- Acute Myeloid Leukemia (AML)
Through a Board of Directors (CA) and a Scientific Committee (CS), both comprising clinician and biologist investigators, ALFA has the following objectives:
- To initiate and promote any research in adult AML biology and treatment
- To collect and manage the funds for this purpose
- To support ALFA members in the acquisition of new competences and knowledge in the AML field
- To diffuse knowledge and promote training in this field
- To encourage and facilitate connections between the actors of AML patients’ care and research on AML, including universities, hospitals, private companies, charity structures and patients’ associations
- To contribute to a better equipment and management of hospital clinical units and laboratories, as well as university research labs
- To support contacts with other national, European, and international cooperative groups or societies working in the AML field
The means of action are:
- The organization of periodic scientific or teaching meetings
- The realization of clinical and biological research studies
- The design, promotion, and coordination of its own clinical, biological, and therapeutically studies and trials
- The participation in studies and trials from other cooperative groups
- The analysis and publication of the results of these studies and trials (original articles, reviews, thesis…)
- The participation in national and international conferences, workshops, and scientific meetings
- The employment of assistant persons for study/trial monitoring or meeting organization
- Targeted therapy
- Immunotherapy
- Hematopoietic stem cell transplant
- Chemotherapy
Scientific
1. Identification of new prognostic markers of AML responding poorly to current treatments, especially susceptible to be enrolled in clinical trials assessing new therapeutic agents:
- LSC 17 stemness Gene Signature in AML (in collaboration with John Dick’s team (Toronto); Ng SWK et al Nature 2016; 540: 433)
- New genomic classifier of AML patients ≥ 60 years (in collaboration with the German SAL group; Itzykson R et al Blood 2021; 138: 507)
2. Identification of coexisting genomic abnormalities modifying the prognosis of AML usually considered of favorable risk:
- ASXL2 gene mutation in core binding factor-AML with t (8;21) /RUNX1-RUNX1T1 chromosomal translocations (in collaboration with the MSKCC (New York) and French pediatric teams; Micol JB et al Blood 2014; 124: 1445)
- Impact of chromosomal abnormalities in NPM1-Mutated AML (in the setting an international-multigroup study; Angenendt L et al J Clin Oncol 2019; 37: 2632)
3. Description of the prognostic impact of common germline mutations in AML:
- Prognostic impact of DDX1 germline mutations in AML (in collaboration with the FILO group; Duployez N et al Blood 2022; 140: 756)
Medical
1. Assessment of a new administration schedules of gemtuzumab ozogamicin (G.O. , Mylotarg®) in combination with intensive chemotherapy, leading to the reapproval of this antibody-drug conjugate (ADC) as treatment of AML:
- Phase 3 randomized trial used as pivotal study for the reapproval of GO (Castaigne S et al Lancet 2012; 379: 1508)
- Metanalysis of randomized GO trials (as part of an international multigroup study Hills; RK et al Lancet Oncology 2014; 15: 986)
2. Evaluation of gene mutations and minimal residual disease as prognosis markers AML:
- CBF 2006 study (in collaboration with the FILO group Jourdan E et al Blood 2013; 121: 2213)
- ALFA-1200 (Gardin Blood Advances 2021
3. National Backbone Inter Group Study (BIG-1), a large randomized platform comparing different drugs or drugs dosages used as induction or consolidation treatments, documenting the interest of unified allogeneic stem cell transplantation procedures and including several nested randomized phase 2 trials which aim to improve post-remission therapy:
- Ongoing analysis of the initial randomized phases (in collaboration with the FILO group)
4. Frontline evaluation of IDH1/2 and comparison of FLT3 inhibitors in 2 large randomized trials:
- Ongoing HOVON 150 and HOVON 156 clinical trials (in collaboration with the Dutch HOVON group and the German AMLSG group)
- Preudhomme C, Sagot C, Boissel N, Cayuela JM, Tigaud I, de Botton S, Thomas X, Raffoux E, Lamandin C, Castaigne S, Fenaux P, Dombret H; ALFA Group. Favorable prognostic significance of CEBPA mutations in patients with de novo acute myeloid leukemia: a study from the Acute Leukemia French Association (ALFA). Blood. 2002 Oct 15;100(8):2717-23.
- Boissel N, Renneville A, Biggio V, Philippe N, Thomas X, Cayuela JM, Terre C, Tigaud I, Castaigne S, Raffoux E, De Botton S, Fenaux P, Dombret H, Preudhomme C. Prevalence, clinical profile, and prognosis of NPM mutations in AML with normal karyotype. Blood. 2005 Nov 15;106(10):3618-20.
- Boissel N, Nibourel O, Renneville A, Gardin C, Reman O, Contentin N, Bordessoule D, Pautas C, de Revel T, Quesnel B, Huchette P, Philippe N, Geffroy S, Terre C, Thomas X, Castaigne S, Dombret H, Preudhomme C. Prognostic impact of isocitrate dehydrogenase enzyme isoforms 1 and 2 mutations in acute myeloid leukemia: a study by the Acute Leukemia French Association group. J Clin Oncol. 2010 Aug 10;28(23):3717-23.
