G-CSF administration prior to donor lymphocyte apheresis promotes anti-leukaemic effects in allogeneic HCT patients.
Corina SchneidawindSimona JahnkeIrmtraud Schober-MelmsMichael SchummRupert HandgretingerChristoph FaulLothar KanzWolfgang BethgeDominik SchneidawindPublished in: British journal of haematology (2019)
Donor lymphocyte infusion (DLI) is an effective method to establish full donor chimerism or to prevent and treat relapse after allogeneic haematopoietic cell transplantation (allo-HCT). Usually, DLIs are collected from naïve donors as steady-state lymphocytes. When donor lymphocytes are collected during stem cell apheresis, donors are pre-treated with granulocyte colony-stimulating factor (G-CSF). However, the impact of G-CSF stimulation and the resulting composition of DLIs on beneficial anti-leukaemic responses and survival remain elusive. Therefore, we performed a retrospective analysis to evaluate the role of G-CSF-DLIs: 44 patients received either steady-state DLIs or G-CSF-DLIs to prevent and treat relapse or establish full donor chimerism after allo-HCT. The G-CSF-DLI patient cohort showed an improved conversion to full donor chimerism and a lower cumulative incidence of relapse or disease progression without a significantly increased cumulative incidence of graft-versus-host disease (GVHD). CD34+ cells, monocytic myeloid-derived suppressor cells and monocytes as well as donor age and the subsequent occurrence of chronic GVHD were identified as risk factors that significantly improve overall survival after DLI administration. In conclusion, our data suggest that administration of G-CSF-DLIs results in graft-versus-leukaemia effects without exacerbating GVHD, therefore, improving survival after DLIs.
Keyphrases
- risk factors
- allogeneic hematopoietic stem cell transplantation
- peripheral blood
- cell cycle arrest
- stem cells
- end stage renal disease
- newly diagnosed
- ejection fraction
- induced apoptosis
- stem cell transplantation
- free survival
- cerebrospinal fluid
- prognostic factors
- acute myeloid leukemia
- cell therapy
- risk assessment
- patient reported outcomes
- cell proliferation
- oxidative stress
- acute lymphoblastic leukemia
- cell death
- dendritic cells
- artificial intelligence
- pi k akt
- drug induced
- data analysis
- recombinant human