Adult Acute Myeloid Leukemia Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Classification of Adult Acute Myeloid Leukemia
Patients with FLT3/ITD mutations, and possibly those with FLT3 point mutations, are consistently reported to have an increased relapse rate and reduced overall survival.[40,41] The complete remission rate for patients with FLT3 mutant AML is generally reported to be no different than that for patients with AML with nonmutant FLT3, but most studies examining this clinical parameter used results from patients treated with intensive chemotherapy regimens, and some data are available to suggest that the conventional 7+3 regimen leads to a reduced remission rate in this group of patients.[Level of evidence: 3iiiDiv]
One study from the German-Austrian Acute Myeloid Leukemia Study Group examined data on 872 patients with cytogenetically normal AML treated with intensive induction and postremission regimens over an 11-year period.[Level of evidence: 3iiiA] The study group found that patients with a mutant CCAAT/enhancer binding-protein alpha (CEBPA) or a nucleophosmin mutation (NPM1) without fms-related tyrosine kinase 3-internal tandem duplication (FLT3-ITD) had higher complete response rates, disease-free survival rates, and overall survival (OS) rates (with a 4-year OS rate of 62% and 60%, respectively) than other cytogenetically normal AML patients (who had a 4-year OS rate of between 25% and 30%). As yet, no clear strategy exists for improving patient outcome in FLT3 mutant AML, or in patients with abnormalities other than CEBPA or the NPM1 without the FLT3-ITD, but small molecule FLT3 inhibitors are in development, and the role of allogeneic transplant is being considered.
Acute Myeloid Leukemia With Multilineage Dysplasia
Note: In the WHO classification, refractory anemia with excess blasts in transformation (RAEB-t) is no longer considered a distinct clinical entity and is instead included within the broader category "AML with multilineage dysplasia" as one of the following:
- AML evolving from an MDS.
- AML following an MDS.
AML with multilineage dysplasia is characterized by 20% or more blasts in the blood or bone marrow and dysplasia in two or more myeloid cell lines, generally including megakaryocytes. To make the diagnosis, dysplasia must be present in 50% or more of the cells of at least two lineages and must be present in a pretreatment bone marrow specimen.[4,44] AML with multilineage dysplasia may occur de novo or following MDS or a myelodysplastic and myeloproliferative disorder (MDS and MPD). (Refer to the PDQ summaries on Myelodysplastic Syndromes Treatment and Myelodysplastic/ Myeloproliferative Neoplasms for more information.) The diagnostic terminology "AML with multilineage dysplasia evolving from a myelodysplastic syndrome" should be used when an MDS precedes AML.
This category of AML occurs primarily in older patients.[4,45] Patients with this type of AML frequently present with severe pancytopenia.
Common morphologic features include the following:
- Multilineage dysplasia in the blood or bone marrow.
- Dysplasia in 50% or more of the cells of two or more cell lines.
- Dysgranulopoiesis (neutrophils with hypogranular cytoplasm, hyposegmented nuclei or bizarrely segmented nuclei).
- Dyserythropoiesis (megaloblastic nuclei, karyorrhexis, or multinucleation of erythroid precursors and ringed sideroblasts).
- Dysmegakaryopoiesis (micromegakaryocytes and normal size or large megakaryocytes with monolobed or multiple separated nuclei).