Inotuzumab ozogamicin in pediatric patients with relapsed/refractory acute lymphoblastic leukemia.
Inotuzumab ozogamicin in pediatric patients with relapsed/refractory acute lymphoblastic leukemia.
复制标题
DOI：
10.1038/s41375-018-0265-z
复制
发表时间：
2019-04
期刊：
影响因子：
11.4
通讯作者：
Rheingold SR
中科院分区：
文献类型：
--
作者：
Bhojwani D;Sposto R;Shah NN;Rodriguez V;Yuan C;Stetler-Stevenson M;O'Brien MM;McNeer JL;Quereshi A;Cabannes A;Schlegel P;Rossig C;Dalla-Pozza L;August K;Alexander S;Bourquin JP;Zwaan M;Raetz EA;Loh ML;Rheingold SR
虽然inotuzumab ozogamicin（InO）被认为是成人复发性急性淋巴细胞白血病（ALL）的有效药物，但儿科患者的安全性和疗效数据很少。我们报告了InO在51例复发/难治性ALL儿童中的使用，这些儿童在同情使用项目中接受治疗。在这个经过大量预治疗的队列中，67%的明显骨髓疾病患者达到完全缓解。大多数（71%）应答者的微小残留病为阴性。无论细胞遗传学亚型或既往治疗方案的数量或类型如何，均观察到缓解。InO耐受性良好; 6例（12%）患者出现3级肝转氨酶或高胆红素血症，11例（22%）患者出现3/4级感染。在InO治疗期间没有患者发生窦阻塞综合征（SOS）;然而，在InO治疗后接受造血干细胞移植（HSCT）的21例患者中有11例（52%）发生SOS。在三名InO后随后复发的患者中，检测到表面CD 22下调是一种可能的逃避机制。我们的结论是，InO是一种耐受性良好，有效的治疗儿童复发性ALL和前瞻性研究是必要的。目前正在确定制定HSCT后SOS的风险因素和缓解该风险的策略。
Although inotuzumab ozogamicin (InO) is recognized as an effective agent in relapsed acute lymphoblastic leukemia (ALL) in adults, data on safety and efficacy in pediatric patients are scarce. We report the use of InO in 51 children with relapsed/refractory ALL treated in the compassionate use program. In this heavily pretreated cohort, complete remission was achieved in 67% of patients with overt marrow disease. The majority (71%) of responders were negative for minimal residual disease. Responses were observed irrespective of cytogenetic subtype or number or type of prior treatment regimens. InO was well-tolerated; grade 3 hepatic transaminitis or hyperbilirubinemia were noted in 6 (12%) and grade 3/4 infections in 11 (22%) patients. No patient developed sinusoidal obstruction syndrome (SOS) during InO therapy; however, 11 of 21 (52%) patients who underwent hematopoietic stem cell transplantation (HSCT) following InO developed SOS. Downregulation of surface CD22 was detected as a possible escape mechanism in three patients who developed a subsequent relapse after InO. We conclude that InO is a well-tolerated, effective therapy for children with relapsed ALL and prospective studies are warranted. Identification of risk factors for developing post-HSCT SOS and strategies to mitigate this risk are ongoing.
登录
查看更多内容
影响因子：
11.4
作者：
Sun W;Malvar J;Sposto R;Verma A;Wilkes JJ;Dennis R;Heym K;Laetsch TW;Widener M;Rheingold SR;Oesterheld J;Hijiya N;Sulis ML;Huynh V;Place AE;Bittencourt H;Hutchinson R;Messinger Y;Chang B;Matloub Y;Ziegler DS;Gardner R;Cooper T;Ceppi F;Hermiston M;Dalla-Pozza L;Schultz KR;Gaynon P;Wayne AS;Whitlock JA
通讯作者：
Whitlock JA
影响因子：
51.1
作者：
Kantarjian, Hagop;Thomas, Deborah;O'Brien, Susan
通讯作者：
O'Brien, Susan
影响因子：
11.5
作者：
Lamb, Yvette N.
通讯作者：
Lamb, Yvette N.
影响因子：
28.4
作者：
Jabbour, Elias;Ravandi, Farhad;Kantarjian, Hagop
通讯作者：
Kantarjian, Hagop
影响因子：
3.2
作者：
Sun W;Orgel E;Malvar J;Sposto R;Wilkes JJ;Gardner R;Tolbert VP;Smith A;Hur M;Hoffman J;Rheingold SR;Burke MJ;Wayne AS
通讯作者：
Wayne AS