{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T15:22:26Z","timestamp":1772464946965,"version":"3.50.1"},"reference-count":57,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T00:00:00Z","timestamp":1772409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Linda Perry Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2013100 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\u2212 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.<\/jats:p>","DOI":"10.3390\/ijms27052338","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T14:06:56Z","timestamp":1772460416000},"page":"2338","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["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"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2417-3120","authenticated-orcid":false,"given":"Catherine M.","family":"Njeru","sequence":"first","affiliation":[{"name":"Michael Cuccione Childhood Cancer Research Program, British Columbia Children\u2019s Hospital Research Institute, University of British Columbia, Vancouver, BC V5Z 4H4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8688-3873","authenticated-orcid":false,"given":"Bernard","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Statistics, Centre for Molecular Medicine and Therapeutics, British Columbia Children\u2019s Hospital, University of British Columbia, Vancouver, BC V5Z 4H4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sayeh","family":"Abdossamadi","sequence":"additional","affiliation":[{"name":"Michael Cuccione Childhood Cancer Research Program, British Columbia Children\u2019s Hospital Research Institute, University of British Columbia, Vancouver, BC V5Z 4H4, Canada"},{"name":"Department of Pediatrics, British Columbia Children\u2019s Hospital Research Institute, University of British Columbia, 950 West 28th Ave, Rm 3102, Vancouver, BC V5Z 4H4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alima","family":"Suleimenova","sequence":"additional","affiliation":[{"name":"Michael Cuccione Childhood Cancer Research Program, British Columbia Children\u2019s Hospital Research Institute, University of British Columbia, Vancouver, BC V5Z 4H4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen Dolores","family":"De Luca","sequence":"additional","affiliation":[{"name":"Michael Cuccione Childhood Cancer Research Program, British Columbia Children\u2019s Hospital Research Institute, University of British Columbia, Vancouver, BC V5Z 4H4, Canada"},{"name":"Department of Hematology\/Oncology, Cell and Gene Therapy, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Bambino Ges\u00f9 Children\u2019s Hospital, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vaishnavi","family":"Parthasarathy","sequence":"additional","affiliation":[{"name":"Allen Institute for Immunology, Seattle, WA 98109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1673-467X","authenticated-orcid":false,"given":"Laura M.","family":"Sly","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, British Columbia Children\u2019s Hospital Research Institute, University of British Columbia, 950 West 28th Ave, Rm 3102, Vancouver, BC V5Z 4H4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregor S. D.","family":"Reid","sequence":"additional","affiliation":[{"name":"Michael Cuccione Childhood Cancer Research Program, British Columbia Children\u2019s Hospital Research Institute, University of British Columbia, Vancouver, BC V5Z 4H4, Canada"},{"name":"Department of Pediatrics, British Columbia Children\u2019s Hospital Research Institute, University of British Columbia, 950 West 28th Ave, Rm 3102, Vancouver, BC V5Z 4H4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chia Huan","family":"Ng","sequence":"additional","affiliation":[{"name":"Starship Blood and Cancer Centre, Starship Children\u2019s Hospital, Auckland 1142, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kirk R.","family":"Schultz","sequence":"additional","affiliation":[{"name":"Michael Cuccione Childhood Cancer Research Program, British Columbia Children\u2019s Hospital Research Institute, University of British Columbia, Vancouver, BC V5Z 4H4, Canada"},{"name":"Department of Pediatrics, British Columbia Children\u2019s Hospital Research Institute, University of British Columbia, 950 West 28th Ave, Rm 3102, Vancouver, BC V5Z 4H4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1007\/s11899-019-00502-2","article-title":"Hematopoietic Stem Cell Transplantation in Pediatric Acute Lymphoblastic Leukemia","volume":"14","author":"Merli","year":"2019","journal-title":"Curr. 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