Department of Medicine, North Shore Medical Center, Salem, Massachusetts, USA.
Biol Blood Marrow Transplant. 2013 Aug;19(8):1190-6. doi: 10.1016/j.bbmt.2013.05.018. Epub 2013 Jun 5.
Invasive fungal disease (IFD) is a major cause of morbidity and mortality after hematopoietic stem cell transplantation (HCT). We performed a retrospective review of 271 adults with a hematologic malignancy undergoing allogeneic HCT to determine the incidence of and risk factors for IFD and to examine the impact of IFD on nonrelapse mortality and overall survival. We defined IFD using standard criteria and selected proven and probable cases for analysis. Diagnoses in the study group included acute leukemia (42%), non-Hodgkin lymphoma (24%), myelodysplastic syndrome (15%), chronic lymphocytic leukemia (5%), and other hematologic disorders (14%). Conditioning included reduced-intensity (64%) and myeloablative (36%) regimens. Donor sources were HLA-matched sibling (60%), matched unrelated (20%), haploidentical (12%), and cord blood (8%). A total of 51 episodes of IFD were observed in 42 subjects (15%). Aspergillus spp (47%) was the most frequent causative organism, followed by Candida spp (43%). The majority of IFD cases (67%) were reported after day +100 post-HCT. In multivariate analysis, haploidentical donor transplantation (hazard ratio [HR], 3.82; 95% confidence interval [CI], 1.49-9.77; P = .005) and grade II-IV acute graft-versus-host disease (HR, 2.55; 95% CI, 1.07-6.10; P = .03) were risk factors for the development of IFD. Conversely, higher infused CD34(+) cell dose was associated with a lower risk of IFD (HR, 0.80; 95% CI, 0.68-0.94; P = .006, per 1 × 10(6) cells/kg increase in CD34(+) cell infusion). IFD-related mortality was 33.3%. Nonrelapse mortality was significantly higher in patients who developed IFD compared with those without IFD (P < .001, log-rank test). Patients with IFD had lower overall survival (5.8 months versus 76.1 months; P < .001, log-rank test). Further studies exploring strategies to increase the infused cell dose and determine adequate prophylaxis, especially against aspergillus, beyond day +100 are needed.
侵袭性真菌病（IFD）是造血干细胞移植（HCT）后发病率和死亡率的主要原因。我们对 271 名接受异基因 HCT 的血液系统恶性肿瘤成人进行了回顾性研究，以确定 IFD 的发病率和危险因素，并研究 IFD 对非复发死亡率和总生存率的影响。我们使用标准标准定义了 IFD，并选择了已证明和可能的病例进行分析。研究组的诊断包括急性白血病（42％），非霍奇金淋巴瘤（24％），骨髓增生异常综合征（15％），慢性淋巴细胞白血病（5％）和其他血液系统疾病（14％）。调理包括强度降低（64％）和骨髓清除（36％）方案。供体来源为 HLA 匹配的兄弟姐妹（60％），匹配的无关供体（20％），半相合（12％）和脐带血（8％）。在 42 名患者中观察到 51 例 IFD 发作（15％）。曲霉属（47％）是最常见的病原体，其次是念珠菌属（43％）。大多数 IFD 病例（67％）在 HCT 后第 100 天报告。在多变量分析中，半相合供体移植（危险比[HR]，3.82；95％置信区间[CI]，1.49-9.77；P =.005）和 II-IV 级急性移植物抗宿主病（HR，2.55；95％CI，1.07-6.10；P =.03）是 IFD 发展的危险因素。相反，较高的输注 CD34（+）细胞剂量与 IFD 的风险降低相关（HR，0.80；95％CI，0.68-0.94；P =.006，每 1×10（6）个细胞/kg 的 CD34（+）细胞输注增加）。IFD 相关死亡率为 33.3％。与未发生 IFD 的患者相比，发生 IFD 的患者的非复发死亡率明显更高（P <.001，对数秩检验）。发生 IFD 的患者总生存率较低（5.8 个月与 76.1 个月；P <.001，对数秩检验）。需要进一步研究探索增加输注细胞剂量和确定适当预防措施的策略，特别是在第 100 天之后针对曲霉菌的预防措施。
