Hyper-CVAD-Based Stem Cell Microtransplant as Post-Remission Therapy in Acute Lymphoblastic Leukemia

Area of Science:

• Hematology
• Oncology
• Cellular Therapy

Background:

• Current post-remission strategies for acute lymphoblastic leukemia (ALL) primarily include multiagent chemotherapy and allogeneic stem cell transplant (allo-SCT).
• Cellular therapies are rarely incorporated into ALL post-remission treatment regimens.
• The efficacy of chemotherapy combined with mismatched granulocyte colony-stimulating factor mobilized peripheral blood mononuclear cell infusion (microtransplant, MST) is established in acute myeloid leukemia but remains undetermined in ALL.

Purpose of the Study:

• To evaluate the efficacy and safety of hyper-CVAD-based microtransplant (MST) as a post-remission strategy for patients with acute lymphoblastic leukemia (ALL).
• To assess overall survival (OS), leukemia-free survival (LFS), and relapse rates in ALL patients treated with MST.
• To identify prognostic factors influencing outcomes in ALL patients receiving MST.

Main Methods:

• A cohort of 48 patients with ALL received hyper-CVAD-based MST between July 2009 and January 2018.
• The study monitored for adverse events, including graft-versus-host disease (GVHD), and assessed survival outcomes (OS, LFS) and relapse rates.
• Donor chimerism/microchimerism was analyzed, and multivariate analyses were performed to identify prognostic factors.

Main Results:

• No instances of acute or chronic graft-versus-host disease were observed in patients undergoing MST.
• The 4-year overall survival (OS) and leukemia-free survival (LFS) were 62% and 35%, respectively, with a 4-year relapse rate of 65%.
• No patient experienced non-relapse mortality; adult patients showed a trend towards better 4-year LFS and lower relapse rates compared to adolescent and young adult patients.

Conclusions:

• Hyper-CVAD-based MST is a feasible and safe post-remission strategy for ALL patients, characterized by mild toxicity and no non-relapse mortality.
• The study identified key prognostic factors, including white blood cell count at diagnosis, hyper-CVAD cycles, B-cell phenotype, and infused CD34+ cell count, influencing patient outcomes.
• MST demonstrates potential as a valuable cellular therapy option in the management of ALL, warranting further investigation.