The prognostic value of serum C-reactive protein, ferritin, and albumin prior to allogeneic transplantation for acute myeloid leukemia and myelodysplastic syndromes

Abstract

We sought to confirm the prognostic importance of simple clinically available biomarkers of C-reactive protein, serum albumin, and ferritin prior to allogeneic hematopoietic cell transplantation. The study population consisted of 784 adults with acute myeloid leukemia in remission or myelodysplastic syndromes undergoing unrelated donor transplant reported to the Center for International Blood and Marrow Transplant Research. C-reactive protein and ferritin were centrally quantified by ELISA from cryopreserved plasma whereas each center provided pre-transplant albumin. In multivariate analysis, transplant-related mortality was associated with the pre-specified thresholds of C-reactive protein more than 10 mg/L (P=0.008) and albumin less than 3.5 g/dL (P=0.01) but not ferritin more than 2500 ng/mL. Only low albumin independently influenced overall mortality. Optimal thresholds affecting transplant-related mortality were defined as: C-reactive protein more than 3.67 mg/L, log(ferritin), and albumin less than 3.4 g/dL. A 3-level biomarker risk group based on these values separated risks of transplant-related mortality: low risk (reference), intermediate (HR=1.66, P=0.015), and high risk (HR=2.7, P<0.001). One-year survival was 74%, 67% and 56% for low-, intermediate- and high-risk groups. Routinely available pre-transplant biomarkers independently risk-stratify for transplant-related mortality and survival.

Figure 1.

Receiver operating characteristic (ROC) curves for day 180 transplant-related mortality for three groups: biomarker panel group alone (panel gp only), clinical characteristics alone, or both [panel group (gp) and clinical characteristics].

Figure 2.

Outcomes after unrelated donor allogeneic transplant in each biomarker risk score group. (A) Transplant related mortality for low, intermediate and high biomarker risk panel group. (B) Overall survival for low, intermediate and high biomarker risk panel group.

Figure 3.

Overall survival for low, intermediate and high biomarker risk panel groups in myeloablative (MA) conditioning cohort (A) and reduced intensity/non-myeloablative regimen cohorts (NMA) (B). Transplant-related mortality for low, intermediate and high biomarker risk panel groups in MA conditioning cohort (C) and reduced intensity/NMA regimen cohorts (D).