Cord blood chimerism and relapse after haplo-cord transplantation

Leuk Lymphoma. 2017 Feb;58(2):288-297. doi: 10.1080/10428194.2016.1190970. Epub 2016 Jun 23.

Abstract

Haplo-cord stem cell transplantation combines the infusion of CD34 selected hematopoietic progenitors from a haplo-identical donor with an umbilical cord blood (UCB) graft from an unrelated donor and allows faster count recovery, with low rates of disease recurrence and chronic graft-versus-host disease (GVHD). But the contribution of the umbilical cord blood graft to long-term transplant outcome remains unclear. We analyzed 39 recipients of haplo-cord transplants with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), engrafted and in remission at 2 months. Median age was 66 (18-72) and all had intermediate, high, or very-high risk disease. Less than 20% UCB chimerism in the CD33 lineage was associated with an increased rate of disease recurrence (54% versus 11% p < 0.0001) and decrease in one year progression-free (20% versus 55%, p = 0.004) and overall survival (30% versus 62%, p = 0.02). Less than 100% UCB chimerism in the CD3 lineage was associated with increase rate of disease recurrence (46% versus 12%, p = 0.007). Persistent haplo-chimerism in the CD3 lineage was associated with an increased rate of disease recurrence (40% versus 15%, p = 0.009) Chimerism did not predict for treatment related mortality. The cumulative incidence of acute GVHD by day 100 was 43%. The cumulative incidence of moderate/severe chronic GVHD was only 5%. Engraftment of the umbilical cord blood grafts provides powerful graft-versus-leukemia (GVL) effects which protect against disease recurrence and is associated with low risk of chronic GVHD. Engraftment of CD34 selected haplo-identical cells can lead to rapid development of circulating T-cells, but when these cells dominate, GVL-effects are limited and rates of disease recurrence are high.

Keywords: Clinical results; leukemias and dysplasias; marrow and stem cell transplantation; myeloid; neoplasia; transplantation; umbilical cord blood.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Alleles
  • Cord Blood Stem Cell Transplantation* / adverse effects
  • Female
  • Graft vs Host Disease / diagnosis
  • Graft vs Host Disease / epidemiology
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / prevention & control
  • HLA Antigens / genetics
  • HLA Antigens / immunology
  • Haplotypes*
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Incidence
  • Leukemia, Myeloid, Acute / therapy
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care
  • Recurrence
  • Survival Analysis
  • Tissue Donors
  • Transplantation Chimera*
  • Transplantation, Homologous
  • Young Adult

Substances

  • HLA Antigens
  • Immunosuppressive Agents