Clofarabine Preconditioning followed by Allogeneic Transplant Using TBI and Post-Transplant Cyclophosphamide for Relapsed Refractory Leukemia

Int J Mol Sci. 2024 Jan 12;25(2):957. doi: 10.3390/ijms25020957.

Abstract

Acute myeloid leukemia patients with induction failure or relapsed refractory disease have minimal chance of achieving remission with subsequent treatments. Several trials have shown the feasibility of clofarabine-based conditioning in allogeneic stem cell transplants (allo-HSCT) for non-remission AML patients. Pre-transplant conditioning with clofarabine followed by reduced-intensity allo-HSCT has also demonstrated a potential benefit in those patients with human leukocyte antigen (HLA)-identical donors, but it is not commonly used in haploidentical and mismatched transplants. In this case report, we describe our experience of seven cases of non-remission AML who received clofarabine preconditioning followed by an allo-HSCT with PTCy. The 2-year overall survival and disease-free survival was 83.3% (95% confidence interval (CI): 27.3-97.9%) and 85.7% (95% CI: 33.4-97.9%). Median days of neutrophil and platelet recovery were 16 (range of 13-23) and 28 (range of 17-75), respectively. The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) at day 100 and chronic GVHD at 1-year showed 28.6% (95% CI: 8-74.2%) and 28.6% (95% CI: 3-63.9%), respectively. The two-year relapse rate was 14.3% (95% CI: 2.14-66.6%). One-year GVHD-free relapse-free survival (GFRS) at 1-year was 71.4% (95% CI: 25.8-92%). Our patients showed successful outcomes with clofarabine preconditioning to reduce the leukemic burden at the pre-transplant period followed by PTCy to reduce GVHD resulting in lower relapsed rate and better GFRS in these patients.

Keywords: AML: acute myeloid leukemia; Allo-HSCT: allogeneic transplant; Clo: clofarabine; PTCy: post-transplant cyclophosphamide.

Publication types

  • Case Reports

MeSH terms

  • Allografts
  • Clofarabine
  • Cyclophosphamide / therapeutic use
  • Graft vs Host Disease* / etiology
  • Graft vs Host Disease* / prevention & control
  • Humans
  • Leukemia, Myeloid, Acute* / therapy

Substances

  • Clofarabine
  • Cyclophosphamide

Grants and funding

The Arlene Witmer Memorial Fund for Bone Marrow Cancer Research, The John and Denise Gilliland Fund for the Cancer Genetics Program, G. R. Sponaugle Employee Cancer Research Fund, and Richard E. and Stephanie A. Ziegler Charitable Foundation Endowment in Hematology.