title: Phase I/II study of gemtuzumab ozogamicin added to fludarabine, melphalan and allogeneic hematopoietic stem cell transplantation for high-risk CD33 positive myeloid leukemias and myelodysplastic syndrome.
abstract: We investigated the hypothesis that gemtuzumab ozogamicin (GO), an anti-CD33 immunotoxin would improve the efficacy of fludarabine/melphalan as a preparative regimen for allogeneic hematopoietic stem cell transplantation (HSCT) in a phase I/II trial. Toxicity was defined as grades III-IV organ damage, engraftment failure or death within 30 days. 'Response' was engraftment and remission (CR) on day +30. We sought to determine the GO dose (2, 4 or 6 mg m(-2)) giving the best trade-off between toxicity and response. All patients were not candidates for myeloablative regimens. Treatment plan: GO (day -12), fludarabine 30 mg m(-2) (days -5 to -2), melphalan 140 mg m(-2) (day -2) and HSCT (day 0). GVHD prophylaxis was tacrolimus and mini-methotrexate. Diagnoses were AML (n=47), MDS (n=4) or CML (n=1). Median age was 53 years (range, 13-72). All but three patients were not in CR. Donors were related (n=33) or unrelated (n=19). Toxicity and response rates at 4 mg m(-2) were 50% (n=4) and 50% (n=4). GO dose was de-escalated to 2 mg m(-2): 18% had toxicity (n=8) and 82% responded (n=36). 100-day TRM was 15%; one patient had reversible hepatic VOD. Median follow-up was 37 months. Median event-free and overall survival was 6 and 11 months. GO 2 mg m(-2) can be safely added to fludarabine/melphalan, and this regimen merits further evaluation.
authors.affiliation: Department of Stem Cell Transplantation and Cell Therapy, U.T.M.D. Anderson Cancer Center, Houston, TX 77030-4009, USA. mdelima@mdanderson.org
authors.forename: M
authors.initials: M
authors.lastname: de Lima
authors.forename: R E
authors.initials: RE
authors.lastname: Champlin
authors.forename: P F
authors.initials: PF
authors.lastname: Thall
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: T G
authors.initials: TG
authors.lastname: Martin
authors.forename: J D
authors.initials: JD
authors.lastname: Cook
authors.forename: G
authors.initials: G
authors.lastname: McCormick
authors.forename: M
authors.initials: M
authors.lastname: Qazilbash
authors.forename: P
authors.initials: P
authors.lastname: Kebriaei
authors.forename: D
authors.initials: D
authors.lastname: Couriel
authors.forename: E J
authors.initials: EJ
authors.lastname: Shpall
authors.forename: I
authors.initials: I
authors.lastname: Khouri
authors.forename: P
authors.initials: P
authors.lastname: Anderlini
authors.forename: C
authors.initials: C
authors.lastname: Hosing
authors.forename: K W
authors.initials: KW
authors.lastname: Chan
authors.forename: B S
authors.initials: BS
authors.lastname: Andersson
authors.forename: P A
authors.initials: PA
authors.lastname: Patah
authors.forename: Z
authors.initials: Z
authors.lastname: Caldera
authors.forename: E
authors.initials: E
authors.lastname: Jabbour
authors.forename: S
authors.initials: S
authors.lastname: Giralt
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000617:Aminoglycosides / Q000008:administration & dosage* / Q000633:toxicity; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000633:toxicity; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use* / Q000633:toxicity; D018572:Disease-Free Survival; D005260:Female; D000079982:Gemtuzumab; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006801:Humans; D007951:Leukemia, Myeloid / Q000401:mortality / Q000628:therapy*; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000401:mortality / Q000628:therapy*; D012074:Remission Induction; D063268:Sialic Acid Binding Ig-like Lectin 3; D015996:Survival Rate; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D000617:Aminoglycosides; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C571163:CD33 protein, human; D063268:Sialic Acid Binding Ig-like Lectin 3; D000079982:Gemtuzumab; D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan