Clinical comorbidity measures enhance the estimates of HCT tolerance and outcomes, thereby aiding therapeutic decisions. Ex vivo T cell depletion (TCD) of the graft reduces the risk of graft-versus-host disease and improves the tolerability of allogeneic transplantation in patients with impaired pretransplant performance. However, prediction tools such as the hematopoietic cell transplantation-specific comorbidity index (HCT-CI), have only been validated in conventional T-replete HCT. To improve outcome prediction in TCD transplants we therefore evaluated published comorbidity measures and other potential biomarkers of outcome in a series of myeloablative TCD transplant recipients. Pre transplant (week -2) factors measured were: HCT-CI, ECOG performance status, serum C-reactive protein (CRP), albumin (ALB), pre-albumin (PAB), ferritin, absolute lymphocyte counts (ALC), and absolute lymphocyte / monocyte ratio (LMR). CRP was also studied serially post transplant. CRP increased after conditioning, peaked (p =0.0001) in the first week of HCT, with recovery to baseline at 5 weeks post-HCT. We evaluated outcomes in a cohort of 79 patients in our institute with hematological malignancies receiving myeloablative total-body irradiation, and an HLA-identical sibling peripheral blood HCT, T cell depleted using Miltenyi CD34+ selection. The median age of recipients was 43 years (range 13-68 years). Of the 79, 34 (43%) had standard risk disease, and 45 (57%) recipients had high-risk disease. At a median follow up of ∼ 5 years, overall survival (OS) was 42.9% and nonrelapse mortality (NRM) was 33.9%. Comorbidity measures were first screened to eliminate highly-correlated covariates. Univariate Cox regression models were used to identify significant factors (p<0.05) associated with OS and NRM (with relapse as a competing risk), which were then further evaluated by multivariable Cox regression models. In the initial analysis we eliminated pre-HCT ECOG (94% were ECOG 0) and ferritin (median 1408 mcg/L, range 11-1444), which were highly correlated (p =0.003) to the HCT-CI score (median 3, range 0-9). Similarly, ALB (median 3.9 g/L, range 2.1-5.1, p = 0.002), PAB (median 25.6 mg/dL, range 6.9-56, p =0.001) and ferritin levels (p =0.005) were excluded as highly correlated to the pre-HCT CRP (preCRP) (median 5.8 mg/L, range 0.92-96.8). CRP levels measured at 2 weeks post transplant (postCRP) (median 10.4 mg/L, range 1.9-180) and ALC (median 0.96 K/uL, range 0.02-104.6) were not correlated to the pretransplant CRP. The independent pretransplant comorbidity variables identified for further testing were HCT-CI, preCRP, post CRP, ALC and LMR. In univariable analysis of OS, significant co-variates were HCT-CI scores ≥ 5 (HR 2.09 p= 0.02), preCRP (HR=1.016, p=0.07, a trend), postCRP (HR=1.014, p<0.001) and LMR ≤ 1.3 (HR=2.04, p= 0.04). In multivariable models of OS, postCRP ≥ 15 (HR 2.39, p =0.009) and LMR ≤ 1.3 (HR 2.25, p =0.04) retained significance. Confining the model to pretransplant data, then significant factors were pre CRP (HR 1.024 p= 0.02), HCT-CI≥5 (HR 2.08 p= 0.03) and LMR ≤1.3 (HR 2.43 p= 0.02). In univariable analysis of NRM, only continuous postCRP and postCRP ≥10 were significantly associated with NRM (HR=2.5, p =0.03) and in multivariable modeling of NRM, only postCRP ≥10 (HR=2.57, p=0.04) or continuous postCRP (HR=1.018, p=0.004) was found to be significant. LMR ≤ 1.3 and ECOG > 0 were found to be significantly associated with the cumulative incidence of relapse (both p=0.01). In conclusion, this is the first study to explore comorbidity scores and biomarkers to predict outcome after ex vivo TCD HCT. Our results suggest that HCT-CI score, preCRP, postCRP and the LMR are important independent clinical predictors of OS and NRM in TCD HCT.


No relevant conflicts of interest to declare.

Author notes


Asterisk with author names denotes non-ASH members.