Efficacy and Safety of CLAG-Based Sequential Conditioning Followed by Allogeneic Hematopoietic Stem Cell Transplantation in Non-Remission Relapsed or Refractory Acute Leukemia.

Abstract

Background: The optimal bridge-to-transplant strategy for patients with relapsed or refractory (R/R) acute leukemia who remain in non-remission (NR) is undefined. We evaluated the strategy-level use of CLAG (cladribine, cytarabine, and granulocyte colony-stimulating factor) as part of sequential conditioning, rather than as stand-alone salvage therapy, before allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Methods: This single-center retrospective case series included nine consecutive patients with R/R acute leukemia and bone marrow blasts ≥10% who underwent CLAG-based sequential conditioning followed by allo-HSCT between January 2021 and July 2023. Engraftment, transplant-related complications, non-relapse mortality, relapse, disease-free survival (DFS), and overall survival (OS) were evaluated descriptively; no control group was available.

Results: All nine patients achieved neutrophil and platelet engraftment and complete donor chimerism at approximately day +30. At a routine MFC/NGF analytical sensitivity of 10^-4, all patients had negative bone marrow assessments at day +30 and month +3; abnormal/leukemic cells subsequently re-emerged in all five patients who relapsed, at months 4.1-9.8. Seven of nine patients (77.8%) developed infections during neutropenia, including one severe pulmonary infection with probable Aspergillus that improved with antifungal therapy. GVHD occurred in 3/9 patients (33.3%), and hemorrhagic cystitis occurred in 2/9 (22.2%). No non-relapse mortality occurred. Five patients (55.6%) relapsed, and all five deaths were relapse-related. Estimated 2-year DFS and OS were both 44.4% (95% confidence interval, 13.6-71.9%).

Conclusion: In this highly selected cohort of nine NR patients, CLAG-based sequential conditioning permitted engraftment without non-relapse mortality, but infection and relapse remained frequent. These findings support technical feasibility only and should be regarded as exploratory and hypothesis-generating; efficacy or superiority cannot be established without larger prospective, multicenter, controlled studies.