---
title: "Incidence and Risk Factors for CNS Relapse After Allogeneic HCT in Adult ALL"
id: "pubmed-42348785"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42348785"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42348785/"
doi: "10.1182/bloodadvances.2026020594"
published_at: "2026-09-22T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Incidence and Risk Factors for CNS Relapse After Allogeneic HCT in Adult ALL
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42348785
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42348785/)
- **DOI:** [10.1182/bloodadvances.2026020594](https://doi.org/10.1182%2Fbloodadvances.2026020594)
- **Published At:** 2026-09-22T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Multicenter retrospective study of 636 adults with acute lymphoblastic leukemia (ALL) who underwent first allogeneic hematopoietic cell transplantation (HCT) between 2011 and 2021 at Stanford Health Care or University of Washington/Fred Hutchinson Cancer Center. - The 1-year and 3-year cumulative incidences of post-HCT **CNS relapse** were 3% and 6%, respectively. - Three factors were associated with decreased risk of post-HCT CNS relapse: absence of CNS involvement before HCT, pre-HCT measurable residual disease (**MRD**) negativity, and receipt of total body irradiation (**TBI**)-based conditioning. - These three characteristics defined a composite low-risk group with significantly lower risk of post-HCT CNS relapse (hazard ratio [HR], 0.31; 95% confidence interval [CI], 0.15–0.68; P = .0032). - Post-HCT **CNS relapse** was strongly associated with shorter overall survival (OS) (HR, 7.33; 95% CI, 5.12–10.49; P < .0001), and earlier CNS relapse after HCT correlated with worse outcomes. - The authors propose that future studies should assess whether patients meeting the low-risk composite criteria may safely undergo de-escalation of CNS-directed interventions during HCT. - Study design: retrospective, multicenter, modern-era cohort (2011–2021). Detailed methods, patient demographics, and granular treatment or salvage data were not reported in the abstract and would require consulting the full text for additional specifics.
## Clinical Analysis & Structured Key Points
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more resources ](https://pubmed.ncbi.nlm.nih.gov/42348785/#linkout) Title & authors Abstract Conflict of interest statement Figures Similar articles References Publication types MeSH terms Related information LinkOut - more resources Multicenter Study Blood Adv Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Blood+Adv%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Blood+Adv%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42348785/) . 2026 Sep 22;10(18):6145-6152. doi: 10.1182/bloodadvances.2026020594. # Incidence and risk factors for CNS relapse in adult ALL after allogeneic hematopoietic cell transplantation [Catherine T Le](https://pubmed.ncbi.nlm.nih.gov/?term=Le+CT&cauthor_id=42348785)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42348785/#full-view-affiliation-1 "Department of Medicine, Stanford University School of Medicine, Stanford, CA."), [Amy Zhang](https://pubmed.ncbi.nlm.nih.gov/?term=Zhang+A&cauthor_id=42348785)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42348785/#full-view-affiliation-2 "Quantitative Sciences Unit, Department of Medicine, Stanford University School of Medicine, Stanford, CA."), [Rutu D Vyas](https://pubmed.ncbi.nlm.nih.gov/?term=Vyas+RD&cauthor_id=42348785)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42348785/#full-view-affiliation-3 "Division of Hematology and Oncology, Department of Medicine, University of Washington, Seattle, WA."), [Joanne Otani](https://pubmed.ncbi.nlm.nih.gov/?term=Otani+J&cauthor_id=42348785)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42348785/#full-view-affiliation-4 "Division of Blood and Marrow Transplantation & Cellular Therapy, Department of Medicine, Stanford University School of Medicine, Stanford, CA."), [Kathryn Russell](https://pubmed.ncbi.nlm.nih.gov/?term=Russell+K&cauthor_id=42348785)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42348785/#full-view-affiliation-3 "Division of Hematology and Oncology, Department of Medicine, University of Washington, Seattle, WA.")[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42348785/#full-view-affiliation-5 "Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA."), [Ryan D Cassaday](https://pubmed.ncbi.nlm.nih.gov/?term=Cassaday+RD&cauthor_id=42348785)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42348785/#full-view-affiliation-3 "Division of Hematology and Oncology, Department of Medicine, University of Washington, Seattle, WA.")[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42348785/#full-view-affiliation-5 "Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA."), [Lori Muffly](https://pubmed.ncbi.nlm.nih.gov/?term=Muffly+L&cauthor_id=42348785)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42348785/#full-view-affiliation-4 "Division of Blood and Marrow Transplantation & Cellular Therapy, Department of Medicine, Stanford University School of Medicine, Stanford, CA."), [Emily C Liang](https://pubmed.ncbi.nlm.nih.gov/?term=Liang+EC&cauthor_id=42348785)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42348785/#full-view-affiliation-3 "Division of Hematology and Oncology, Department of Medicine, University of Washington, Seattle, WA.")