Background: Several approaches using antibodies to CD33 in the treatment of relapsed or refractory AML have been attempted, including the use of gemtuzumab ozogamicin. We decided to conduct a pilot study in pediatric patients with CD33 positive relapsed or refractory AML of targeted immunotherapy with GO combined with FLAG-IDA, to determine whether this combination would be effective and well tolerated.

Patients and Methods: Eligibility criteria included CD33 positive relapsed or refractory AML and baseline serum bilirubin and creatinine ≤ 1.5 mg/ml. The patients received GO on day 1 of the course. FLAG-IDA consists of idarubicin, fludarabine, cytarabine, and G-CSF. Toxicity was assessed using the National Cancer Institute common toxicity criteria. Complete response (CR) was defined as less than 5% blasts on a bone marrow aspirate of adequate cellularity showing evidence of trilineage regeneration with a peripheral ANC to 1.0×109/l and platelet count to 100×109l. CRp was defined as a response with incomplete platelet recovery but platelet transfusion independence. Overall response (OR) was calculated by adding CR and CRp rates.

Results: Between September 2005 and January 2006, five patients received GO with FLAG-IDA up to 3 infusions. All patients received GO doses of 3 mg/m2 for induction which reduced to 0.75–1.25 mg/m2 for consolidation. Median age was 9.7 (3.3–16.1) years and there were 4 boys and 1 girl. The median interval between initial diagnosis and GO administration was 1.2 (0.5–3.1) years. Three patients were relapsed state after stem cell transplantations (2 UCBT, 1 sibling BMT), 1 patient was refractory state and 1 patient was relapsed state after chemotherapy. Most common infusion-related reactions were fever and transient elevations of liver transaminases and bilirubin were noted, but VOD was not observed. The median number of days required to reach an ANC of more than 0.5×109/l were 30 (21–51) days and spontaneous platelet recovery to more than 20×109/l was 48 (9–60) days. Overall response rates were 80% and 1 patient was refractory state and 1 patient died of TMA after subsequent UBMT.

Conclusion: GO with FLAG-IDA was a valuable treatment option for children with relapsed or refractory CD33 positive AML. No cases of VOD occurred in our series, even after SCT in two responders. GO with FLAG-IDA was well tolerated, even during repeated infusions.

Treatment responses and outcomes

UPNCourseANC, recovery 0.5×109/l, 1×109/l (d)PLT, revocery 20×109/l, 100×109/l (d)ResponseFurther TreatmentTreatment outcomes
1 1 37, 41 49, NR CRp None Alive with disease free (342 days) 
 2 48, 51 60, NR CRp   
 3 51, 58 51, 143 CR   
2 1 30, 31 35, 40 CRp UBMT Died of TMA (251 days) 
 2 33, 35 48, NR CR   
3 1 21, 24* 9, 16* CR DLI Alive with disease free (289 days) 
4 1 31, 31 NR, NR Refractory Supportive treatment Alive with refractory AML(251 days) 
 2 27, NR NR, NR Refractory   
5 1 24, 25 28, 31 CR 2nd UCBT Alive with disease free (214 days) 
 2 23, 24 26, 27 CR   
UPNCourseANC, recovery 0.5×109/l, 1×109/l (d)PLT, revocery 20×109/l, 100×109/l (d)ResponseFurther TreatmentTreatment outcomes
1 1 37, 41 49, NR CRp None Alive with disease free (342 days) 
 2 48, 51 60, NR CRp   
 3 51, 58 51, 143 CR   
2 1 30, 31 35, 40 CRp UBMT Died of TMA (251 days) 
 2 33, 35 48, NR CR   
3 1 21, 24* 9, 16* CR DLI Alive with disease free (289 days) 
4 1 31, 31 NR, NR Refractory Supportive treatment Alive with refractory AML(251 days) 
 2 27, NR NR, NR Refractory   
5 1 24, 25 28, 31 CR 2nd UCBT Alive with disease free (214 days) 
 2 23, 24 26, 27 CR   
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Topics:
child, gemtuzumab, leukemia, myelocytic, acute, c-reactive protein, cyclic amp receptor protein, epley maneuver, cd33 antigen, tissue microarray, toxic effect, trimethylamine

Disclosure: No relevant conflicts of interest to declare.

Author notes

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Corresponding author

2006, The American Society of Hematology
2006
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