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Ann Hematol. 2018 Nov;97(11):2107-2115. doi: 10.1007/s00277-018-3424-4. Epub 2018 Jul 15.

Molecular remission at the end of treatment is a necessary goal for a good outcome in ELN favorable-risk acute myeloid leukemia: a real-life analysis on 201 patients by the Rete Ematologica Lombarda network.

Author information

1
Division of Hematology, Foundation IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy. p.zappasodi@smatteo.pv.it.
2
Department of Hematology, Niguarda Ca' Granda Hospital, Milan, Italy.
3
Department of Hematology, Spedali Civili, Brescia, Italy.
4
Department of Hematology, Ospedale San Gerardo, Monza, Italy.
5
Hematology and Bone Marrow Unit, San Raffaele Scientific Institute, Milan, Italy.
6
Department of Hematology, Foundation, IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
7
Division of Hematology, Foundation IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy.
8
Department of Molecular Medicine, University of Pavia, Pavia, Italy.

Abstract

Favorable acute myeloid leukemia (AML) patients (pts.) demonstrate a relatively good outcome with standard induction; thus, pts. are generally not addressed to allogeneic transplant in first remission. However, it is not clear if also in a real-life setting, the outcome is homogeneous in the different favorable molecular groups and which are the parameters significantly associated to an increased relapse risk, useful to suggest the need of an intensified approach. In order to clarify this point, we collected clinical data on consecutive unselected AML pts. assigned to favorable category (modified ELN 2010 due to the inclusion of double-mutated CEBPA-positive cases), diagnosed and treated in six centers of the Italian network Rete Ematologica Lombarda (REL) from 2007 to 2015. We assessed response (CR, mCR), relapse rate (CIR), and outcome (OS, DFS) after first-line treatment. A total of 201 pts. was studied and the analysis was performed globally and in each molecular group: t(8;21)(q22;q22)/RUNX1-RUNX1T1 (30 pts., 14.9%), inv. (16)(p13q22) or t(16;16)(p13q22)/CBFB-MIH11 (35 pts., 17.4%), normal karyotype and mutated NPM1 and negative FLT3-ITD (116 pts., 57.7%) or double-mutated CEBPA (CEBPAdm) (20 pts., 10%). Complete remission (CR) was obtained in 188 pts. (93.5%), molecular CR (mCR) in 114 (67.5%); After a median follow-up of 2.4 years, cumulative incidence of relapse (CIR) was documented in 78 of 188 responding pts. (41%) after a median time of 11.3 months. CIR was higher in the CBFB-MIH11 group, in pts. achieving only a hematological response without mCR (72.1 vs 28.1%, p < 0.001), in older pts. and it resulted independently associated with a lower median cytarabine cumulative dose (CCD). Median OS was not reached: after 5 years it was 66.3%, and median DFS was 5.3 years, both without difference among groups. Molecular CR reached at any time, during or after the end of first-line treatment, was significantly associated with better DFS, and in particular, mCR assessed at the end of treatment was confirmed in multivariate analysis as an independent prognostic factor both for DFS and OS. In conclusion, the present study confirms in a real-life context the overall good prognosis of favorable-risk AML; the achievement of any molecular negativity during first-line treatment, particularly when assessed at the end of treatment, is associated with lower relapse and better survival. Increasing age at diagnosis has a negative prognostic impact, while CCD higher than 18 g/sqm is associated with better outcome.

KEYWORDS:

Acute myeloid leukemia; Favorable risk; Outcome; Real life

PMID:
30009341
DOI:
10.1007/s00277-018-3424-4
[Indexed for MEDLINE]

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