- Janin M, Mylonas E, Saada V, Micol JB, Renneville A, Quivoron C, Koscielny S, Scourzic L, Forget S, Pautas C, Caillot D, Preudhomme C, Dombret H, Berthon C, Barouki R, Rabier D, Auger N, Griscelli F, Chachaty E, Leclercq E, Courtier MH, Bennaceur-Griscelli A, Solary E, Bernard OA, Penard-Lacronique V, Ottolenghi C, de Botton S. Serum 2-hydroxyglutarate production in IDH1- and IDH2-mutated de novo acute myeloid leukemia: a study by the Acute Leukemia French Association group. J Clin Oncol. 2014 Feb 1;32(4):297-305.
- Duployez N, Marceau-Renaut A, Boissel N, Petit A, Bucci M, Geffroy S, Lapillonne H, Renneville A, Ragu C, Figeac M, Celli-Lebras K, Lacombe C, Micol JB, Abdel-Wahab O, Cornillet P, Ifrah N, Dombret H, Leverger G, Jourdan E, Preudhomme C. Comprehensive mutational profiling of core binding factor acute myeloid leukemia. Blood. 2016 May 19;127(20):2451-9.
- Balsat M, Renneville A, Thomas X, de Botton S, Caillot D, Marceau A, Lemasle E, Marolleau JP, Nibourel O, Berthon C, Raffoux E, Pigneux A, Rodriguez C, Vey N, Cayuela JM, Hayette S, Braun T, Coudé MM, Terre C, Celli-Lebras K, Dombret H, Preudhomme C, Boissel N. Postinduction Minimal Residual Disease Predicts Outcome and Benefit From Allogeneic Stem Cell Transplantation in Acute Myeloid Leukemia With NPM1 Mutation: A Study by the Acute Leukemia French Association Group. J Clin Oncol. 2017 Jan 10;35(2):185-193.
- Fournier E, Duployez N, Ducourneau B, Raffoux E, Turlure P, Caillot D, Thomas X, Marceau-Renaut A, Chantepie S, Malfuson JV, Lemasle E, Cheok M, Celli-Lebras K, Guerin E, Terré C, Lambert J, Pautas C, Dombret H, Castaigne S, Preudhomme C, Boissel N. Mutational profile and benefit of gemtuzumab ozogamicin in acute myeloid leukemia. Blood. 2020 Feb 20;135(8):542-546.
- Fenwarth L, Thomas X, de Botton S, Duployez N, Bourhis JH, Lesieur A, Fortin G, Meslin PA, Yakoub-Agha I, Sujobert P, Dumas PY, Récher C, Lebon D, Berthon C, Michallet M, Pigneux A, Nguyen S, Chantepie S, Vey N, Raffoux E, Celli-Lebras K, Gardin C, Lambert J, Malfuson JV, Caillot D, Maury S, Ducourneau B, Turlure P, Lemasle E, Pautas C, Chevret S, Terré C, Boissel N, Socié G, Dombret H, Preudhomme C, Itzykson R. A personalized approach to guide allogeneic stem cell transplantation in younger adults with acute myeloid leukemia. Blood. 2021 Jan 28;137(4):524-532.
- Duchmann M, Micol JB, Duployez N, Raffoux E, Thomas X, Marolleau JP, Braun T, Adès L, Chantepie S, Lemasle E, Berthon C, Malfuson JV, Pautas C, Lambert J, Boissel N, Celli-Lebras K, Caillot D, Turlure P, Vey N, Pigneux A, Recher C, Terré C, Gardin C, Itzykson R, Preudhomme C, Dombret H, de Botton S. Prognostic significance of concurrent gene mutations in intensively treated patients with IDH-mutated AML: an ALFA study. Blood. 2021 May 20;137(20):2827-2837.
- Itzykson R, Fournier E, Berthon C, Röllig C, Braun T, Marceau-Renaut A, Pautas C, Nibourel O, Lemasle E, Micol JB, Adès L, Lebon D, Malfuson JV, Gastaud L, Goursaud L, Raffoux E, Wattebled KJ, Rousselot P, Thomas X, Chantepie S, Cluzeau T, Serve H, Boissel N, Terré C, Celli-Lebras K, Preudhomme C, Thiede C, Dombret H, Gardin C, Duployez N. Genetic identification of patients with AML older than 60 years achieving long-term survival with intensive chemotherapy. Blood. 2021 Aug 19;138(7):507-519.
- Lambert J, Lambert J, Thomas X, Marceau-Renaut A, Micol JB, Renneville A, Clappier E, Hayette S, Récher C, Raffoux E, Pigneux A, Berthon C, Terré C, Celli-Lebras K, Castaigne S, Boissel N, Rousselot P, Preudhomme C, Dombret H, Duployez N. Early detection of WT1 measurable residual disease identifies high-risk patients, independent of transplantation in AML. Blood Adv. 2021 Dec 14;5(23):5258-5268.
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