Figure 4.
Evaluating recipient chimerism dynamics to identify a threshold of chimerism rate of change affecting the risk of leukemia relapse after allo-HCT. (A) Day-to-day fold change of chimerism proportions, calculated between 2 consecutive highly sensitive chimerism measurements after transplant in BMAs, PB-derived CD33+ myeloid cells, and PB-derived CD3+ T cells in the first 540 days after allo-HCT, excluding time points at which relapsed disease was already present and/or time points that self-fulfilled the relapse prophecy (see “Methods”). P values (B) and HRs (C) from the Cox proportional hazard regression (unadjusted and adjusted for confounding covariates) with chimerism fold change per day as a time-dependent covariate, computed over a range of thresholds incrementally increasing between 0.9-fold per day and 1.1-fold per day. (D) Probability (cumulative incidence) of relapse with follow-up in a 5-year window (1825 days) after allo-HCT for a representative chimerism fold change. Ticks represent individuals who were censored using the interval censoring approach. A generalized additive model was used to smooth fit the P values (blue line), which were truncated when HRs gave infinite CIs; the HR gray ribbon represents the 95% CI; n.max, the maximum number of patients at risk; adj, adjusted.

Evaluating recipient chimerism dynamics to identify a threshold of chimerism rate of change affecting the risk of leukemia relapse after allo-HCT. (A) Day-to-day fold change of chimerism proportions, calculated between 2 consecutive highly sensitive chimerism measurements after transplant in BMAs, PB-derived CD33+ myeloid cells, and PB-derived CD3+ T cells in the first 540 days after allo-HCT, excluding time points at which relapsed disease was already present and/or time points that self-fulfilled the relapse prophecy (see “Methods”). P values (B) and HRs (C) from the Cox proportional hazard regression (unadjusted and adjusted for confounding covariates) with chimerism fold change per day as a time-dependent covariate, computed over a range of thresholds incrementally increasing between 0.9-fold per day and 1.1-fold per day. (D) Probability (cumulative incidence) of relapse with follow-up in a 5-year window (1825 days) after allo-HCT for a representative chimerism fold change. Ticks represent individuals who were censored using the interval censoring approach. A generalized additive model was used to smooth fit the P values (blue line), which were truncated when HRs gave infinite CIs; the HR gray ribbon represents the 95% CI; n.max, the maximum number of patients at risk; adj, adjusted.

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