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    • Azacitidine was administered at a dose of mg m daily

    2019-05-20

    Azacitidine was administered at a dose of 75mg/m2/daily subcutaneously for 7 consecutive days every 28days. Transient neutropenia was observed until the seventh erbb2 inhibitor of the azacitidine treatment was completed. A gradual increase in his blood cell count was noted and the patient eventually became transfusion independent. Hematological responses after 8 cycles of the azacitidine treatment were considered to be hematologic improvements, with erythroid (HI-E) and platelet (HI-P) responses according to the International Working Group (IWG) 2006 criteria (Table 1). A reduction in myelofibrosis occurred after 4 cycles and repeated bone marrow biopsies revealed a significant improvement in the grade of myelofibrosis (Fig. 1D). The percentage of myeloblasts after 8 cycles was 4.5%. However, the absolute neutrophil count (ANC) was less than 1.0×109/L. The efficacy of the azacitidine treatment was judged to be marrow complete remission (marrow CR) with HI-E and HI-P responses. The ANC increased gradually and exceeded 1.0×109/L. CR was obtained after 14 cycles of the azacitidine treatment (Table 1). A total of 20 cycles of this treatment have been completed to date. Hyperplastic bone marrow with mild myelofibrosis, an increased number of megakaryocytes, and tri-lineage dysplasia with severe dysmegakaryopoiesis still remains (Fig. 1E). Hematologic improvements have been ongoing for 12months, during which time 12 cycles of the azacitidine treatment have been completed (Table 1).
    Discussion The pathogenesis of myelofibrosis in MDS patients is unknown. Clinical trials on azacitidine demonstrated the significant and clinically meaningful prolongation of OS in high-risk MDS patients [1]. However, the successful response of MDS-F patients to the azacitidine treatment has not yet been reported. Although thalidomide was previously shown to have anti-fibrotic effects in a MDS-F patient [11], suitable therapeutic agents for MDS-F patients have not yet been established. Allogeneic SCT is currently the only curative treatment for MDS patients with/without myelofibrosis. The grade of myelofibrosis is known to affect the engraftment of allogeneic SCT in MDS patients; however, only severe myelofibrosis has been shown to influence survival due to the higher risk of relapse [2]. We showed that azacitidine exhibited therapeutic activity in our MDS-F patient. If the severity of myelofibrosis can be reduced by azacitidine, this treatment may lead to significant prolongation of OS after allogeneic SCT in MDS-F patients. Epigenetic changes play an important role in the pathogenesis of myeloid neoplasms. Decitabine was previously shown to be effective in an idiopathic myelofibrosis patient [12]. However, the pathogenesis of myelofibrosis in ET / PV patients remains unclear. A previous study that evaluated the activity of azacitidine in patients with myelofibrosis (primary and post-ET / PV) reported that 19 (70%) of 27 patients had the JAK2 (V617F) mutation [3]. Responses included limited clinical improvements in 7 (21%) patients and a partial response in only 1 (3%) patient. These findings indicated that azacitidine exhibited limited therapeutic activity for myelofibrosis in patients with myeloproliferative neoplasms such as primary and post-ET / PV myelofibrosis. Whereas, ruxolitinib, a potent and selective JAK1 and 2 inhibitor, as compared with the best available therapy, in patients with myelofibrosis (primary and post-ET / PV) has demonstrated rapid reductions in splenomegaly, marked improvement in myelofibrosis-associated symptoms, and the prolongation of overall survival regardless of their status with respect to the JAK2 (V617F) mutation [9]. JAK1 and 2 inhibitor therapy was considered for our patient with myelofibrosis if azacitidine treatment was not successful.
    Introduction NMAT has emerged over the last 2 decades as a promising alternative with reduced TRM for patients who would otherwise not be eligible for MAT. Aggressive disease poses a challenge, while patients in complete remission (CR) at the time of transplant can benefit from NMAT [1,2]. We summarize our prospective phase II clinical trial of fludarabine and cyclophosphamide for NMAT, with a focus on evaluating the efficacy of NMAT in patients with high-risk/aggressive disease.