Obstructive and restrictive pulmonary dysfunction in long-term lymphoma survivors after high-dose therapy with autologous stem cell transplantation

<b>Background:</b> Obstructive and restrictive dysfunction in long-term lymphoma survivors (LSs) after high-dose therapy with autologous stem-cell transplantation (HDT-ASCT) has not been addressed systematically previously. <b>Material and methods:</b> LSs treated in Norway 1987–2008 with HDT-ASCT who performed spirometry, measurement of static lung volumes and echocardiography 2012–2014 at either Oslo or St. Olavs University Hospitals was eligible. Smoking data were recorded by questionnaire. Treatment data were collected from medical records or hospital databases. Factors associated with obstructive and restrictive impairments (dichotomous outcomes) were examined by Poisson regression. Linear regression with the margins post-estimation command was used to derive adjusted mean values of forced expiratory volume in 1 s (FEV₁). We used the normative reference data recommended by the European Respiratory Society for calculating percent predicted values. <b>Results:</b> A total of 226 LSs were studied, of whom 11.5 and 5.8% had obstructive and restrictive impairment, respectively. For women and men, mean FEV₁ was 2.31 and 3.34 l corresponding to 11.4%- and 11.1%-points below that predicted from norms, respectively. In multivariable regression analyses, cumulative doxorubicin dose (400–775 mg/m²) and current smoking were associated with increased risk of obstructive impairment, and chest RT (&gt;13–66 Gy) was associated with increased risk of restrictive impairment. Currently smoking LSs within the highest doxorubicin category (400–775 mg/m²), had the lowest adjusted mean FEV₁. <b>Conclusions:</b> Despite intensive cancer treatment, our analysis showed modest reductions in obstructive parameters among long-term LSs after HDT-ASCT compared to normative reference data. To limit obstructive impairments in LSs after HDT-ASCT, we suggest that targeted smoking-cessation advice is directed towards patients who have received high cumulative doses of doxorubicin.

<b>背景：</b> 接受高剂量化疗联合自体干细胞移植（high-dose therapy with autologous stem-cell transplantation, HDT-ASCT）后的长期淋巴瘤幸存者（long-term lymphoma survivors, LSs）所出现的阻塞性与限制性肺功能障碍，此前尚未得到系统性研究。<b>材料与方法：</b> 本研究纳入1987年至2008年间于挪威接受HDT-ASCT治疗的LSs，且于2012年至2014年间在奥斯陆大学医院或圣奥拉夫大学医院完成肺量测定法（spirometry）、静态肺容量检测及超声心动图（echocardiography）检查者。吸烟相关数据通过问卷调查获取，治疗相关数据从病历或医院数据库中提取。针对阻塞性与限制性肺功能损伤（二分类结局）的相关影响因素，采用泊松回归（Poisson regression）进行分析；采用带边际后估计命令的线性回归（linear regression），推导一秒用力呼气容积（forced expiratory volume in 1 s, FEV₁）的校正均值。本研究采用欧洲呼吸学会（European Respiratory Society, ERS）推荐的正常参考值数据，计算各项指标的预测百分比值。<b>结果：</b> 本研究共纳入226名LSs，其中分别有11.5%和5.8%的受试者存在阻塞性与限制性肺功能损伤。女性与男性的平均FEV₁分别为2.31 L与3.34 L，较正常参考值的预测值分别低11.4个百分点与11.1个百分点。多变量回归分析结果显示，累积多柔比星（doxorubicin）剂量（400~775 mg/m²）与当前吸烟状态，均与阻塞性肺损伤风险升高显著相关；而胸部放疗（chest RT）剂量（>13~66 Gy）则与限制性肺损伤风险升高相关。处于最高多柔比星剂量组（400~775 mg/m²）且当前仍吸烟的LSs，其校正后平均FEV₁水平最低。<b>结论：</b> 尽管接受了高强度肿瘤治疗，本研究分析显示，与正常参考值数据相比，接受HDT-ASCT后的长期LSs的阻塞性肺功能参数仅出现轻度降低。为降低HDT-ASCT术后长期LSs的阻塞性肺损伤风险，我们建议针对接受过高累积剂量多柔比星的患者，提供针对性的戒烟指导。