[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42348785/#full-view-affiliation-5 "Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA.") Affiliations Expand ### Affiliations * 1 Department of Medicine, Stanford University School of Medicine, Stanford, CA. * 2 Quantitative Sciences Unit, Department of Medicine, Stanford University School of Medicine, Stanford, CA. * 3 Division of Hematology and Oncology, Department of Medicine, University of Washington, Seattle, WA. * 4 Division of Blood and Marrow Transplantation & Cellular Therapy, Department of Medicine, Stanford University School of Medicine, Stanford, CA. * 5 Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA. * PMID: **42348785** * PMCID: [ PMC13583936 ](https://pmc.ncbi.nlm.nih.gov/articles/PMC13583936/) * DOI: [ 10.1182/bloodadvances.2026020594 ](https://doi.org/10.1182/bloodadvances.2026020594) Item in Clipboard Multicenter Study # Incidence and risk factors for CNS relapse in adult ALL after allogeneic hematopoietic cell transplantation Catherine T Le et al. Blood Adv. 2026. Show details Display options Display options Format Abstract PubMed PMID Blood Adv Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Blood+Adv%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Blood+Adv%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42348785/) . 2026 Sep 22;10(18):6145-6152. doi: 10.1182/bloodadvances.2026020594. ### Authors [Catherine T Le](https://pubmed.ncbi.nlm.nih.gov/?term=Le+CT&cauthor_id=42348785)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42348785/#short-view-affiliation-1 "Department of Medicine, Stanford University School of Medicine, Stanford, CA."), [Amy Zhang](https://pubmed.ncbi.nlm.nih.gov/?term=Zhang+A&cauthor_id=42348785)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42348785/#short-view-affiliation-2 "Quantitative Sciences Unit, Department of Medicine, Stanford University School of Medicine, Stanford, CA."), [Rutu D Vyas](https://pubmed.ncbi.nlm.nih.gov/?term=Vyas+RD&cauthor_id=42348785)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42348785/#short-view-affiliation-3 "Division of Hematology and Oncology, Department of Medicine, University of Washington, Seattle, WA."), [Joanne Otani](https://pubmed.ncbi.nlm.nih.gov/?term=Otani+J&cauthor_id=42348785)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42348785/#short-view-affiliation-4 "Division of Blood and Marrow Transplantation & Cellular Therapy, Department of Medicine, Stanford University School of Medicine, Stanford, CA."), [Kathryn Russell](https://pubmed.ncbi.nlm.nih.gov/?term=Russell+K&cauthor_id=42348785)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42348785/#short-view-affiliation-3 "Division of Hematology and Oncology, Department of Medicine, University of Washington, Seattle, WA.")[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42348785/#short-view-affiliation-5 "Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA."), [Ryan D Cassaday](https://pubmed.ncbi.nlm.nih.gov/?term=Cassaday+RD&cauthor_id=42348785)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42348785/#short-view-affiliation-3 "Division of Hematology and Oncology, Department of Medicine, University of Washington, Seattle, WA.")[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42348785/#short-view-affiliation-5 "Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA."), [Lori Muffly](https://pubmed.ncbi.nlm.nih.gov/?term=Muffly+L&cauthor_id=42348785)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42348785/#short-view-affiliation-4 "Division of Blood and Marrow Transplantation & Cellular Therapy, Department of Medicine, Stanford University School of Medicine, Stanford, CA."), [Emily C Liang](https://pubmed.ncbi.nlm.nih.gov/?term=Liang+EC&cauthor_id=42348785)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42348785/#short-view-affiliation-3 "Division of Hematology and Oncology, Department of Medicine, University of Washington, Seattle, WA.")[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42348785/#short-view-affiliation-5 "Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA.") ### Affiliations * 1 Department of Medicine, Stanford University School of Medicine, Stanford, CA. * 2 Quantitative Sciences Unit, Department of Medicine, Stanford University School of Medicine, Stanford, CA. * 3 Division of Hematology and Oncology, Department of Medicine, University of Washington, Seattle, WA. * 4 Division of Blood and Marrow Transplantation & Cellular Therapy, Department of Medicine, Stanford University School of Medicine, Stanford, CA. * 5 Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA. * PMID: **42348785** * PMCID: [ PMC13583936 ](https://pmc.ncbi.nlm.nih.gov/articles/PMC13583936/) * DOI: [ 10.1182/bloodadvances.2026020594 ](https://doi.org/10.1182/bloodadvances.2026020594) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID ## Abstract Relapse in the central nervous system (CNS) is a devastating outcome in acute lymphoblastic leukemia (ALL). Allogeneic hematopoietic cell transplantation (HCT) in ALL