Harmonized immune recovery monitoring after HCT: evidence and practical guidance from the Westhafen Intercontinental Group

Allogeneic hematopoietic cell transplantation (allo-HCT) is a curative option for patients with high-risk malignancies and nonmalignant disorders. Long-term survival depends on robust immune reconstitution (IR), which governs overall immune homeostasis and risks of infection, graft-versus-host disease, and relapse. However, despite its centrality to posttransplant outcomes, IR is not consistently monitored across transplant centers, limiting ability to generate meaningful, comparable, and translatable data. This review synthesizes current knowledge on numerical and functional IR milestones after allo-HCT, with a primary focus on flow cytometry-based monitoring of key immune cell subsets. Importantly, early CD4+ T-cell recovery (achieving >50 cells per μL by day 100 after transplant), is supported by strong clinical evidence and correlates with improved outcomes. Although emerging data suggest that additional subsets (CD8+ T cells, natural killer cells, B cells, naïve and recent thymic emigrant T cells, and γδ T cells) may also influence clinical trajectories, further harmonized, multicenter studies are needed to validate prognostic relevance across transplant settings. We propose practical, evidence-based guidelines for IR monitoring, including recommended time points, preferred assays, and flow cytometry panel components. Additionally, we highlight modifiable factors (eg, immunosuppressive drug exposures, graft manipulation) offering interventional opportunities for influencing IR. Harmonized monitoring strategies will support robust correlation between IR and clinical outcomes, guide real-time risk stratification, and facilitate the development of targeted, individualized transplant approaches. Standardization efforts led by consortia and registries are essential for advancing knowledge and optimizing care. We provide a roadmap for implementing uniform IR monitoring to improve outcomes and quality of life for allo-HCT recipients.

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Publication Details

Journal
Blood Advances
Published
2025-09-03
DOI
https://doi.org/10.1182/bloodadvances.2025016915
Citations
2
Primary Topic
Hematopoietic Stem Cell Transplantation
Type
article
Field-Weighted Citation Impact
3.54

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article

Harmonized immune recovery monitoring after HCT: evidence and practical guidance from the Westhafen Intercontinental Group

Jaap Jan Boelens, Krzysztof Kałwak, Michael A. Pulsipher, Taymour M. Hammoudi et al.
2 citations
Blood Advances
Hematopoietic Stem Cell Transplantation
3.54
article

Harmonized immune recovery monitoring after HCT: evidence and practical guidance from the Westhafen Intercontinental Group

Jaap Jan Boelens, Krzysztof Kałwak, Michael A. Pulsipher, Taymour M. Hammoudi, Michael R. Verneris, Herbert Pichler, Jean‐Hugues Dalle, Dean A. Lee, Franco Locatelli, Silvia Nucera, Nirali N. Shah, Jochen Buechner, Antonio Pérez‐Martínez, John E. Levine, Caroline A. Lindemans, Susan E. Prockop, Roland Meisel, Giorgio Ottaviano, Kirk R. Schultz, Alice Bertaina, Selim Corbacioglu, Adriana Balduzzi, Marc Ansari, Stefan Nierkens, Julie‐An Talano, Sanjay Tewari, A. Lucas
article en
2 citations

Abstract

Allogeneic hematopoietic cell transplantation (allo-HCT) is a curative option for patients with high-risk malignancies and nonmalignant disorders. Long-term survival depends on robust immune reconstitution (IR), which governs overall immune homeostasis and risks of infection, graft-versus-host disease, and relapse. However, despite its centrality to posttransplant outcomes, IR is not consistently monitored across transplant centers, limiting ability to generate meaningful, comparable, and translatable data. This review synthesizes current knowledge on numerical and functional IR milestones after allo-HCT, with a primary focus on flow cytometry-based monitoring of key immune cell subsets. Importantly, early CD4+ T-cell recovery (achieving >50 cells per μL by day 100 after transplant), is supported by strong clinical evidence and correlates with improved outcomes. Although emerging data suggest that additional subsets (CD8+ T cells, natural killer cells, B cells, naïve and recent thymic emigrant T cells, and γδ T cells) may also influence clinical trajectories, further harmonized, multicenter studies are needed to validate prognostic relevance across transplant settings. We propose practical, evidence-based guidelines for IR monitoring, including recommended time points, preferred assays, and flow cytometry panel components. Additionally, we highlight modifiable factors (eg, immunosuppressive drug exposures, graft manipulation) offering interventional opportunities for influencing IR. Harmonized monitoring strategies will support robust correlation between IR and clinical outcomes, guide real-time risk stratification, and facilitate the development of targeted, individualized transplant approaches. Standardization efforts led by consortia and registries are essential for advancing knowledge and optimizing care. We provide a roadmap for implementing uniform IR monitoring to improve outcomes and quality of life for allo-HCT recipients.

Blood AdvancesVol. 9(23)
Intermountain Healthcare (US), University of Geneva (CH), Oslo University Hospital (NO), Boston Children's Hospital (US), National Institutes of Health (US), Nationwide Children's Hospital (US), Primary Children's Hospital (US), Royal Marsden NHS Foundation Trust (GB), Memorial Sloan Kettering Cancer Center (US), Palo Alto University (US), Medical College of Wisconsin (US), Université Paris Cité (FR), University of Utah (US), Hospital Universitario La Paz (ES), Huntsman Cancer Institute (US), University Medical Center Utrecht (NL), University Hospital Regensburg (DE), Wroclaw Medical University (PL), Assistance Publique – Hôpitaux de Paris (FR), European Society for Blood and Marrow Transplantation (NL), University Hospital of Geneva (CH), Center for Cancer and Blood Disorders (US), Azienda Ospedaliera San Gerardo (IT), Cancer Research Institute of the Slovak Academy of Sciences (SK), Royal Marsden Hospital (GB), Bambino Gesù Children's Hospital (IT), St Anna Children's Hospital (AT), Groupe Hospitalier Cochin - Port-Royal, Hôtel-Dieu, Broca - La Collégiale (FR), Hôpital Robert-Debré (FR), Princess Máxima Center (NL), Tisch Hospital (US), Stanford Medicine (US), National Cancer Institute (US), Center for Cancer Research (US), Boston Children's Museum (US), Istituti di Ricovero e Cura a Carattere Scientifico (IT), BC Children's Hospital (CA), European Society for Blood and Marrow Transplantation (FR), Dana-Farber/Boston Children's Cancer and Blood Disorders Center (US), St. Anna Children's Cancer Research Institute, Heinrich Heine University Düsseldorf (DE), University of Colorado Anschutz Medical Campus (US), University of Regensburg (DE), Geneva College (US), University of Milano-Bicocca (IT), Stanford University (US), Icahn School of Medicine at Mount Sinai (US)
U.S. Department of Health and Human Services, Bristol-Myers Squibb, Sanofi, Celgene, Memorial Sloan-Kettering Cancer Center, Les Laboratories Pierre Fabre, Atara Biotherapeutics, bluebird bio, Swedish Orphan Biovitrum, Medac, National Institutes of Health, National Cancer Institute, NIH Clinical Center
Openalex Percentile: Top 7%
Hematopoietic Stem Cell Transplantation
3.54
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