title: Salvage treatment for children with refractory first or second relapse of acute myeloid leukaemia with gemtuzumab ozogamicin: results of a phase II study.
abstract: The prognosis of children with relapsed/refractory acute myeloid leukaemia (AML) is poor, and new therapies are needed. Gemtuzumab ozogamicin (GO) is an anti-CD33 antibody linked to the antitumor antibiotic calicheamicin. We conducted an investigator-initiated phase II study with GO to assess its efficacy and safety, administering two dosages of 7.5 mg/m(2) with a 14 d-interval. Thirty children who were refractory to re-induction at first relapse or suffered from second relapse of AML received a total of 64 infusions of GO. The response rate [complete remission (CR) and CR with insufficient platelet recovery] was 37%. Nine patients were subsequently transplanted (median time to transplant, 4 weeks, range 3-21 weeks), and three of these patients are currently in continuous CR with a median follow-up of >3 years, and can considered to be cured. This resulted in a statistically significant survival advantage for children who responded to GO versus those who did not [27% (standard error 13%) vs. 0%, respectively, P = 0.001]. All other children died, mainly from progressive disease. The treatment was generally well tolerated by most patients. The frequency of transient transaminatis was low. All but one patient received defibrotide prophylaxis during the transplant procedure, and no cases of veno-occlusive disease were noted. This study showed a favourable safety/efficacy profile of single-agent GO in children with refractory first or second relapse of AML.
authors.affiliation: Department of Paediatric Oncology/Haematology, Sophia Children's Hospital, Erasmus Medical Centre, Rotterdam, The Netherlands. c.m.zwaan@erasmusmc.nl <c.m.zwaan@erasmusmc.nl>
authors.forename: Christian M
authors.initials: CM
authors.lastname: Zwaan
authors.forename: Dirk
authors.initials: D
authors.lastname: Reinhardt
authors.forename: Martin
authors.initials: M
authors.lastname: Zimmerman
authors.forename: Henrik
authors.initials: H
authors.lastname: Hasle
authors.forename: Jan
authors.initials: J
authors.lastname: Stary
authors.forename: Batia
authors.initials: B
authors.lastname: Stark
authors.forename: Michael
authors.initials: M
authors.lastname: Dworzak
authors.forename: Ursula
authors.initials: U
authors.lastname: Creutzig
authors.forename: Gertjan J L
authors.initials: GJ
authors.lastname: Kaspers
mesh_terms: D000293:Adolescent; D000617:Aminoglycosides / Q000009:adverse effects / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D005260:Female; D000079982:Gemtuzumab; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D012008:Recurrence; D016019:Survival Analysis
chemical_list: D000617:Aminoglycosides; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000079982:Gemtuzumab