Tragiannidis Athanasios, Antari Vassiliki, Tsotridou Eleni, Sidiropoulos Theodoros, Kaisari Aikaterini, Palabougiouki Maria, Vyzantiadis Timoleon-Achilleas, Hatzipantelis Emmanuel, Galli-Tsinopoulou Assimina, Goussetis Evgenios
Children & Adolescent Hematology-Oncology Unit, Second Department of Pediatrics, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
Stem Cell Transplant Unit, "Agia Sofia Children's Hospital", 11527 Athens, Greece.
Hematol Rep. 2024 Sep 27;16(4):579-584. doi: 10.3390/hematolrep16040056.
Despite the progress achieved regarding survival rates in childhood acute lymphoblastic leukemia (ALL), relapsed or refractory disease still poses a therapeutic challenge. Inotuzumab ozogamicin is a CD22-directed monoclonal antibody conjugated to calicheamicin, which has been approved by the Food and Drug Administration for adults and pediatric patients 1 year and older with relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukemia. Herein, we present the case of a 23-month-old girl with high-risk B-ALL who experienced very early isolated medullary relapse; following the failure of conventional chemotherapy according to the ALL-IC REL 2016 protocol, she went on to receive the bispecific T-cell engager (BiTE) blinatumomab and subsequently, due to refractory disease, the combination of fludarabine, cytarabine, and the proteasome inhibitor bortezomib without achieving remission. Given the high CD22 expression by the lymphoblasts, off-label use of inotuzumab ozogamicin (InO) was chosen and administrated in a 28-day cycle as a salvage treatment. The minimal residual disease (MRD) was 0.08% on day 28, and InO was continued, thus achieving MRD negativity; the patient successfully underwent an allogeneic stem cell transplantation from a matched family donor. Our case highlights the efficacy and safety of InO as a salvage treatment in the setting of relapsed B-ALL refractory not only to conventional chemotherapy but also to novel treatments, such as blinatumomab and bortezomib.
尽管儿童急性淋巴细胞白血病（ALL）的生存率已取得进展，但复发或难治性疾病仍然是一个治疗挑战。奥英妥珠单抗是一种与卡奇霉素偶联的靶向CD22的单克隆抗体，已被美国食品药品监督管理局批准用于治疗复发或难治性CD22阳性B细胞前体急性淋巴细胞白血病的1岁及以上成人和儿科患者。在此，我们报告一例23个月大的高危B-ALL女孩病例，该患儿经历了非常早期的孤立性髓系复发；按照ALL-IC REL 2016方案进行的传统化疗失败后，她接受了双特异性T细胞衔接器（BiTE）博纳吐单抗治疗，随后，由于疾病难治，又接受了氟达拉滨、阿糖胞苷和蛋白酶体抑制剂硼替佐米的联合治疗，但未实现缓解。鉴于原始淋巴细胞高表达CD22，选择了奥英妥珠单抗（InO）的非标签用药，并以28天为周期进行挽救治疗。第28天时最小残留病（MRD）为0.08%，继续使用InO，从而实现了MRD阴性；该患者成功接受了来自匹配家庭供体的异基因干细胞移植。我们的病例突出了InO作为挽救治疗在复发B-ALL中的疗效和安全性，这些复发B-ALL不仅对传统化疗难治，而且对新型治疗如博纳吐单抗和硼替佐米也难治。
