transplantation of stem cells derived another individual) has given better disease-free survival results than autologous transplantation and, based on recent uncontrolled studies, should be considered in DS-AMKL cases that have relapsed after their first chemotherapy-induced complete remission. Prognosis
The 5-year event free survival, disease-free survival, and overall survival rate in the phase 3 clinical study in DS-AMKL were 79, 89, 84 percent, respectively. Other studies that use a treatment regimen similar to that used in the phase 3 clinical study report overall survival rates of ~80% and long-term survivals of 74-91%. However, DS-AMKL patients who relapse following chemotherapy have a far poorer outlook with 3 year overall survival rate in one study of only 26%. There also appears to be little role for stem cell transplantation in DS-AMKL given the success of initial chemotherapy and the relatively poor results in DS-AMKL patients given this transplantation. Non-DS-AMKL
Pathophysiology
The most common genetic abnormality occurring in non-Down-AMKL is a nonreciprocal translocation between the short or p arm at position 13 on chromosome 1 (i.e. 1p13) and the p arm at position 13 on chromosome 22 (i.e. 22p13). Nonreciprocal translocations are exchanges of genes between two chromosomes that are not homologs, i.e. that are not maternal and paternal copies of the same chromosome. This particular translocation, designated t(1;22)(p13;q13), occurs mainly in infants but also is seen in children up to the age of 7 years with non-DS-AMKL. This translocation involves the RBM15 gene on chromosome 1 and the MKL1 gene (also termed MRTFA) on chromosome 22 to create a RBM15-MKL1 fusion gene.
Non-DS-AMKL has many clinical and laboratory features similar to and must be distinguished from Acute panmyelosis with myelofibrosis, a disorder characterized by bone marrow fibrosis, abnormal megakaryocytes, macrocytic erythropoiesis, defects in neutrophil production, reduced blood levels of most circulating cells (i.e. pancytopenia), and low levels of circulating blast cells. Analyses of circulating and bone marrow blast cells for features of AMKL (see Diagnosis section of DS-AMKL) and genetic aberrations is helpful in distinguishing the two diseases. Treatment
In a review of 153 patients treated for non-DS-AMKL between 1990 and 2014 with various intensive chemotherapy protocols that included cytarabine, an anthracycline (e.g. daunorubicin, doxorubicin), and in 25% of cases human stem cell transplantation, the probability of overall 4 year survival rate, probability of 4 year event-free survival, and probability of 4 year cumulative relapse rate were 56, 51, and 29%, respectively. A more recent treatment regimen that is similar to that used to treat DS-AMKL as described above (except it employs the high dose of cytarabine used to treat AML) gives better results and has been recommended for non-DS-AMKL. The response to this regimen approached that seen in non-DS-AMKL, i.e. its complete remission and estimated 10 year survival rates were both 76%. Similar to DS-AMKL treatment regimens, allogenic rather than autologous stem cell bone marrow transplantation should be considered in non-DS-AMKL cases that have relapsed following their first chemotherapy-induced complete remission.