Summary table of evidence and recommendations for IR monitoring and harmonization
| Immune system component or function . | Prognostic outcome: overall quality of evidence∗,†,‡ . | Preferred assay . | Recommended intervals or milestones for assay§ . | Strength of recommendationǁ (application)¶ . | |||||
|---|---|---|---|---|---|---|---|---|---|
| OS . | TRM/NRM . | DFS/EFS/RFS . | aGVHD . | cGVHD . | VR . | ||||
| CD4+ T cells | 1 | 1 | 2 | 1 | 1 | 2 | Flow cytometry | IAt months: 1, 2, 3, 6, 9, 12, 18, 24 | A (clinical) |
| CD8+ T cells | 2 | 2 | 2 | 2 | 2 | 2 | B (clinical) | ||
| CD19+ B cells | 2 | 2 | — | 2 | 2 | — | B (clinical) | ||
| CD56+CD16-/+ NK cells | 1 | 2 | 2 | 2 | — | 2 | B (clinical) | ||
| RTEs, naïve T cells, TRECs | 2 | 2 | 2 | 2 | 2 | 2 | Flow cytometry (sequencing) | MWith CD4 T-cell reconstitution (CD4 of >200 cells per μL), until normal | B (research) |
| Treg cells | 2 | 2 | — | 2 | 2 | — | Flow cytometry | MWith CD4 T-cell reconstitution (CD4 of >200 cells per μL), until normal | B (research) |
| γδ T cells | — | — | 2 | — | — | — | Flow cytometry | Not established | C (research) |
| Vaccine response | — | — | — | — | — | — | Antibody titers | MAfter revaccination | C (clinical) |
| Isohemagglutinin switch | — | — | — | — | — | — | Serological titer | MWith B-cell reconstitution (>25-50 cells per μL), stop at detection | C (clinical) |
| IgG production | — | — | — | — | — | — | Quantitative immunoturbidimetry | IEvery 2-4 weeks until IVIG independence | C (clinical) |
| IgM and IgA production | — | — | — | — | — | — | Quantitative immunoturbidimetry | MWith B-cell reconstitution (>25-50 cells per μL), until normal | C (clinical) |
| NK cytolysis and cytokine production | 2 | 3 | 3 | — | — | — | Chromium release assay, flow cytometry | MWith NK cell reconstitution and off immunosuppression, until normal | C (research) |
| T-cell proliferative and cytokine responses | 2 | — | — | — | — | 3 | Flow cytometry | MWith T-cell reconstitution (CD4 of >200 cells per μL) and off immunosuppression, until normal | C (research) |
| TCR diversity | — | — | 3 | — | — | 3 | Next-generation sequencing | MWith evidence of thymopoiesis (by RTEs/TRECs), until normal | NR (research) |
| Immune system component or function . | Prognostic outcome: overall quality of evidence∗,†,‡ . | Preferred assay . | Recommended intervals or milestones for assay§ . | Strength of recommendationǁ (application)¶ . | |||||
|---|---|---|---|---|---|---|---|---|---|
| OS . | TRM/NRM . | DFS/EFS/RFS . | aGVHD . | cGVHD . | VR . | ||||
| CD4+ T cells | 1 | 1 | 2 | 1 | 1 | 2 | Flow cytometry | IAt months: 1, 2, 3, 6, 9, 12, 18, 24 | A (clinical) |
| CD8+ T cells | 2 | 2 | 2 | 2 | 2 | 2 | B (clinical) | ||
| CD19+ B cells | 2 | 2 | — | 2 | 2 | — | B (clinical) | ||
| CD56+CD16-/+ NK cells | 1 | 2 | 2 | 2 | — | 2 | B (clinical) | ||
| RTEs, naïve T cells, TRECs | 2 | 2 | 2 | 2 | 2 | 2 | Flow cytometry (sequencing) | MWith CD4 T-cell reconstitution (CD4 of >200 cells per μL), until normal | B (research) |
| Treg cells | 2 | 2 | — | 2 | 2 | — | Flow cytometry | MWith CD4 T-cell reconstitution (CD4 of >200 cells per μL), until normal | B (research) |
| γδ T cells | — | — | 2 | — | — | — | Flow cytometry | Not established | C (research) |
| Vaccine response | — | — | — | — | — | — | Antibody titers | MAfter revaccination | C (clinical) |
| Isohemagglutinin switch | — | — | — | — | — | — | Serological titer | MWith B-cell reconstitution (>25-50 cells per μL), stop at detection | C (clinical) |
| IgG production | — | — | — | — | — | — | Quantitative immunoturbidimetry | IEvery 2-4 weeks until IVIG independence | C (clinical) |
| IgM and IgA production | — | — | — | — | — | — | Quantitative immunoturbidimetry | MWith B-cell reconstitution (>25-50 cells per μL), until normal | C (clinical) |
| NK cytolysis and cytokine production | 2 | 3 | 3 | — | — | — | Chromium release assay, flow cytometry | MWith NK cell reconstitution and off immunosuppression, until normal | C (research) |
| T-cell proliferative and cytokine responses | 2 | — | — | — | — | 3 | Flow cytometry | MWith T-cell reconstitution (CD4 of >200 cells per μL) and off immunosuppression, until normal | C (research) |
| TCR diversity | — | — | 3 | — | — | 3 | Next-generation sequencing | MWith evidence of thymopoiesis (by RTEs/TRECs), until normal | NR (research) |
DFS, disease-free survival; EFS, event-free survival; NR, not recommended; VR, viral reactivations.
Taxonomy adopted from Ebell et al.123
Good quality (level 1): systematic review/meta-analysis of good-quality cohort studies; or prospective cohort study with good follow-up.
Limited quality (level 2): systematic review/meta-analysis of lower-quality cohort studies or with inconsistent results; or retrospective cohort study or prospective cohort study with poor follow-up; or case-control study; or case series.
Other evidence (level 3): consensus guidelines; extrapolations from bench research; usual practice; opinion; disease-oriented evidence (intermediate or physiological outcomes only); or case series for studies of diagnosis, treatment, prevention, or screening.
I, intervals to perform regular measurement; M, milestone to achieve before first measurement, then regularly at serial time points (eg, 6, 9, 12, 18, and 24 mo).
A, recommendation based on consistent and good-quality patient-oriented evidence; B, recommendation based on inconsistent or limited-quality patient-oriented evidence; C, recommendation based on consensus, usual practice, disease-oriented evidence, case series for studies of screening, and/or opinion; NR, no recommendation.
Clinical: readily performed in most clinical settings; Research: readily performed in centralized, clinical, and/or research laboratories, not sufficiently validated for widespread use.