Klumpp T R, Herman J H, Schnell M K, Goldberg S L, Mangan K F
Temple University Bone Marrow Transplant Program, Temple University Cancer Center, Philadelphia, PA 19140, USA.
Bone Marrow Transplant. 1996 Sep;18(3):559-64.
Previous reports have suggested that antibodies reactive with neutrophils (ARN) are frequently detectable in patients undergoing bone marrow or blood stem cell transplantation (BMT), and that such antibodies result in steroid-responsive delayed neutrophil engraftment or steroid-responsive post-engraftment neutropenia in some patients. However, the true incidence and significance of ARN in the BMT setting remain poorly established because most of the published data are in the form of retrospective case reports. Therefore, we prospectively studied the incidence of ARN, the rate of neutrophil engraftment, and the incidence of post-engraftment neutropenia in a cohort of 40 BMT candidates. Sixteen of the 36 evaluable patients (44%) had detectable ARN following transplant vs none of 25 concurrently studied healthy controls (P < 0.0001). Patients with detectable ARN in the post-transplant period recovered to an absolute neutrophil count (ANC) of 500 x 10(9)/l a median of 3.5 days later than patients without detectable ARN; multivariate analysis controlling for the potential effects of diagnosis, conditioning regimen, amount of prior therapy, and other factors revealed that only the administration of hematopoietic growth factors (P = 0.008) and the presence of ARN in the post-transplant period (P = 0.016) were independently predictive of the rate of neutrophil engraftment following BMT. Four of the 16 patients with detectable ARN (25%) satisfied previously published criteria for post-engraftment neutropenia, ie a fall in the ANC to less than 500 x 10(9)/l for at least 2 consecutive days, following initial engraftment to an ANC of at least 1000 x 10(9)/l for at least 2 consecutive days. In contrast, none of the 20 patients without detectable post-transplant ARN developed post-engraftment neutropenia. Multivariate analysis revealed that only the presence of ARN in the post-transplant period (P = 0.022) was independently predictive of post-engraftment neutropenia. All four patients with ARN-associated post-engraftment neutropenia responded to steroid-based therapy. These prospectively gathered data support previously published primarily case report data suggesting that ARN occur frequently following BMT and are associated with an increased incidence of delayed neutrophil engraftment and post-engraftment neutropenia. As is the case in the non-transplant setting, ARN-associated neutropenia occurring following BMT may respond to steroid-based therapy.
既往报告提示，在接受骨髓或造血干细胞移植（BMT）的患者中，经常可检测到与中性粒细胞反应的抗体（ARN），且在部分患者中，此类抗体可导致类固醇反应性中性粒细胞植入延迟或植入后中性粒细胞减少。然而，由于大多数已发表的数据为回顾性病例报告形式，ARN在BMT环境中的真实发生率及意义仍未明确。因此，我们前瞻性地研究了40例BMT候选者队列中ARN的发生率、中性粒细胞植入率及植入后中性粒细胞减少的发生率。36例可评估患者中有16例（44%）在移植后检测到ARN，而25例同期研究的健康对照者均未检测到（P<0.0001）。移植后检测到ARN的患者恢复至绝对中性粒细胞计数（ANC）≥500×10⁹/L的时间，比未检测到ARN的患者中位数晚3.5天；多因素分析控制了诊断、预处理方案、既往治疗量及其他因素的潜在影响，结果显示，仅造血生长因子的应用（P = 0.008）及移植后ARN的存在（P = 0.016）可独立预测BMT后中性粒细胞植入率。16例检测到ARN的患者中有4例（25%）符合既往发表的植入后中性粒细胞减少标准，即ANC降至<500×10⁹/L至少连续2天，此前ANC至少连续2天≥1000×10⁹/L。相比之下，20例移植后未检测到ARN的患者均未发生植入后中性粒细胞减少。多因素分析显示，仅移植后ARN的存在（P = 0.022）可独立预测植入后中性粒细胞减少。所有4例与ARN相关的植入后中性粒细胞减少患者对基于类固醇的治疗均有反应。这些前瞻性收集的数据支持了既往主要以病例报告形式发表的数据，提示BMT后ARN频繁出现，并与中性粒细胞植入延迟及植入后中性粒细胞减少的发生率增加相关。与非移植环境情况相同，BMT后发生的与ARN相关的中性粒细胞减少可能对基于类固醇的治疗有反应。
