PO.PR01.05 · 预防研究
静脉注射免疫球蛋白减少慢性淋巴细胞白血病感染:一项单中心回顾性分析
Reduction of infections with intravenous immunoglobulin in chronic lymphocytic leukemia: A single-center retrospective analysis
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
低丙种球蛋白血症在慢性淋巴细胞白血病(CLL)中很常见。指南建议对反复发生严重感染(例如需要静脉抗生素或住院者)且IgG < 500 mg/dL的患者进行静脉注射免疫球蛋白(IVIG)预防。既往试验显示IVIG减少了感染但无生存获益,但这些试验早于现代CLL治疗。本研究评估了2005年至2022年间接受IVIG的CLL患者的感染结局。
这是一项针对CLL患者的单机构回顾性队列研究。患者通过接受IVIG来识别,若IVIG用于其他适应证(例如自身免疫性溶血性贫血)则被排除。评估了IVIG开始前一年和开始后一年内的感染频率和严重程度。还收集了治疗史、同期治疗和基线免疫球蛋白水平。
在79例接受IVIG治疗的患者中,根据可供仔细审阅的病历,48例符合IVIG用于低丙种球蛋白血症和感染的纳入标准。IVIG开始时的中位年龄为58岁;从CLL诊断到IVIG开始的平均时间为10.5年。开始时,52%为Rai 0-II期疾病,48%为Rai III-IV期疾病。IVIG前基线平均IgG为411 mg/dL(范围93-894 mg/dL),基线平均IgA为42 mg/dL(范围4-177 mg/dL)。
IVIG前:73%的患者在IVIG开始前一年内经历至少一次2级或3级感染。大多数患者有反复感染;2级或以上感染的平均次数为1.6次(范围0-4)。IVIG开始前一年内仅有两名患者发生3级感染,但值得注意的是,另有15人自CLL诊断以来曾发生3级感染。总计17名患者(35%)在IVIG前任何时候发生过3级感染。
IVIG后:在IVIG开始后一年内,仅有12名患者(25%)经历2级或以上感染,平均0.375次感染(范围0-4)。其中两名患者(4%)发生3级感染,分别为多灶性肺炎和蜂窝织炎。这代表了66%的相对风险降低,以及2.1的需治疗人数(NNT)以预防IVIG开始后一年内的2级或以上感染(RR 0.34,P = 0.0001,95% CI:0.20-0.58)。在有和无IVIG后感染的患者之间,既往CLL治疗(75% vs. 83%,p = 0.57)、基线IgG(p = 0.91)或IgA水平(p = 0.93)均未观察到显著差异。
总之,IVIG预防显著减少了中度(2级或以上)感染,与既往数据一致。虽然IVIG主要推荐用于严重感染患者(2025 NCCN指南),但我们的发现提示IVIG也可能有意义地减少2级感染并改善生活质量。未来的IVIG研究应纳入生活质量指标,以界定IVIG在现代CLL治疗中的作用。
查看英文原文 English abstract
Hypogammaglobulinemia is common in chronic lymphocytic leukemia (CLL). Guidelines recommend Intravenous Immunoglobulin (IVIG) prophylaxis for patients with recurrent, serious infections (e.g., those requiring IV antibiotics or hospitalization) and IgG < 500 mg/dL. Prior trials showed reduced infections with IVIG without survival benefit, but predate modern CLL therapy. This study evaluates infectious outcomes in CLL patients who received IVIG between 2005 - 2022.
This was a single-institution retrospective cohort study of CLL patients. Patients were identified by IVIG receipt and excluded if IVIG was given for other indications (e.g., autoimmune hemolytic anemia). Infection frequency and severity were assessed during the year prior to and the year following IVIG initiation. Treatment history, concurrent therapy, and baseline immunoglobulin levels were also collected.
Of 79 patients identified with IVIG treatment, 48 met inclusion criteria of IVIG use for hypogammaglobulinemia and infections, based on charts available for close review. The median age at IVIG initiation was 58 years; mean time from CLL diagnosis to IVIG initiation was 10.5 years. At initiation, 52% had Rai stage 0-II disease and 48% had Rai stage III - IV disease. Baseline mean IgG prior to IVIG was 411 mg/dL (range 93 - 894 mg/dL) and baseline mean IgA was 42 mg/dL (range 4 - 177 mg/dL).
Pre-IVIG: 73% of patients experienced at least one grade 2 or 3 infection in the year prior to initiation of IVIG. Most patients had recurrent infections; the average number of grade 2 or higher infections was 1.6 (range 0 - 4). Only two patients had a grade 3 infection in the year prior to IVIG initiation, though notably 15 others had prior grade 3 infections since they were diagnosed with CLL. In total, 17 patients (35%) had a grade 3 infection at any time prior to IVIG.
Post-IVIG: Only 12 patients (25%) experienced a grade 2 or higher infection in the year following IVIG initiation, with a mean of 0.375 infections (range 0 - 4). Two of these patients (4%) had grade 3 infections, which were multifocal pneumonia and cellulitis. This represents a 66% relative risk reduction, and a Number Needed to Treat (NNT) of 2.1 to prevent grade 2 or higher infections in the year following IVIG initiation (RR 0.34, P = 0.0001, 95% CI: 0.20 - 0.58). No significant differences were observed between patients with and without post-IVIG infections in prior CLL treatment (75% vs. 83%, p = 0.57), baseline IgG (p = 0.91) or IgA levels (p = 0.93).
To conclude, IVIG prophylaxis significantly reduced both moderate (grade 2 or higher) infections, consistent with prior data. While IVIG is recommended primarily for patients with severe infections (2025 NCCN guidelines), our findings suggest IVIG may also meaningfully reduce grade 2 infections and improve quality of life. Future IVIG studies should incorporate quality of life metrics to define the role of IVIG in modern CLL care.
利益披露 Disclosure
N. Shah, None..
T. Patel, None..
T. J. Kipps, None..
M. Y. Choi, None.