CXCL9, an Early Inflammatory Marker As Prognostic Indicator Following Allogeneic Stem Cell Transplantation: A Single Prospective cohort study

Document Type

Conference Proceeding

Publication Date

2-1-2026

Publication Title

Transplant Cell Ther

Keywords

biological marker, granulocyte colony stimulating factor, methotrexate, acute graft versus host disease, acute leukemia, adult, allogeneic stem cell transplantation, cell differentiation, chronic graft versus host disease, chronic myelomonocytic leukemia, clinical article, cohort analysis, conference abstract, controlled study, drug combination, drug therapy, engraftment, female, follow up, graft versus host reaction, human, immune response, inflammation, lymphocyte migration, male, mobilization, special situation for pharmacovigilance

Abstract

Background: CXCL9, a cytokine involved in T-cell recruitment and differentiation, has been known to play a role in the immune response and lymphocyte migration to inflamed tissues. This interferon-inducible chemokine of the CXC family is also increased in GVHD. McCurdy and Luznik identified T conv recovery, when coupled with elevated CXCL9 at D28 predicted aGVHD development after PTCy in MAC haplo BM transplant setting. Whether the same paradigms apply to RIC regimens or PB-based SCT strategies, where process of G-CSF mobilization programs distinct immune pathways, or other GVHD prophylaxis regimens remains to be explored. Methods: This is a single center prospective cohort study. EASIX and CXCL9 were measured at D28 ±2 post allogeneic SCT. Results: 34 patients post PB allo SCT were enrolled in this study. There were 19 males and 15 females, with median age of 61.5 (27-74). HCTCI was > 3 in 47% of pts. 65% had acute leukemia, 18% had MDS/MPN/CMML, and 17% others. 29% received MAC and 71% received RIC. Donors were 58% MUD, 18% MRD, 18% MMUD and 6% haplo. Median donor age was 30 (22-56). GVHD prophylaxis was ABA based in 44%, PTCY based in 38%, Tacro MMF or MTX in 18%. No GF, median time to ANG engraftment was day 15, all pts received GCSF post-SCT. Median to follow up 429 days. only 2 patients had aGVHD, Grade III-IV by Day +180. CXCL9 was not significantly associated with Grade III-IV aGVHD (HR = 1.001, 95% CI: 0.998-1.00, p=0.56). 11 pts developed moderate or severe cGVHD at any time. Stratification by CXCL9 cutoff of 647 showed no clear separation between groups and Gray's test confirmed no significant difference in CIF curves (p=0.15 for cGVHD, p=0.07 for competing events). However, using the clinical reference cutoff of 647 pg/ml, patients with higher CXCL9 (>647) had significantly worse OS (log-rank test p value =0.02) Fig1. EASIX was not significant for OS (HR=1.04, 95% CI: 0.91-1.19, p=0.56) Conclusion: Despite heterogeneity in conditioning regimens and GVHD prophylaxis, in this small single center prospective cohort study of patients undergoing PB allogeneic SCT, elevated CXCL9 level (CXCL9>647 pg/ml), measured at Day +28, was significantly associated with worse OS. Importantly, several patients with CXCL9>647 pg/ml did not experience events, suggesting that CXCL9 may serve more as a risk stratifier rather than a deterministic predictor. EASIX or CXCL9 were not associated with severe acute GVHD or chronic GVHD, but we had very few events to make any conclusion. The trial is ongoing. (ClinicalTrials.gov ID: NCT05718791)

Volume

32

Issue

2

First Page

S469

Last Page

S470

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