Hematopoietic Stem Cell Transplant with Thiotepa-Based Conditioning for Adult T-ALL
Authors: Zhao Lu , Liu Yuqing , Chen Ting , Feng Yimei , Yao Han , Zhu Lidan , Liu Jia , Liu Huanfeng , Gao Shichun , Wang Lu , Tang Shuhan , Gao Lei , Kong Peiyan , Zhang Xi 
Published: December 2024

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematological neoplasm with a poor prognosis. Unlike children, adult T-ALL patients have a high recurrence chance and the remission rate after relapse is below 10%. The reported five-year overall survival (OS) of adult T-ALL patients varied from 20-40%. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been a well-recognized post-remission treatment to improve outcomes. However, the standard conditioning regimen for T-ALL adults has not been established yet, the relapse rate and OS after allo-HSCT are still not satisfying. Thiotepa is an alkylating agent that can cross the blood-brain barrier efficiently and distribute through the tissues extensively, which makes it good for patients with CNS leukemia risk. Aiming at improving the clinical outcome of adult T-ALL patients, we evaluated the safety and effectiveness of a modified thiotepa-based condition regimen for HSCT for adult T-ALL patients.
This single-arm study has recruited 14 T-ALL adult patients, conditioned with Me-CCNU, thiotepa, busulfan, and CTX (MeCCNU+TT+BU+CTX) before HSCT. 6 patients received PBSC from HLA-matched related or unrelated donors, and 8 patients received PBSC plus BM from haploidentical related donors. The longest follow-up time is 28 months, with a median follow-up time of 10 months. One patient experienced extramedullary relapse at cervical lymph nodes 2 months after HSCT, without bone marrow relapse, and achieved remission after donor lymphocyte infusion. Another patient died of relapse 5 months after HSCT. The 10-month OS and LFS are 92.3% and 85.1% respectively, which is better than our historical data (83.6% and 62.3%). All patients received standard CNS leukemia prophylaxis with intrathecal (IT) chemotherapy, no patient developed central nervous leukemia after HSCT in this study. The day 100 cumulative incidence (CI) of grade II-IV acute GVHD was 35.7%, and a total of 8 patients (57.14%) developed chronic GVHD, among them one is grade IV cGVHD of the liver and is still under treatment. 2 patients (8.3%) experienced severe mucositis, 3 patients (21.4%) had severe infection during myelosuppression, no TRM was observed up to now.
In adult patients with T-ALL, most relapses take place within the first two years after allo-HSCT, and many start from the central nervous system or other extramedullary relapse. It is reported that conditioning regimens with thiotepa have a 2-year OS (46.5%) and leukemia-free survival (LFS) (33%) similar to patients conditioned with TBI-based regimens. Though with a relatively short follow-up time and limited patient number, our thiotepa-based condition regimen for adult patients with T-ALL has already shown a promising OS and DFS better than the historical control and literature report and was well tolerated. Notably, this conditioning regimen contains two blood-brain barrier crossing drugs meCCNU and thiotepa, which could contribute to its great potential in preventing CNS leukemia in T-ALL patients.