Chronic kidney disease, survival and graft-versus-host-disease-free/relapse-free survival in recipients of allogeneic hematopoietic stem cell transplant

Abstract

Background: Advances in allogeneic hematopoietic stem cell transplant (HSCT) have increased patient survival, although substantial treatment-related toxicity remains, including chronic kidney disease (CKD). We assessed the association between CKD and survival and transplant-specific outcomes in HSCT recipients.

Methods: We conducted a retrospective study of all 408 adult patients with allogenic HSCT at Princess Margaret Cancer Centre (Toronto, Canada, 2015-18). We used logistic regression to identify risk factors for CKD at 1 year post-transplant. Associations between CKD at 1 year and overall survival, relapse-free survival, graft-versus-host-disease (GVHD)-free/relapse-free survival, relapse and transplant-related mortality were examined using extended time-varying Cox models. In a sensitivity analysis, we restricted the cohort to survivors at 1 year, using standard Cox proportional hazard models to examine associations between CKD and overall survival, relapse-free survival and GVHD-free/relapse-free survival, and Fine and Gray's competing risk models to determine associations between CKD and relapse/transplant-related mortality.

Results: The prevalence of CKD at 1 year was 19% (46 patients) with median follow-up of 23 months. Multivariable regression identified age at transplant [adjusted OR (aOR) 1.09, 95% confidence interval (95% CI) = 1.05-1.14; P < 0.0001), female gender (aOR 2.83, 95% CI = 1.34-5.97; P = 0.006) and acute kidney injury during the first 100 days (aOR 3.86, 95% CI = 1.70-8.73; P = 0.001) as risk factors for CKD at 1 year. Patients with CKD at 1 year had significantly poorer overall survival than those without CKD, when adjusted for relevant covariates [adjusted HR (aHR) 1.93, 95% CI = 1.02-3.66; P = 0.04 in the time-varying Cox model, and aHR 2.06, 95% CI = 1.04-4.07; P = 0.04 using the standard Cox model]. CKD at 1 year was also associated with worse GVHD-free/relapse-free survival (aHR 1.65, 95% CI = 1.04-2.61; P = 0.03).

Conclusions: CKD adversely affects the long-term prognosis for allogeneic HSCT recipients, with increased mortality risk and worse GVHD-free/relapse-free survival.

Keywords: GVHD-free/relapse-free survival; allogeneic hematopoietic stem cell transplant; chronic kidney disease; long-term survival.

Graphical Abstract

FIGURE 1:

Median eGFR of the cohort among alive patients at baseline (time of transplant), 100 days post-transplant, 1 year post-transplant and last follow-up. Median total follow-up time was 22.5 (range 1.0–70.0) months. Box plots show 25th and 75th percentiles.

FIGURE 2:

Overall survival at last follow-up based on CKD at 1 year status. Time origin is 1 year post-transplant, n = 236 (survivors at 1 year).