Favorable outcome in infants with AML after intensive first- and second-line treatment: an AML-BFM study group report

Abstract

Infants o1 year of age have a high prevalence of prognostically unfavorable leukemias and a presumed susceptibility to treatment-related toxicities. A total of 125 infants with acute myeloid leukemia (AML) were treated in studies AML-BFM-98 (n ¼ 59) and -2004 (n ¼ 66). Treatment regimens of both studies were comparable, consisting of intensive induction followed by four courses (mainly high-dose cytarabine and anthracyclines). Allogeneic-hematopoietic stem-cell-transplantation (allo-HSCT) in 1st remission was optional for high-risk (HR) patients. Most infants (120/125 ¼ 96%) were HR patients according to morphological, cytogenetic/molecular genetic and response criteria. Five-year overall survival was 66±4%, and improved from 61±6% in study-98 to 75±6% in study-2004 (P logrank 0.14) and event-free survival rates were 44±6% and 51±6% (P logrank 0.66), respectively. Results in HR infants were similar to those of older HR children (1-o2-or 2-o10-year olds, P logrank 0.90 for survival). Survival rates of HSCT in 1st remission, initial partial response and after relapse were high (13/14, 2/8 and 20/30 patients, respectively). The latter contributes to excellent 5-year survival after relapse (50±8%). Despite more severe infections and pulmonary toxicities in infants, treatment-related death rate was identical to that of older children (3%). Our data indicate that intensive frontline and relapse AML treatment is feasible in infants, toxicities are manageable, and outcome is favorable.

Effect of age and body weight on toxicity and survival in pediatric acute myeloid leukemia: results from NOPHO-AML 2004

“…The outcome for infants treated according to NOPHO-AML 2004 was excellent (5-year EFS: 66%, 95%CI: 46%-79%, 5-year OS: 82%, 95%CI: 63%-91%) and confirm previous reports showing favorable outcome for infants. 19,34 High-dose cytarabine seems safe and effective in treating infants with AML, and our results do not support further dose reductions in infants as recommended by others. 14 Children aged 10-17 years were at higher risk of toxicity.…”

“…To our knowledge, no previous studies have reported such a thorough review of toxicities and associations with age and body weight at diagnosis, though many studies suggest similar associations. 12,13,18,19,26,27 We found a trend for age 10-17 years being associated with poorer survival. In contrast to previous studies, 12,13 we found a trend for being overweight being associated with improved survival in children aged 10-17 years.…”

“…The NOPHO-AML 2004 protocol did not seem to be more toxic for infants compared to the three previous BFM protocols (AML-BFM-98, -98-Interim and -2004), 19 despite the higher doses of cytarabine. In particular, the rate of central neurotoxicity (a known cytarabine toxicity 35 ) following the high-dose cytarabine consolidation courses was low, and during consolidation infants did not have more toxicity than children aged 2-9 years.…”

Acute myeloid leukemia in children. Prospects for the optimization of treatment (review)

“…В частности, транслокация t(1;12) (p15;q13) ассоциирована с М7-подтипом ОМЛ, трансло-кация (7;12)(q36;p13) обычно сопровождается трисо-мией 19-й хромосомы или реже трисомией 8-й хромо-сомы. Транслокации, вовлекающие 11-ю хромосому, обычно выявляются при миеломонобластном и моноб-ластном подтипе ОМЛ, причем глобальная встречае-мость 11q23/MLL варьирует в различных исследованиях у детей от 35 до 50 % [12,13].…”

Insights into cell ontogeny, age, and acute myeloid leukemia

“…As well as the predominance of MLL rearrangements, rare aberrations almost exclusively seen in this cohort include t(7;12)(MNX1/ETV6), [22] t(1;22)(RBM15(OTT)-MKL1(MAL)) [49] and inv(16)(CBFA2T3/GLIS2) [21], the latter two associated with non-DS AMKL. In contrast, CBF AML and APML are rare in infants [9,50]. Like GATA1 mutations in ML-DS, MLL rearrangements occur in utero evidenced by twin concordance studies [36] and by the detection of MLL rearrangements in patient matched leukaemic samples and newborn blood spots [37].…”