Impact of graft-versus-host disease and graft-versus-leukemia effect based on minimal residual disease in Philadelphia chromosome-positive acute lymphoblastic leukemia

Br J Haematol. 2020 Jul;190(1):84-92. doi: 10.1111/bjh.16540. Epub 2020 Mar 2.

Abstract

The impacts of graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effect might differ depending on minimal residual disease (MRD). Therefore, we examined 1,022 recipients who underwent their first allogeneic hematopoietic stem cell transplantation (HSCT) for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL) in first complete remission. MRD status at HSCT was negative in 791 (77·4%) and positive in 231 (22·6%). The impact of GVHD as a time-dependent covariate on transplant outcomes were analyzed while adjusting for other possible variables. Mild acute GVHD [hazard ratio (HR), 0·90; 95% confidence interval (CI), 0·70-1·16; P = 0·901] and chronic GVHD (HR, 0·82, 95% CI, 0·58-1·14; P = 0·238) were not significantly associated with overall mortality, whereas severe acute GVHD (HR, 2·26, 95% CI, 1·64-3·11; P < 0·001) resulted in inferior overall survival due to high non-relapse mortality. Moreover, even in the subgroup analyses stratified according to MRD status, acute and chronic GVHD were not significantly associated with better overall survival. Therefore, less intensive GVHD prophylaxis to achieve a GVL effect is not recommended for Ph-positive ALL.

Keywords: Philadelphia chromosome-positive acute lymphoblastic leukemia; graft-versus-host disease; graft-versus-leukemia effect; minimal residual disease; tyrosine kinase inhibitor.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Female
  • Graft vs Host Disease / immunology*
  • Graft vs Leukemia Effect / immunology*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm, Residual / complications*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / complications*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Young Adult