Faculty Collaboration Database

Mylotarg (gemtuzumab ozogamicin) therapy is associated with hepatic venoocclusive disease in patients who have not received stem cell transplantation. Cancer 2001 Jul 15;92(2):406-13

Date

07/24/2001

Pubmed ID

11466696

DOI

10.1002/1097-0142(20010715)92:2<406::aid-cncr1336>3.0.co;2-u

Scopus ID

2-s2.0-0035878068 (requires institutional sign-in at Scopus site)   249 Citations

Abstract

BACKGROUND: Mylotarg (Wyeth-Ayerst Laboratories, St. Davids, PA) is the brand name for a calicheamicin-conjugated humanized anti-CD33 monoclonal antibody (gemtuzumab ozogamicin, CMA-676) and has been approved recently for the treatment of a subset of elderly patients who have relapsed acute myeloid leukemia (AML). Mylotarg is associated with an incidence of approximately 20% Grade 3 or 4 hyperbilirubinemia and liver transaminitis in this patient population. Hepatic venoocclusive disease (VOD) has been reported in patients who have undergone stem cell transplantation (SCT) after Mylotarg therapy. Outside of the SCT setting, VOD has been associated very rarely with cytotoxic therapy.

METHODS: The authors assessed the incidence of VOD in 119 patients who were receiving Mylotarg-containing non-SCT regimens. VOD was diagnosed through the use of standard Seattle and Baltimore criteria.

RESULTS: A cohort of 119 (61 previously untreated, 58 with relapsed disease) patients with AML (92 patients), advanced myelodysplastic syndrome (25 patients), or chronic myeloid leukemia in blast phase (2 patients), received Mylotarg-based regimens. Fourteen (12%) developed VOD. The diagnosis of VOD was supported by histology in 2 patients and radiologic studies in a further 10 patients. Five (36%) of 14 patients with VOD had received no prior antileukemic cytotoxic therapy, including 2 patients who received single-agent Mylotarg therapy.

CONCLUSIONS: Mylotarg was shown to be associated with the development of potentially fatal VOD in patients with leukemia who had not received SCT. VOD occurred when Mylotarg was used either as a single agent or when it was given with other cytotoxic agents. VOD occurred in Mylotarg-treated patients who had received no prior cytotoxic therapy. The current study concluded that risk factors for VOD should be assessed when considering Mylotarg therapy, and that attempts to avoid and treat VOD are warranted in patients who receive Mylotarg therapy.

Author List

Giles FJ, Kantarjian HM, Kornblau SM, Thomas DA, Garcia-Manero G, Waddelow TA, David CL, Phan AT, Colburn DE, Rashid A, Estey EH

Author

Alexandria T. Phan MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Aged
Aminoglycosides
Anti-Bacterial Agents
Antibodies, Monoclonal
Antineoplastic Agents
Cohort Studies
Female
Hematopoietic Stem Cell Transplantation
Hepatic Veno-Occlusive Disease
Humans
Incidence
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Male
Middle Aged
Myelodysplastic Syndromes
Retrospective Studies
Risk Factors