Chronic granulomatous disease (CGD) is an inborn error of immunity (IEI) caused by genetic mutations impairing function of the phagocyte NADPH oxidase, leading to frequent severe bacterial and fungal infections. While allogeneic donor hematopoietic stem cell transplant (alloHSCT) is curative, identifying factors predictive of post-transplant morbidity and mortality would be helpful to design individualized best management of patients. The immune deficiency and dysregulation activity score for IEI (IDDA) (1), developed to predict transplant outcome, is a weighted scoring system assessing pre-transplant disease burdens. We assessed whether the IDDA scoring system is a valid prognosticator for CGD patients by performing a retrospective analysis of the IDDA scoring of CGD patients who underwent alloHSCT at the National Institutes of Health (NIH) Clinical Center. The cohort received a busulfan- and alemtuzumab-based alloHSCT from 2016 to 2022. We calculated the IDDA, pre-transplant and preconditioning, for the total cohort of 40 patients with a median follow-up of 54 months (range 0.5–115). For IDDA, inpatient hospitalization days were counted during the time of 100 days before Day -14 of transplant. Acute graft-versus-host disease (GvHD) of grades III and IV, any grade of chronic GvHD, graft rejection early or late, graft failure, or death from any cause were defined as post-transplant events. We found a significant difference in the median IDDA scores between the survived and expired patients (survived = 13, range 6–56; expired = 30, range 21–37; p = 0.001). Also, median pre-transplant IDDA scores between patients who had no post-transplant event and those who had one differed (no event = 12, range 6–56; event = 29, range 12–37; p = 0.01). From this, we performed a receiver operating characteristic analysis to find the optimal threshold for low vs. high IDDA. We categorized the patients with IDDA below 20 as low IDDA patients; equal to or above 20 as high. The 3-year overall survival rate (OSR) in the low IDDA patients was 100% compared to 50% for the high (p 0.0001). The 3-year event-free survival (EFS) in the low IDDA patients was 92% compared to 57% for the high (p = 0.007). We have also determined that a C-reactive protein (CRP) level ≥100 mg/dL in the 45 days before initiation of transplant conditioning delineates high-risk patients from standard risk in our CGD transplants using our conditioning regimen. The 3-year OSR in the standard risk patients was 97% compared to 0% for the high risk (p 0.0001). The 3-year EFS in the standard risk patients was 91% compared to 0% for the high risk (p 0.0001). The R-squared value for IDDA vs. CRP was 0.34, indicating no significant correlation between the two values. Although IDDA scoring can predict outcomes of HSCT for CGD patients, we believe that CRP is as good if not a better predictor, and that given the ease of IDDA vs. CRP calculation, CRP is the more useful marker in CGD transplant patients.
Kim et al. (Tue,) studied this question.