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Randomized Controlled Trial
. 2014 Sep;99(9):1472-8.
doi: 10.3324/haematol.2014.104182. Epub 2014 Apr 24.

The prognostic significance of early treatment response in pediatric relapsed acute myeloid leukemia: results of the international study Relapsed AML 2001/01

Ursula Creutzig  1 , Martin Zimmermann  2 , Michael N Dworzak  3 , Brenda Gibson  4 , Rienk Tamminga  5 , Jonas Abrahamsson  6 , Shau-Yin Ha  7 , Henrik Hasle  8 , Alexey Maschan  9 , Yves Bertrand  10 , Guy Leverger  11 , Christine von Neuhoff  2 , Bassem Razzouk  12 , Carmelo Rizzari  13 , Petr Smisek  14 , Owen P Smith  15 , Batia Stark  16 , Dirk Reinhardt  2 , Gertjan L Kaspers  17
Affiliations
Randomized Controlled Trial

The prognostic significance of early treatment response in pediatric relapsed acute myeloid leukemia: results of the international study Relapsed AML 2001/01

Ursula Creutzig et al. Haematologica. 2014 Sep.

Abstract

The prognostic significance of early response to treatment has not been reported in relapsed pediatric acute myeloid leukemia. In order to identify an early and easily applicable prognostic factor allowing subsequent treatment modifications, we assessed leukemic blast counts in the bone marrow by morphology on days 15 and 28 after first reinduction in 338 patients of the international Relapsed-AML2001/01 trial. Both day 15 and day 28 status was classified as good (≤20% leukemic blasts) in 77% of patients. The correlation between day 15 and 28 blast percentages was significant, but not strong (Spearman correlation coefficient = 0.49, P<0.001). Survival probability decreased in a stepwise fashion along with rising blast counts at day 28. Patients with bone marrow blast counts at this time-point of ≤5%, 6-10%, 11-20% and >20% had 4-year probabilities of survival of 52%±3% versus 36%±10% versus 21%±9% versus 14%±4%, respectively, P<0.0001; this trend was not seen for day 15 results. Multivariate analysis showed that early treatment response at day 28 had the strongest prognostic significance, superseding even time to relapse (< or ≥12 months). In conclusion, an early response to treatment, measured on day 28, is a strong and independent prognostic factor potentially useful for treatment stratification in pediatric relapsed acute myeloid leukemia. This study was registered with ISRCTN code: 94206677.

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Figures

Figure 1.
Figure 1.
Probability of 4-year survival after relapse according to blast count on day 15. SE = standard error, 0–5% vs. >20%, P(logrank) <0.0001; 6–10% vs. >20% P=0.011; 11–20% vs. >20% P=0.0011; all other comparisons P>0.68.
Figure 2.
Figure 2.
Probability of 4-year survival after relapse according to blast count on day 28. SE = standard error. 0–5% vs. 11–20%, P(logrank)=0.0010; 0–5% vs. >20%, P<0.0001; 6–10% vs. >20%, P=0.0031; all other comparisons P>0.15.
Figure 3.
Figure 3.
Probability of 4-year survival after relapse combining blast count data on day 15 and day 28. SE = standard error. BM day 15 ≤20% and day 28 ≤20% vs. BM day 15 ≤20% and day 28 >20%, P(logrank)<0.0001; BM day 15 ≤20% and day 28 ≤20% vs. BM day 15 >20% and day 28 ≤20% P=0.0070; BM day 15 ≤20% and day 28 ≤20% vs. BM day 15 >20% and day 28 >20%, P<0.0001; BM day 15 ≤20% and day 28 >20% vs. BM day 15 >20% and day 28 ≤20%, P=0.0089; BM day 15 ≤20% and day 28 >20% vs. BM day 15 >20% and day 28 >20%, P=0.76; BM day 15 >20% and day 28 ≤20% vs. BM day 15 >20% and day 28 >20%, P=0.013.
Figure 4.
Figure 4.
Probability of 4-year survival after relapse according to time of relapse and blast count on day 28. SE = standard error. Late relapse and BM day 28 ≤20% vs. late relapse and BM day 28>20%, P(logrank)=0.0004; late relapse and BM day 28 ≤20% vs. early relapse and BM day 28 ≤20%, P=0.05; late relapse and BM day 28 ≤20% vs. early relapse and BM day 28 >20%, P<0.0001; late relapse and BM day 28 >20% vs. early relapse and BM day 28 ≤20%, P=0.028; late relapse and BM 28 >20% vs. early relapse and BM day 28 >20%, P=0.022; early relapse and BM 28 ≤20% vs. early relapse and BM day 28 >20%, P<0.0001.
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References

    1. Goemans BF, Tamminga RY, Corbijn CM, Hahlen K, Kaspers GJ. Outcome for children with relapsed acute myeloid leukemia in the Netherlands following initial treatment between 1980 and 1998: survival after chemotherapy only? Haematologica 2008;93(9):1418–20. - PubMed
    1. Gorman MF, Ji L, Ko RH, Barnette P, Bostrom B, Hutchinson R, et al. Outcome for children treated for relapsed or refractory acute myelogenous leukemia (rAML): a Therapeutic Advances in Childhood Leukemia (TACL) Consortium study. Pediatr Blood Cancer. 2010;55(3):421–9. - PubMed
    1. Abrahamsson J, Clausen N, Gustafsson G, Hovi L, Jonmundsson G, Zeller B, et al. Improved outcome after relapse in children with acute myeloid leukaemia. Br J Haematol. 2007;136(2):229–36. - PubMed
    1. Aladjidi N, Auvrignon A, Leblanc T, Perel Y, Benard A, Bordigoni P, et al. Outcome in children with relapsed acute myeloid leukemia after initial treatment with the French Leucemie Aique Myeloide Enfant (LAME) 89/91 protocol of the French Society of Pediatric Hematology and Immunology. J Clin Oncol. 2003;21(23): 4377–85. - PubMed
    1. Rubnitz JE, Razzouk BI, Lensing S, Pounds S, Pui CH, Ribeiro RC. Prognostic factors and outcome of recurrence in childhood acute myeloid leukemia. Cancer. 2007; 109(1):157–63. - PubMed

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