Acute Myeloid Leukemia in Patients Living with HIV Infection: Several Questions, Fewer Answers

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.

Spectrum of HIV Associated Malignancies: A Retrospective Study of 42 Patients over a Period of 16 Years Attending a Tertiary Care Hospital

“…In general, life time risk of developing cancer in PLWH receiving ART remains 25-40%, whereas malignancy accounts for approximately 33% of all HIV related deaths. [8] The treatment decisions require an understanding of the patients HIV disease as well as curative potential of the malignancy encountered. The treatment outcome of PLWH and malignancy has improved in the past two decades.…”

“…Forghieri F observed only 2 HIV positive patients out of 276 AML patients over a period of 10 years from 2009-2018. [8] The etiology is not well understood till date. The treatment of AML in a patient with well-controlled HIV infection should no longer be considered per se a contraindication to standard intensive chemotherapy for AML and patient's inclusion in clinical trials may certainly help to improve and standardize their clinical management.…”

“…[5] In AIDS patients the risk of developing malignancy is higher than in non HIV population, cancer cervix being 5-7 times, anal cancer 13 times [6], cancer lung 5-7 times and Hodgkin's lymphoma 5-14 times, NHL 10-20 times [7], head and neck 3 times and leukemia 2.5 times. [8] No increased risk was observed for breast, prostate and colorectal cancers in the HIV positive cohort. [9] In the past, the PLWH were excluded from the oncologic clinical research trials with the aim of assessing the efficacy and toxicity profile of the immune check point inhibitors (ICPi) because of an increased theoretical risk of inducing adverse events and a feared decreased efficacy in the immune compromised population.…”

Detection of CCR5Δ32 Mutant Alleles in Heterogeneous Cell Mixtures Using Droplet Digital PCR

“…The knockout of this gene apparently has no significant effect on the health of its carriers, but is a factor in the immunity of T cells to the human immunodeficiency virus (HIV-1), more precisely to its R5 strain (the most common and contagious one) ( Balotta et al, 1997 ; Michael et al, 1997 ; Barmania and Pepper, 2013 ; Surdo et al, 2013 ; Qi et al, 2018 ). Because acute lymphoblastic leukemia is common among HIV-1 carriers, such patients need bone marrow replacement after chemotherapy or radiation therapy ( Forghieri et al, 2020 ). If an immune-compatible donor is a homozygous carrier of the rare CCR5Δ32 mutation, then the virus can be completely eliminated from the HIV-1 patient.…”

Acute promyelocytic leukemia in a long-standing HIV-positive patient: Case report and literature review

“…The use of antiretroviral therapy (ART) has drastically improved the prognosis and quality of life of people living with the human immunodeficiency virus (HIV). Due to longer life expectancy in the ART era, aging has increased the incidence of non-AIDS-defining malignancies [1] . Several factors, including immune system deregulation, chronic stimulation, and direct viral pathogenicity, may play a role in this predisposition [2] .…”