SNDROMES MIELODISPLSTICAS - .SNDROMES MIELODISPLSTICAS . Silvia M M Magalh£es. Universidade

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Transcript of SNDROMES MIELODISPLSTICAS - .SNDROMES MIELODISPLSTICAS . Silvia M M Magalh£es. Universidade

  • DIANSTICO E CLASSIFICAONOVOS CONCEITOS

    SNDROMES MIELODISPLSTICAS

    Silvia M M MagalhesUniversidade Federal do Cear

  • DECLARAO DE CONFLITO DE INTERESSE

    Nenhum conflito de interesse

  • Myelodysplastic syndrome is a heterogeneous group of bone marrow neoplasms characterized by ineffective hematopoiesis, peripheral blood

    cytopenias and a significant risk of progression to acute myeloid leukemia

    https://www.google.com.br/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&ved=0ahUKEwjT9NbmvZrQAhWKkpAKHYhxCW4QjRwIBw&url=https://www.steamgifts.com/discussion/l250z/20-years-of-life&psig=AFQjCNGMtudX91uCgqil8oTIk3rmMboKJQ&ust=1478739963398917

  • Neukirchen J et al Leuk Res 2015; 39: 679.

    The improvement of the prognosis was restricted to high-riskMDS patients diagnosed between 2002 and 2014 in comparisonto the patient group diagnosed between 1982 and 2001(19 vs. 13 months, p < 0.001).

    The prognosis of low-risk MDS patients did not changesignificantly.

    Dusseldorf - Germany

    1982 - 2001

    2002 - 2014

  • MDS OVERALL SURVIVAL

    Gangat N et al. Blood Cancer J 2016 Apr; 6: e414.

    2004 AZACITIDINE2005 LENALIDOMIDE2006 DECITABINE

  • OUTCOME OF MDS PATIENTS

    Steensma DP Leuk Lymphoma 2016; 57: 17.

  • Platzbecker U et al Haematologica 2016; 101: 891

    NEW CONCEPTSPHISIOPATHOLOGY TREATMENT

    https://www.google.com.br/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwjh99iBv5rQAhUFFJAKHRX9BjgQjRwIBw&url=https://sevenstories10years.wordpress.com/2015/03/20/10-years-of-seven-stories-in-numbers/&bvm=bv.138169073,d.Y2I&psig=AFQjCNECma5tyXJILtzl2xm3dO-kuiOh_w&ust=1478740261825426

  • NOVOS CONCE

  • FAB 1982

    OMS 2001

    OMS 2008

    OMS 2016

    CLASSIFICAO

  • Arber DA et al Blood 2016 May; 127: 2391.

  • Classificao de acordo com displasias e % de blastos10% de displasia: critrio para diagnstico de SMDExcluso de causas no-clonaisCitopenias

    so condio necessria para o diagnsticocitopenias especficas tm pouco impacto na classificao no podem ser previstas a partir da linhagem displsica

    Arber DA et al Blood 2016 May; 127: 2391.

  • Definio de citopenia como definido pelo IPSS (1997)Hb< 10 g/dL

    neutrfilos < 1.800/mm3

    plaquetas

  • Greenberg P et al Blood. 2016 Aug 17 [Epub ahead of print]

    IWG-PM

  • IPSS (1997) PadroHEMOGLOBINA g/dL 10 12(M); 13 (H)NEUTROFILOS /mm3 1.800 1.800PLAQUETAS /mm3 100.000

  • Eliminados os termos:anemia refratrianeutropenia refratriatrombocitopenia refratria

    Steensma D Leuk Res 2016 Oct ; 51: 22.

  • SMD com sideroblastos em anel

    marcador molecular

    15% sideroblastos em anel (SA) 5% SA na presena de mutao SF3B1

    displasia em nica linhagem

    displasia em mltiplas linhagens

  • Leucemia mielide aguda

    Definio WHO 2008: LMA the 50% rule50% precursores eritrides20% blastos na populao no eritride

    Definio WHO 2016:20% blastos na populao de clulas nucleadas da medula ssea: LA

  • BLASTOS: 4 % do total de clulas nucleadas

    the 50% rule

    BLASTOS: 13% (4/30) do total de clulas noeritrides em paciente com 70% de precursoreseritrides

    AR AREB-2

    http://www.google.com.br/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwiZnNHy0JrQAhUFF5AKHcKbBQMQjRwIBw&url=http://animagehub.com/tag/arrow-images/&psig=AFQjCNGamgZRzi3e60_IGpX2uIhtGjcnIw&ust=1478745080483498

  • Bennett JM et al Leuk Res 2016 Aug; 47: 63.

    1,448 patients in the Dusseldorf MDS registry

  • Bennett JM et al Leuk Res 2016 Aug; 47: 63.

    In a series of MDS patients 15.7% of cases have 50% or more erythroid precursors.

    The 50% rule does not enhance the prognostic impact of the classifications on survival or time to transformation.

    This method of classification is no longer recommended.

  • Arenillas L et al J Clin Oncol 2016 Sep; 34: 3284.

    3,692 patients in the Spanish MDS registry

    Improved prognostic prediction after multivariable adjustment whenNEC was used as the denominator for the marrow blast percentage

    calculation, rather than TNC

  • THE IMPORTANCE OF ERYTHROID ENUMARATION IN MYELOID NEOPLASIA

    Zeidan AM et al Ann Hematol 2016 Oct [Epub ahead of print]

    Investigators: to combine datasets to analyze question more carefullyMorphologists: to be clear about the method used for blast calculation

  • SMD com del(5q)

    marcador molecular A presena de del(5q) isolada ou associada a uma alterao

    citogentica adicional exceto -7 ou del(7q) WHO 2016 recomenda pesquisa de mutao TP53: define

    pior resposta lenalidomida e pior prognstico

    Jadersten M et al. J Clin Oncol . 2011, 29:1971.

