Mixed phenotype acute leukemia (MPAL) is a rare leukemia and is regarded as a high-risk entity with a poor prognosis. Induction therapy of an acute lymphoblastic leukemia type or hybrid regimen and hematopoietic stem cell transplantation has been recommended for MPAL. However, the optimal therapies for relapsed or refractory MPAL remain unclear, especially for relapse after stem cell transplantation. Donor-derived chimeric antigen receptor T (CAR-T) cell therapy may be a promising therapeutic option for patients with MPAL who express target antigens and have relapsed after stem cell transplantation. However, recurrence remains a challenge, and reinfusion of CAR-T cells is not always effective. An infusion of secondary donor-derived humanized CD19-modified CAR-T cells may be effective in inducing remission. We report a case of MPAL with CD19 expression. The patient was treated with acute lymphoblastic leukemia-like induction and consolidation therapies but remained positive for SET-NUP214 fusion gene transcript. He subsequently underwent a haploidentical stem cell transplantation but relapsed within 6 months. He then underwent donor-derived CD19-targeted CAR-T cell therapy and achieved a sustained, complete molecular remission. Unfortunately, he developed a CD19-positive relapse after 2 years. Donor-derived humanized CD19-directed CAR-T cells induced a second complete molecular remission without severe cytokine release syndrome or acute graft-versus-host disease. This case demonstrated the efficacy and safety of humanized donor-derived CD19-modified CAR-T cell infusion for treating the recurrence of MPAL previously exposed to murine-derived CD19-directed CAR-T cells.

中文翻译：

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二次供体来源的人源化 CD19 修饰 CAR-T 细胞诱导同种异体造血干细胞移植后复发/难治性混合表型急性白血病的缓解：病例报告。

混合表型急性白血病（MPAL）是一种罕见的白血病，被认为是一种预后不良的高危实体。MPAL 已推荐急性淋巴细胞白血病类型或混合方案的诱导治疗和造血干细胞移植。然而，复发或难治性 MPAL 的最佳疗法仍不清楚，尤其是干细胞移植后的复发。对于表达靶抗原并在干细胞移植后复发的 MPAL 患者，供体来源的嵌合抗原受体 T (CAR-T) 细胞疗法可能是一种有前途的治疗选择。然而，复发仍然是一个挑战，再输注 CAR-T 细胞并不总是有效的。输注二次供体来源的人源化 CD19 修饰的 CAR-T 细胞可能有效诱导缓解。我们报告了一例带有 CD19 表达的 MPAL。该患者接受了急性淋巴细胞白血病样诱导和巩固治疗，但 SET-NUP214 融合基因转录物仍然呈阳性。他随后接受了半相合干细胞移植，但在 6 个月内复发。然后，他接受了供体来源的 CD19 靶向 CAR-T 细胞疗法，并实现了持续、完全的分子缓解。不幸的是，他在 2 年后出现了 CD19 阳性复发。供体来源的人源化 CD19 导向 CAR-T 细胞诱导第二次完全分子缓解，没有严重的细胞因子释放综合征或急性移植物抗宿主病。