利妥昔单抗治疗华氏巨球蛋白血症时的特殊反应

目的:研究抗CD20单克隆抗体利妥昔(rituximab)治疗华氏巨球蛋白血症(Waldenstrom macroglobu-linemia,WM)时血清IgM异常增高现象及其表现和处理,并复习相关文献,推荐处理方法。方法:1例68岁患者通过骨髓细胞学、病理学和免疫固定电泳等检查确诊为WM,并给予利妥昔(375 mg/m2,d1)联合复达拉滨(30mg/m2,i.v.d1-3)作为初始治疗,对治疗前后的血清IgM水平进行监测。结果:在第一疗程RF治疗结束后四周,患者的血清IgM水平从治疗前的34.8g/L增高至115g/L,同时出现头痛和眼底出血,但骨髓浆细胞和淋巴样浆细胞无明显增多。在停用利妥昔,改用FC(复达拉滨和环磷酰胺)方案治疗四疗程后,IgM下降至治疗前水平,然后进一步下降达部分缓解。结论:WM患者在接受以利妥昔为基础的治疗后,血清IgM可明显增高,并导致高黏滞综合征等高IgM相关并发症。尽管此种异常增高并不提示利妥昔单抗治疗失败,但在治疗过程中仍需密切。在治疗开始的前二个疗程中避免使用利妥昔单抗可减少此现象的发生。

Marked increase in serum IgM level during treatment of Waldenstrom's macroglobulinemia with rituximab

Objective:To investigate the initial upsurge in immunoglobulin M(IgM) levels and its related complications and clinical managements after treatment with rituximab in patients with Waldenstrom macroglobulinemia(WM).Methods:WM was diagnosed by bone marrow aspirate and biopsy and immunofixation electrophoresis in a 68-year-old man.The patient`s initial therapy consisted of infusions of rituximab at 375 mg/m2 per cycle and fludarabine at 30 mg/m2 per day for 3 days.Pre-and post-therapy serum IgM levels were determined by nephelometry.Results:Patient’s IgM level rose from 34.8g/L to a peak of 115g/L,which occurred at 4 weeks following initiation of therapy.Coincident with the rise in serum IgM levels,the patient experienced worsening headaches and fundus hemorrhage.Therefore,we omitted the rituximab and administered the combination of fludarabine(30mg/m2,i.v.d1-3) and cyclophosphamide(300mg/m2,i.v.d1-3).IgM level fell to below baseline after 4 cycles of FC,and the patient continued to experience disease partial remission throughout 12 additional months of follow-up.Conclusion:Marked increase in serum IgM level commonly occur following rituximab therapy in WM.Careful clinical and laboratory monitoring is warranted,particularly if patients have high pretherapy serum IgM level.The omission of rituximab can also be considered for the first 1 or 2 cycles of treatment in order to decrease the incidence of the abrupt IgM increase.However,the IgM aggravation may last for several weeks,even months,and did not perseherald treatment failure.