title: High efficacy and safety profile of fractionated doses of Mylotarg as induction therapy in patients with relapsed acute myeloblastic leukemia: a prospective study of the alfa group.
abstract: Pivotal phase II studies in acute myeloblastic leukemia (AML) patients in first relapse have used gemtuzumab ozogamicin (GO) (Mylotarg) at a dose of 9 mg/m(2) on days 1 and 14. These studies showed a 26% response rate (13% complete remission (CR) and 13% CRp (complete remission with incomplete platelet recovery)) but with high degree of hematological and liver toxicities. Based on in vitro studies showing a re-expression of CD33 antigenic sites on the cell surface of blasts cells after exposure to GO, we hypothesized that fractionated doses of GO may be efficient and better tolerated. Fifty-seven patients with AML in first relapse received GO at a dose of 3 mg/m(2) on days 1, 4 and 7 for one course. Fifteen patients (26%) achieved CR and four (7%) CRp. Remission rate correlated strongly with P-glycoprotein and MRP1 activities. The median relapse-free survival was 11 months, similar for CR or CRp patients. Median duration of neutropenia < 500/microl and thrombocytopenia < 50,000/microl were, respectively, 23 and 21 days. No grade 3 or 4 liver toxicity was observed. No veno-occlusive disease occurred after GO or after hematopoietic stem cell transplantation given after GO in seven patients. Mylotarg administered in fractionated doses demonstrated an excellent efficacy/safety profile.
authors.affiliation: Département d'Hématologie et Oncologie, Hôpital Mignot, Versailles, Université de Versailles-Saint Quentin en Yvelines, France.
authors.forename: A-L
authors.initials: AL
authors.lastname: Taksin
authors.forename: O
authors.initials: O
authors.lastname: Legrand
authors.forename: E
authors.initials: E
authors.lastname: Raffoux
authors.forename: T
authors.initials: T
authors.lastname: de Revel
authors.forename: X
authors.initials: X
authors.lastname: Thomas
authors.forename: N
authors.initials: N
authors.lastname: Contentin
authors.forename: R
authors.initials: R
authors.lastname: Bouabdallah
authors.forename: C
authors.initials: C
authors.lastname: Pautas
authors.forename: P
authors.initials: P
authors.lastname: Turlure
authors.forename: O
authors.initials: O
authors.lastname: Reman
authors.forename: C
authors.initials: C
authors.lastname: Gardin
authors.forename: B
authors.initials: B
authors.lastname: Varet
authors.forename: S
authors.initials: S
authors.lastname: de Botton
authors.forename: F
authors.initials: F
authors.lastname: Pousset
authors.forename: H
authors.initials: H
authors.lastname: Farhat
authors.forename: S
authors.initials: S
authors.lastname: Chevret
authors.forename: H
authors.initials: H
authors.lastname: Dombret
authors.forename: S
authors.initials: S
authors.lastname: Castaigne
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000097:blood; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000617:Aminoglycosides / Q000008:administration & dosage* / Q000009:adverse effects; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD / Q000097:blood; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D000079982:Gemtuzumab; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000097:blood; D012008:Recurrence; D012074:Remission Induction; D063268:Sialic Acid Binding Ig-like Lectin 3
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000617:Aminoglycosides; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000970:Antineoplastic Agents; D000079982:Gemtuzumab; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D063268:Sialic Acid Binding Ig-like Lectin 3; C571163:CD33 protein, human; C421109:multidrug resistance-associated protein 1