Haploidentical transplantation for acute myeloid leukemia patients with minimal/measurable residual disease at transplantation

Am J Hematol. 2019 Dec;94(12):1382-1387. doi: 10.1002/ajh.25647. Epub 2019 Oct 21.

Abstract

There have been conflicting results regarding the impact of minimal/measurable disease at transplant on acute myeloid leukemia (AML) outcomes after haploidentical transplantation (haplo-SCT). We assessed the impact of pre-transplant disease status on post-transplant outcomes of 143 patients treated with haplo-SCT using fludarabine-melphalan (FM) conditioning and post-transplant cyclophosphamide (PTCy). With a median follow-up of 29 months, the two-year PFS for all patients was 41%. Compared to patients in complete remission (CR) at transplant, those with active disease (n = 29) and CR with incomplete count recovery (CRi) (n = 39) had worse PFS. They had hazard ratios (HR) of 3.5 (95% CI: 2.05-6.1; P < .001) and 2.3 (95% CI: 1.3-3.9; P = .002), respectively. Among patients who were in CR at transplant, there were no differences in PFS between those who had minimal residual disease (MRD) positive (n = 24), and MRD negative (n = 41) (HR 1.85, 95%CI: 0.9-4.0; P = .1). In multivariable analysis for patients in CR, only age was predictive for outcomes, while MRD status at transplant did not influence the treatment outcomes. Our findings suggest that haplo-SCT with FM conditioning regimen and PTCy-based GVHD prophylaxis has a protective effect, and may potentially abrogate the inferior outcomes of MRD positivity for patients with AML. Patients with positive MRD may benefit from proceeding urgently to a haplo-SCT, as this does not appear to negatively impact transplant outcomes.

MeSH terms

  • Adult
  • Aged
  • Bone Marrow / pathology
  • Disease-Free Survival
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Leukemia, Myeloid, Acute / pathology
  • Leukemia, Myeloid, Acute / therapy*
  • Male
  • Melphalan / therapeutic use
  • Middle Aged
  • Neoplasm, Residual
  • Progression-Free Survival
  • Proportional Hazards Models
  • Remission Induction
  • Retrospective Studies
  • Transplantation Conditioning
  • Transplantation, Haploidentical*
  • Treatment Outcome
  • Vidarabine / analogs & derivatives
  • Vidarabine / therapeutic use
  • Young Adult

Substances

  • Vidarabine
  • fludarabine
  • Melphalan