Prognostic significance of chromosomal abnormalities at relapse in children with relapsed acute myeloid leukemia: A retrospective cohort study of the Relapsed AML 2001/01 Study

Abstract

Background In addition to treatment response, cytogenetic and molecular aberrations are the most important prognostic factors in children with de novo acute myeloid leukemia (AML). However, little is known about cytogenetics at the time of relapse. Methods This international study analyzed the prognostic value of cytogenetic profiles and karyotypic changes in pediatric relapsed AML in relation to the probability of event‐free (pEFS) and overall survival (pOS). For this purpose, cytogenetic reports from all patients registered on the Relapsed AML 2001/01 Study were reviewed and classified. Results Cytogenetic information at relapse was available for 403 (71%) of 569 registered patients. Frequently detected aberrations at relapse were t(8;21)(q22;q22) (n = 60) and inv(16)(p13.1q22)/t(16;16)(p13.1;q22) (n = 24), both associated with relatively good outcome (4‐year pOS 59% and 71%, respectively). Monosomy 7/7q−, t(9;11)(p22;q23), t(10;11)(p12;q23), and complex karyotypes were associated with poor outcomes (4‐year pOS 17%, 19%, 22%, and 22%, respectively). Of 261 (65%) patients for whom cytogenetic data were reliable at both diagnosis and relapse, pEFS was inferior for patients with karyotypic instability (n = 128, 49%), but pOS was similar. Unstable karyotypes with both gain and loss of aberrations were associated with inferior outcome. Early treatment response, time to relapse, and cytogenetic profile at time of relapse were the most important prognostic factors, both outweighing karytoypic instability per se. Conclusion The cytogenetic subgroup at relapse is an independent risk factor for (event‐free) survival. Cytogenetic assessment at the time of relapse is of high importance and may contribute to improved risk‐adapted treatment for children with relapsed AML.

Single‐dose (4.5 mg/m2) gemtuzumab ozogamicin in combination with fludarabine, cytarabine and anthracycline as reinduction therapy in relapsed or refractory paediatric acute myeloid leukaemia

“…In our study, the favourable cytogenetic group had an OS of 86% (CI95% [63; 100]), which includes CBF AML, compared to 51% in the intermediate group and 0% in the high-risk group. This benefit in terms of survival in function of cytogenetic risk group has also been shown at relapse in the study of Klein et al 28 but also in the Kasper et al study concerning the in the CBF AML subgroup. 11 The safety profile of the reinduction regimen in our study was deemed acceptable without toxic death directly attributable to reinduction therapy and only one allergic reaction linked to GO infusion.…”

“…In our study, the favourable cytogenetic group had an OS of 86% (CI95% [63; 100]), which includes CBF AML, compared to 51% in the intermediate group and 0% in the high‐risk group. This benefit in terms of survival in function of cytogenetic risk group has also been shown at relapse in the study of Klein et al 28 but also in the Kasper et al study concerning the in the CBF AML subgroup 11 …”

Development and validation of a prognostic scoring model to risk stratify childhood acute myeloid leukaemia

“…In our study, cytogenetic and molecular aberrations remained the most powerful predictors for childhood AML prognosis. Previous publications reported similar prognostic significance with ‐7/del(7q) and ‐5/del(5q) carrying the poorest prognosis 18,19 . Hasle et al 20 reported HSCT could not prolong the survival of patients with monosomy 7 or del(7).…”

“…Previous publications reported similar prognostic significance with -7/del(7q) and -5/del(5q) carrying the poorest prognosis. 18,19 Hasle et al 20 reported HSCT could not prolong the survival of patients with monosomy 7 or del (7). More effective therapies are warranted for these patients.…”

Treatment results of children and adolescents with relapsed AML who were initially treated according to the AML-MM-2006 protocol

“…Прогноз при рецидиве ОМЛ существенно лучше при так называемых CBF-лейкозах (t(8;21)(q22;q22.1)/ RUNX1::RUNX1T1 и inv(16)(p13.1q22)/CBFβ::MYH11) [6]. Существенное значение имеет длительность интервала от достижения ПР1 до возникновения рецидива: при раннем рецидиве (в первые 12 месяцев после достижения ПР1) вероятность достижения второй ремиссии (ПР2) составляет около 50 %, а 5-летняя общая выживаемость (ОВ) -10-15 %; в то время как при позднем рецидиве ( 1 года после достижения ПР1) -75 и 37 % соответственно.…”