title: Gemtuzumab ozogamicin (Mylotarg) monotherapy for relapsed AML after hematopoietic stem cell transplant: efficacy and incidence of hepatic veno-occlusive disease.
abstract: Gemtuzumab ozogamicin (GO) (Mylotarg, CMA-676) is a novel chemotherapeutic agent consisting of an anti-CD33 monoclonal antibody linked to calicheamicin, and is associated with a 30% response rate in patients with CD33-positive acute myeloid leukemia (AML) in first relapse. GO therapy has a 20% incidence of grade 3 or 4 hepatotoxicity, and has recently been associated with hepatic veno-occlusive disease (VOD). The efficacy and toxicity of GO in patients with AML who have relapsed after hematopoietic stem cell transplant (HSCT) is unknown, as this population was largely excluded from phase II studies. We reviewed the outcomes of eight consecutive patients with AML who received GO following relapse after HSCT. Two (25%) had responses to GO. One patient, who had had two previous HSCT and prior hyperbilirubinemia, developed severe VOD and died 14 days after GO therapy. The other seven patients did not meet diagnostic criteria for VOD. We conclude that GO can be safe and effective in patients who relapse following HSCT, but that caution is warranted in patients with multiple risk factors for VOD.
authors.affiliation: Hematologic Malignancies Program and the Bone Marrow and Stem Cell Transplantation Program, University of Pennsylvania Cancer Center, Philadelphia, PA 19104, USA.
authors.forename: A D
authors.initials: AD
authors.lastname: Cohen
authors.forename: S M
authors.initials: SM
authors.lastname: Luger
authors.forename: C
authors.initials: C
authors.lastname: Sickles
authors.forename: P A
authors.initials: PA
authors.lastname: Mangan
authors.forename: D L
authors.initials: DL
authors.lastname: Porter
authors.forename: S J
authors.initials: SJ
authors.lastname: Schuster
authors.forename: D E
authors.initials: DE
authors.lastname: Tsai
authors.forename: S
authors.initials: S
authors.lastname: Nasta
authors.forename: A M
authors.initials: AM
authors.lastname: Gewirtz
authors.forename: E A
authors.initials: EA
authors.lastname: Stadtmauer
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000633:toxicity; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000633:toxicity; D061067:Antibodies, Monoclonal, Humanized; D002423:Cause of Death; D005260:Female; D000079982:Gemtuzumab; D018380:Hematopoietic Stem Cell Transplantation; D006504:Hepatic Veno-Occlusive Disease / Q000139:chemically induced / Q000209:etiology; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage / Q000633:toxicity; D015994:Incidence; D007951:Leukemia, Myeloid / Q000150:complications / Q000188:drug therapy* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016879:Salvage Therapy; D013810:Therapeutic Equivalency; D016896:Treatment Outcome
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000922:Immunotoxins; D000079982:Gemtuzumab