  • Saft L et al Haematologica. 2014; 99: 1041.

    This study validates p53 immunohistochemistry as a strong and useful predictive tool in patients with lower-risk del(5q) MDS

    Strong p53 expression in 1% of bone marrow progenitor cells (35% of patients) was significantly associated with:

    higher acute myeloid leukemia risk (p=0.0006)shorter overall survival (p=0.0175)lower cytogenetic response rate (p=0.009)

    p53

  • Saft L et al Haematologica. 2014; 99: 1041.

    Strong p53 expression in 1% of bone marrow progenitor cells

    p53

  • p53

    McGraw KL et al Haematologica. 2016 Aug;101: e320

    cellular TP53 mutation burden (next-generation sequencing) was strongly correlated with strength of p53 expression

  • McGraw KL et al Haematologica. 2016 Aug;101: e320

    p53

  • Belickova M et al Oncotarget 2016 Jun 14; 7: 36266

    high correlation in the mutational data from cells of the peripheral blood and those of the bone marrow: peripheral blood is a reliable source for

    mutation monitoring

  • INDOLENT MYELOID HEMATOPOIETIC DISORDERS

  • ICUS

    IDUSCHIPCCUS

  • HEALTH CHIP CCUS MDS

    Moyo TK et al Curr Hematol Malig Rep 2016 Oct 12. [Epub ahead of print]

    DIAGNOSIS - WHAT IS THE ROLE OF MOLECULAR TESTING?

    identification of genetic mutations cannot lead to a diagnosis of MDS if morphologic criteria are not met

  • MOLECULAR TESTING IN PATIENTS WITH SUSPECTED MYELODYSPLASTIC

    SYNDROMES

    Moyo TK et al Curr Hematol Malig Rep 2016 Oct [Epub ahead of print]

  • Moyo TK et al Curr Hematol Malig Rep 2016 Oct 12. [Epub ahead of print]

  • IPSS-RM

    http://www.google.com.br/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwjB4en7pZ7PAhXFkJAKHSy1DEMQjRwIBw&url=http://www.clipartkid.com/cute-question-mark-cliparts/&psig=AFQjCNGrX4ih0tMCOMx51usDaj4SMgcreA&ust=1474472923878707

  • Malcovati L et al Blood 2014; 124: 1513.

  • the prognostic overlap between the genomic and clinical data highlights the challenge in

    combining clinical and mutational data

    Papaemmanuil E et al Blood 2013; 122: 3616.Haferlach T et al Leukemia 2014; 28: 241.

  • 508 MDS treated patients (primary, secondary and CMML)

    training cohort: 333validation cohort: 175

    Nazha A et al Leukemia 2016 Nov; 30: 2214.

  • The addition of mutational data to the IPSS-R makes itdynamic, increases the C-index substantially andenhances its predictive ability in treated MDS patientsregardless of their initial or subsequent therapies (C-index 0.73)

    Independent significant prognostic factors for survivalincluded age, IPSS-R, EZH2, SF3B1 and TP53

    Nazha A et al Leukemia 2016 Nov; 30: 2214.

    http://www.google.com.br/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwiTvbv60ZrQAhVDCpAKHfccDlsQjRwIBw&url=http://www.nature.com/leu/&bvm=bv.138169073,d.Y2I&psig=AFQjCNH_a_Zrohgrkwui-jJMak9Wk5pAEw&ust=1478745373738945

  • Nazha A et al Leukemia 2016 Nov; 30: 2214.

    http://www.google.com.br/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwiTvbv60ZrQAhVDCpAKHfccDlsQjRwIBw&url=http://www.nature.com/leu/&bvm=bv.138169073,d.Y2I&psig=AFQjCNH_a_Zrohgrkwui-jJMak9Wk5pAEw&ust=1478745373738945

  • Nazha A et al Leukemia 2016 Nov; 30: 2214.

    Validation in a larger cohort from a multi-institutional data set to confirm this result andassure the translation of this model into the clinicis currently underway through the InternationalWorking Group (IWG-PM) .

  • UNIVERSIDADE FEDERAL DO CEARHospital Universitrio Walter Cantdio

    Servio de Hematologia

    silviamm@ufc.br

    Nmero do slide 1Nmero do slide 2Nmero do slide 3Nmero do slide 4MDS OVERALL SURVIVALOUTCOME OF MDS PATIENTSNmero do slide 7Nmero do slide 8Nmero do slide 9Nmero do slide 10Nmero do slide 11Nmero do slide 12Nmero do slide 13Nmero do slide 14Nmero do slide 15SMD com sideroblastos em anelmarcador molecularLeucemia mielide agudaNmero do slide 18Nmero do slide 19Nmero do slide 20Nmero do slide 21Nmero do slide 22Nmero do slide 23SMD com del(5q) marcador molecularNmero do slide 25Nmero do slide 26Nmero do slide 27Nmero do slide 28Nmero do slide 29Nmero do slide 30Nmero do slide 31Nmero do slide 32Nmero do slide 33Nmero do slide 34Nmero do slide 35Nmero do slide 36Nmero do slide 37Nmero do slide 38Nmero do slide 39Nmero do slide 40Nmero do slide 41Nmero do slide 42Nmero do slide 43Nmero do slide 44