Acute myeloid leukemia (AML) in older patients is characterized by unfavorable prognosis due to adverse disease features and a high rate of treatment-related complications. Classical therapeutic options range from intensive chemotherapy in fit patients, potentially followed by allogeneic hematopoietic cell transplantation (allo-HCT), to hypomethylating agents or palliative care alone for unfit/frail ones. In the era of precision medicine, the treatment paradigm of AML is rapidly changing. On the one hand, a plethora of new targeted drugs with good tolerability profiles are becoming available, offering the possibility to achieve a prolonged remission to many patients not otherwise eligible for more intensive therapies. On the other hand, better tools to assess patients’ fitness and improvements in the selection and management of those undergoing allo-HCT will hopefully reduce treatment-related mortality and complications. Importantly, a detailed genetic characterization of AML has become of paramount importance to choose the best therapeutic option in both intensively treated and unfit patients. Finally, improving supportive care and quality of life is of major importance in this age group, especially for the minority of patients that are still candidates for palliative care because of very poor clinical conditions or unwillingness to receive active treatments. In the present review, we discuss the evolving approaches in the treatment of older AML patients, which is becoming increasingly challenging following the advent of new effective drugs for a very heterogeneous and complex population.

Background: Accurate assessment of elderly acute myeloid leukemia (AML) patients is essential before intensive induction chemotherapy and subsequent allogeneic hematopoietic stem cell transplantation. In this context, we investigated the capacity of three scores for frailty prediction. Methods: At diagnosis, 197 patients were clinically evaluated for appropriate treatment intensity. In parallel and independently, the G8-score, the Hematopoietic Stem Cell Index (HCT-CI) and the AML-score for CR were determined for each patient and analyzed with respect to overall survival (OS). Results: The G8-score and the HCT-CI were able to significantly separate “fit” from “unfit” patients, <0.001 and p = 0.008. In univariate Cox models, the predictive role for OS was confirmed: for the G8-score (HR: 2.35, 95% CI 1.53–3.60, p < 0.001), the HCT-CI (HR: 1.91, 95% CI 1.17–3.11, p = 0.009) and the AML-score (HR: 5.59, 95% CI 2.04–15.31, p = 0.001), the latter was subsequently used to verify the cohort. In the multivariate Cox model, the results were confirmed for the G8- (HR: 2.03, p < 0.001) and AML-score (HR: 3.27, p = 0.001). Of interest, when combining the scores, their prediction capacity was significantly enhanced, p < 0.001. Conclusions: The G8-, the HCTCI and the AML-score represent valid tools in the frailty assessment of elderly AML patients at diagnosis.

Patients with post-transplant cytopenias due to poor graft function or primary engraftment failure show poor prognosis with a high mortality rate mainly because of graft versus host disease (GVHD), infection and/or bleeding. Treatment options are scarce and a CD34+ stem cell boost or a second bone marrow transplantation may be required to restore adequate haematopoiesis. In the present study patients with primary engraftment failure (n = 1) and refractory poor graft function (n = 11) were treated with eltrombopag in a single centre. The reason for eltrombopag treatment was trilineage cytopenia in six patients, bilineage cytopenia in three patients and single lineage cytopenia in three patients. Eltrombopag was initiated at a median of 214 (range: 120–877) days after haematopoietic stem cell transplantation (HCST) and administered for a median time of 114 (range: 12 days to >490) days. In 8/12 patients eltrombopag was introduced at a dose of 75 mg/day and then increased to 150 mg/day after 1 week; 1 patient was given 50 mg eltrombopag per day, and 3 patients received 75 mg daily. In 10/12 patients eltrombopag significantly enhanced blood count values and patients became transfusion independent. Once stable haematological response was obtained, treatment was tapered until final discontinuation in 9/10 responding patients. No grade 3 or 4 toxicities were observed. At time of last follow up, 3/12 patients were dead, 2 due to disease relapse, 1 due to GVHD and pneumonia. All patients except one maintained their complete response and remain transfusion independent at a median of 858 (range: 429–1119) days. These preliminary data confirm that eltrombopag is able to rescue multilineage haematopoiesis in patients with treatment-refractory cytopenias after allogeneic HSCT.

In a retrospective analysis, 21 acute myeloid leukemia patients receiving single-agent sorafenib maintenance therapy in complete remission (CR) after hematopoietic stem cell transplantation (HSCT) were compared with a control group of 22 patients without maintenance. Sorafenib was initiated a median of 3 months (IQR: 2.3–3.5) after allogeneic HSCT with a median daily dosage of 400 mg (range: 200–800) orally, and lasted a median of 11.3 months (IQR: 3.3–24.4). No significant increase in graft versus host disease or toxicity was observed. Adverse events were reversible with dose adjustment or temporary discontinuation in 19/19 cases. With a median follow-up of 34.7 months (IQR: 16.9–79.5), sorafenib maintenance significantly improved cumulative incidence of relapse (p = 0.028) as well as overall survival (OS) (p = 0.016), especially in patients undergoing allogeneic HSCT in CR1 (p < 0.001). In conclusion, sorafenib maintenance after allogeneic HSCT is safe and may improve cumulative incidence of relapse and OS in FLT3–ITD-mutated AML.

Introduction: Post-transplant relapse of acute myeloid leukemia and myelodysplastic syndrome faces restricted effective salvage regimens. We retrospectively analyzed the use of Azacitidine–donor lymphocyte infusion (AZA/DLI) in this setting. Furthermore, data on bone marrow Wilms tumor gene 1 (WT1) expression were collected. Methods: A Cox proportional hazards model, an outcome-oriented approach for the lowest smoothed plot of the martingale residuals, was performed for the cut-point determination of the respective WT1 expression levels. Finally, a Cox proportional hazards model investigated the association of overall survival (OS) with predictors. Results: An overall response of 41.4% with a median duration of 11.9 months for stable disease and 19.5 months for complete response (CR) patients was achieved. The disease risk index (DRI) high-/very high-risk patients had a shorter OS of 4.4 months than intermediate-risk patients, with 14.5 months, p = 0.007. At transplant, WT1-overexpressing patients (>150 copies) had a shorter median OS of 5.3 months than low-WT1-expressing ones, with 13.5 months, p = 0.024. Furthermore, patients with ≤1000 WT1 copies at relapse had a significantly longer OS with 15.3 months than patients overexpressing WT1, with 4.4 months, p = 0.0002. Conclusions: DRI and WT1 expression associate significantly with OS after AZA/DLI. Hence, WT1 may represent an MRD marker, especially in CR patients at high risk.