Abstract
Acute promyelocytic leukemia (APL) is a rare and aggressive subtype of acute myelogenous leukemia (AML), characterized by the PML-RARA fusion gene. When APL presents concurrently with acquired immunodeficiency syndrome (AIDS), it creates unique challenges in diagnosis and treatment due to the immunocompromised state of the patient. This case report describes a 46-year-old male patient with long-standing AIDS who developed APL. Initial treatment involved all-trans retinoic acid (ATRA) monotherapy due to the patient’s severe lung infection and liver dysfunction, followed by the addition of arsenic trioxide (ATO) once infection and liver function improved. The patient achieved complete remission (CR) after combined ATRA and ATO therapy, with successful molecular remission of the PML-RARA fusion gene. We discuss the complexity of managing APL in the context of HIV infection, including the challenges posed by infections, liver dysfunction, and the impact of chemotherapy on antiretroviral therapy (ART). This case highlights the need for immediate initiation of ATRA in APL patients, even before genetic confirmation, and the potential therapeutic role of ATO in both leukemia treatment and HIV reservoir management. Further studies are needed to optimize treatment protocols for patients with concurrent AIDS and APL, focusing on personalized approaches to maximize efficacy while minimizing complications.
1 Introduction
Acquired immunodeficiency syndrome (AIDS) is a severe immunodeficiency disease caused by human immunodeficiency virus (HIV) infection, which predisposes patients to various malignancies (1). Acute promyelocytic leukemia (APL) is a specific subtype of acute myelogenous leukemia (AML), characterized by a chromosomal translocation t(15;17)(q22;q12), resulting in the formation of the PML-RARA fusion gene. This fusion protein blocks cell differentiation and inhibits apoptosis, representing the primary molecular mechanism underlying APL (, ). APL typically affects young and middle-aged individuals, with a mean onset age of 44 years. It accounts for 10% to 15% of AML cases, with an incidence rate of approximately 0.23 per 100,000 (). As a distinct AML subtype, APL presents unique clinical features and treatment responses. When AIDS and APL occur simultaneously, the complexity of diagnosis and treatment increases significantly, posing significant clinical challenges.
2 Case report
A 46-year-old male patient, living with HIV infection for over a decade, had not received treatment for four consecutive years after his diagnosis (Figure 1). The patient self-reported that in 2017, diagnostic findings confirmed progression to the AIDS stage, prompting initiation of antiretroviral therapy (ART). During this period, the patient underwent viral load and CD4+ T-cell count monitoring at the local CDC in their hometown; however, specific reports are unavailable. The patient self-reported a CD4+ T-cell count of approximately 300 cells/μL during ART, still indicating incomplete immune reconstitution. The current treatment regimen comprises tenofovir (TDF), lopinavir/ritonavir (LPV/r), and lamivudine (3TC). In December 2023, the patient presented with dizziness lasting over two months, accompanied by fever, cough, and sputum for two days. A routine blood test revealed a 28% blast cell population in peripheral blood, leading to his immediate hospitalization. Complete bone marrow analysis indicated an increase in promyelocytes, with visible azurophilic granules and Auer rods, suggestive of APL (Table 1) (Figures 2A, B). The diagnosis was confirmed by flow cytometry and positive PML-RARA fusion gene results (Figures 2C, D).
Figure 1
Table 1
| Indicators | December 28th | January 6 | January 25 | February 4 |
|---|---|---|---|---|
| White blood cells (× 109/L) | 1.2 | 10.1 | 1.2 | 6.1 |
| Neutrophil granulocyte (× 109/L) | 0.3 | 3.6 | 0.9 | 4 |
| Lymphocyte (× 109/L) | 0.5 | 0.9 | 0.3 | 1.3 |
| Blood platelet (× 109/L) | 5 | 42 | 51 | 348 |
| Hemoglobin (g/L) | 72 | 74 | 71 | 96 |
| Procalcitonin (ng/ml) | 0.17 | 0.06 | – | – |
| Alanine Aminotransferase (U/L) | 20 | 139 | 35 | 28 |
| Aspartate Aminotransferase (U/L) | 37 | 104 | 25 | 30 |
| Partial prothrombin activity time (s) | 1.13 | 18.5 | 30.3 | 29 |
| Fibrinogen (g/L) | 3.78 | 1.61 | 4.47 | 3.6 |
| D-Dimer (μg/ml) | >20000 | 1663 | 585 | – |
Dynamic changes of laboratory indexes in AIDS patients with APL.
