High incidence of invasive aspergillosis associated with intestinal graft-versus-host disease following nonmyeloablative transplantation
High incidence of invasive aspergillosis associated with intestinal graft-versus-host disease following nonmyeloablative transplantation
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DOI：
10.1016/j.bbmt.2007.06.013
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发表时间：
2007-10-01
影响因子：
4.3
通讯作者：
Roy, Jean
中科院分区：
文献类型：
--
作者：
labbe, Annie-Claude;Su, Shi Hann;Roy, Jean
侵袭性曲霉病（IA）仍然是异基因造血干细胞移植（HSCT）后的主要并发症。与传统的 HSCT 相比，很少有研究人员检查与非骨髓清除 (NMA) 方案相关的 IA 危险因素，这些方案的特点是门诊给药、免疫抑制而不是细胞减灭术以及移植后中性粒细胞减少症持续时间短。我们报告了 125 名接受同质治疗的患者的结果，这些患者接受了 6/6 匹配的同胞 NMA HSCT，设计在门诊进行。预处理方案包括氟达拉滨（30 mg/m(2) x 5天）和环磷酰胺（300 mg/m(2) x 5天），然后回输至少4 x 10(6) CD34(+)细胞/kg。急性移植物抗宿主病（aGVHD）预防措施包括他克莫司和吗替麦考酚酯（MMF）。总体而言，13 名患者在 NMA HSCT 后 44-791 天（中位数 229 天）发生 IA（5 例确诊，6 例可能，2 例可能），第 1 年的风险为 7%，第 2 年的风险为 11%，第 3 年的风险为 15%。患有 IA 的患者总体生存率较差（粗风险比 2.3；95% 置信区间 [CI] 1.0-5.4；P = 0.045）。肠道 aGVHD 或慢性 GVHD (cGVHD) 与 1 年（27% 对 3%，P = .003）、2 年（27% 对 8%，P = .01）和 3 年（37% 对 10%，P = .005）时的 IA 显着相关。达珠单抗的使用也与 3 年时的 IA 显着相关（47% 对比 12%，P = .02）。年龄、性别、诊断、既往自体移植、中性粒细胞减少症持续时间、巨细胞病毒血症的发生、类固醇或 MMF 摄入持续时间、aGVHD、cGVHD 和累计住院天数与 IA 无关。经过多变量分析，肠道 GVHD 仍然是 1 年 (P = .003)、2 年 (P = .01) 和 3 年 (P = .005) 时 IA 唯一具有统计学意义的危险因素。我们的结论是，在 NMA HSCT 中，IA 的风险随着时间的推移而增加，并且与肠道 GVHD 显着相关。由于目前 NMA HSCT 后尚无免疫功能的替代体外标志物，因此这一临床发现对于识别应针对霉菌预防的高风险人群特别重要。 (C) 2007 年美国血液和骨髓移植协会。
Invasive aspergillosis (IA) remains a major complication following allogeneic hematopoietic stem cell transplant (HSCT). In contrast to conventional HSCT, few investigators have examined risk factors of IA associated with nomnyeloablative (NMA) regimens characterized by outpatient administration, immunosuppression rather than cytoreduction, and short duration of neutropenia posttransplant. We report our results on a cohort of 125 patients treated homogenously who received a 6/6 matched sibling NMA HSCT designed to be performed on an outpatient basis. Conditioning regimen included fludarabine (30 mg/m(2) x 5 days) and cyclophosphamide (300 mg/m(2) x 5 days) followed by reinfusion of a minimum of 4 x 10(6) CD34(+) cells/kg. Acute graft-versus-host disease (aGVHD) prophylaxis consisted of tacrolimus and mycophenolate mofetil (MMF). Overall, 13 patients developed IA (5 proved, 6 probable, 2 possible) 44-791 days (median 229) after NMA HSCT, with a risk of 7% at 1, 11% at 2, and 15% at 3 years. Patients who suffered from IA had poorer overall survival (crude hazard ratio 2.3; 95% confidence interval [CI] 1.0-5.4; P = .045). Intestinal aGVHD or chronic GVHD (cGVHD) was significantly associated with IA at 1 (27% versus 3%, P = .003), 2 (27% versus 8%, P = .01), and 3 years (37% versus 10%, P = .005). The use of daclizumab was also significantly associated with IA at 3 years (47% versus 12%, P = .02). Age, sex, diagnosis, previous autologous transplant, duration of neutropenia, occurrence of cytomegalovirus viremia, duration of steroids or MMF intake, aGVHD, cGVHD, and cumulative number of days spent in hospital were not associated with IA. After multivariate analysis, intestinal GVHD remained the only statistically significant risk factor for IA at 1 (P = .003), 2 (P = .01), and 3 years (P = .005). We conclude that in NMA HSCT, the risk of IA increases over time and is significantly associated with intestinal GVHD. Because there is currently no surrogate in vitro markers of immunocompetence following NMA HSCT, this clinical finding is of particular importance to identify a population at higher risk who should be targeted for antimold prophylaxis. (C) 2007 American Society for Blood and Marrow Transplantation.