LEUCEMIA MIELOIDE AGUDA M4 PDF

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La leucemia mielógena aguda también se conoce como «leucemia mieloide aguda», «leucemia mieloblástica aguda», «leucemia. Aleukemic acute myeloid leukemia | Leucemia mielóide aguda aleucémica. Article (PDF Mielóide Aguda, subtipo M4. A leucemia mielóide aguda (LMA) é. En la leucemia mieloide aguda, se fabrica una cantidad excesiva de glóbulos blancos inmaduros (denominados blastos mieloides). Se trata de células.

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Expert-reviewed information summary about the treatment of childhood acute myeloid leukemia, myelodysplastic syndromes, and other myeloproliferative disorders. This PDQ aguds information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of childhood acute myeloid leukemia and other myeloid malignancies.

It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions. Dramatic improvements in survival have been achieved for children and adolescents with cancer. Myelodysplastic syndromes occur much less frequently in children than leucemi adults and almost invariably represent clonal, preleukemic conditions that may evolve from congenital marrow failure syndromes such as Fanconi anemia and Shwachman-Diamond syndrome.

The general characteristics of myeloid leukemias and other myeloid malignancies are described below:. TAM blasts most commonly have megakaryoblastic differentiation characteristics and distinctive mutations involving the GATA1 gene.

TAM may occur in phenotypically normal infants with genetic mosaicism in the bone marrow for trisomy While TAM is generally not characterized by cytogenetic abnormalities other than trisomy 21, the presence of additional cytogenetic findings may predict an increased risk of developing subsequent Mieloive. The presence of a karyotype abnormality in a hypocellular marrow agudaa consistent with MDS and transformation to AML should be expected.

JMML characteristically presents with hepatosplenomegaly, lymphadenopathy, fever, and skin rash along with an elevated white blood cell WBC count and increased circulating monocytes.

In addition, patients often have an elevated hemoglobin F, hypersensitivity mkeloide the leukemic cells to granulocyte-macrophage colony-stimulating factor GM-CSFmonosomy 7, and leukemia auda mutations in a gene involved in RAS pathway signaling e.

CML is a clonal panmyelopathy that involves all hematopoietic cell lineages. While the WBC count can be extremely elevated, the bone marrow does not show increased numbers of leukemic blasts during the chronic phase of this disease. CML is caused by the presence of the Philadelphia chromosome, a translocation between chromosomes mileoide and 22 i.

Other chronic myeloproliferative syndromes, such as polycythemia vera and essential thrombocytosis, are extremely rare in children.

Genetic abnormalities cancer predisposition syndromes are associated with the development of AML. There is a high concordance rate of AML in identical twins; however, this mielolde not believed to be related to genetic risk, but rather to shared circulation and the inability of one twin to reject leukemic cells from the other twin gauda fetal development.

There is an estimated twofold to fourfold increased risk of developing leukemia for the fraternal twin of a pediatric leukemia patient up to about age 6 years, after which the risk is not significantly greater than that of the general population. The development of AML leucemiia also been associated with a variety of inherited, acquired, and familial syndromes that result from chromosomal imbalances mieloise instabilities, defects in DNA repair, altered cytokine receptor or signal transduction pathway activation, and altered protein synthesis.

Nonsyndromic genetic susceptibility to AML is also being studied. This classification system, which has been replaced by the World Health Organization WHO system described below, categorized AML into major subtypes aguea on the basis of morphology and immunohistochemical detection of lineage markers.

Other extremely rare leucmeia of AML include acute eosinophilic leukemia and acute basophilic leukemia. Inthe WHO proposed a new classification system that incorporated diagnostic cytogenetic information and that more reliably correlated with outcome. Inthe Meloide classification underwent revisions to incorporate the kieloide knowledge of leukemia biomarkers that are significantly important to the diagnosis, prognosis, and treatment of leukemia. With emerging technologies aimed at genetic, epigenetic, proteomic, and immunophenotypic classification, AML classification will certainly continue to evolve and provide informative prognostic and biologic guidelines to clinicians and researchers.

For the group of acute leukemias that have characteristics of both AML and acute lymphoblastic leukemia ALLthe acute leukemias of ambiguous lineage, the WHO classification system is summarized in Table 1. The criteria for lineage assignment for a diagnosis of mixed phenotype acute leukemia MPAL are provided in Table 2. Biphenotypic cases represent the majority of mixed phenotype leukemias.

Some studies suggest that patients with biphenotypic leukemia may fare better with a lymphoid, as opposed to a myeloid, treatment regimen, although the optimal treatment for patients remains unclear. Traditionally, Agda classification systems have been divided into several distinct categories based on the presence of the following:.

The revision to the WHO classification has removed focus on the specific lineage anemia, thrombocytopenia, or neutropenia and now distinguishes cases with dysplasia in single versus multiple lineages. No changes were made in the childhood MDS classification, and the category of refractory cytopenia of childhood is retained as a provisional entity. The bone marrow and peripheral blood findings for the myelodysplastic syndromes according to the WHO classification schema are summarized in Tables 3 and 4.

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A pediatric approach to the WHO classification of myelodysplastic and myeloproliferative diseases was published in For instance, refractory anemia with ring sideroblasts is rare in children, and refractory anemia and refractory anemia with excess blasts is more common. This group can show mixed myeloproliferative and moeloide myelodysplastic features. A subgroup of children younger than 4 years at diagnosis with JMML associated with monosomy 7 are considered to have a subtype of JMML characterized by lower WBC count, higher percentage of circulating monocytes, higher mean cell agyda for red blood cells, a lower bone marrow myeloid to erythroid ratio, and, often, normal to moderately increased fetal hemoglobin.

Special histochemical stains performed on bone marrow specimens of children agdua acute leukemia can be helpful to confirm their diagnosis. The stains most commonly used include myeloperoxidase, periodic acid-Schiff, Sudan Black B, and esterase.

Histochemical stains have been mostly replaced by flow cytometric immunophenotyping. The midloide of monoclonal antibodies to determine cell-surface antigens of AML cells is helpful to reinforce the histologic diagnosis.

Various lineage-specific monoclonal antibodies that detect antigens on AML cells should be used at the time of initial diagnostic workup, along with a battery of lineage-specific T-lymphocyte and B-lymphocyte markers to help distinguish AML from ALL and acute leukemias of ambiguous lineage.

Leuucemia aberrant expression leuucemia lymphoid-associated antigens by Mieloidd cells is relatively common but generally has no prognostic significance. These cases are distinct from ALL with myeloid coexpression in that the mleloide lineage cannot be determined by immunophenotypic and histochemical studies. The definition of leukemia of ambiguous lineage varies among studies, although most investigators now use criteria established by the European Group for the Immunological Characterization of Leukemias EGIL or the more stringent WHO criteria.

This is not the case for the EGIL classification. The revision to the WHO classification also denotes that in some cases, leukemia with otherwise classic B-cell ALL immunophenotype may also express low-intensity MPO without other myeloid features, and the clinical significance of that finding is unclear such that one should be cautious before designating these cases as MPAL.

Genetic analyses of leukemia using both conventional cytogenetic methods and molecular methods are performed agida children with acute myeloid leukemia AML because both chromosomal and molecular abnormalities are important diagnostic and prognostic markers. Leukemias with the chromosomal abnormalities t 8;21 and inv 16 are called core-binding factor leukemias; core-binding factor a transcription factor involved in hematopoietic stem cell differentiation is disrupted by each of these abnormalities.

Molecular abnormalities can aid in risk stratification and aguds allocation. For example, mutations of NPM and CEBPA are associated with favorable outcome while certain mutations of FLT3 portend a high risk of relapse, and identifying these mutations may allow for targeted therapy.

The revision to the World Health Organization WHO classification of myeloid neoplasms and acute leukemia emphasizes that recurrent chromosomal translocations in pediatric AML may be unique or have a different prevalence than in adult AML.

The pediatric AML chromosomal translocations that are found by conventional chromosome analysis and those that are cryptic identified only with fluorescence in situ hybridization or molecular techniques occur at higher rates than in adults. These recurrent translocations are summarized in Table 6. Table 6 also shows, in the bottom three rows, additional relatively common recurrent translocations observed in children with AML.

Specific recurring cytogenetic and molecular abnormalities are briefly described below. The abnormalities are listed by those in clinical use that identify patients with favorable or unfavorable prognosis, followed by other abnormalities. The nomenclature of the revision to the WHO classification of myeloid neoplasms and acute leukemia is incorporated for disease entities where relevant. Quantitative RT-PCR allows identification of the three common transcript variants and is used for monitoring response on treatment and early detection of molecular relapse.

Other much less common translocations involving the retinoic acid receptor alpha can also result in APL e.

Identification of cases with the t 11;17 q23;q21 is important because of their decreased sensitivity to all- trans retinoic acid. Studies of children with AML suggest a lower rate of occurrence of NPM1 mutations in children compared with adults with normal cytogenetics. NPM1 mutations are associated with a favorable prognosis in patients with AML characterized by a normal karyotype. For the pediatric population, conflicting reports have been published regarding the prognostic significance of an NPM1 mutation when a FLT3-ITD mutation sguda also present.

However, very low numbers of children with single-allele mutants were included in these two studies only 13 total patientswhich makes a conclusion regarding the prognostic significance of single-allele CEBPA mutations in children premature.

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Translocation t(8;21)(q22;q22) in Acute Myeloid Leukaemia

GATA1 mutations confer increased sensitivity to cytarabine by down-regulating cytidine deaminase mieloids, possibly providing an explanation for the superior outcome of children with Down syndrome and M7 AML when treated with cytarabine-containing regimens. In the past, patients with del 7q were also considered to be at high risk of treatment failure, and data from adults with AML support a poor prognosis for both del 7q and monosomy 7. However, outcome for children with del 7qbut not monosomy 7, appears comparable to that of other children with AML.

The presence of del 7q does not abrogate the prognostic significance of favorable cytogenetic characteristics e. Chromosome 5 and 7 abnormalities appear to lack prognostic significance in AML patients with Down syndrome who are aged 4 years and younger. It remains unclear whether FLT3 mutations are associated with poorer prognosis in patients with APL who are treated with modern therapy that includes all- trans retinoic acid and mieloidd trioxide.

Activating point mutations of FLT3 have also been identified in both adults and children with AML, although the clinical significance of these mutations is not clearly defined. However, significantly older median ages are seen at presentation of pediatric cases with t 6;11 q27;q23 12 years and t 11;17 q23;q21 9 years.

Anemias y Leucemias

However, as the KMT2A gene can leucejia in translocations with many different fusion partners, the specific fusion partner appears to influence prognosis, as demonstrated by a large international retrospective study evaluating outcome for children with 11q or KMT2A-rearranged AML. While reports from single clinical trial groups have variably described more favorable prognosis for patients with AML who have t 9;11 p An international collaborative retrospective study of 51 t 1;22 cases reported that patients with this abnormality had a 5-year EFS of A substantial proportion of infants diagnosed with t 8;16 AML in the first month of life show spontaneous remission, although AML recurrence may occur peucemia to years later.

These observations suggest that a watch and wait policy could be considered in cases of t 8;16 AML diagnosed in the neonatal period if close long-term monitoring can be ensured. The prognostic significance of KIT mutations occurring in pediatric core-binding factor AML remains unclear, although the largest pediatric study reported to date observed no prognostic significance for KIT mutations. Activating mutations in CSF3R are also observed in patients with severe congenital neutropenia.

These mutations are not the cause of severe congenital neutropenia, but rather arise as somatic mutations and can represent an early step in the pathway to AML. Leukemia is considered to be disseminated in the hematopoietic system at diagnosis, even in children with acute myeloid leukemia AML who present with isolated chloromas also called granulocytic or myeloid sarcomas.

If these children do not receive systemic chemotherapy, they invariably develop AML in months or years. AML may invade nonhematopoietic extramedullary tissue such as meninges, brain parenchyma, testes or ovaries, or skin leukemia cutis.

Mieloied leukemia is more common in infants than in older children with AML. It can also be diagnosed by mieloiee of a chloroma.

Lrucemia remission CR has traditionally been agua in the United States using morphologic criteria such as the following:.

Alternative definitions of remission using morphology are used in AML because of the prolonged myelosuppression caused by intensive chemotherapy and include CR with incomplete platelet recovery and CR with incomplete marrow recovery typically absolute neutrophil count.

Whereas the use of incomplete platelet recovery provides a clinically meaningful response, the traditional CR definition remains the gold standard because patients in CR were found to be more likely to survive longer than those in incomplete platelet recovery. Achieving a hypoplastic bone marrow using morphology is usually the first step in obtaining remission in AML with the exception ,ieloide the M3 subtype acute promyelocytic leukemia [APL] ; a hypoplastic marrow phase is often not necessary before the achievement of remission in APL.

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Correlation with blood cell counts and clinical status is imperative in passing final judgment on the results of early bone marrow findings in AML. If the findings are in doubt, the bone marrow aspirate should be repeated in 1 to 2 weeks.

In addition to morphology, more precise methodology e. Refer to the Prognostic Factors in Childhood AML section of this summary for more information about these methodologies. The mainstay of the therapeutic approach is systemically administered combination chemotherapy. Approaches involving risk-group stratification and biologically targeted therapies are being tested to improve antileukemic treatment while sparing normal tissue.

Optimal treatment of AML requires control of bone marrow and systemic disease.