Lee Ji Won, Kang Eun-Suk, Sung Ki Woong, Yi Eunsang, Lee Soo Hyun, Yoo Keon Hee, Koo Hong Hoe
Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Pediatr Blood Cancer. 2017 Jun;64(6). doi: 10.1002/pbc.26399. Epub 2016 Dec 24.
We performed a pilot study (NCT 00793351) to evaluate the effectiveness and feasibility of a strategy incorporating high-dose I-metaiodobenzylguanidine (HD-MIBG) treatment into killer immunoglobulin-like receptor (KIR)/HLA-ligand mismatched haploidentical stem cell transplantation (haplo-SCT) in improving the survival of children with neuroblastoma who failed previous tandem autologous SCT.
If the patient remained progression free with salvage treatment, HD-MIBG treatment (18 mCi/kg) was given prior to reduced-intensity conditioning (cyclophosphamide + fludarabine + antithymocyte globulin). Grafts from KIR/HLA-ligand mismatched, preferably BX haplotype, haploidentical donors were transplanted to enhance the graft-versus-tumor (GVT) effect.
A total of seven patients were enrolled and three donors had a BX haplotype. Toxicities during HD-MIBG treatment and reduced-intensity conditioning were mild. Neutrophil recovery and complete or near complete donor chimerism were rapidly achieved. Six patients experienced acute graft-versus-host disease (GVHD; grade I in five and grade III in one), and four of six evaluable patients experienced chronic GVHD (two mild and two severe). Four patients died from tumor progression, one died from sepsis without progression, and the other two remained alive in complete response during 34 and 48 months posttransplant. All three patients remained progression free after BX haplotype SCT, whereas the other four experienced progression after AA haplotype SCT.
Our results suggest that the incorporation of HD-MIBG treatment in haplo-SCT and the use of BX haplotype donors might improve outcome, but this approach is currently limited by unacceptable GVHD. Further work focused on enhancement of GVT effects in relapsed neuroblastoma should be coupled with efforts to reduce GVHD.
我们开展了一项试点研究（NCT 00793351），以评估将高剂量碘代间位碘苄胍（HD-MIBG）治疗纳入杀伤细胞免疫球蛋白样受体（KIR）/人类白细胞抗原（HLA）配体不匹配的单倍体相合干细胞移植（haplo-SCT）策略，对改善既往串联自体SCT失败的神经母细胞瘤患儿生存率的有效性和可行性。
如果患者经挽救治疗后病情无进展，则在减低剂量预处理（环磷酰胺+氟达拉滨+抗胸腺细胞球蛋白）前给予HD-MIBG治疗（18 mCi/kg）。移植来自KIR/HLA配体不匹配、最好是BX单倍型的单倍体相合供者的移植物，以增强移植物抗肿瘤（GVT）效应。
共纳入7例患者，3例供者为BX单倍型。HD-MIBG治疗和减低剂量预处理期间的毒性反应较轻。中性粒细胞迅速恢复，且迅速实现完全或接近完全的供者嵌合。6例患者发生急性移植物抗宿主病（GVHD；5例为I级，1例为III级），6例可评估患者中有4例发生慢性GVHD（2例轻度，2例重度）。4例患者死于肿瘤进展，1例死于无进展的败血症，另外2例在移植后34个月和48个月时仍处于完全缓解状态存活。3例患者在接受BX单倍型SCT后均无疾病进展，而另外4例在接受AA单倍型SCT后病情进展。
我们的结果表明，在haplo-SCT中纳入HD-MIBG治疗以及使用BX单倍型供者可能改善预后，但目前这种方法受到不可接受的GVHD的限制。针对复发性神经母细胞瘤增强GVT效应的进一步工作应与减少GVHD的努力相结合。
