Clinical features and prognosis of patients with typeⅠcryoglobulinemia related to multiple myeloma
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摘要: 目的 探讨7例多发性骨髓瘤(multiple myeloma，MM)继发Ⅰ型冷球蛋白血症(cryoglobulinemia，CG)患者的临床特征、治疗及转归。方法 回顾性分析2015年1月—2023年3月北京协和医院确诊的7例MM继发Ⅰ型CG患者的临床资料、治疗方案和生存结局。结果 7例患者中，男5例，中位诊断年龄为56(40~71)岁。4例继发于冒烟型骨髓瘤。CG受累器官包括皮肤(n=5)、周围神经(n=4)、关节(n=4)和肾脏(n=1)。中位冷球蛋白水平为13 046.5(693.8~33 988.0) mg/L，所有患者均为IgG单克隆型冷球蛋白，与M蛋白类型一致。7例患者均接受了抗浆细胞治疗，其中1例因CG相关急性肾衰竭同时进行了血浆置换。6例有随访资料的患者均获得了MM血液学缓解，4例有CG相关症状者均达到临床缓解。中位随访37(10~45)个月后，1例失访，1例因治疗相关感染死亡。结论 MM是Ⅰ型CG相对少见病因，对于有皮肤、周围神经、关节等受累表现的MM患者，应考虑到继发性CG的可能。Abstract: Objective To explore the clinical characteristics, treatment and outcomes of 7 patients with typeⅠ cryoglobulinemia(CG) related to multiple myeloma(MM).Methods Seven patients with typeⅠCG related to MM at Peking Union Medical College Hospital between January 2015 and March 2023 were enrolled in this retrospective study. The clinical characteristics, treatment and outcomes of patients were analyzed.Results A total of 7 patients(including 5 males) were enrolled in the study, with a median age of 56 years(range, 40-71 years). Four patients were secondary to smoldering MM. The CG-involved organs included the skin(n=5), peripheral nerves(n=4), joints(n=4) and kidney(n=1). The median concentration of cryoglobulin level was 13 046.5(693.8-33 988.0) mg/L, and IgG-monoclonal component of cryoglobulin was identified in all patients, consistent with the isotype of M protein. All patients received anti-plasma cell therapy. Furthermore, one patient received plasma exchange due to acute kidney impairment. The patients(n=6) available for assessment all achieved hematological remission on MM, and 4 patients with organ involvement by CG also achieved clinical remission. The median duration of follow-up was 37 months(range 10-45 months). One patient was lost to follow-up and one patient died due to therapy-related infection.Conclusion MM is a relatively rare cause of typeⅠCG, and the possibility of secondary CG should be considered in MM patients with skin lesion, peripheral neuropathy and arthralgia.
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Key words:
- multiple myeloma /
- cryoglobulin /
- typeⅠcryoglobulinemia
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表 1 7例MM继发Ⅰ型CG患者的临床特征
例号 性别 年龄/岁 ISS分期 MM相关症状 CG相关症状 冷球蛋白 高危细胞遗传学 HGB/(g/L) Cr/(μmol/L) Ca/(mmol/L) LDH/(U/L) M蛋白 dflc/(mg/L) 类型 冷沉淀/% 冷球蛋白定量/(mg/L) 1 男 40 ND 无 皮肤紫癜 IgG-κ 36.0 ND ND 111 ND ND ND IgG-κ，0.3 g/L ND 2 男 65 Ⅰ期 无 皮肤网状青斑，肢体疼痛，关节肿痛，AKI IgG-λ 5.0 ND 阴性 156 79 2.2 127 IgG-λ，18.3 g/L ND 3 男 66 Ⅰ期 无 皮肤网状青斑，肢体麻木，关节肿痛 IgG-λ 12.0 14 498.5 t(4；14) 103 251 2.2 382 IgG-λ，14.1 g/L 2.2 4 男 56 Ⅲ期 骨痛，乏力 无 IgG-κ 50.0 33 988.0 1q21+ 100 91 2.2 115 IgG-κ，68.6 g/L 180.0 5 女 51 Ⅲ期 骨痛，乏力，肾损 无 IgG-λ 16.0 858.9 17p-，t(4；14) 70 159 2.4 87 IgG-λ，38.5 g/L 365.6 6 女 53 Ⅱ期 乏力 皮肤紫癜，肢体疼痛，关节肿痛 IgG-κ 1.0 639.8 1q21+ 90 43 2.3 166 IgG-κ，15.8 g/L 309.2 7 男 71 Ⅰ期 无 皮肤紫癜、溃疡，肢体麻木，关节肿痛 IgG-κ 65.0 13 046.5 阴性 109 89 2.3 326 IgG-κ，32.0g/L 159.5 AKI：急性肾功能不全；dflc：受累和未受累轻链差值；ND：未做。 
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表 2 7例MM继发Ⅰ型CG患者的治疗及转归
例号 治疗方案 MM疗效评估 CG疗效评估 转归 1 不详 ND ND 失访 2 BCD PR PRa，CRb 死于感染 3 BCD+PE PR CRa，PRb 存活 4 VRd，ASCT sCR ND 存活 5 VRd，ASCT sCR ND 存活 6 VRd，ASCT sCR CRa，CRb 存活 7 DPD PR PRa，CRb 存活 ASCT：自体造血干细胞移植；PE；血浆置换；a：临床评估；b：血液学评估。
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