Wermke Martin, Eckoldt Julia, Götze Katharina S, Klein Stefan A, Bug Gesine, de Wreede Liesbeth C, Kramer Michael, Stölzel Friedrich, von Bonin Malte, Schetelig Johannes, Laniado Michael, Plodeck Verena, Hofmann Wolf-Karsten, Ehninger Gerhard, Bornhäuser Martin, Wolf Dominik, Theurl Igor, Platzbecker Uwe
Medizinische Fakultät Carl-Gustav-Carus der Technischen Universität, Medizinische Klinik und Poliklinik I, University Hospital Carl-Gustav-Carus, Dresden, Germany; National Center for Tumor Diseases (NCT)-Partner Site Dresden, Dresden, Germany; Medizinische Fakultät der Technischen Universität, Universitäts KrebsCentrum, Early Clinical Trial Unit, Dresden, Germany; German Cancer Consortium (DKTK), Partner Site Dresden, Germany.
Medizinische Fakultät Carl-Gustav-Carus der Technischen Universität, Medizinische Klinik und Poliklinik I, University Hospital Carl-Gustav-Carus, Dresden, Germany.
Lancet Haematol. 2018 May;5(5):e201-e210. doi: 10.1016/S2352-3026(18)30036-X. Epub 2018 Apr 5.
The effect of systemic iron overload on outcomes after allogeneic haemopoietic cell transplantation (HCT) has been a matter of substantial debate. We aimed to investigate the predictive value of both stored (MRI-derived liver iron content) and biologically active iron (enhanced labile plasma iron; eLPI) on post-transplantation outcomes in patients with acute myeloid leukaemia or myelodysplastic syndrome undergoing allogenic HCT.
The prospective, multicentre, observational, ALLogeneic Iron inVEstigators (ALLIVE) trial recruited patients at five centres in Germany. We enrolled patients with acute myeloid leukaemia or myelodysplastic syndrome undergoing allogeneic HCT. Patients underwent cytotoxic conditioning for a median of 6 days (IQR 6-7) before undergoing allogeneic HCT and were followed up for up to 1 year (±3 months) post-transplantation. eLPI was measured in serum samples with the FeROS eLPI kit (Aferrix, Tel-Aviv, Israel) and values greater than 0·4 μmol/L were considered to represent raised eLPI. Liver iron content was measured by MRI. The primary endpoints were the quantitative delineation of eLPI dynamics during allogeneic HCT and the correlation coefficient between liver iron content before HCT and dynamic eLPI (eLPI; maximum eLPI minus baseline eLPI). All patients with available data were included in all analyses. This is the final analysis of this completed trial, which is registered with ClinicalTrials.gov, number NCT01746147.
Between Dec 13, 2012, and Dec 23, 2014, 112 patients underwent allogeneic HCT. Liver iron content before allogeneic HCT was not significantly correlated with eLPI (ρ=0·116, p=0·22). Serum eLPI concentrations rapidly increased during conditioning, and most (79 [73%] of 108) patients had raised eLPI by the day of transplantation. Patients with a pretransplant liver iron content greater than or equal to 125 μmol/g had an increased incidence of non-relapse mortality (20%, 95% CI 14-26) compared with those with lower concentrations (7%, 2-12; p=0·039) at day 100. Patients who had raised eLPI at baseline also had a significantly increased incidence of non-relapse mortality at day 100 (33%, 15-52) compared with those who had normal eLPI at baseline (7%, 2-13; p=0·00034).
eLPI is a possible biological mediator of iron-related toxicity. Peritransplantation eLPI-scavenging strategies could be explored in prospective interventional clinical trials for patients with systemic iron overload.
The Technical University of Dresden and Novartis.
全身铁过载对异基因造血细胞移植（HCT）后结局的影响一直是激烈争论的焦点。我们旨在研究储存铁（磁共振成像衍生的肝脏铁含量）和生物活性铁（增强的不稳定血浆铁；eLPI）对接受异基因HCT的急性髓系白血病或骨髓增生异常综合征患者移植后结局的预测价值。
前瞻性、多中心、观察性的异基因铁研究（ALLIVE）试验在德国的五个中心招募患者。我们纳入了接受异基因HCT的急性髓系白血病或骨髓增生异常综合征患者。患者在接受异基因HCT前接受了为期6天（四分位间距6 - 7天）的细胞毒性预处理，并在移植后随访长达1年（±3个月）。使用FeROS eLPI试剂盒（Aferrix，以色列特拉维夫）测定血清样本中的eLPI，eLPI值大于0.4 μmol/L被认为代表eLPI升高。通过磁共振成像测量肝脏铁含量。主要终点是异基因HCT期间eLPI动态变化的定量描述以及HCT前肝脏铁含量与动态eLPI（eLPI；最大eLPI减去基线eLPI）之间的相关系数。所有有可用数据的患者均纳入所有分析。这是这项已完成试验的最终分析，该试验已在ClinicalTrials.gov注册，编号为NCT01746147。
在2012年12月13日至2014年12月23日期间，112例患者接受了异基因HCT。异基因HCT前的肝脏铁含量与eLPI无显著相关性（ρ = 0.116，p = 0.22）。在预处理期间血清eLPI浓度迅速升高，大多数（108例中的79例[73%]）患者在移植当天eLPI升高。移植前肝脏铁含量大于或等于125 μmol/g的患者在第100天的非复发死亡率发生率（20%，95%CI 14 - 26）高于浓度较低的患者（7%，2 - 12；p = 0.039）。基线时eLPI升高的患者在第100天的非复发死亡率发生率（33%，15 - 52）也显著高于基线时eLPI正常的患者（7%，2 - 13；p = 0.00034）。
eLPI可能是铁相关毒性的生物学介质。对于全身铁过载患者，可在前瞻性干预性临床试验中探索移植期间清除eLPI的策略。
德累斯顿工业大学和诺华公司。
