Dr. Xingyu Cao

Hebei Yanda Ludao Pei Hospital

Acute T-cell lymphoblastic leukemia (T-ALL) is a highly heterogeneous malignant tumor of the hematopoietic system caused by the malignant transformation of T-cell precursors. It has significant differences from B-cell precursor acute lymphoblastic leukemia (BCP-ALL) in clinical features, cellular genetics, molecular biology, and abnormal signal transduction pathways. T-ALL accounts for 10%-15% in children and 20%-25% in adults. Adult T-ALL has a poor prognosis due to primary chemotherapy resistance and early recurrence, with a 5-year event-free survival rate of only 20%-50%. The main challenge for T-ALL patients after transplantation is recurrence. From April 23-26, 2023, the EBMT Annual Meeting was grandly held in Paris, France. At the meeting, Dr. Cao Xingyu from Hebei Yanda Ludao Pei Hospital reported a clinical study (abstract number: 351), which suggested that the use of Chidamide for maintenance treatment might improve the survival of T-ALL patients after allogeneic hematopoietic stem cell transplantation (Allo-HSCT).

Research Background

Relapse after Allo-HSCT is a major challenge for T-ALL patients. Epigenetic abnormalities are common in T-ALL. Histone deacetylase (HDAC) 1 and HDAC4 are often overexpressed in tumor cells of T-ALL patients compared to normal bone marrow samples. Chidamide is an HDAC inhibitor with antitumor activity that can also enhance the cytotoxicity mediated by immune cells against tumor cells. Approved in China in 2014, Chidamide might reduce the relapse rate of T-ALL after allo-HSCT through graft-versus-leukemia effects. This study explored the safety and effectiveness of Chidamide maintenance therapy in T-ALL patients after allo-HSCT, hoping to improve survival rates by reducing post-transplant recurrence.

Research Methods

We retrospectively analyzed 12 T-ALL patients who underwent allo-HSCT at Hebei Yanda Ludao Pei Hospital from June 2017 to May 2020. All patients received Chidamide maintenance treatment after transplantation. The survival and adverse events during medication were analyzed. Patients began receiving Chidamide when they met the following conditions: 1) Complete remission (CR) before transplantation; 2) Hematopoietic recovery and minimal residual disease (MRD) negativity after transplantation.

Research Results

Of the 12 patients, one was female (8.3%), with a median age of 14 years (range: 7-37 years). Five patients (41.7%) were fusion gene positive. Before allo-HSCT, one patient (8.3%) was MRD positive, and the other 11 (91.7%) were MRD negative.

Eventually, 9 patients (75%) underwent haploidentical hematopoietic stem cell transplantation (haplo-HSCT), and the other 3 (25%) underwent sibling-matched HSCT. The median time to start taking Chidamide after transplantation was 183 days (range: 30-532 days). The dosage of Chidamide was determined based on the patient’s weight, hematopoietic recovery, etc., ranging from once a week at 5 mg to twice a week at 15 mg each time. The median duration of Chidamide treatment was 358 days (range: 74-762 days).

The most common adverse event was hematological toxicity. The cumulative relapse rate (RI) of patients at 6 months was 8.3% (95% CI: 1.3%-54.4%), and the 1-year, 2-year, and 5-year RIs were 16.7% (95% CI: 4.7%-59.1%), 25% (95% CI: 9.4%-66.6%), and 25% (95% CI: 9.4%-66.6%), respectively. The overall survival rate (OS) of all patients at 2 years was 83.3% (95% CI: 58.2%-98.1%), and the 5-year OS was 66.7% (95% CI: 38.8%-89.3%). Two years post-transplant, the relapse rate plateaued. The 2-year and 5-year leukemia-free survival rate (LFS) was 66.7% (95% CI: 38.8%-89.3%).

“Figure 1. RI, OS, and LFS of T-ALL patients after allo-HSCT maintenance treatment with Chidamide.”

Analyses showed that SET-CAN and STIL-TAL1 fusion genes are indicators of poor prognosis in T-ALL. Four patients died, with reasons including diffuse alveolar hemorrhage (n=1) and recurrence (n=3).

Research Conclusions

Our preliminary research indicates that Chidamide, as a maintenance treatment after allo-HSCT for T-ALL patients, is safe and does not increase the occurrence rate of adverse events. However, due to the small cohort, long-term survival and increased case numbers need to be studied further.

Researcher Comments

High-risk acute myeloid leukemia (AML) can use maintenance treatments such as azacitidine, decitabine, sorafenib, and gilteritinib to reduce the relapse rate. Our center’s data shows that the 5-year RI for T-ALL patients in CR undergoing allo-HSCT is 11.8% for haplo-HSCT and 16.1% for sibling-matched HSCT. The prognosis for patients with post-transplant recurrence of T-ALL is extremely poor. Clinical cases of T-ALL are relatively

few, resulting in a lack of large-scale prospective studies on post-transplant maintenance treatment. This research provides a potential approach for post-transplant maintenance therapy, indicating that the combination of Chidamide and allo-HSCT might be a new strategy to improve the survival of T-ALL patients.