Lin Na, Liu Zhenghua, Li Yan, Yan Xiaojing, Wang Lei
Department of Hematology, The First Affiliated Hospital of China Medical University, Shenyang, China.
Front Oncol. 2021 Mar 26;11:651494. doi: 10.3389/fonc.2021.651494. eCollection 2021.
fusion is a recurrent event most commonly seen in T-cell acute lymphoblastic leukemia (T-ALL). It is related to resistance to glucocorticoids and chemotherapy; however, the reported prognosis of T-ALL with fusion is diverse, and the optimal treatment option remains undetermined. Here, we present the treatment process of an illuminating case of T-ALL with fusion. The patient showed early resistance to routine VICLP chemotherapy (at 15 day, 79.2% blasts), but the leukemia burden was significantly reduced after 28-day induction chemotherapy (18.85% blasts), even though she still didn't achieve complete remission (CR) after a second course of high-dose methotrexate (3 g/m2) and pegaspargase. Ex vivo drug sensitivity screening using a panel of 165 kinds of cytotoxic drugs, targeted therapy drugs, combination chemotherapy drugs, etc., was conducted on the refractory leukemia cells, which showed extensive resistance to various regimens. Surprisingly, AML-like scheme DAE scheme (daunorubicin + cytarabine + etoposide) and carfilzomib showed the highest ex vivo inhibition rate. The patient received DAE regimen chemotherapy, and finally achieved complete remission and received allogenic hematopoietic stem cell transplantation (allo-HSCT). According to our own findings and a literature survey, we found that T-ALL patients with fusion usually shows early resistance to chemotherapy, but they have a delayed response, and the CR rate is not compromised; thus, a chemotherapy regimen featuring a 28-day long course, such as that used in GRAALL 2003 or 2005, is recommended for induction therapy. For refractory patients, AML-like therapy such as DAE or CLAG in combination with asparaginase may be beneficial. In addition, carfilzomib may be a useful therapeutic drug and is worthy of further study. Allo-HSCT improves prognosis and we recommend HSCT if possible. Additional chromosomal or molecular events may affect the prognosis, and further investigation is needed. We believe that through proper treatment, the prognosis of patients with fusion can be greatly improved, at least not worse than that of other T-ALL patients.
融合是一种常见于T细胞急性淋巴细胞白血病（T-ALL）的复发性事件。它与对糖皮质激素和化疗的耐药性有关；然而，报道的伴有融合的T-ALL的预后各不相同，最佳治疗方案仍未确定。在此，我们展示了一例伴有融合的T-ALL的典型病例的治疗过程。该患者对常规VICLP化疗早期耐药（第15天时，原始细胞比例为79.2%），但在28天诱导化疗后白血病负担显著降低（原始细胞比例为18.85%），尽管在第二疗程大剂量甲氨蝶呤（3 g/m2）和培门冬酶治疗后仍未达到完全缓解（CR）。对难治性白血病细胞进行了165种细胞毒性药物、靶向治疗药物、联合化疗药物等的体外药敏筛选，结果显示对各种方案均有广泛耐药。令人惊讶的是，AML样方案DAE方案（柔红霉素+阿糖胞苷+依托泊苷）和卡非佐米显示出最高的体外抑制率。该患者接受了DAE方案化疗，最终实现完全缓解并接受了异基因造血干细胞移植（allo-HSCT）。根据我们自己的发现和文献调查，我们发现伴有融合的T-ALL患者通常对化疗早期耐药，但有延迟反应，且CR率不受影响；因此，推荐使用如GRAALL 2003或2005中使用的为期28天的长疗程化疗方案进行诱导治疗。对于难治性患者，DAE或CLAG等AML样治疗联合天冬酰胺酶可能有益。此外，卡非佐米可能是一种有用的治疗药物，值得进一步研究。allo-HSCT可改善预后，我们建议尽可能进行HSCT。其他染色体或分子事件可能影响预后，需要进一步研究。我们相信，通过适当治疗，伴有融合的患者的预后可得到极大改善，至少不比其他T-ALL患者差。