Figure 2
Upon admission, the patient’s CD4+ T-cell count was measured at 329.6 cells/μL (indicating moderate immunosuppression), accompanied by severe pulmonary infection, along with prolonged prothrombin time and activated partial thromboplastin time due to APL, elevated D-dimer levels, granulocytopenia, thrombocytopenia, anemia, and other signs suggestive of disseminated intravascular coagulation (). Given that the patient was stratified as low-risk for APL prognosis, Treatment was initiated with all-trans retinoic acid (ATRA) (25mg·m-2·d-1) to induce differentiation (while deferring arsenic trioxide (ATO) (0.16mg·kg-1·d-1) due to the severe lung infection). Simultaneously, supportive therapies were administered, including anti-infective measures, bleeding prevention, multiple plasma and platelet transfusions, and anti-HIV treatment. The patient subsequently developed liver dysfunction and leukocytosis (white blood cell count exceeding 10×109/L), prompting adjustments in treatment strategy. Concurrently, the patient received comprehensive supportive care comprising: cefotaxime 2.0g IV q12h, piperacillin-sulbactam 4.5g IV q8h (escalated from cefotaxime based on clinical suspicion of extended-spectrum beta-lactamase (ESBL)-producing pathogens), and micafungin 100mg IV qd for antimicrobial prophylaxis; bleeding prevention measures; multiple fresh frozen plasma and platelet transfusions; and antiretroviral therapy for HIV comanagement. During the treatment course, the patient developed hepatotoxicity accompanied by leukocytosis (white blood cell count >10×109/L). Therapeutic interventions were escalated with hydroxyurea 0.5g PO bid (days 8–10 post-diagnosis) and idarubicin 8mg/m2 IV daily (days 9–11 post-diagnosis) for leukocyte cytoreduction, supplemented by hepatoprotective agents including ursodeoxycholic acid and glutathione infusion. Hydroxyurea (0.5g bid 8–10 days in the course of the disease) and idarubicin (8mg·m-2·d-1 Days 9–11 of the course of disease) were used to reduce leukocytosis, and liver protection measures were implemented. Follow-up exams showed improvement in the lung infection and normalization of liver function, with bone marrow tests performed on day 20 indicating partial remission.
The patient then began ATO (0.16mg·kg-1·d-1) intravenous chemotherapy combined with oral ATRA (25mg·m-2·d-1), continuing with the first treatment course for induction therapy. During this phase, he experienced fever again, and chest CT revealed patchy and nodular density shadows in both lungs. A regimen of meropenem and micafungin was administered, improving the infection, with serial monitoring of CD4+ T-cell counts revealing a nadir of 148.4 cells/μL on day 26 of the disease course. On day 33 of the disease course, a follow-up evaluation was performed. Continued induction therapy led to morphological remission in bone marrow. After another course of ATO (0.16mg·kg-1·d-1) and ATRA (25mg·m-2·d-1), the PML-RARA fusion gene turned negative, and the patient achieved complete remission (CR). At the end of the second treatment course, follow-up testing revealed a CD4+ T-cell count of 369.9 cells/μL. Currently, the patient is undergoing consolidation therapy, showing an increased CD4+ T-cell count, persistent fusion gene negativity, and only mild anemia.
3 Discussion
APL presents with severe clinical manifestations, with high risks of bleeding and embolism during onset and induction therapy, potentially leading to fatal outcomes. Over the past three decades, the standardized clinical use of ATRA and ATO has transformed APL into a curable leukemia without the need for hematopoietic stem cell transplantation (, ).
A review of 11 previously reported AIDS-related APL cases (–) highlights that most patients achieved remission with ATRA alone or in combination with chemotherapy (anthracyclines or arsenic) (Table 2). Only one high-risk patient succumbed to severe disseminated intravascular coagulation. Long-term remission was achieved in most cases through consolidation and maintenance therapy. One patient who discontinued ATRA due to nausea relapsed one year later but achieved a second CR following salvage therapy with ATO ().
