ALL-056 Late Intensification With Autologous HSCT After Non-Myeloablative CEAM Conditioning Can't Improve Results of Therapy in Adults With T-Cell Acute Lymphoblastic Leukemia (ALL) Treated by Non-Intensive Protocol: Data of the Multicentral Prospective Randomized RALL Study.

BACKGROUND: The Russian ALL group applied a protocol based on a less intensive and also non-interruptive approach. RALL-2009 study showed that fulfilled auto-hematopoietic stem cell transplantation (HSCT) in T-cell ALL could reliably improve disease free survival (DFS). This is a non-randomized trial, and selection is limited to patients with auto-HSCT vs chemotherapy (ChT) only.

AIM: To appreciate the role of fulfilled auto-HSCT in T-ALL adult patients treated by RALL-2006 protocol.

PATIENTS: In RALL-2016 protocol all T-ALL patients who achieved complete response (CR) were brought to randomization after the informed consent to one of two groups: auto-HSCT vs ChT only. 267 Ph-negative ALL adult patients were included from Dec 2016 until Apr 2022. 111 patients had T-ALL, 74% were male, and median age was 31.

RESULTS: 5y overall survival (OS) and DFS in T-ALL patients were 68% and 66%, respectively. We observed that early T-cell precursor (ETP)-ALL is group of patients with reliably poor prognosis, with high probability of relapse (PR) (52% in 1st year after CR). 87 T-ALL patients (pts) were randomized: 43 pts to ChT, and 44 to auto-HSCT. 1 patient refused in ChT group, and 4 refused in auto-HSCT; patients were censored on data of refuse. We observed similar number of deaths in CR in both arms, and similar cases of patients who went to allo-HSCT - mixed-lineage leukemia (MLL) leukemia, Niimegem syndrome or long MRD persistence). 25 auto-HSCT were done. For transplanted patients: time from CR to transplant was 7 months. All pts were conditioned with iomustine, etoposide, cytarabine, and melphalan (CEAM) before auto-HSCT. Maintenance start was 1.5 months after HSCT. Transplant-related mortality was 5%. Landmark analysis from a median of 7 months post-HSCT, didn't detect differences in DFS and PR (67% vs 78%, and 25% vs 22% auto-HSCT vs ChT). Auto-HSCT does not improve DFS in T-ALL with MRD after induction. In both auto-HSCT and only ChT groups with MRD persistence after induction have poor DFS (MRD-: 86% vs 81% and MRD+: 67% and 40%, respectively ChT vs auto-HSCT).

CONCLUSIONS: We didn't detect that auto-HCST could improve long-term result for T-cell ALL. ETP-phenotype is an independent poor prognostic factor. Addition of auto-HSCT as late high-dose consolidation for T-ALL with MRD persistence does not improve results of therapy.