Language
English
Publication Date
7-25-2023
Journal
Blood Advances
DOI
10.1182/bloodadvances.2022009478
PMID
37042921
PMCID
PMC10368780
PubMedCentral® Posted Date
4-13-2023
PubMedCentral® Full Text Version
Post-print
Abstract
Overall survival after reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT) using alemtuzumab, fludarabine, and melphalan is associated with high rates of mixed chimerism (MC) and secondary graft failure (GF). We hypothesized that peritransplantation alemtuzumab levels or specific patterns of inflammation would predict these risks. We assessed samples from the Bone Marrow Transplant Clinical Trials Network 1204 (NCT01998633) to study the impact of alemtuzumab levels and cytokine patterns on MC and impending or established secondary GF (defined as donor chimerism < 5% after initial engraftment and/or requirement of cellular intervention). Thirty-three patients with hemophagocytic lymphohistiocytosis (n = 25) and other IEIs (n = 8) who underwent HCTs with T-cell–replete grafts were included. Patients with day 0 alemtuzumab levels ≤0.32 μg/mL had a markedly lower incidence of MC, 14.3%, vs 90.9% in patients with levels >0.32 μg/mL (P = .008). Impending or established secondary GF was only observed in patients with day 0 alemtuzumab levels >0.32 μg/mL (P = .08). Unexpectedly, patients with impending or established secondary GF had lower CXCL9 levels. The cumulative incidence of impending or established secondary GF in patients with a day 14+ CXCL9 level ≤2394 pg/mL (day 14+ median) was 73.6% vs 0% in patients with a level >2394 pg/mL (P = .002). CXCL9 levels inversely correlated with alemtuzumab levels. These data suggest a model in which higher levels of alemtuzumab at day 0 deplete donor T cells, inhibit the graft-versus-marrow reaction (thereby suppressing CXCL9 levels), and adversely affect sustained engraftment in the nonmyeloablative HCT setting. This trial was registered at www.clinicaltrials.gov as #NCT01998633
Keywords
Humans, Alemtuzumab, Antibodies, Monoclonal, Humanized, Melphalan, Hematopoietic Stem Cell Transplantation, Tissue Donors, Chemokine CXCL9
Published Open-Access
yes
Recommended Citation
Geerlinks, Ashley V; Scull, Brooks; Krupski, Christa; et al., "Alemtuzumab and CXCL9 Levels Predict Likelihood of Sustained Engraftment After Reduced-Intensity Conditioning HCT" (2023). Faculty, Staff and Students Publications. 2006.
https://digitalcommons.library.tmc.edu/baylor_docs/2006
Graphical Abstract
BLOODA_ADV-2022-009478-gr1.jpg (170 kB)
Figure 1