一项关于钇-90替伊莫单抗治疗复发/难治性CD20阳性非霍奇金淋巴瘤儿童和青少年的I期研究：一项儿童肿瘤学组研究。

A phase I study of 90yttrium-ibritumomab-tiuxetan in children and adolescents with relapsed/refractory CD20-positive non-Hodgkin's lymphoma: a Children's Oncology Group study.

作者信息

Cooney-Qualter Erin, Krailo Mark, Angiolillo Anne, Fawwaz Rashid A, Wiseman Gregory, Harrison Lauren, Kohl Virginia, Adamson Peter C, Ayello Janet, vande Ven Carmella, Perkins Sherrie L, Cairo Mitchell S

机构信息

Division of Pediatric Heamtology and Blood and Marrow Transplantation, Medicine and Pathology, Columbia University, New York, New York 10032, and Children's Hospital of Philadelphia, PA, USA.

出版信息

Clin Cancer Res. 2007 Sep 15;13(18 Pt 2):5652s-5660s. doi: 10.1158/1078-0432.CCR-07-1060.

DOI:10.1158/1078-0432.CCR-07-1060

PMID:17875803

Abstract

PURPOSE

The prognosis for children with recurrent CD20+ non-Hodgkin's lymphoma is dismal. A radiolabeled anti-CD20 antibody, 90yttrium-ibritumomab-tiuxetan (90Y-IT), is Food and Drug Administration approved for adults with recurrent indolent CD20+ B cell-non-Hodgkin's lymphoma. There is no data on the safety and feasibility of 90Y-IT in refractory childhood CD20+ lymphoma.

EXPERIMENTAL DESIGN

Children and adolescents with refractory/relapsed CD20+ lymphoma were eligible for this phase I radioimmunotherapy study. Patients (n=5) received rituximab (250 mg/m2 i.v.) on days 0 and 7 and indium-111 ibritumomab-tiuxetan (5 mCi i.v.) on day 0. Dosimetry studies were done on days 0, 1, 3, and 6. Immediately after rituximab on day 7, patients received 90Y-IT if dosimetry studies showed<2000 cGy exposure to all solid organs and<300 cGy to marrow, as well as 0.4 mCi/kg in patients with good marrow reserve (n=3) and 0.1 mCi/kg in patients with poor marrow reserve (after bone marrow transplant; n=2).

RESULTS

No patients experienced nonhematologic or hematologic dose-limiting toxicity. Human antimurine antibody/human antichimeric antibody incidence was 0%. One patient experienced grade II infusion-related chills associated with rituximab. The following are the means of organ radiation exposure (cGy): kidneys 341 (112-515), liver 345 (83-798), lungs 309 (155-519), marrow 46 (20-78), spleen 565 (161-816), and total body 42 (14-68).

CONCLUSIONS

Based on these findings, an expanded investigator-initiated limited institutional phase II study has been designed to further evaluate the safety, tolerability, and response rate with 90Y-IT dose stratification based on marrow reserve.

摘要

目的

复发性CD20+非霍奇金淋巴瘤患儿的预后很差。一种放射性标记的抗CD20抗体，钇-90伊布替膦酸（90Y-IT），已获美国食品药品监督管理局批准用于复发性惰性CD20+B细胞非霍奇金淋巴瘤成人患者。目前尚无关于90Y-IT用于难治性儿童CD20+淋巴瘤的安全性和可行性的数据。

实验设计

难治性/复发性CD20+淋巴瘤的儿童和青少年 eligible for this phase I radioimmunotherapy study。患者（n = 5）在第0天和第7天接受利妥昔单抗（250 mg/m2静脉注射），并在第0天接受铟-111伊布替膦酸（5 mCi静脉注射）。在第0、1、3和6天进行剂量测定研究。在第7天利妥昔单抗注射后，如果剂量测定研究显示所有实体器官的照射剂量<2000 cGy且骨髓照射剂量<300 cGy，以及骨髓储备良好的患者（n = 3）接受0.4 mCi/kg、骨髓储备差的患者（骨髓移植后；n = 2）接受0.1 mCi/kg，则患者接受90Y-IT。

结果

没有患者出现非血液学或血液学剂量限制毒性。人抗鼠抗体/人抗嵌合抗体发生率为0%。一名患者出现与利妥昔单抗相关的II级输液相关寒战。以下是器官辐射暴露（cGy）的平均值：肾脏341（112 - 515），肝脏345（83 - 798），肺309（155 - 519），骨髓46（20 - 78），脾脏565（161 - 816），全身42（14 - 68）。