Association Between C-Reactive Protein in the First 1-3 Days Post-Transplant and Allogeneic Immune Reactions in Pediatric Haploidentical Stem Cell Transplantation

Background: C-reactive protein (CRP) has been shown to be a reliable biomarker of innate immunity. The purpose of the current study was to evaluate whether CRP levels in the first 1-3 days could predict allogeneic immune reactions including engraftment syndrome (ES) or acute graft-versus-host disease (GVHD) under haploidentical stem cell transplantation (SCT) in children.

Patients and methods: The study population comprised 175 consecutive pediatric patients (age no more than 18 years) who received haploidentical SCT from Oct, 2009 to Dec, 2014. All the children followed Beijing protocol in our institute as previously described. Allogeneic immune reactions include engraftment syndrome and acute GVHD. ROC analysis was performed to identify cutoff CRP value in the first 1-3 days post-transplant that best identified patients with allogeneic immune reactions. Patients were classified into 2 groups as high-CRP group (≥cut-off value) and low-CRP group (<cut off value).

Results:Totally, 129 patients (73.7%) were alive and without primary disease.The median age of recipients was 14 years (range: 2-18 years). The primary diseases were as follows: ALL in 95 (54.3%), AML in 62 (35.4%), hybrid acute leukemia in 3 (1.7%), CML in 10 (5.7%), and MDS in 5 (2.9%). Of the 175 patients, 68 (38.9%) developed ES on a median of day 10 (range: 7-16). 51(29.1%) out of 175 children developed 2-4 grade acute GVHD on a median of day 30 (range: 22-89) including 15 (8.6%) patients of severe acute GVHD on a median of day 29 (range: 22-85). Higher incidence of ES, 2-4 grade GVHD and 3-4 grade GVHD were totally observed in high-CRP group, compared to the low-CRP. A multivariate analysis demonstrated that high-level CRP(≥20.1 mg/L)in day 1-3 post-transplant was a risk factor for the development of allogeneic immune reactions. High CRP group was associated with an increased occurrence of ES (HR=2.046; 95%CI=1.204-3.477; P=0.008), II-IV aGVHD (HR=2.203; 95%CI=1.192-4.073; P=0.001) and severe GVHD (HR=6.371; 95%CI=1.798-22.581; P=0.004).

Conclusions: Our data suggested higher CRP level during the first 1-3 days post-transplant could be a predictor of allogeneic immune reactions in pediatric haploidentical SCT.