The outcome of acute leukemia patients with SET-NUP214 fusion after allogeneic stem cell transplantation.

SET-NUP214 fusion gene, also known as TAF-1-CAN and SET-CAN, is observed in acute myeloid leukemia (AML) and T-cell lymphoblastic leukemia (T-ALL). SET-NUP214 fusion in T-cell lymphoblastic leukemia is associated with chemotherapy resistance, but the prognosis of patients with AML with SET-NUP214 has rarely been reported. In the present study, we retrospectively analyzed all patients with acute leukemia including AML and T-ALL patients with SET-NUP214 fusion who underwent allogeneic stem cell transplantation (alloHSCT) in our center from July 2017 to November 2022. Of the total 11 patients, 5 patients were diagnosed with AML and 6 patients were diagnosed with T-ALL de novo. All patients received myeloablative regimens in CR1, and there were three (60%) AML patients who relapsed post-alloHSCT and three T-ALL (50%) patients who relapsed post-alloHSCT. Only one patient with AML who relapsed post-alloHSCT responded to subsequent chemotherapy plus donor lymphocyte infusion and survived the last follow-up. The estimated 1-year overall survival and 3-year overall survival for all these 11 patients were 69.3% and 38.5%, respectively. The estimated 1-year leukemia-free survival and 3-year leukemia-free survival for all patients were 69.3% and 38.5%, respectively. The research shows a high incidence of relapse for patients with acute leukemia with the SET-NUP214 fusion gene, even after alloHSCT. More clinical trials or research with larger samples are urgently needed for this group of patients.

SET-CAN/NUP214 fusion gene in leukemia: general features and clinical advances.

SET-CAN/NUP214 fusion is a recurrent event commonly observed in adult male patients diagnosed with T-cell acute lymphoblastic leukemia (T-ALL) and has occasionally been reported in other diseases such as acute myeloid leukemia (AML), myeloid sarcoma (MS), acute undifferentiated leukemia (AUL), chronic myeloid leukemia (CML) and B-cell acute lymphoblastic leukemia (B-ALL). This fusion gene is derived from chromosome del(9)(q34.11;q34.13) or t(9;9)(q34;q34) and may have an inhibitory effect on primitive progenitor differentiation. The prognosis of the reported patients is varied, with these patients often show resistance to chemotherapy regimens that include high doses of glucocorticoids. The optional treatment has not been determined, more cases need to be accumulated and evaluated. The scope of this review is to summarize the general features and prognostic significance in leukemia associated with the SET-CAN/NUP214 fusion gene and to discuss the methods of detection and treatment, aiming at providing some useful references for relevant researchers in the field of blood tumor.

Determining the Appropriate Treatment for T-Cell Acute Lymphoblastic Leukemia With SET-CAN/NUP214 Fusion: Perspectives From a Case Report and Literature Review.

SET-CAN/NUP214 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 SET-CAN/NUP214 fusion is diverse, and the optimal treatment option remains undetermined. Here, we present the treatment process of an illuminating case of T-ALL with SET-CAN/NUP214 fusion. The patient showed early resistance to routine VICLP chemotherapy (at 15th 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 SET-CAN/NUP214 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 SET-CAN/NUP214 fusion can be greatly improved, at least not worse than that of other T-ALL patients.