Impact of cladribine, cytarabine, and G-CSF (CLAG) as a bridging therapy prior to allogeneic hematopoietic stem cell transplantation in relapsed or refractory acute myeloid leukemia

Ann Hematol. 2024 Jul;103(7):2463-2473. doi: 10.1007/s00277-024-05791-z. Epub 2024 May 17.

Abstract

The combination of cladribine, cytarabine, and G-CSF (CLAG) has exhibited robust synergistic anti-leukemia activity as an induction therapy (IT) in acute myeloid leukemia (AML). However, the impact of CLAG as a bridging therapy (BT) administered between IT and allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with relapsed or refractory (R/R) AML remains uncertain. In this retrospective study, we examined the efficacy of CLAG as a transitional strategy prior to allo-HSCT in R/R AML. We included 234 patients with R/R AML who received the modified busulfan plus cyclophosphamide conditioning regimen for allo-HSCT in our center during the past 6 years, performed a propensity-score matching analysis, partitioned them into four distinct cohorts, and further integrated them into the CLAG group and non-CLAG group based on response to IT and utilization of CLAG. Our cohorts encompassed 12 patients in Cohort A (modified composite complete remission (mCRc) after IT, CLAG), 31 in Cohort B (mCRc after IT, non-CLAG), 35 in Cohort C (non-complete remission (non-CR) after IT, CLAG), and 80 in Cohort D (non-CR after IT, non-CLAG). Intriguingly, among patients with non-CR status, the administration of CLAG correlated with a notably statistically diminished risk of relapse and improved survival at 2-year follow-up (Cohort C vs. Cohort D). Employing CLAG as a BT prior to allo-HSCT demonstrates substantial effectiveness, a relative degree of safety, and manageable toxicity in selected R/R AML cases.

Keywords: Allogeneic hematopoietic stem cell transplantation; Bridging therapy; Cladribine; Relapsed or refractory acute myeloid leukemia.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Allografts
  • Antineoplastic Combined Chemotherapy Protocols* / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Cladribine* / administration & dosage
  • Cladribine* / therapeutic use
  • Cytarabine* / administration & dosage
  • Cytarabine* / therapeutic use
  • Female
  • Granulocyte Colony-Stimulating Factor* / administration & dosage
  • Granulocyte Colony-Stimulating Factor* / therapeutic use
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Leukemia, Myeloid, Acute* / drug therapy
  • Leukemia, Myeloid, Acute* / therapy
  • Male
  • Middle Aged
  • Recurrence
  • Retrospective Studies
  • Transplantation Conditioning / methods
  • Transplantation, Homologous
  • Young Adult

Substances

  • Cytarabine
  • Granulocyte Colony-Stimulating Factor
  • Cladribine

Supplementary concepts

  • CLAG protocol