高危神经母细胞瘤中高剂量 I-间碘苄胍治疗与串联大剂量化疗和自体干细胞移植联合应用：SMC NB-2009 研究结果。
Incorporation of high-dose I-metaiodobenzylguanidine treatment into tandem high-dose chemotherapy and autologous stem cell transplantation for high-risk neuroblastoma: results of the SMC NB-2009 study.
机构信息
Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 135-710, Republic of Korea.
Department of Pediatric Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 135-710, Republic of Korea.
出版信息
J Hematol Oncol. 2017 May 16;10(1):108. doi: 10.1186/s13045-017-0477-0.
BACKGROUND
In our previous SMC NB-2004 study of patients with high-risk neuroblastomas, which incorporated total-body irradiation (TBI) with second high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT), the survival rate was encouraging; however, short- and long-term toxicities were significant. In the present SMC NB-2009 study, only TBI was replaced with I-meta-iodobenzylguanidine (MIBG) treatment in order to reduce toxicities.
METHODS
From January 2009 to December 2013, 54 consecutive patients were assigned to receive tandem HDCT/auto-SCT after nine cycles of induction chemotherapy. The CEC (carboplatin + etoposide + cyclophosphamide) regimen and the TM (thiotepa + melphalan) regimen with (for metastatic MIBG avid tumors) or without (for localized or MIBG non-avid tumors) I-MIBG treatment (18 or 12 mCi/kg) were used for tandem HDCT/auto-SCT. Local radiotherapy, differentiation therapy with 13-cis-retinoic acid, and immunotherapy with interleukin-2 were administered after tandem HDCT/auto-SCT.
RESULTS
Fifty-two patients underwent the first HDCT/auto-SCT and 47 patients completed tandem HDCT/auto-SCT. There was no significant immediate toxicity during the I-MIBG infusion. Acute toxicities during the tandem HDCT/auto-SCT were less severe in the NB-2009 study than in the NB-2004 study. Late effects such as growth hormone deficiency, cataracts, and glomerulopathy evaluated at 3 years after the second HDCT/auto-SCT were also less significant in the NB-2009 study than in NB-2004 study. There was no difference in the 5-year event-free survival (EFS) between the two studies (67.5 ± 6.7% versus 58.3 ± 6.9%, P = 0.340).
CONCLUSIONS
Incorporation of high-dose I-MIBG treatment into tandem HDCT/auto-SCT could reduce short- and long-term toxicities associated with TBI, without jeopardizing the survival rate.
TRIAL REGISTRATION
ClinicalTrials.gov NCT03061656.
背景
在我们之前的 SMC NB-2004 研究中，对高危神经母细胞瘤患者采用全身照射（TBI）联合二次高剂量化疗和自体干细胞移植（HDCT/auto-SCT），结果令人鼓舞；然而，短期和长期毒性作用显著。在本次 SMC NB-2009 研究中，仅用间碘苄胍（MIBG）治疗替代 TBI，以降低毒性作用。
方法
从 2009 年 1 月至 2013 年 12 月，54 例连续患者接受 9 个周期诱导化疗后行串联 HDCT/auto-SCT。采用 CEC（卡铂+依托泊苷+环磷酰胺）方案和 TM（噻替哌+美法仑）方案，联合（用于转移性 MIBG 亲和力肿瘤）或不联合（用于局限性或 MIBG 非亲和力肿瘤）I-MIBG 治疗（18 或 12mCi/kg）进行串联 HDCT/auto-SCT。在串联 HDCT/auto-SCT 后给予局部放疗、13-顺式维甲酸分化治疗和白细胞介素-2 免疫治疗。
结果
52 例患者接受了第一次 HDCT/auto-SCT，47 例患者完成了串联 HDCT/auto-SCT。I-MIBG 输注期间无明显即刻毒性。与 SMC NB-2004 研究相比，在 SMC NB-2009 研究中，串联 HDCT/auto-SCT 期间的急性毒性作用较轻。在第二次 HDCT/auto-SCT 后 3 年评估的生长激素缺乏、白内障和肾小球病等迟发性效应在 SMC NB-2009 研究中也比 SMC NB-2004 研究轻。两项研究的 5 年无事件生存率（EFS）无差异（67.5±6.7%比 58.3±6.9%，P=0.340）。
结论
将大剂量 I-MIBG 治疗纳入串联 HDCT/auto-SCT 可降低 TBI 相关的短期和长期毒性作用，而不影响生存率。
试验注册
ClinicalTrials.gov NCT03061656。
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