Table 2
| Case | Age/sex | Time from diagnosis of AIDS to discovery of APL | Initial WBC/PLT count (×109/L) | APL risk groups | AIDS treatment regimen at the time of diagnosis of APL | Induction therapy regimen | Response to induction therapy | Consolidation treatment | Maintenance treatment | Survival outcome/duration of follow-up | Ref |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 30/M | 2 years | 4.8/2 | Moderate risk | NA | ATRA alone | Morphological CR was achieved on day 29 | Daunorubicin, cytarabine/mitoxantrone, and cytarabine | NA | Survival/8 months | () |
| 2 | 36/M | coordinate expression | 4/NA | Low risk | NA | ATRA alone | Morphological remission was achieved, but relapse occurred 303 days later | NA | Mitoxantrone/6-MP | Death/350 days | () |
| 3 | 27/M | 8 years | 8/19 | Moderate risk | Indinavir was replaced by nelfinavir, 3TC, and zidovudine was replaced by stavudine | ATRA, idarubicin, and cytarabine | Morphological CR was achieved at 30 days. Cytogenetic and molecular CR was achieved at week 9 | High-dose cytarabine | ATRA/mitoxantrone/6-MP | Survival/40 months | () |
| 4 | 46/F | 2 years | 5.1/1 | Moderate risk | Efavirenz, TDF, 3TC | ATRA and idarubicin | Molecular CR | ATRA, idarubicin/ATRA, and mitoxantrone | ATRA/mitoxantrone/6-MP | Survival/21 months | () |
| 5 | 35/M | 10 years. The patient has a history of primary central nervous system lymphoma and achieved CR after whole brain radiation therapy. | 1.6/28 | Moderate risk | Stavudine and LPV/r | ATRA and idarubicin | Morphological and molecular CR | ATRA | NA | Survival/14 months | () |
| 6 | 37/M | 7 years | 1.6/112 | Low risk | 3TC, nevirapine, and desanosine | ATRA and idarubicin | Morphological and cytogenetic CR was achieved on day 77 | NA | ATRA (poor adherence due to nausea) | Relapsed 1 year later and was treated with ATO as salvage therapy, achieving a second CR. Survival/17 months | () |
| 7 | 43/F | coordinate expression | 40.7/15 | High risk | Azanavir was replaced with fosanavir, TDF/emtricitabine, and lategravir | ATRA and idarubicin | Day 29 Morphological and molecular CR | ATRA, idarubicin/ATRA, and mitoxantrone | ATRA/mitoxantrone/6-MP | Survival/8 months | () |
| 8 | 32/M | 5 months | 4/22 | Moderate risk | Abacavir/3TC, darunavir, r | ATRA, idarubicin, and cytarabine | CR was achieved on day 40 | ATRA, idarubicin/ATRA, and mitoxantrone | ATRA/mitoxantrone/6-MP | Survival/38 months | () |
| 9 | 46/M | 5 months | 10/19 | Moderate risk | Raltegravir, emtricitabine, TDF | ATRA and idarubicin | Morphological remission by day 31 | ATRA, idarubicin/ATRA, and mitoxantrone | Maintenance therapy was not performed because of liver dysfunction | Survival/30 months | () |
| 10 | 49/M | 18 years | 89/55 | High risk | 3TC, TDF, LPV/r, atazanavir | ATRA, cytarabine, and daunorubicin (not available for idarubicin) | non-remission | NA | NA | Died on the 10th day after admission due to refractory DIC with severe pulmonary hemorrhage | () |
| 11 | 67/M | 5 days | 1.2/45 | Low risk | Biktarvy | ATRA and ATO | The specific duration of remission was not specified | ATR and ATO | ATRA and ATO | Survival/NA | () |
| 12 | 46/M | 10years | 1.2/5 | Low risk | After 20 days of ATRA treatment alone (when liver function improved), ATO was added | Morphological remission was achieved on day 32 | ATR and ATO | ATRA and ATO | Survival/more than 7 months | In this example |
Review of previous cases and a detailed case report on APL combined with AIDS.
AIDS, acquired immunodeficiency syndrome; APL, acute promyelocytic leukemia; ATO, arsenic trioxide; ATRA, all-trans retinoic acid; CR, complete remission; LPV/r, lopinavir and ritonavir; PLT, platelets; 6-MP, 6-Mercaptopurine; TDF, tenofovir disoproxil; 3TC, lamivudine; WBC, white blood cell.
NA, Not Applicable.
Given the high mortality associated with APL, immediate ATRA treatment is recommended based on cytological and clinical criteria, while awaiting genetic confirmation (, ). In this case, the patient’s severe lung infection and liver dysfunction posed risks for initial ATO combination therapy. Since 1986, Shanghai Ruijin Hospital has successfully utilized ATRA-induced differentiation therapy for APL, with a CR rate of 75% to 85% for ATRA alone (). Therefore, we opted for ATRA monotherapy during the early treatment phase. After the infection and liver function improved, ATO was added, and ATRA was continued for one week, achieving morphological remission, as observed in two other cases treated with ATRA alone (, ).
