Rettinger Eva, Merker Michael, Salzmann-Manrique Emilia, Kreyenberg Hermann, Krenn Thomas, Dürken Matthias, Faber Jörg, Huenecke Sabine, Cappel Claudia, Bremm Melanie, Willasch Andre, Bakhtiar Shahrzad, Jarisch Andrea, Soerensen Jan, Klingebiel Thomas, Bader Peter
University Hospital Frankfurt/Main, Department for Children and Adolescents, Division for Stem Cell Transplantation and Immunology, Goethe-University Frankfurt/Main, Germany.
University Hospital Frankfurt/Main, Department for Children and Adolescents, Division for Stem Cell Transplantation and Immunology, Goethe-University Frankfurt/Main, Germany.
Biol Blood Marrow Transplant. 2017 Jan;23(1):87-95. doi: 10.1016/j.bbmt.2016.10.006. Epub 2016 Oct 11.
Monitoring of minimal residual disease (MRD) or chimerism may help guide pre-emptive immunotherapy (IT) with a view to preventing relapse in childhood acute lymphoblastic leukemia (ALL) after transplantation. Patients with ALL who consecutively underwent transplantation in Frankfurt/Main, Germany between January 1, 2005 and July 1, 2014 were included in this retrospective study. Chimerism monitoring was performed in all, and MRD assessment was performed in 58 of 89 patients. IT was guided in 19 of 24 patients with mixed chimerism (MC) and MRD and by MRD only in another 4 patients with complete chimerism (CC). The 3-year probabilities of event-free survival (EFS) were .69 ± .06 for the cohort without IT and .69 ± .10 for IT patients. Incidences of relapse (CIR) and treatment-related mortality (CITRM) were equally distributed between both cohorts (without IT: 3-year CIR, .21 ± .05, 3-year CITRM, .10 ± .04; IT patients: 3-year CIR, .18 ± .09, 3-year CITRM .13 ± .07). Accordingly, 3-year EFS and 3-year CIR were similar in CC and MC patients with IT, whereas MC patients without IT experienced relapse. IT was neither associated with an enhanced immune recovery nor an increased risk for acute graft-versus-host disease. Relapse prevention by IT in patients at risk may lead to the same favorable outcome as found in CC and MRD-negative-patients. This underlines the importance of excellent MRD and chimerism monitoring after transplantation as the basis for IT to improve survival in childhood ALL.
监测微小残留病（MRD）或嵌合状态可能有助于指导抢先免疫治疗（IT），以期预防儿童急性淋巴细胞白血病（ALL）移植后复发。本回顾性研究纳入了2005年1月1日至2014年7月1日期间在德国法兰克福/美因河畔连续接受移植的ALL患者。所有患者均进行了嵌合状态监测，89例患者中的58例进行了MRD评估。24例混合嵌合（MC）且有MRD的患者中有19例接受了IT指导，另外4例完全嵌合（CC）患者仅根据MRD接受了IT指导。未接受IT治疗的队列3年无事件生存率（EFS）为0.69±0.06，接受IT治疗的患者为0.69±0.10。复发率（CIR）和治疗相关死亡率（CITRM）在两个队列中分布均衡（未接受IT治疗：3年CIR，0.21±0.05，3年CITRM，0.10±0.04；接受IT治疗的患者：3年CIR，0.18±0.09，3年CITRM 0.13±0.07）。因此，接受IT治疗的CC和MC患者的3年EFS和3年CIR相似，而未接受IT治疗的MC患者出现了复发。IT既未与免疫恢复增强相关，也未增加急性移植物抗宿主病的风险。对有风险的患者通过IT预防复发可能会带来与CC和MRD阴性患者相同的良好结局。这突出了移植后出色的MRD和嵌合状态监测作为IT改善儿童ALL生存率基础的重要性。
