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Comparison of procalcitonin and C-reactive protein as early diagnostic marker for the identification of transplant-related adverse events after allogeneic hematopoietic stem cell transplantation in pediatric patients

  • Original Article – Clinical Oncology
  • Published:
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Abstract

Purpose

To evaluate serum procalcitonin (PCT) and C-reactive protein (CRP) as diagnostic biomarkers of transplant-related adverse events (TRAE) in pediatric patients undergoing hematopoietic stem cell transplantation (HSCT).

Methods

This study analyzed PCT and CRP levels of 214 pediatric patients with a median age of 8.5 years (0.4–17.8 years) undergoing allogeneic HSCT with respect to major TRAE.

Results

26 patients (12.1%) did not experience TRAE (control group), and 188 (87.9%) experienced median 2 (range 1–4) TRAE. Median CRP and PCT were highly and significantly increased during sepsis/SIRS and bacteremia (17.24 mg/dl | 6.30 ng/ml; p < 0.0001 vs. prior values), graft rejection (14.73 mg/dl | 3.20 ng/ml; p < 0.0001), and liver GvHD (6.88 mg/dl | 2.29 ng/ml; p < 0.01). Strong CRP increases and slight/minimal/no PCT increases occurred during fungemia (8.85 mg/dl | 0.72 ng/ml; p < 0.001), intestinal GvHD (8.73 mg/dl | 1.06 ng/ml; p < 0.0001), VOD (10.84 mg/dl | 0.59 ng/ml; p < 0.01), mucositis (8.84 mg/dl | 0.81 ng/ml; p < 0.0001), and viremia (3.62 mg/dl; p < 0.0001 | 0.43 ng/ml; below normal limit). During skin GvHD, CRP and PCT were slightly increased (2.03 mg/dl | 0.93 ng/ml; p < 0.0001).

Conclusions

CRP and PCT did not show congruent changes during TRAE. PCT was a clinically relevant marker for the early detection and differentiation of severe mucositis and sepsis/SIRS and bacteremia during the critical neutropenic period after HSCT. PCT helped to discriminate acute intestinal GvHD from adenovirus viremia and liver GvHD from hepatic VOD. Thus, PCT may be a valuable parameter to enable a prompt and appropriate treatment during these complications, improving patient outcomes.

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Abbreviations

ADV:

Adenovirus

ALL:

Acute lymphoblastic leukemia

AML:

Acute myeloid leukemia

ATG:

Anti-thymocyte globulin

BSA:

Body surface area

CML:

Chronic myeloid leukemia

CMV:

Cytomegalovirus

CRP:

C-reactive protein

EBV:

Epstein-Barr virus

GvHD:

Graft-versus-host disease

HHV-6:

Human herpes virus 6

HSCT:

Hematopoietic stem cell transplantation

HSV:

Human herpes simplex virus

JMML:

Juvenile myelomonocytic leukemia

kg:

Kilogram

kg BW:

Kilogram bodyweight

MDS:

Myelodysplastic syndromes

MFD:

Matched family donor

µg:

Microgram

µg kg−1 BW−1 d−1 :

µg per kg body weight and day

µl:

Microliter

MMFD:

Mismatched family donor

MUD:

Matched unrelated donor

n :

Sample size

p:

Probability value

PCT:

Procalcitonin

SD:

Standard deviation

VZV:

Varicella zoster virus

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Acknowledgements

This work was supported by the Stefan-Morsch-Stiftung, Birkenfeld, Germany and the Bettina-Bräu-Stiftung, Fürstenfeldbruck, Germany. The authors would like to thank the nurses at the bone marrow transplant ward and the immunology laboratory of the University Children’s Hospital Tübingen.

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Authors and Affiliations

  1. Department I-General Pediatrics, Haematology/Oncology, University Hospital Tübingen-Children’s Hospital, Hoppe-Seyler-Str.1, 72076, Tübingen, Germany

    Karin Melanie Cabanillas Stanchi, Manon Queudeville, Carmen Malaval, Judith Feucht, Patrick Schlegel, Markus Dobratz, Christian Seitz, Peter Lang, Rupert Handgretinger & Michaela Döring

  2. Division of Pediatric Stem Cell Transplantation and Immunology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany

    Ingo Müller

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  1. Karin Melanie Cabanillas Stanchi
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Contributions

MD and KMCS have made substantial contributions to conception and the design, acquisition, analysis, and interpretation of the data, and have written the paper. IM and RH made substantial contributions to conception, design, analysis, and interpretation of the data. MD, KMCS, MQ, JF, and CM have been involved in acquisition of funding and collection of data. MQ, PS, CM, CS, MaDo, and JF participated in the collection, analysis, and interpretation of data. PL and RH have been involved in revising the manuscript critically for important intellectual content. All authors read and approved the final manuscript.

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Correspondence to Michaela Döring.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Cabanillas Stanchi, K.M., Queudeville, M., Malaval, C. et al. Comparison of procalcitonin and C-reactive protein as early diagnostic marker for the identification of transplant-related adverse events after allogeneic hematopoietic stem cell transplantation in pediatric patients. J Cancer Res Clin Oncol 145, 2779–2791 (2019). https://doi.org/10.1007/s00432-019-03008-9

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