Liver failure after treatment with inotuzumab and polychemotherapy including PEG-asparaginase in a patient with relapsed Philadelphia chromosome-negative acute lymphoblastic leukemia.

Acute lymphoblastic leukemia Extramedullary relapse Inotuzumab ozogamicin Liver failure Pegaspargase

Journal

Annals of hematology
ISSN: 1432-0584
Titre abrégé: Ann Hematol
Pays: Germany
ID NLM: 9107334

Informations de publication

Date de publication:
24 Nov 2023
Historique:
received: 03 07 2023
accepted: 03 10 2023
medline: 24 11 2023
pubmed: 24 11 2023
entrez: 24 11 2023
Statut: aheadofprint

Résumé

We present the case of a 58-year-old female patient who presented with an extramedullary B-ALL relapse after prior allogenic HSCT and blinatumomab therapy. The patient died from complications of a drug-induced acute liver failure after a salvage therapy combining inotuzumab ozogamicin (InO)-based induction followed by consolidation with high dose MTX and pegaspargase based on the GMALL protocol for older ALL patients. After a diagnosis of the extramedullary relapse in the form of a retro vesical chloroma, the patient received an individualized multi-agent chemotherapy based on induction chemotherapy for older patients in combination with InO. After four administrations of InO, in combination with vincristine, dexamethasone, cytarabine, and cyclophosphamide, CT-imaging showed a reduction in volume of the chloroma and response to therapy. Consolidation with high-dose methotrexate and pegaspargase was administered. The patient developed toxic liver damage manifested by hyperbilirubinemia and progressive hepatic encephalopathy. The diagnostic criteria for VOD were met, and therapy with defibrotide was initiated. Liver biopsy revealed no histological signs of VOD but instead steatohepatitis indicative of drug-induced toxicity. The patient ultimately died of hemorrhagic shock through postinterventional hemorrhage after liver biopsy. In conclusion, although InO shows promising results in the therapy of r/r ALL with and without additional chemotherapy, the combination with MTX and pegaspargase in an intensively pretreated patient with relapse after HCST may impart an increased risk for liver-related toxicity. Special caution is required when assessing fitness for further liver toxic regimens. A key takeaway is also the reminder that InO can cause liver damage not only in the form of VOD but also through direct hepatocellular toxicity.

Identifiants

pubmed: 37999763
doi: 10.1007/s00277-023-05495-w
pii: 10.1007/s00277-023-05495-w
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2023. The Author(s).

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Auteurs

Daniel Fischer (D)

Department of Medicine, Hematology and Oncology, University Hospital, Goethe University Frankfurt, Frankfurt am Main, Germany.

Rosa Toenges (R)

Department of Medicine, Hematology and Oncology, University Hospital, Goethe University Frankfurt, Frankfurt am Main, Germany.

Kati Kiil (K)

Senckenberg Institute of Pathology, University Hospital, Goethe University Frankfurt, Frankfurt am Main, Germany.

Sabine Michalik (S)

Department of Radiology, University Hospital, Goethe University Frankfurt, Frankfurt am Main, Germany.

Axel Thalhammer (A)

Department of Radiology, University Hospital, Goethe University Frankfurt, Frankfurt am Main, Germany.

Gesine Bug (G)

Department of Medicine, Hematology and Oncology, University Hospital, Goethe University Frankfurt, Frankfurt am Main, Germany.

Nicola Gökbuget (N)

Department of Medicine, Hematology and Oncology, University Hospital, Goethe University Frankfurt, Frankfurt am Main, Germany.

Fabian Lang (F)

Department of Medicine, Hematology and Oncology, University Hospital, Goethe University Frankfurt, Frankfurt am Main, Germany. f.lang@med.uni-frankfurt.de.

Classifications MeSH