Abstract
Introduction The SET::CAN (SET::NUP214) fusion, occurring in 4-6% of T-cell acute lymphoblastic leukemia(T-ALL) cases,confers glucocorticoid resistance and suboptimal chemotherapy response,predicting poor prognosis (median OS:22 months). Although allogeneic hematopoietic stem cell transplantation(allo-HSCT) demonstrates therapeutic potential, current evidence remains limited to retrospective analyses and case reports. We therefore conducted a 12-year single-center cohort study assessing allo-HSCT outcomes for SET::CAN-positive hematologic malignancies.
Methods We retrospectively analyzed 36 patients with SET::CAN-positive hematologic malignancies receiving allo-HSCT at Lu Daopei Hospitals (Oct 2012-Aug 2024). SET::CAN fusion was detected via polymerase chain reaction (PCR) screening and confirmed by quantitative reverse transcription PCR (RT-qPCR). All received standard first-line pre-transplant therapy. Follow-up data were censored Jan 1, 2025.
Results The cohort comprised 36 patients (24 male, 12 female) with a median age of 28 years (range 12-52).Disease distribution showed T-ALL as the most frequent diagnosis (18/36,50%), followed by mixed-phenotype acute leukemia (MPAL;9/36,25%), B/T-lymphoblastic lymphoma (B/T-LBL;5/36,13.9%), and acute myeloid leukemia (AML; 4/36,11.1%). Thirty-two patients (88.9%) received the first transplant, while 4 received the second transplants. Molecular profiling identified gene mutations in 22 patients (61.1%), with PHF6 (9/36, 25%), NOTCH1 (8/36, 22.2%), and NRAS (6/36, 16.7%). Prior to transplantation, 29 patients (80.6%) achieved complete remission (CR), while 7 patients (19.4%) got non-response/partial response (NR/PR). The cumulative incidence of grade III-IV acute GVHD by day+100 was 16.7%(95%CI, 8.0-34.6%),and moderate-to-severe chronic GVHD was 14.5%(95% CI, 6.4-32.7%).
The median follow-up duration was 12.5 months (range, 0.1-145.1), with one patient lost to follow-up at 12 months post-transplant. A total of 23 patients died, of whom 15 (65.2%) died within 1-year post-HSCT. Four patients (11.1%) experienced day+100 transplant-related mortality (TRM). The 13 surviving patients had a median follow-up duration of 83.8 months (range,7.3-145.1). The estimated 2-year OS rates were 50% for AML and MPAL cohorts,38.4% for T-ALL and 20% for B/T-LBL.
Patients undergoing transplantation in NR/PR status (n=7) exhibited significantly poorer outcomes,whom (100%) expired within 12 months.The 6-month OS and leukemia-free survival (LFS) were 42.86% (95% CI:6.20-79.52%) and 28.57% (95% CI:0-62.04%), the cumulative relapse incidence (RI) was 85.71% (95% CI: 63.34-100%), and the non-relapse mortality (NRM) was 57.14% (95% CI:30.08-100%).
Remarkably improved survival outcomes were observed in the CR cohort (n=29) receiving HSCT. The estimated 1-, 2-, 3-, and 5-year OS were 82.76% (95% CI,69.01-96.5%), 50.83%(95%CI,31.41-70.24%), 42.35% (95%CI,22.95-61.76%), and 42.35% (95% CI, 22.95-61.76%), respectively. Corresponding LFS were 72.41% (95% CI, 56.15-88.68%), 41.68% (95% CI, 22.86-60.49%), 41.68% (95%CI, 22.86-60.49%), and 37.05% (95% CI,18.26-55.83%). The cumulative RI and NRM were 41.92%(95%CI,26.56-66.16%) and 29.79%(95%CI,16.56-53.59%), respectively. All outcomes were significantly better than those in the NR/PR group (all p < 0.05).
Patients achieving SET::CAN negativity prior to HSCT(n=12) demonstrated a trend toward improved survival compared to those fusion-positive (n=17).The fusion-negative group showed superior 2- and 5-year OS (72.92% vs 38.01% and 60.76% vs 31.67%, respectively) and LFS (64.29% vs 29.41% and 51.43% vs 29.41%). However, these differences did not reach statistical significance (all p>0.05).
Conclusion This study establishes allo-HSCT as an effective therapeutic strategy for SET::CAN-positive hematological malignancies, with optimal outcomes observed in patients achieving both CR and SET::CAN-negative prior to transplantation. Notably,B/T-LBL cases demonstrate the most unfavorable post-transplant outcomes. AML and MPAL patients may experience superior survival compared to T-ALL.However, maintenance therapy within the initial two years post-transplant remains essential to prevent relapse.
