Gemtuzumab ozogamicin (Mylotarg) in children with refractory or relapsed acute myeloid leukemia.
BACKGROUND
Gemtuzumab ozogamicin (GO) is an immunoconjugate consisting of the CD33 antibody and calicheamicin, a potent cytotoxic agent. Developed for targeted treatment of CD33-positive AML, studies in adults showed its efficacy in relapsed and refractory AML.


METHODS
We report 12 children with multiple relapsed or refractory AML receiving GO as compassionate use. 11 children had initially been treated according to the AML-BFM 93 or 98 protocol, 1 girl received relapse treatment (liposomal daunorubicin/FLAG) due to secondary AML. After relapse, 10 children received an intensive relapse therapy (AML-BFM 97 or international AML-Relapse Study 2001/01). 2 of them had been transplanted in first or second CR before GO therapy.


RESULTS
5 of 12 children responded to treatment with blast reduction to below 5%, but no child achieved CR after GO. Time until reoccurrence of blasts in almost all children with GO response was 3-8 months. In 5 children stem cell transplantation (SCT) was performed after GO therapy. 4 of them suffered from further progression of AML, 1 boy is in second remission with a follow-up of 8 months. 2 children had severe side effects. An anaphylactic reaction with severe hypotension was managed by catecholamine support and intensive care. In 1 girl, who relapsed after SCT in first remission, a veno-occlusive disease of the liver occurred, but could be treated successfully with defibrotide.


CONCLUSIONS
GO therapy can induce blast reduction in children who have no further conventional treatment options. Frequency and severity of adverse events are limited, and therapy seems to be feasible for children with a sufficient general condition. Controlled studies are necessary to learn more about efficacy and side effects, especially implications for further therapy.
Reinhardt
D
D
Children's Hospital, Department of Pediatric Hematology/Oncology, University of Münster, Germany. dreinh@uni-muenster.de
Diekamp
S
S
Fleischhack
G
G
Corbacioglu
C
C
Jürgens
H
H
Dworzak
M
M
Kaspers
G
G
Creutzig
U
U
Zwaan
C M
CM
D000208:Acute Disease; D000293:Adolescent; D000617:Aminoglycosides / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D002648:Child; D002675:Child, Preschool; D005260:Female; D000079982:Gemtuzumab; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007223:Infant; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000401:mortality*; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality*; D010166:Palliative Care / Q000379:methods*; D012008:Recurrence; D017211:Treatment Failure; D016896:Treatment Outcome
D000617:Aminoglycosides; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000079982:Gemtuzumab