Abstract
Both human immunodeficiency virus (HIV) infection and acute myeloid leukemia (AML) may be considered relatively uncommon disorders in the general population, but the precise incidence of AML in people living with HIV infection (PLWH) is uncertain. However, life expectancy of newly infected HIV-positive patients receiving anti-retroviral therapy (ART) is gradually increasing, rivaling that of age-matched HIV-negative individuals, so that the occurrence of AML is also expected to progressively increase. Even if HIV is not reported to be directly mutagenic, several indirect leukemogenic mechanisms, mainly based on bone marrow microenvironment disruption, have been proposed. Despite a well-controlled HIV infection under ART should no longer be considered per se a contraindication to intensive chemotherapeutic approaches, including allogeneic hematopoietic stem cell transplantation, in selected fit patients with AML, survival outcomes are still generally unsatisfactory. We discussed several controversial issues about pathogenesis and clinical management of AML in PLWH, but few evidence-based answers may currently be provided, due to the limited number of cases reported in the literature, mainly as case reports or small retrospective case series. Prospective multicenter clinical trials are warranted to more precisely investigate epidemiology and cytogenetic/molecular features of AML in PLWH, but also to standardize and further improve its therapeutic management.
Highlights
Human immunodeficiency virus (HIV) infection causes disruption of the adaptive immune system through dysfunction and loss of CD4+ T cells [1,2]
HIV infection is associated with chronic immune activation and systemic inflammation, concurrently with immunosenescence and T cell exhaustion, which could causally be linked to the increased cancer risk [3–5]
In addition to HIV-related immunosuppression, which impairs the control of oncogenic viral infections, people living with HIV infection (PLWH) are more frequently exposed to cancer risk factors, such as smoking and alcohol abuse, potentially contributing to elevated risk of malignancy [6,7]
Summary
Human immunodeficiency virus (HIV) infection causes disruption of the adaptive immune system through dysfunction and loss of CD4+ T cells [1,2]. Progressive deterioration of host immunity occurs with increased risk of opportunistic infections and malignancy compared with the general population and possible development of acquired immunodeficiency syndrome (AIDS) [2,3]. The incidence of ADC continues to be higher than in the general population, and aging due to longer life expectancy in the ART era has led to increased incidence of non-AIDS-defining malignancies [3,6,11–13]. The lifetime risk of developing cancer still remains 25% to 40% in PLWH receiving ART, with malignancies accounting for approximately 33% of all HIV-related deaths [11,14–17]. The elevation of cancer-related mortality for many malignancy subtypes among HIV-infected patients compared with HIV-uninfected subjects is related to advanced tumor stage or differences in treatment approaches, and potentially reflects a direct correlation between immunosuppression and tumor progression [18]. Acute myeloid leukemia (AML) is considered among non-AIDS-defining hematological malignancies and several challenging topics about its epidemiology, pathogenesis, and clinical outcomes in PLWH will be discussed below
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