Acute myeloid leukemia arising from chronic myelomonocytic leukemia during hypomethylating therapy

which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Acute myeloid leukemia arising from chronic myelomonocytic leukemia during hypomethylating therapy TO THE EDITOR: Acute myeloid leukemia (AML) arising from chronic myelomonocytic leukemia (CMML) exhibits a poor prognosis [1, 2] and represents a great challenge during hematological clinical practice. The introduction of hypomethylating therapies, such as azacitidine [3, 4] and decitabine [5], in CMML management has provided some important advances; however, currently the majority of CMML cases progress into AML. We present the characteristics of 2 patients, in whom the atypical and sudden progression from CMML to AML was observed when they were administered azacitidine. Previously, both cases had achieved a very good response to this agent. The first case is a 60-year-old man with a suspected therapy related CMML, which arose 3 years after receiving che-mo-radiotherapy treatment for a solid head and neck tumor. When diagnosed as having CMML, hypercellular bone marrow (BM) with 15% blasts was noted. Furthermore, the JAK2 V617F mutation was identified by quantitative PCR analysis, whereas standard cytogenetic and FISH analysis using BM and peripheral blood showed no abnormalities (normal karyotype). The MD Anderson Prognostic Scoring System (MDAPS) [6] classification was 4 (high risk). The patient received azacitidine at a dosage of 75 mg/m 2 for 5+2 days (excluding weekends) every 4 weeks. After the fourth cycle of azacitidine, complete remission (CR) of CMML (BM blasts ＜5%) was recorded, although the patient continued the treatment during allogeneic hematopoietic stem cell transplantation. However, soon after the sixth cycle of azacitidine, a sudden evolution into AML (myelo-monoblastic subtype) occurred. A very rapid transition from near normal peripheral blood counts to a very marked level of blastic leukocytosis was observed within 4 days: the WBC count was 120×10 9 /L and 70% of myelomonoblastic cells FISH analysis confirmed a deletion of the long arm of chromosome 7 in 80% of blastic cells. Molecular studies detected the previously observed JAK2 V617F mutation, as well as the IDH2 R172K mutation; however, no AML-related alterations , such as CBFb/MYH11, DEK/CAN, NPM1, FLT3, and RUNX1/ETO, were identified. The patient received 1 course of chemotherapy for AML but soon died of disease progression. The second case was a 72-year-old-man who was attended to because of pancytopenia with monocytosis. A BM aspirate and trephine biopsy showed hypercellular BM with 18% blasts, resulting in a diagnosis of …