TY - JOUR
T1 - Salvage treatment for children with refractory first or second relapse of acute myeloid leukaemia with gemtuzumab ozogamicin
T2 - Results of a phase II study
AU - Zwaan, Christian M.
AU - Reinhardt, Dirk
AU - Zimmerman, Martin
AU - Hasle, Henrik
AU - Stary, Jan
AU - Stark, Batia
AU - Dworzak, Michael
AU - Creutzig, Ursula
AU - Kaspers, Gertjan J.L.
PY - 2010/3
Y1 - 2010/3
N2 - 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/m2 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.
AB - 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/m2 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.
KW - Acute myeloid leukaemia
KW - Children
KW - Gemtuzumab ozogamicin
KW - Phase II study
KW - Relapse
UR - http://www.scopus.com/inward/record.url?scp=76449104667&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2141.2009.08011.x
DO - 10.1111/j.1365-2141.2009.08011.x
M3 - Article
C2 - 19995399
AN - SCOPUS:76449104667
SN - 0007-1048
VL - 148
SP - 768
EP - 776
JO - British Journal of Haematology
JF - British Journal of Haematology
IS - 5
ER -