0.032% in bone marrow (BM). Rituximab depleted CD20+ cells completely in PB and BM. Tumor load in PB and BM at day 40 and in PB at day 70 did not change in comparison to prior to therapy (0.037% in PB, 0.026% in BM). At day 90, the tumor load increased to 0.066% in PB. At day 120, the patient relapsed with 0.65% CD38++/CD138+/CD20- plasma cells and furthermore no CD20+ B cells in PB. The expansion of plasma cells was accompanied by an increase in the tumor load in both compartments (PB: 0.65%, BM: 1.8%). The accumulation of plasma cells during disease progression without the reappearance of CD20+ cells did not sustain the role of circulating clonotypic B cells as proliferative compartment in our patient. However, it cannot be excluded that rituximab was not able to eradicate malignant B cells, which subsequently contributed to relapse.

摘要

在多发性骨髓瘤(MM)中,循环中的恶性B细胞被认为是该疾病的增殖部分。鉴于多发性骨髓瘤与原发性浆细胞白血病(PCL)之间的密切关系,抗CD20抗体治疗也可被视为PCL患者的巩固治疗方法。一名55岁诊断为PCL的患者在自体移植后实现了完全缓解。共给予四个周期的利妥昔单抗(375mg/m²),每周一次。在抗体治疗前,通过流式细胞术评估外周血(PB)中CD20⁺细胞占单核细胞的22.6%,并通过磁珠分选(MACS)进行富集。在富集的CD20⁺组分中,使用基于有限稀释的定量聚合酶链反应(PCR)检测到0.093%的克隆型细胞。PB中克隆型细胞的比例为0.034%,骨髓(BM)中为0.032%。利妥昔单抗使PB和BM中的CD20⁺细胞完全耗竭。与治疗前相比,第40天PB和BM以及第70天PB中的肿瘤负荷没有变化(PB中为0.037%,BM中为0.026%)。在第90天,PB中的肿瘤负荷增加到0.066%。在第120天,患者复发,外周血中出现0.65%的CD38⁺⁺/CD138⁺/CD20⁻浆细胞,且外周血中不再有CD20⁺B细胞。浆细胞的扩增伴随着两个部位肿瘤负荷的增加(PB:0.65%,BM:1.8%)。在疾病进展过程中浆细胞的积累而未出现CD20⁺细胞,这并不支持循环克隆型B细胞作为我们患者增殖部分的作用。然而,不能排除利妥昔单抗未能根除恶性B细胞,而这些细胞随后导致了复发。

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