NextGen 2024: Bone Marrow Transplantation (BMT) Session Part 3
NextGen 2024: Bone Marrow Transplantation (BMT) Session Part 3
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Key Insights
- Multiple approaches exist to assess immune recovery and reconstitution, and combining them can optimize outcomes.
- For rare diseases, standardizing immune reconstitution evaluation after BMT is crucial for therapeutic efficacy.
- Poor outcomes post-BMT in JIA patients are associated with infections, macrophage activation syndrome, and disease relapse, all linked to poor immune reconstitution.
- Novel methods are needed to evaluate immune reconstitution in JIA BMT, as current methods like chimerism and flow cytometry are inadequate.
- Evaluation should prioritize innate immune activity, regulatory and effector T cells, thymic function, B cells, plasma cells, and the influence of donor HLA-haplotype and phenotype.
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Explore the complexities of immune recovery after bone marrow transplant, particularly in the context of Systemic Juvenile Idiopathic Arthritis (SJIA). This explores current measurement techniques, limitations, and the importance of innovative approaches for improved patient outcomes.
#sjiafoundation
#sjia
#bmt
#curesjia
NextGen 2024: Bone Marrow Transplantation (BMT) Session Part 3
@SJIA_Foundation3 months ago
Immune Reconstitution after Bone Marrow Transplant
NextGen Therapies in SJIA, Still's & MAS Conference
November 14, 2024 Jim Connelly, MD
Vanderbilt University Medical Center
- o Focus in BMT has been on T (transplanter) cells and mostly on CD4+ recovery
- o Advantages: Basic flow cytometry available at most centers; sorted cells can be used to evaluate split chimerism
- o Disadvantages: Limited ability to look at early (
- o Advantages: Can evaluate memory response to specific antigens for decisions on viral monitoring/prophylaxis
- o Disadvantages: Less available at many centers; Response depends on exposure to antigen of interest
- · Transcriptome (gene expression through RNA analysis) o Advantages: Provides large amount of gene expression data at the single cell level; identify donor versus recipient at the single cell level o Disadvantages: Expensive (difficult to do across multiple time points); Not all inflammation is bad
- · Secretome (cytokines, chemokines)
- o Advantages: Inexpensive; Can be conducted before cellular recovery (
- o Disadvantages: Not all cytokines/chemokine measurements are sensitive (IL1); Certain cytokines/chemokines may be applicable to only particular diseases (IL18, CXCL9)
- o Advantages: Predictive of relapse in malignancy and disease remission in some non-malignant disorders
- o Disadvantages: May not be as predictive of disease remission in immune dysregulatory disorders; Usually limited to myeloid (CD33) and T (CD3) cells
- o Almost all analyses have been done on recipient peripheral blood with focus on T-(transplanter)-cell
- o Static analyses for dynamic recovery
- o Inability to measure donor versus recipient IR via non-genetic means
- o Studies conducted on large cohorts with variable disease and transplant approaches
- o Large IR variability complicates analysis in rare diseases with small patient numbers
- · Multiple ways to evaluate immune recovery and reconstitution and combining modalities can maximize success and minimize deficiencies of each strategy
- · For rare diseases, it is imperative to harmonize IR evaluation post-BMT amongst a variable patient population to assess therapeutic efficacy
- · Poor outcomes in patients with JIA post-BMT are highlighted by significant infectious disease, macrophage activation syndrome, and relapsed disease, all potential consequences of poor IR
- · For JIA BMT we need to develop novel ways to look at IR given that current methods (peripheral blood, chimerism, flow cytometry) are inadequate
- o Evaluation should focus on innate activity (secretome, monocyte/macrophage*), regulatory and effector T cells, thymic function, B cells and plasma cells*, and impact of donor HLA-haplotype and phenotype on outcomes *Higher resistance to conditioning therapy
Immune Recovery after BMT

Measures of Immune Reconstitution (IR)
· Immune cell phenotyping
· Immune cell function
Measures of Immune Reconstitution (IR)
Measures of Immune Reconstitution (IR)
· Chimerism (donor versus recipient)
· Limitations on studies to date:
Importance of T-cell (CD4+), B-cell Recovery
Non-Relapse Mortality (NRM) and chronic (c)GVHD based on CD4+ T-cell (>57 cells/µL), B-cell (>35 cells/µL) Recovery at D+100


Immune Recovery in JIA
T-cell Recovery after Pediatric BMT Segregated by Conditioning Serotherapy
Lymphocyte Recovery after BMT for JIA

Impact of Chimerism on BMT Outcomes in JIA

Macrophage (rheuMatologist) Cell
Murine Alveolar Macrophage (AM) Recovery after Congenic BMT with Different Conditioning Regimens

Summary of BMT and JIA BMT IR

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