Essa Mohammed F, Abdellatif Reem, Elimam Naglla, Ballourah Waleed, Alsudairy Reem, Alkaiyat Mohammad, Alsultan Abdulrahman, Jastaniah Wasil
Department of Pediatric Hematology/Oncology, King Abdullah Specialist Children's Hospital, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia.
College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
Pediatr Hematol Oncol. 2022 Oct;39(7):613-628. doi: 10.1080/08880018.2022.2049936. Epub 2022 Apr 23.
The management of Refractory/Relapsed B-cell Acute Lymphoblastic Leukemia (R/R ALL) remains challenging. Incorporating blinatumomab in R/R ALL treatment has shown encouraging results. We describe the outcome and predictors of response in children receiving blinatumomab as a bridge to definitive therapy. Immunoglobulin (Ig) G and viral serology before and after therapy were evaluated. Thirty-three patients that failed standard first-line treatments due to relapsed ALL ( 22), persistent minimal residual disease (MRD) ( 8), or refractory disease ( 3) received blinatumomab. Grade 2 toxicity occurred in 27.2% of patients. MRD remission (<0.01%) was achieved in 72.7% of patients. Pre-blinatumomab absolute lymphocyte count (ALC) and MRD/ALC ratio significantly associated with MRD-response. Patients with translocation had lower response rate, compared to all other cytogenetic categories ( 0.013). One-year event-free survival (EFS) and overall survival (OS) were 69.2% and 79.7%, respectively. Analysis of OS and EFS showed pre-blinatumomab MRD level, ALC, MRD/ALC ratio, , and post-blinatumomab MRD remission associated with survival. Following blinatumomab, 83% (15/18) of tested patients had low IgG levels. IgG seronegative status was observed in 83% (12/15) for varicella zoster, 35% (6/17) for herpes zoster, 18% (3/17) for cytomegalovirus, and 26% (5/17) for Epstein Barr virus. Blinatumomab produced encouraging results in children with R/R ALL and low disease burden bridging to definitive therapy. Incorporating baseline genetics and biomarkers may help identify subgroups likely to be responsive/resistant to therapy. Viral serological testing pre- and post-blinatumomab is recommended to optimize supportive and preemptive therapy.Supplemental data for this article is available online at https://doi.org/10.1080/08880018.2022.2049936 .
难治性/复发性B细胞急性淋巴细胞白血病（R/R ALL）的治疗仍然具有挑战性。在R/R ALL治疗中加入博纳吐单抗已显示出令人鼓舞的结果。我们描述了接受博纳吐单抗作为确定性治疗桥梁的儿童的治疗结果和反应预测因素。评估了治疗前后的免疫球蛋白（Ig）G和病毒血清学。33例因复发性ALL（22例）、持续性微小残留病（MRD）（8例）或难治性疾病（3例）而未能通过标准一线治疗的患者接受了博纳吐单抗治疗。27.2%的患者出现2级毒性反应。72.7%的患者实现了MRD缓解（<0.01%）。博纳吐单抗治疗前的绝对淋巴细胞计数（ALC）和MRD/ALC比值与MRD反应显著相关。与所有其他细胞遗传学类别相比，具有 易位的患者缓解率较低（P = 0.013）。一年无事件生存率（EFS）和总生存率（OS）分别为69.2%和79.7%。对OS和EFS的分析表明，博纳吐单抗治疗前的MRD水平、ALC、MRD/ALC比值、 以及博纳吐单抗治疗后的MRD缓解与生存率相关。接受博纳吐单抗治疗后，83%（15/18）的受试患者IgG水平较低。水痘带状疱疹病毒的IgG血清阴性状态在83%（12/15）的患者中观察到，带状疱疹病毒为35%（6/17），巨细胞病毒为18%（3/17），爱泼斯坦-巴尔病毒为26%（5/17）。博纳吐单抗在患有R/R ALL且疾病负担较轻的儿童中产生了令人鼓舞的结果，这些儿童可作为确定性治疗的桥梁。纳入基线遗传学和生物标志物可能有助于识别可能对治疗有反应/耐药的亚组。建议在博纳吐单抗治疗前后进行病毒血清学检测，以优化支持性和预防性治疗。本文的补充数据可在https://doi.org/10.1080/08880018.2022.2049936在线获取。
