Diagnosis
The diagnosis of DS-AMKL in young children is indicated by: a history of TMD; findings of increased presence of blast cells (e.g. ≥20% of nucleated cells) that have the megakaryoblast phenotype in blood and/or bone marrow as defined by the morphology of these cells in blood or bone marrow smears; failure to obtain a bone marrow aspirate because of marrow fibrosis; and immunophenotyping analyses of platelet precursor cells lineage as determined by flow cytometry and immunohistochemistry. Malignant megakaryoblasts are usually medium-sized to large cells with a high nuclear-cytoplasmic ratio. Nuclear chromatin is dense and homogeneous. There is scanty, variable basophilic cytoplasm which may be excessively vacuolated. An irregular cytoplasmic border is often noted in some of the megakaryoblasts and occasionally projections resembling budding atypical platelets are present. Megakaryoblasts lack myeloperoxidase (MPO) activity and stain negatively with Sudan Black B. They are alpha naphthyl butyrate esterase negative and manifest variable alpha naphthyl acetate esterase activity usually in scattered clumps or granules in the cytoplasm. PAS diastase staining varies from negative to focal or granular positivity to strongly positive.
Immunochemical analyses, often conducted by flow cytometry, of the surface antigens on leukemic blast cells are positive for CD41, CD42b, CD51, and Von Willebrand factor in AMKL but not leukemia involving non-platelet malignant cells.Where indicated and available, the diagnosis of DS-AMKL is further supported by; immunophenotyping analysis using monoclonal antibody directed against megakaryocyte restricted antigen (CD41 and CD61) and DNA sequencing to detect GATA1  mutations that are projected to cause the gene to make GATA1-S but not GATA1 transcription factors. Treatment
The chemotherapy regimens used for all types of AMKL are similar to those used for AML. A final confirmation of safety and efficacy phase 3 study consisted of 4 cycles of induction therapy with cytarabine and daunorubicin followed by a single course of intensification therapy consisting of cytarabine and L-asparaginase, and concluded with a central nervous system consolidation course of 3 additional doses of intrathecal cytarabine. The dosages of cytarabine in this study were kept low because DS-AMKL patients proved highly susceptible to the toxic effects of the regimen which used a higher cytarabine dosage to treat AML. The low-dose cytarabine regimen achieved excellent results in DS-AMKL with relatively reduced overall toxicity and is currently recommended as a preferred treatment regimen for the disease.Autologous hematopoietic stem cell transplantation (i.e. transplantation of stem cells derived from the individual being transplanted) did not improve relapse-free survival in one large study of DS-AMKL. Allogenic hematopoietic stem cell transplantation (i.e.