Chemotherapeutic treatment reduces circulating levels of surfactant protein-D in children with acute lymphoblastic leukemia.
Surfactant protein D (SP-D) is a host defense molecule of the innate immune system that enhances pathogen clearance and modulates inflammatory responses. We hypothesized that circulating SP-D levels are associated with chemotherapy-induced mucositis and infectious morbidity in children with acute lymphoblastic leukemia (ALL).



In a prospective study, 43 children receiving treatment for ALL were monitored for mucosal toxicity from diagnosis through the induction phase of treatment. Serial blood draws were taken to determine the levels of SP-D, interleukin-6 (IL-6), C-reactive protein, and white blood cells. Data on fever, antibiotics, and bacteremia were collected. Baseline levels of circulating SP-D were compared with healthy controls.



Baseline values of circulating SP-D were similar to levels in healthy controls (median: 829 ng/ml vs. 657 ng/ml, respectively, P > 0.05). After initiation of chemotherapy, a significant reduction in SP-D levels was observed at all time points: 704 ng/ml at day 8, 413 ng/ml at day 15, 395 ng/ml at day 22, and 520 ng/ml at day 29 (all, P < 0.05). No significant associations between SP-D values, the occurrence of mucosal toxicity, or infectious morbidity were observed. However, loss of circulating SP-D from days 8 to 15 was associated with more systemic inflammation, and lower SP-D values at day 15 were associated with elevated intestinal mucositis scores (P < 0.05).



The current study supports the hypothesis that the detrimental effect of chemotherapy on patients' immune functions includes decreased circulating levels of innate mucosal molecules such as SP-D, potentially aggravating mucosal and systemic inflammatory responses.
Department of pediatric hematology and oncology, Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark.|OPEN, Odense Patient Data Explorative Network, Odense University Hospital, Odense, Denmark.
Mathias
M
Rathe
Department of Cancer and Inflammation, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
Grith L
GL
Sorensen
Department of pediatric hematology and oncology, Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark.
Peder S
PS
Wehner
Department of Cancer and Inflammation, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
Uffe
U
Holmskov
Section of Comparative Pediatrics and Nutrition, Department of Clinical Veterinary and Animal Science, University of Copenhagen, Denmark.
Per T
PT
Sangild
Department of Paediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen University Hospital, Denmark.
Kjeld
K
Schmiegelow
Department of Paediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen University Hospital, Denmark.|Department of Rheumatology, The Institute of Inflammation Research, Rigshospitalet, Copenhagen University Hospital, Denmark.
Klaus
K
Müller
Department of pediatric hematology and oncology, Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark.
Steffen
S
Husby
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D002097:C-Reactive Protein / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D052016:Mucositis / Q000097:blood / Q000139:chemically induced / Q000175:diagnosis*; D009092:Mucous Membrane / Q000187:drug effects; D009367:Neoplasm Staging; D011014:Pneumonia / Q000097:blood / Q000139:chemically induced / Q000175:diagnosis*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D011379:Prognosis; D011446:Prospective Studies; D037663:Pulmonary Surfactant-Associated Protein D / Q000097:blood*
C508600:IL6 protein, human; D015850:Interleukin-6; D037663:Pulmonary Surfactant-Associated Protein D; D002097:C-Reactive Protein
acute lymphoblastic leukemia; chemotherapy-induced mucositis; mucosal barrier injury; pediatric hematology/oncology; surfactant protein D