Uric acid as a novel biomarker for bone-marrow function and incipient hematopoietic reconstitution after aplasia in patients with hematologic malignancies

Abstract

Purpose

Prolonged aplasia and graft failure (GF) represent life-threatening complications after hematopoietic cell transplantation (HCT) requiring suitable biomarkers for early detection and differentiation between GF and poor graft function (PGF). Uric acid (UA) is a strong immunological danger signal.

Methods

Laboratory results were analyzed from patients undergoing either allogeneic or autologous HCT or induction chemotherapy for acute leukemia (n = 50 per group, n = 150 total).

Results

During therapy, UA levels declined from normal values to hypouricemic values (all p < 0.001). Alongside hematopoietic recovery, UA serum levels returned to baseline values. During aplasia, UA levels remained low and started steadily increasing (defined as >two consecutive days, median one 2-day increase) at a median of 1 day before rising leukocytes in allogeneic HCT (p = 0.01) and together with leukocytes in autologous HCT (median one 2-day increase). During induction chemotherapy, a UA increase was also observed alongside rising leukocytes/neutrophils but also several times during aplasia (median 3 increases). Most HCT patients had no detectable leukocytes during aplasia, while some leukocytes remained detectable after induction therapy. No increase in UA levels was observed without concomitant or subsequent rise of leukocytes.

Conclusions

Changes in UA serum levels can indicate incipient or remaining immunological activity after HCT or induction therapy. They may, therefore, help to differentiate between PGF and GF.

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