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The effect of N-acetyl-l-cysteine (NAC) on liver toxicity and clinical outcome after hematopoietic stem cell transplantation
Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Inst, Sweden.
Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
Karolinska Inst, Sweden; Univ Sharjah, U Arab Emirates.
Karolinska Inst, Sweden.
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2018 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 8293Article in journal (Refereed) Published
Abstract [en]

Busulphan (Bu) is a myeloablative drug used for conditioning prior to hematopoietic stem cell transplantation. Bu is predominantly metabolized through glutathione conjugation, a reaction that consumes the hepatic glutathione. N-acetyl-l-cysteine (NAC) is a glutathione precursor used in the treatment of acetaminophen hepatotoxicity. NAC does not interfere with the busulphan myeloablative effect. We investigated the effect of NAC concomitant treatment during busulphan conditioning on the liver enzymes as well as the clinical outcome. Prophylactic NAC treatment was given to 54 patients upon the start of busulphan conditioning. These patients were compared with 54 historical matched controls who did not receive NAC treatment. In patients treated with NAC, aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) were significantly (P amp;lt; 0.05) decreased after conditioning compared to their start values. Within the NAC-group, liver enzymes were normalized in those patients (30%) who had significantly high start values. No significant decrease in enzyme levels was observed in the control group. Furthermore, NAC affected neither Bu kinetics nor clinical outcome (sinusoidal obstruction syndrome incidence, graft-versus-host disease and/or graft failure). In conclusion: NAC is a potential prophylactic treatment for hepatotoxicity during busulphan conditioning. NAC therapy did not alter busulphan kinetics or affect clinical outcome.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP , 2018. Vol. 8, article id 8293
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Gastroenterology and Hepatology
Identifiers
URN: urn:nbn:se:liu:diva-149375DOI: 10.1038/s41598-018-26033-zISI: 000433290900024PubMedID: 29844459OAI: oai:DiVA.org:liu-149375DiVA, id: diva2:1229740
Note

Funding Agencies|Swedish Cancer Society [CAN2011/595, CAN2014/759]; Swedish Childhood Cancer Foundation [PR2017-0083]; Radiumhemmets [161082]

Available from: 2018-07-02 Created: 2018-07-02 Last updated: 2018-08-02

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