**7. Conclusion**

(48%) HSCT compared to ICC (30%) [81]. However, despite this improved LFS and higher relapse rate in patients getting ICC, OS was similar in the three groups, since majority of

Currently is the era of targeted agents for treatment of malignancies. These targeted therapies for each AML patient are based on unique molecular features. Hypothesis -based study designs can give us proper risk stratification for prognosis and predictive treatment options in

NGS technologies have made a huge impact in research and clinical diagnostics. It has expanded genes that are causing malignancies and will soon replace routine testing for single-gene mutations with NGS-based gene panel diagnostics. The information will be acquired from NGS assay and will play a role in personalized medicine. This will provide the basis for more comprehensive knowledge data banks that can serve as valuable tools to advance individualized treatment approaches [82]. In addition, we also recorded rapid technical advances that allow for more accurate MRD assessment and started to offer the possibility of capturing leukemia heterogeneity at the single-cell level. NGS will serve as a powerful tool for gaining deeper insights into leukemia stem cell phenotypes, signaling pathways, and function [83]. Finally, population based information will be used in the future to tailor NGS panels, and useful prognostic and predictive markers can be identified. Novel targeted therapeutic approaches hold promise for improving patient outcomes, but it will be important that genomic-based outcome prediction systems stay flexible and adaptable to reflect advances in

AML biology is rapidly expanding, and there is a great need to apply knowledge to the clinical context as soon as possible in order to improve the outcomes of our patients. Clinical outcomes will improve to enhance the clinical care of patients with AML, especially older patients for whom clinical outcomes have improved little over the past several decades. Instead of delaying introduction of novel agents to the setting of relapsed/ refractory disease, we propose consideration of frontline treatment with targeted agents either alone or in combination with chemotherapy, in the context of multicenter and/or cooperative group clinical

AML. In the following section, promising novel agents in development are described:

patients relapsing after ICC successfully salvaged with autologous HSCT.

**3.** New chemotherapies (tipifarnib, cloretazine (VNP40101M), clofarabine)

**5.6. Novel agents in development**

76 Myeloid Leukemia

**1.** Tyrosine kinase inhibitors. **2.** Epigenetic targeting agents

**5.** Antiangiogenic agents

**6. Future direction**

trials, when available.

**4.** Agents overcoming chemo resistance

treatment and changes in disease monitoring.

AML is a biologically and clinically heterogeneous disease. Established therapies have given some survival benefit according to risk stratification but overall long-term survival remains poor. Most of the patients on diagnosis are elderly, and they have adverse cytogenetic profile. At the same time, these patients are susceptible for transplant-related complications. The novel targeted therapies may have a good antileukemic activity with reduced toxicity versus available chemotherapeutic options. However, given the molecular diversity of AML, it is unlikely that targeted therapies such as FLT3 tyrosine kinase inhibitors will provide a sole treatment option in FLT3-mutated patients. With improved diagnostic genetic profiling, risk stratification will result in incremental gains in remission and survival.

Furthermore, the identification of cell-specific surface antigens can provide another targetable therapeutic option for recombinant monoclonal antibodies. But now difficulty in selecting to target leukemic myeloid cells while sparing non-malignant myeloid precursors. Lastly, the development of well-tolerated oral therapies, such as clofarabine, will increasingly broaden the range of available treatment for elderly patients at a higher risk of mortality from standard chemotherapy regimens. It is the beginning of a new era in the treatment of AML to make them survive with novel agents with little toxicity, particularly in relapsed or refractory diseases and poor cytogenetic features.
