NIH response criteria measures are associated with important parameters of disease severity in patients with chronic GVHD

Abstract

Lack of standardized criteria measuring therapeutic response remains an obstacle to the development of better treatments for chronic GVHD (cGVHD). This cross-sectional prospective study examined the concurrent and predictive validity of 18 clinician-reported ('Form A') and 8 patient-reported ('Form B') response measures proposed by NIH criteria. Concurrent parameters of interest were NIH global score, cGVHD activity, Lee symptom score and SF36 PCS. Patient cohort included 193 adults with moderate-to-severe cGVHD. Measures associated with the highest number of outcomes were lung function score (LFS), 2-min walk, grip strength, 4-point health-care provider (HCP) and patient global scores, 11-point clinician- and patient-reported global symptom severity scores, and Karnofsky performance score (KPS). Measures associated with survival in univariate analyses led to a Cox model containing skin erythema, LFS, KPS, eosinophil count and interval from cGVHD diagnosis to enrollment as jointly associated with survival. In conclusion, 4-point HCP and patient global scores and 11-point clinician- and patient-reported global symptom severity scores are associated with the majority of concurrent outcomes. Skin erythema is a potentially reversible sign of cGVHD that is associated with survival. These results define a subset of measures that should be prioritized for evaluation in future studies.

Conflict of interest statement

CONFLICT OF INTEREST

The authors declare no conflict of interest.

Figures

Figure 1.

Clinician-reported measures and their association with four concurrent outcomes of interest reflective of cGVHD disease burden. Univariate comparison of clinician measures with four outcomes. For the dichotomous outcomes, P values were measured presented in the following way; P <0.001 corresponded to a highly significant association indicated with solid blocks, and P <0.05 corresponded to a trend toward significance as represented by the faded blocks. For the continuous outcomes, r values were measured and presented as follows; r>0.5 corresponded to a strong to moderately strong correlation as indicated in solid blocks and r = 0.3 to 0.5 corresponded to a weak to moderately strong correlation as indicated by faded blocks. Blocks that are white represent clinician- or patient-reported parameters where there was a weak or absent association with the clinical outcomes of interest. ALT = alanine aminotransferase; NIH = National Institutes of Health; PCS = physical component scale; SF36 = short-form 36.

Figure 2.

Patient-reported measures and their association with four concurrent outcomes of interest reflective of cGVHD disease burden. Univariate comparison of patient-reported measures with four outcomes. For the dichotomous outcomes, P-values were measured and presented in the following way; P <0.001 corresponded to a highly significant association indicated with solid blocks, and P <0.05 corresponded to a trend toward significance as represented by the faded blocks. For the continuous outcomes, r values were measured and presented as follows; r>0.5 corresponded to a strong to moderately strong correlation as indicated in solid blocks and r = 0.3 to 0.5 corresponded to a weak to moderately strong correlation as indicated by faded blocks. NIH = National Institutes of Health; PCS = physical component scale; SF36 = short-form 36.