A comparison of long-term outcomes of donor lymphocyte infusions and tyrosine kinase inhibitors in patients with relapsed CML after allogeneic hematopoietic cell transplantation

Clin Lymphoma Myeloma Leuk. 2014 Feb;14(1):87-92. doi: 10.1016/j.clml.2013.09.010. Epub 2013 Oct 1.

Abstract

Background: Donor lymphocyte infusion (DLI) and tyrosine kinase inhibitors (TKIs) are the 2 standard treatment options in chronic myeloid leukemia (CML) that relapses after hematopoietic cell transplantation (HCT), but reports comparing long-term outcomes of these modalities are rare.

Patients and methods: A total of 46 patients were treated with either DLI (n = 28) or TKIs (n = 18) during a first relapse of CML after HCT between 1993 and 2012. The stage of relapse was the chronic phase in 37 patients and the advanced phase in 9 patients. All patients had myeloablative conditioning without T-cell depletion during HCT. The median interval between HCT and treatment for relapse was 34 (range, 2-197) months.

Results: At a median follow-up of 146 and 70 months, respectively, 32% of the DLI group and 33% of the TKI group had died. Six (21%) patients initially treated with DLI received TKIs during a second relapse. In multivariable analyses, DLI was associated with inferior overall survival (OS) (hazard ratio [HR], 37.4; 95% confidence interval [CI], 2.2-625.4; P = .01), shorter failure-free survival (FFS) (HR, 21.15; 95% CI, 1.8-251; P = .02), higher cumulative incidence of failure (CIF) (HR, 19.5; 95% CI, 1.6-236.5; P = .02), and increased incidence of treatment-induced graft vs. host disease (GVHD) (68% vs. 6%; P = .001).

Conclusion: TKIs appear better than DLI in chronic-phase relapses after myeloablative non-T-cell-depleted HCT. Outcomes were poor in advanced-phase relapses irrespective of treatment modality.

Keywords: Chronic myeloid leukemia; Donor lymphocyte infusion; Hematopoietic cell transplantation; Relapse; Tyrosine kinase inhibitor.

MeSH terms

  • Adult
  • Female
  • Granulocyte Precursor Cells / drug effects
  • Granulocyte Precursor Cells / metabolism
  • Hematopoietic Stem Cell Transplantation / methods
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / surgery
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / therapy*
  • Lymphocyte Transfusion / methods
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / surgery
  • Neoplasm Recurrence, Local / therapy*
  • Protein Kinase Inhibitors / therapeutic use*
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / metabolism
  • Transplantation Conditioning / methods

Substances

  • Protein Kinase Inhibitors
  • Protein-Tyrosine Kinases