Department of Clinical Hematology and Medical Oncology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Transpl Infect Dis. 2023 Oct;25(5):e14123. doi: 10.1111/tid.14123. Epub 2023 Aug 12.
Infections are a significant cause of morbidity and mortality after autologous hematopoietic cell transplantation (AHCT) in multiple myeloma (MM) patients. There has been a rapid advancement and evolution in MM treatment landscape in the last decade. There is limited information on post-AHCT infectious complications among MM patients with or without levofloxacin prophylaxis from developing countries.
We performed a retrospective study to explore the incidence, pattern, and clinical outcome of infections following AHCT in MM patients from 2010 to 2019 at our center. Patient-specific, disease-specific, and transplant-specific details were retrieved from the case files. The characteristics of infectious complications (site, intensity, organism, treatment, and outcomes) were analyzed. All patients who underwent transplantation from 2010 to 2016 received levofloxacin antibiotic prophylaxis. Common terminology criteria for adverse events (CTCAE) criteria (v5.0) were used for the grading of infections and regimen-related toxicity. International Myeloma Working Group updated criteria were used for the assessment of disease response before transplant and at day +100.
Ninety-five consecutive patients with newly diagnosed multiple myeloma (NDMM) (n = 85), RRMM (n = 7), plasma cell leukemia (n = 2), and Polyneuropathy, Orgaomegaly, Endocrinopathy, Monoclonal gammopathy, skin abnormalities (POEMS) syndrome (n = 1) underwent AHCT during the study period. Their median age was 55 years (range 33-68); 55.8% were males. Immunoglobulin IgG kappa was the most common monoclonal protein (32.6%), International Staging System stage III disease was present in 45.3%, and 84.2% of patients achieved more than very good partial response before AHCT. The median time from diagnosis to AHCT was 10 months (range 4-144). Eighty-nine patients (93.7%) developed fever after AHCT. Fever of unknown focus, microbiologically confirmed infections, and clinically suspected infections were found in 50.5%, 37.9%, and 5.3% of patients, respectively. Clostridiodes difficile-associated diarrhea was observed in eight patients (8.4%). Neutrophil and platelet engraftment occurred after a median of 11 days (range 9-14) and 12 days (range 9-23), respectively. The median duration of hospital stay was 16 days (range 9-29). Only two patients (2.1%) required readmission for infections within 100 days of AHCT. Transplant-related mortality (TRM) in the study population was 4.2% (n = 4). The levofloxacin prophylaxis group (n = 32, 33.7%) had earlier neutrophil engraftment (day +10 vs. day +11) and platelet engraftment (day +11 vs. day +12), but time to fever onset, duration of fever, hospital stay, TRM, and day +100 readmission rates were not significantly different from those of patients without levofloxacin prophylaxis. There was no significant difference in the spectrum of infections between patients with and without levofloxacin prophylaxis. The overall survival and progression-free survival of the study population at 5 years were 72.7% and 64.8%, respectively.
This study shows that the incidence of infections and TRM are higher in MM patients from lower-middle income countries after AHCT than in those from developed countries. The majority of such patients lack clinical localization and microbiological proof of infection. There was no significant difference in the spectrum of infections and their outcomes in patients with and without levofloxacin prophylaxis.
在多发性骨髓瘤(MM)患者自体造血细胞移植(AHCT)后,感染是发病率和死亡率的重要原因。在过去十年中,MM 治疗领域取得了快速发展和进步。来自发展中国家的 MM 患者在接受 AHCT 后发生感染并发症的信息有限,无论是否接受左氧氟沙星预防。
我们进行了一项回顾性研究,以探讨我们中心 2010 年至 2019 年间 MM 患者 AHCT 后感染的发生率、模式和临床结果。从病历中检索患者特异性、疾病特异性和移植特异性详细信息。分析感染并发症的特征(部位、强度、病原体、治疗和结果)。2010 年至 2016 年接受移植的所有患者均接受左氧氟沙星抗生素预防。使用不良事件常用术语标准(CTCAE)(v5.0)对感染和与方案相关的毒性进行分级。使用国际骨髓瘤工作组更新的标准在移植前和第 +100 天评估疾病反应。
在研究期间,95 例新诊断的多发性骨髓瘤(NDMM)(n = 85)、RRMM(n = 7)、浆细胞白血病(n = 2)和多发性神经病、器官肿大、内分泌病、单克隆丙种球蛋白病、皮肤异常(POEMS)综合征(n = 1)患者接受了 AHCT。他们的中位年龄为 55 岁(范围 33-68);55.8%为男性。免疫球蛋白 IgG kappa 是最常见的单克隆蛋白(32.6%),国际分期系统 III 期疾病占 45.3%,84.2%的患者在 AHCT 前达到了非常好的部分缓解以上。从诊断到 AHCT 的中位时间为 10 个月(范围 4-144)。89 例(93.7%)患者在 AHCT 后发热。不明原因发热、微生物学确诊感染和临床疑似感染分别占 50.5%、37.9%和 5.3%。8 例(8.4%)患者发生艰难梭菌相关性腹泻。中性粒细胞和血小板植入分别发生在中位 11 天(范围 9-14)和 12 天(范围 9-23)后。中位住院时间为 16 天(范围 9-29)。仅 2 例(2.1%)患者在 AHCT 后 100 天内因感染再次入院。研究人群中的移植相关死亡率(TRM)为 4.2%(n = 4)。左氧氟沙星预防组(n = 32,33.7%)中性粒细胞植入较早(第 +10 天 vs. 第 +11 天)和血小板植入较早(第 +11 天 vs. 第 +12 天),但发热开始时间、发热持续时间、住院时间、TRM 和第 +100 天再入院率与无左氧氟沙星预防组无显著差异。有和没有左氧氟沙星预防的患者感染的种类没有显著差异。研究人群的总生存率和无进展生存率在 5 年内分别为 72.7%和 64.8%。
本研究表明,来自中低收入国家的 MM 患者在接受 AHCT 后发生感染和 TRM 的发生率高于来自发达国家的患者。大多数此类患者缺乏临床定位和感染的微生物学证据。有和没有左氧氟沙星预防的患者感染的种类和结局没有显著差异。