Considerable progress has been made in the treatment of acute myeloid leukemia (AML). However, current therapeutic results are still unsatisfactory in untreated high-risk patients and poorer in those with primary refractory or relapsed disease. In older patients, reluctance by clinicians to treat unfit patients, higher AML cell resistance related to more frequent adverse karyotype and/or precedent myelodysplastic syndrome, and preferential involvement of chemorefractory early hemopoietic precursors in the pathogenesis of the disease further account for poor prognosis, with median survival lower than six months. A general agreement exists concerning the administration of aggressive salvage therapy in young adults followed by allogeneic stem cell transplantation; on the contrary, different therapeutic approaches varying in intensity, from conventional salvage chemotherapy based on intermediate–high-dose cytarabine to best supportive care, are currently considered in the relapsed, older AML patient population. Either patients’ characteristics or physicians’ attitudes count toward the process of clinical decision making. In addition, several new drugs with clinical activity described as “promising” in uncontrolled single-arm studies failed to improve long-term outcomes when tested in larger randomized clinical trials. Recently, new agents have been approved and are expected to consistently improve the clinical outcome for selected genomic subgroups, and research is in progress in other molecular settings. While relapsed AML remains a tremendous challenge to both patients and clinicians, knowledge of the molecular pathogenesis of the disease is fast in progress, potentially leading to personalized therapy in most patients.

IDH1/2 mutations are common in acute myeloid leukemia (AML) and represent a therapeutic target. The GIMEMA AML1516 observational protocol was designed to study the prevalence of IDH1/2 mutations and associations with clinico-biological parameters in a cohort of Italian AML patients. We analyzed a cohort of 284 AML consecutive patients at diagnosis, 139 females and 145 males, of a median age of 65 years (range: 19–86). Of these, 38 (14%) harbored IDH1 and 51 (18%) IDH2 mutations. IDH1/2 mutations were significantly associated with WHO PS >2 (p < 0.001) and non-complex karyotype (p = 0.021) when compared to IDH1/2-WT. Furthermore, patients with IDH1 mutations were more frequently NPM1-mutated (p = 0.007) and had a higher platelet count (p = 0.036). At relapse, IDH1/2 mutations were detected in 6 (25%) patients. As per the outcome, 60.5% of IDH1/2-mutated patients achieved complete remission; overall survival and event-free survival at 2 years were 44.5% and 36.1%, respectively: these rates were similar to IDH1/2-WT. In IDH1/2-mutated patients, high WBC proved to be an independent prognostic factor for survival. In conclusion, the GIMEMA AML1516 confirms that IDH1/2 mutations are frequently detected at diagnosis and underlines the importance of recognizing IDH1/2-mutated cases up-front to offer the most appropriate therapeutic strategy, given the availability of IDH1/2 inhibitors.

POEMS syndrome is a disease due to underlying plasma cells (PC) dyscrasia. Because of its rarity, there are no established upfront or second-line therapies. Treatment is borrowed from other PC diso...

Data on the use of azacytidine and decitabine as salvage therapy for acute myeloid leukemia are limited. We retrospectively reviewed clinical records of 100 patients treated with hypomethylating agents (HMA) as salvage therapy in nine Italian institutions. A total of 24% of patients obtained a response to HMA (CR, PR, or CRi), while 26% showed a stable disease (SD); 50% of patients experienced progressive disease. Median OS was 6.5 months. OS in patients with de novo AML was 6.1 months, while OS in patients with secondary AML (sAML) was 12.3 months (p = 0.037). Median OS after HMA in patients with SD as best response to HMA was similar to median OS in patients with response to HMA (10.6 months vs. 13 months). On multivariate analysis, OS difference between patients who obtained a response versus patients who did not was significant (p = 0.0037). OS difference in sAML was significantly better than in de novo AML (p < 0.00001). HMA showed a remarkable efficacy in terms of response rate and OS in a subgroup of patients (sAMLs), historically characterized by a poor outcome. Therefore, 5Azacitidine and decitabine may represent a good clinical option in a selected patient population with relapsed or refractory AML, unsuitable for allo-HSCT.