Access to Therapy for Acute Myeloid Leukemia in the Developing World: Barriers and Solutions

Abstract

Purpose of Review Acute myeloid leukemia (AML) is a costly disease, and its impact is greater in developing countries (DC). We will review the current concept of what are DC, compare the differences in the epidemiology and economic burden of this disease between developed and DC, and finally, analyze the barriers and possible solutions that DC should implement to achieve better results. Recent Findings DC is a frequently misunderstood name. The way we use to measure human development is changing, and multidimension metrics better define what are DC. With this in mind, we show the differences in the AML epidemiology and the impact of economic burden in DC. We analyze the barriers to access therapy from a clinician point of view, to show that most DC shared similar challenges but with a diverse healthcare structure. Finally, we provide several possible solutions for a more integrated and timely treatment that allows better results not only in terms of survival but with a better quality of life. Summary The economic burden of AML treatment in DC is high, and the results are poor. It is crucial to face this challenge and propose new treatment approaches to achieve better results.

Inhibitors of Chemoresistance Pathways in Combination with Ara-C to Overcome Multidrug Resistance in AML. A Mini Review

“…AML is slightly more common in men than in women and less frequently affects children and young people [ 3 ]. The median age at diagnosis is 65 years, and the incidence increases progressively with age, making it the most common type of leukemia in older people [ 1 , 6 ]. Due to the heterogeneity of the disease, different classifications of AML subtypes have been proposed.…”

“…With standard therapy, between 60% and 75% of children achieve an overall survival of 5 years, largely due to fewer genetic mutations and their greater ability to tolerate both high-intensity chemotherapy and HCT [ 1 , 20 , 21 ]. In contrast, only 24% of adult patients who are selected for intensive therapy and 10%–15% of older patients not eligible for intensive therapy survive to five years, [ 1 , 6 , 22 , 23 ] and almost 80% of patients diagnosed at an age ≥65 years die within one year [ 19 ]. AML in the elderly population is a special therapeutic challenge due to the poor functional status of this age group, which results in an increase in therapy-related toxicity [ 24 ].…”

“…Acute myeloid leukemia (AML) is a hematological disease characterized by the clonal expansion of immature myeloid hematopoietic cells (myeloblasts), which accumulate in the bone marrow (BM) and blood (more than 20% of myeloblasts) and can also infiltrate tissues such as the spleen, liver, skin, gums, and central nervous system. The displacement of functional hematopoietic cells in the bone marrow causes marrow failure with a consequent deficit in the production of the cellular components of blood: erythrocytes, leukocytes and platelets [ 1 , 2 , 3 ]. For the past 50 years, the standard of care in AML has been the combination of cytarabine (Ara-C) and anthracyclines, resulting in complete remission of no more than 45% of patients regardless of age group [ 4 ]; however, most of them do not survive long-term (more than five years), largely due to treatment-related mortality and the appearance of relapse associated with chemoresistance [ 2 , 5 , 6 ].…”

“…In recent years, a greater understanding of the molecular biology of leukemia has allowed the development of therapies directed towards mutated genes and molecular targets; however, the new treatments approved by the US Food and Drug Administration (FDA) are only effective in some patients, and the survival period that is achieved does not differ from that obtained with standard therapy. It is clear that more effective and less toxic strategies are required [ 1 , 7 ]. However, the characterization of AML as a highly heterogeneous disease involving a great variety of genes and proteins with altered expression or function simultaneously explains, at least in part, why therapies directed against a single molecular target may not be sufficient to increase the survival of patients with AML.…”

FMS-like tyrosine kinase-3 (FLT3) inhibitors with better binding affinity and ADMET properties than sorafenib and gilteritinib against acute myeloid leukemia: in silico studies

“…Despite the huge progress in the discovery of new drugs, 5 years survival rate for patients with AML under treatment is known (Cancer.Net, 2020). Without treatment, the survival rate is counted in weeks or months (Meillon-Garcia & Demichelis-G omez, 2020). The present 5 years average overall survival (OS) for people 20 years and older is 25% while people younger than 20 years is 67% (Cancer.Net, 2020).…”