Gemtuzumab-Ozogamicin-Related Impaired Hemoglobin-Haptoglobin Scavenging as On-Target/Off-Tumor Toxicity of Anti-CD33 AML Therapy : A Report of Two Cases
Autor: | Hanna Rajala, Mikko A. I. Keränen, Riikka Räty, Veli-Jukka Anttila, Ulla Wartiovaara-Kautto, Mikko Haapio |
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Přispěvatelé: | HUS Comprehensive Cancer Center, University of Helsinki, Hematologian yksikkö, Department of Oncology, HUS Inflammation Center, Infektiosairauksien yksikkö, Helsinki University Hospital Area, HUS Abdominal Center, Research Programs Unit, ATG - Applied Tumor Genomics, Faculty of Medicine |
Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Gemtuzumab ozogamicin
medicine.medical_treatment CD33 3122 Cancers Case Report 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Calicheamicin medicine Diseases of the blood and blood-forming organs Chemotherapy biology business.industry Haptoglobin Myeloid leukemia General Medicine 3. Good health chemistry 030220 oncology & carcinogenesis Toxicity Immunology biology.protein Antibody RC633-647.5 business 030215 immunology medicine.drug |
Zdroj: | Case Reports in Hematology, Vol 2021 (2021) Case Reports in Hematology |
Popis: | Gemtuzumab-ozogamicin (GO) is a humanized anti-CD33 antibody, which is conjugated to a cytotoxic calicheamicin. It is used to treat acute myeloid leukemia (AML) in combination with chemotherapy. We describe here two GO-treated acute myeloid leukemia (AML) cases: both patients suffered from a toxic syndrome, which manifested as impaired hemoglobin-haptoglobin scavenging and accumulation of hemolysis-related products. Our observations and earlier reports indicated that the reaction was caused by GO-targeted destruction of CD33 + CD163+ monocytes/macrophages, which are responsible for the clearance of hemoglobin-haptoglobin complexes. The rise of plasma lactate dehydrogenase was an early sign of the reaction, and both patients had high levels of free plasma hemoglobin, but plasma haptoglobin and bilirubin levels were paradoxically normal. Symptoms included septic fever and abnormalities in cardiac tests and in the case of the first patient, severe neurological symptoms which required intensive care unit admittance. Therapeutic plasma exchanges supported the patients until the recovery of normal hematopoiesis. The symptoms may be easily confounded with infectious complications-related organ damage. Regarding the increasing use of gemtuzumab-ozogamicin and other emerging CD33-targeted cell therapies, we want to highlight this mostly unknown and probably underdiagnosed toxicity. |
Databáze: | OpenAIRE |
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