is reserved for patients with high-risk and/or relapsed/refractory disease. However, there is a paucity of data describing the incidence and factors associated with post-HCT CNS relapse in the modern era. In this multicenter retrospective study of adults with ALL who underwent first HCT between 2011 and 2021 at Stanford Health Care or University of Washington/Fred Hutchinson Cancer Center, we aimed to describe the incidence of post-HCT CNS relapse, factors associated with post-HCT CNS relapse, and the impact of CNS relapse on overall survival (OS). A total of 636 patients were included. The 1- and 3-year cumulative incidences of CNS relapse after HCT were 3% and 6%, respectively. Absence of CNS involvement before HCT, pre-HCT measurable residual disease negativity, and receipt of total body irradiation-based conditioning were significantly associated with decreased risk of post-HCT CNS relapse. These 3 characteristics defined a composite low-risk group that was associated with lower risk of post-HCT relapse (hazard ratio [HR], 0.31; 95% confidence interval [CI], 0.15-0.68; P = .0032). Post-HCT CNS relapse was significantly associated with shorter OS (HR, 7.33; 95% CI, 5.12-10.49; P< .0001); worse outcomes were seen with earlier post-HCT CNS relapse. Future studies will be needed to assess whether low-risk patients may benefit from de-escalation of CNS-directed interventions during HCT. © 2026 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Conflict-of-interest disclosure: E.C.L. reports honoraria from Eisai, Inc; consultancy fees from Glass Health; and divested stock options from Bristol Myers Squibb. R.D.C. reports honoraria from AstraZeneca, Autolus, Clear Pharmaceuticals, Kite/Gilead, Pfizer, and Takeda; consultancy/advisory fees from Amgen, Jazz, Kite/Gilead, Merck, Pfizer, Sana Biotechnology, and Servier; board/committee membership fees from Autolus and PeproMene Bio; and research funding from Amgen, Incyte, Jazz, and Kite/Gilead. The remaining authors declare no competing financial interests. The current affiliation for C.T.L. is Division of Hematology and Oncology, Department of Medicine, Weill Cornell Medicine, New York-Presbyterian/Weill Cornell Medical Center, New York, NY. ## Figures [ ![None](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4894/13583936/21a1154e4e8b/BLOODA_ADV-2026-020594-ga1.gif) ](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4894/13583936/5e48e4822d1e/BLOODA_ADV-2026-020594-ga1.webp) ** Graphical abstract ** ** Graphical abstract ** **Graphical abstract** [ ![Figure 1.](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4894/13583936/575e7ce48ea1/BLOODA_ADV-2026-020594-gr1.gif) ](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4894/13583936/819a92815b72/BLOODA_ADV-2026-020594-gr1.webp) ** Figure 1. ** **Cumulative incidence of CNS relapse.** … ** Figure 1. ** **Cumulative incidence of CNS relapse.** (A-B) Cumulative incidence of overall post-HCT CNS relapse,… **Figure 1.** **Cumulative incidence of CNS relapse.** (A-B) Cumulative incidence of overall post-HCT CNS relapse, including isolated and non-isolated relapse, (A) and isolated post-HCT CNS relapse (B). [ ![Figure 2.](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4894/13583936/52809b265cfa/BLOODA_ADV-2026-020594-gr2.gif) ](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4894/13583936/9a64d76b6033/BLOODA_ADV-2026-020594-gr2.webp) ** Figure 2. ** **Cumulative incidence of post-HCT CNS…** ** Figure 2. ** **Cumulative incidence of post-HCT CNS relapse by risk factors.** (A-C) Cumulative incidence of… **Figure 2.** **Cumulative incidence of post-HCT CNS relapse by risk factors.** (A-C) Cumulative incidence of post-HCT CNS relapse by CNS involvement before HCT (A), pre-HCT MRD status (B), and receipt of TBI-based conditioning (C). [ ![Figure 3.](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4894/13583936/094ef0184be2/BLOODA_ADV-2026-020594-gr3.gif) ](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4894/13583936/73da8084cb91/BLOODA_ADV-2026-020594-gr3.webp) ** Figure 3. ** **Cumulative incidence of post-HCT CNS…** ** Figure 3. ** **Cumulative incidence of post-HCT CNS relapse in low- vs high-risk group.** Low-risk group… **Figure 3.** **Cumulative incidence of post-HCT CNS relapse in low- vs high-risk group.** Low-risk group was defined by no CNS involvement before HCT, pre-HCT MRD negativity, and receipt of a TBI-based conditioning regimen. [ ![Figure 4.](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4894/13583936/1b86d3ad6892/BLOODA_ADV-2026-020594-gr4.gif) ](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4894/13583936/ae6e485e7d90/BLOODA_ADV-2026-020594-gr4.webp) ** Figure 4. ** **Smith-Zee plot of predicted OS…** ** Figure 4. ** **Smith-Zee plot of predicted OS probability in patients with CNS relapse at 1-year…** **Figure 4.** **Smith-Zee plot of predicted OS probability in patients with CNS relapse at 1-year post-HCT and in patients without CNS relapse at 1 year post-HCT.** [See this image and copyright information in PMC](https://pubmed.ncbi.nlm.nih.gov/42348785/) ## Similar articles * [ Implications and Management of Central Nervous System Involvement before Allogeneic
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