Myelodysplasia-Related Features of Acute Myeloid Leukemia Evolving From Philadelphia-Negative Myeloproliferative Neoplasms

Dear Editor, The WHO 2008 classification of myeloid neoplasms lists the following three diagnostic criteria for AML with myelodysplasia-related changes (MRC): AML arising from a previously diagnosed myelodysplastic syndrome (MDS) or MDS/myeloproliferative neoplasm (MPN), AML with an MDS-related cytogenetic abnormality, and AML with multi-lineage dysplasia [1]. However, a history of Philadelphia chromosome-negative MPN (Ph-MPN) does not warrant a diagnosis of AML with MRC. Here, we demonstrate that AML evolving from Ph-MPNs (MPN-AML) has similar cytogenetic characteristics and prognosis to AML evolving from MDS or MDS/MPN (MDS-AML). We identified 103 patients in our bone marrow archive who were diagnosed with AML that evolved from MDS (N =72), MDS/MPN (N=10), or Ph-MPN (N=21) from January 2006 to December 2014. The underlying Ph-MPNs included 13 (61.9%) cases of primary myelofibrosis (PMF), five (23.8%) of essential thrombocythemia (ET), and three (14.3%) of polycythemia vera (PV). MDS-related cytogenetic abnormalities were identified in 31 of 82 (37.8%) MDS-AML patients and in 12 of 21 (57.1%) patients with MPN-AML (P =0.175). The two most common abnormalities were a complex karyotype involving -5/del(5q) and isolated -7/del(7q) in all patients, without significant differences among patient groups (Fig. 1). Multi-lineage dysplasia was more often identified in patients with MDS-AML (28, 34.1%) than in patients with MPN-AML (2, 9.5%; P =0.031). Overall, 13 (61.9%) patients with MPN-AML were diagnosed with AML with MRC on the basis of cytogenetics or cytomorphology. Two patients with PMF received cytotoxic therapy before transformation of PMF to AML. During their progression to AML, one patient had a normal karyotype and the other had a complex karyotype, with both -5 and del(7q) already present during the PMF stage. The median overall survival (OS) and relapse-free survival (RFS) were 7.4 (5.2-9.2) and 22.5 (5.9-39.0) months, respectively, for patients with MDS-AML, and were 4.9 (1.3-11.9) and 4.0 (3.212.4) months, respectively, for those with MPN-AML. However, there were no differences in the OS (P =0.162) and RFS (P = 0.467) between the 2 patient groups (Fig. 2A). Among the MPN-AML patients, those with MRC features had a shorter OS than those without MRC (P =0.008; Fig. 2B). The patients with AML with MRC had significantly poorer clinical outcomes than those with not-otherwise-specified AML [2]. Similar to patients with MDS transforming to AML, a substantial proportion of PMF patients transform to AML [3]. Moreover,