Additional chromosomal abnormalities in patients with acute promyelocytic leukaemia (APL) do not confer poor prognosis: results of APL 93 trial

Abstract

Summary. In spite of the recent improvement in the outcome of acute promyelocytic leukaemia (APL) with treatment combining all trans retinoic acid (ATRA) and chemotherapy (CT), some patients with this disease still have a poor outcome. The prognostic significance of chromosomal abnormalities in addition to t(15;17) in APL is uncertain. We examined the prognostic significance of secondary chromosomal changes in 292 patients included in a European trial who were treated with ATRA and CT. The incidence of chromosomal abnormalities in addition to t(15;17) was 26% and trisomy 8 was the most frequent secondary change (46% of the cases with secondary changes). No significant differences were seen with regard to age, sex, initial white blood cell count, % of circulating blasts, platelet count, fibrinogen level and incidence of microgranular variants between patients with or without additional rearrangements.Outcome was also similar between patients with t(15;17) alone and patients with t(15;17) and other clonal abnormalities for complete remission (92% vs. 93% respectively), event-free survival at 2 years (76´1% vs. 78´1% respectively), relapse at 2 years (16´7% vs. 11´6% respectively) and overall survival at 2 years (79´9% vs. 79´5% respectively). Analysis according to the type of induction treatment (ATRA followed by CT or ATRA plus CT) or the type of maintenance treatment (with ATRA, lowdose CT or both) also failed to show any difference between the two groups. Thus, in a large cohort of APL patients treated with ATRA and CT, additional chromosomal abnormalities had no impact on prognosis.

Clinical impact of FLT3 mutation load in acute promyelocytic leukemia with t(15;17)/PML-RARA

“…It remains speculative whether this aspect could contribute to explain the weaker prognostic impact of the FLT3-ITD in Impact of FLT3-ITD mutation load in acute promyelocytic leukemia haematologica | 2011; 96(12) The frequency of ACA in our cohort (38.8%) was similar to that in previous studies. [32][33] In general we did not find that ACA had a significant impact on prognosis, which is in accordance with our previous study in 50 patients with APL. 34 Cervera et al from the PETHEMA study group found that ACA were associated with higher rates of coagulopathy, lower platelet counts, and higher relapse risk scores in APL, but remission rates of patients with and without ACA were nearly the same, being 90% and 91%, respectively.…”

“…In their study, no specific ACA was an independent risk factor for relapse. 33 The European APL group also did not find that ACA had a significant impact on prognosis, 32 and Slack et al found no difference in overall survival between APL patients with an isolated t(15;17)/PML-RARA and patients with ACA. 26 Accordingly, we were not able to show a significant influence of ACA on outcome in patients with APL.…”

The genetic characterization of acute promyelocytic leukemia with cryptic t(15;17) including a new recurrent additional cytogenetic abnormality i(17)(q10)

“…2 In APL with classic t(15;17), ider(17)t(15;17) is common additional chromosomal abnormality. 7 We set up a hypothesis stating that the comparison of i(17)(q10) to cryptic t(15;17) should be considered as a counterpart of ider(17) to t(15;17) and can be secondary event after submicroscopic insertion. The ratio of i(17)(q10) to cryptic t(15;17) was much higher than that of ider(17) to classic t(15;17) (25 vs 4.9%).…”

Avaliação da citogenética convencional e molecular em portadores de leucemia promielocítica aguda no Serviço de Hematologia do Hospital das Clínicas da Faculdade de Medicina da USP

“…(Schoch et al, 1996;Hiorns et al,1997;De Botton et al, 2000;Pantic et al,2000;Avvisati et al, 2001;Cassinat, Chomienne, 2001;Hernández et al 2001;Xu et al, 2001;Spell et al, 2002;Luatti et al, 2008;Swerdlow et al, 2008). (Sessarego et al, 1997;Hernández et al, 2001;Xu et al, 2001;Luatti et al, 2008;Swerdlow et al, 2008 (Sainty et al, 2000, Grimwade et al, 2000Brockman et al, 2003;Tirado et al,2005;Zhou et al, 2005), submeteu-se as amostras desses sete pacientes à técnica de FISH-ruptura com sonda "LSI RARα Dual Color, Break Apart Rearrangement Probe-Vysis, Inc" especifica para a região 17q12-21.…”

“…Cerca de 30% a 40% dos pacientes com leucemia promielocítica aguda apresentam, durante o diagnóstico, outras alterações cromossômicas em adição a t(15;17); são as chamadas alterações citogenéticas adicionais, sendo as mais freqüentes: trissomia do cromossomo 8, anormalidades estruturais no cromossomo 9, trissomia do cromossomo 21, isocromossomo do braço longo do cromossomo 17. O papel dessas alterações citogenéticas adicionais no prognóstico da doença ainda não é claro, com divergência em vários trabalhos (Schoch et al, 1996;Hiorns et al,1997;De Botton et al, 2000;Pantic et al,2000;Avvisati et al, 2001;Cassinat, Chomienne, 2001;Hernández et al 2001;Xu et al, 2001;Wan et al, 2003;).…”