Page 87 - 2018_09-Mondo

Clofarabine in pediatric AML
Results
Patients and treatment
Between 10th May 2010 and 28th May 2014, 34 AML patients (early first relapse, n=15; refractory first relapse, n=11; ≥2nd relapse, n=8) were recruited. The median age was 8.3 years (range 1.0-19.6 years); the median WBC 4.6x109/L (range 0.3-326x109/L), and 41% of patients were female. We had conclusive cyto(genetic) data from initial diagnosis in 30 of 34 patients, and from time point of inclu- sion in this study in 23 patients. None of these karyotypes included good risk characteristics such as t(8;21)(q22;q22) or inv(16)(p13q22)/t(16;16)(p13;q22). Eighteen patients had been pre-treated with FLAG-DNX reinduction according to protocol AML-BFM 2001/01.2 Twelve patients had received a prior SCT (4 in CR1; 7 in CR2; and 1 unknown), including one patient with 2 prior SCTs. For 32 of 34
Table 2. Patients’ baseline characteristics.
Characteristic
Age, years
Median
Range Sex
Male
FAB at initial diagnosis
Disease status
Early1strel 15 - 1 - 3 6 5 Refractory 1st rel 11 2 1 4 2 2 - ≥2ndrel 821212-
WBC at inclusion (x109/L)
Prior SCT
NOSCT 22 2 1 4 2 8 5 SCTin1stCR 4-112-- SCTin2ndCR 721112- Unknown 1---1--
WBC: white blood cells; FAB: French-American-British; SCT: stem cell transplantation; FLA: fludarabine, cytarabine (Ara-C); DNX: liposomal daunorubicin; CR: complete remis- sion; DL: dose-level; N: number of patients; rel: relapse.
patients, prior cumulative dose of anthracycline was calcu- lated using the equivalent formula, as previously described.29 With respect to the missing equivalent doses, prior amsacrine and prior liposomal daunorubicin were not included in the calculation. Prior anthracycline dosages are heterogenous in this cohort (range 80-686 mg/m2). Detailed patients' characteristics are provided in Table 2.
A total of 46 CLARA-DNX cycles were administered: 12 patients received two cycles (1 in DL3A; 2 in DL3B; 6 in DL4; 3 in DL5). In 31 patients, cycle 1 was given according to the schedule provided in the protocol. Deviations con- cerned intrathecal treatment (delayed or deleted in one patient each), and in one patient cytarabine was halted at day 3 due to an allergic reaction. The median absolute dose of clofarabine in cycle one was 160 mg (range 38-380 mg): 165 mg (range 38-456) for DNX, and 9.37 g (range 1.26-19 g) for cytarabine.
DL2 DL3A DL3B DL4 DL5 N.(%) N. N. N. N. N. N.
8.3 7.1 14.2 12.9 4.6 10.2 2.4
1.0-19.6 2.8-8.8 1.3-15.6 1.0-17.6 2.5-19.6 1.4-18.8 1.3-16.0
ALL patients DL1
(N=34) (N=4) (N=3) (N=6) (N=6) (N=10) (N=5)
20(58.8) 3 3 2 4 6 2 Female 14(41.2) 1 - 4 2 4 3
M0 411--2-
M1 3--1--2
M2 6-1-221
M4 41-2-1-
M5 14 1 - 3 3 5 2
M6 1-1----
Non-classified 2 1 - - 1 - -
4.6 3 6 3 4 3 4 0.3-326 1-5 1-127 1-326 0-34 0-30 1-6
Median
Range
<10
≥10 6-1222-
27 4 2 4 4 6 5
Pre-treatment with FLA-DNX
Yes 18 4 1 6 3 4 - No 16 - 2 - 3 6 5
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