Combination of cladribine and cytarabine is effective for childhood acute myeloid leukemia: results of the St Jude AML97 trial

J E Rubnitz, K R Crews, S Pounds, S Yang, D Campana, V V Gandhi, S C Raimondi, J R Downing, B I Razzouk, C-H Pui, R C Ribeiro, J E Rubnitz, K R Crews, S Pounds, S Yang, D Campana, V V Gandhi, S C Raimondi, J R Downing, B I Razzouk, C-H Pui, R C Ribeiro

Abstract

Because cladribine can increase cytarabine triphosphate levels, we tested a cladribine-cytarabine combination in the St Jude AML97, trial in which this combination was administered before standard chemotherapy to 96 children with acute myeloid leukemia (AML) or myelodysplastic syndrome. Patients received a 5-day course of cladribine (9 mg/m(2) per dose) and cytarabine either as daily 2-h infusions (500 mg/m(2) per dose) (arm A) or a continuous infusion (500 mg/m(2) per day) (arm B). Ara-CTP levels and inhibition of DNA synthesis increased from day 1 to day 2, but were not different between the two arms. In addition, the median blast percentages at day 15 did not differ between arms A and B, but patients treated in arm A had shorter intervals between the initiation of the first and second courses of therapy. Thus, although there were trends toward better complete remission rates and overall survival for patients treated in arm B, the reduced efficacy of arm A may have been partially compensated by more intense timing of therapy for that group. For all patients, 5-year event-free survival and overall survival estimates were 44.1+/-5.4 and 50.0+/-5.5%. Our results suggest that cladribine in combination with continuous-infusion cytarabine is effective therapy for childhood AML.

Figures

Figure 1. AML97 treatment schema
Figure 1. AML97 treatment schema
Patients were randomized to receive cladribine and daily 2-hour infusions (Arm A) or a continuous infusion (Arm B) of cytarabine. The second and third courses of chemotherapy consisted of daunorubicin, cytarabine, and etoposide (DAV). Further therapy was based on risk status and the availability of a matched sibling donor.
Figure 2
Figure 2
Panel A. Event-free survival (EFS) and overall survival (OS) for the 102 patients enrolled in AML97. Panel B. EFS for patients enrolled in Arm A before (Arm A Pre) and after (Arm A Post) treatment amendments, and for patients enrolled in Arm B before (Arm B Pre) and after (Arm B Post) treatment amendments. The curves for Arm B Pre and Arm A Post overlap.

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Source: PubMed

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