There is a risk that delays in the treatment of AML may result in life-threatening complications, such as sepsis, bleeding, leukostasis, and disseminated intravasculary coagulation (DIC) in patients. However, the results obtained from studies comparing the effect of short-term delays (usually < 1 week) from diagnosis to treatment on survival are controversial [15,16,17]. Causes of treatment delays include transfers between hospitals, suspected or documented infections, and management of concomitant acute conditions [15].

In the optimal management of acute leukemia, the importance of the contributions of experienced staff and units with the appropriate infrastructure cannot be ignored, as well as the contributions of the physician who organizes the treatment. Blood bank support and quick access to all kinds of blood products are other keys to successful AML management [18]. The results of a retrospective study showed that 1-month mortality is higher in non-academic centers compared to academic centers, while 5-year overall survival is higher in the latter, after adjustment for patient-specific and treatment-related factors [19]. In a comparison of centers based on the annual number of AML patients treated (≤ 75% vs. > 75%), treatment mortality was found to be lower in hospitals with higher volumes of patients with AML [20]. These differences may be due to infrastructure differences between centers and the presence of experienced personnel [21].

Conventional chemotherapy agents have been available and used for many years to treat AML. More recently, knowledge of the effect of genetic mutations on the pathogenesis of the disease and on its prognosis has supported the development of targeted therapies and led to the reshaping of AML treatment after years during which there were few changes in disease management. Since 2017, agents such as FMS-like tyrosine kinase 3 (FLT3), isocitrate dehydrogenase 1&2 (IDH1&2), and B-cell lymphoma 2 (BCL-2) inhibitors, oral azacytidine, dual-drug liposomal encapsulation of cytarabine and daunorubicin (CPX-351), and glasdegib have been approved for the treatment of various indications in induction and consolidation regimens, both in frontline therapy and in relapsed/refractory AML (r/rAML) patients [13, 22]. The monthly average costs of these current treatments can reach around US$20,000 [23]. The authors of a recent analysis estimated that newly marketed drugs and their preferred use in combination therapeutic regimens will increase drug expenditures in AML; for example, privately insured patients in the USA may face substantial out-of-pocket co-payments for drugs [24].

New therapeutic agents have positive aspects, such as efficacy, safety, ease of administration, and shortening of hospital stay [24]. However, molecules may also have characteristic negative effects. In this context, IDH inhibitors can cause specific side effects, including differentiation syndrome; patients receiving FLT3 inhibitors may experience gastrointestinal toxicities; and venetoclax requires dynamic dose changes and close monitoring during the ramp-up period, and drug-drug interactions can be problematic in patients receiving this drug. It is important for the correct management of the process that the patients and the healthcare institutions where the patients are being treated, when necessary, have information about the treatment plan, side effects of the drugs, and possible drug interactions.

These new targeted therapies come at a high cost and, consequently, these agents may not be accessible to patients who are uninsured and/or of low socioeconomic status, or to patients in developing countries. Due to the relatively long duration of the treatment of AML and the presence of a treatment process open to complications, it can be predicted that conventional treatments are also associated with high costs, with long-term hospitalizations and treatment-related complications accounting for most of these costs. In a study conducted in the USA covering the years 1999–2006, i.e., before the licensing of new drugs, treatment costs were found to be around US$123,000 and US$130,000 for patients who had private insurance or public insurance, respectively, while they were approximately US$100,000 for uninsured patients. This difference was attributed to shorter hospital stays and discontinuation of treatment after induction [25]. In the study by Pandya et al. [26], the cost of AML treatment services was analyzed between 2008 and 2016. Treatment costs were found to have increased over time, amounting to US$198,657 and US$53,081 for the high- and low-intensity induction chemotherapies, respectively, and US$73,428 for high-intensity consolidation chemotherapy. Allogeneic stem cell transplantation (allo-SCT) costs were around US$329,621, and the treatment costs were considerably higher, namely, US$439,104 in r/rAML [26].

Treatment of r/rAML is a therapeutic challenge. The effect of previous treatment processes on the performance capacity of the patients and the permanent comorbid conditions that develop during the treatment process make the management of the cases difficult and may limit the treatment options. The curative treatment of AML is allo-SCT, which may be preferred in the first remission or relapse according to the risk group assessment. Considering the advances in supportive care, risk stratification, donor/graft selection, and peri-transplant management, the application of allo-SCT has increased over time and today is applied in licensed centers that meet appropriate conditions [26]. In the treatment process, it is important to be in contact with experienced and comprehensive centers in the evaluation of patients suitable for allo-SCT, planning the transplantation process, and directing selected cases that are not suitable for other treatments to clinical studies. The participation rate of cancer patients in clinical studies was found below 5% and the most important obstacles were determined as protocol, physician triage, and patient decision [27]. Because of this dynamic and complex process, it is difficult to follow up r/rAML patients in non-academic centers.

The severe acute respiratory syndrome-coronavirus 2 (SARS-Cov-2) pandemic, which began in 2019 (COVID-19), paralyzed healthcare systems on global scale [28]. Patients with AML were at risk for SARS-CoV-2 infection not only due to malignancy-related immunodeficiency but also related to the treatment they received [29]. Hospitalization and repeated outpatient visits have been shown to increase the risk of infection [30]. Travel restrictions during the pandemic period and patients’ avoidance of infection risk may have reduced outpatient attendance [29]. During the pandemic, bed occupancy rates of hospitals increased, inpatient leukemia treatment and allogeneic transplantation processes became more difficult, blood donations decreased, and blood bank reserves decreased, all of which led to problems with supportive care [28]. Under these conditions, alternative treatment options were introduced according to various guideline recommendations, such as induction treatment options that do not require hospitalization in suitable patients, blood product use and transfusion thresholds, treatment of COVID-19 infection, vaccination policies, and management of the transplantation process [30,31,32,33,34].