# Early Marrow Microenvironment Immune Patterns After Hematopoietic Stem Cell Transplant in Pediatric Acute Lymphoblastic Leukemia Are Associated with Later Development of Chronic GvHD and Relapse

## TL;DR

This study finds early immune patterns in bone marrow after stem cell transplants in children with leukemia that may predict later complications like chronic GvHD or relapse.

## Contribution

The study identifies specific immune signatures in early marrow samples that correlate with later clinical outcomes after HSCT in pediatric ALL.

## Key findings

- cGvHD was linked to ER stress in B cells and specific neutrophil and T cell populations.
- ALL relapse was associated with macrophage and T cell markers indicating immune evasion.
- Early marrow immune signatures may serve as potential biomarkers to distinguish GvL from cGvHD.

## Abstract

Hematopoietic stem cell transplant (HSCT) is a curative therapy for acute lymphoblastic leukemia (ALL), but its success is limited by chronic graft-versus-host disease (cGvHD) and disease relapse. A central challenge is uncoupling the graft-versus-leukemia (GvL) effect from cGvHD. Early changes in the bone marrow microenvironment following HSCT may offer a predictive window into these divergent outcomes. We conducted a retrospective, single-center, exploratory study on 14 pediatric ALL HSCT patients. Applying single-cell antibody-sequencing (AbSeq) on archived bone marrow aspirates collected 60–100 days post-HSCT, we evaluated immune patterns associated with the development of cGvHD or ALL relapse after day 114. cGvHD after day 114 was associated with upregulation of the endoplasmic reticulum (ER) stress transcription factor XBP1 in transitional B cell and IgM memory B cell populations, a minclehighPD1− neutrophil population, and exhausted LAG3+ effector memory T cells (TEM). ALL relapse after day 114 was associated with higher CD22, CD24, and ARG1 expression in M(IL-4)-like macrophages and exhausted TIGIT+ TEM. Results from this exploratory study suggest that marrow immune signatures of B cell ER stress preceding later development of cGvHD and macrophage-mediated immune evasion preceding relapse may potentially be early biomarkers for separating GvL from cGvHD in ALL HSCT. Validation with larger cohorts is warranted.