In the consolidation phase, we continued ATRA combined with ATO. Given the patient’s history of HIV and long-term ART, we carefully evaluated whether this chemotherapy regimen might interfere with his HIV treatment. Previous studies indicate that while ATRA upregulates HIV mRNA transcription in infected human HL-60 cell lines, it does not increase viral replication due to blocked HIV mRNA translation and replication. This mechanism ultimately leads to the apoptosis of HIV-infected cells, reducing the proviral DNA load in a dose-dependent manner (). Furthermore, ATRA significantly decreased viral replication in primary lymphocytes from HIV-infected patients, suggesting it may also serve as a therapeutic agent against HIV infection ().
Research from the Chinese Academy of Sciences and Sun Yat-sen University showed that ATO specifically activates latent viral reservoirs without inducing excessive inflammation. In a simian immunodeficiency virus (SIV) model, ATO combined with ART significantly delayed viral rebound post-drug withdrawal, with some monkeys showing no viral rebound after 80 days (compared to 22 days for ART alone). ATO reduced viral reservoirs and enhanced virus-specific immune responses. Moreover, ATO downregulated the expression of CD4 and CCR5 receptors on CD4+ T-cells, essential for HIV entry, thus inhibiting new rounds of viral infection ().
In conclusion, initiating ATRA treatment based on clinical and morphological criteria can significantly improve outcomes in APL patients, even in complex cases like this. Individualized treatment tailored to the patient’s condition may lead to better efficacy. For consolidation and maintenance therapy, further case studies and multicenter clinical trials are needed to confirm whether ATRA combined with ATO is the optimal approach. Continuous optimization of treatment protocols is essential to improve patient outcomes and quality of life.
Statements
Data availability statement
The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors.
Ethics statement
Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.
Author contributions
SD: Funding acquisition, Writing – review & editing. CA: Conceptualization, Writing – original draft. JS: Conceptualization, Visualization, Writing – original draft. HX: Visualization, Writing – review & editing. YX: Funding acquisition, Writing – review & editing.
Funding
The author(s) declare that financial support was received for the research and/or publication of this article. This study was supported by the Qiantang Scholars Fund in Hangzhou City University (Grant No. 210000-581835) and Natural Science Foundation of Zhejiang Province (Grant No. BY24H080010).
Acknowledgments
The authors would like to thank PubMed for the valuable information. Figure 1 was created by BioRender (biorender.com).
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Generative AI statement
The author(s) declare that no Generative AI was used in the creation of this manuscript.
Publisher’s note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
Abbreviations
AIDS, acquired immunodeficiency syndrome; AML, acute myeloid leukemia; APL, acute promyelocytic leukemia; ART, antiretroviral therapy; ATO, arsenic trioxide; ATRA, all-trans retinoic acid; CR, complete remission; ESBL, extended-spectrum beta-lactamase; HIV, human immunodeficiency virus; LPV/r, lopinavir and ritonavir; PLT, platelets; SIV, simian immunodeficiency virus; 6-MP, 6-Mercaptopurine; TDF, tenofovir disoproxil; 3TC, lamivudine; WBC, white blood cell.
References
1
ReidESunejaGAmbinderRFArdKBaiocchiRBartaSKet al. Cancer in people living with HIV, version 1.2018, NCCN clinical practice guidelines in oncology. J Natl Compr Cancer Network. (2018) 16:986–1017. doi: 10.6004/jnccn.2018.0066
2
Doctor Association; Chinese Medical Association, Chinese Medical Doctor Association. Chinese guidelines for diagnosis and treatment of acute promyelocytic leukemia (2018). Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi. (2018) 39:179–83. doi: 10.3760/cma.j.issn.0253-2727.2018.03.002
3
PollyeaDAAltmanJKAssiRBixbyDFathiATForanJMet al. Acute myeloid leukemia, version 3.2023, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. (2023) 21:503–13. doi: 10.6004/jnccn.2023.0025
4
DouXLZhaoTXuLPZhangXHWangYChenHet al. Age-related clinical characteristics and prognosis in non-senile adults with acute myeloid leukemia. Zhonghua Xue Ye Xue Za Zhi. (2018) 39:969–76.
5
ShenZXShiZZFangJGuBWLiJMZhuYMet al. All-trans retinoic acid/As2O3 combination yields a high quality remission and survival in newly diagnosed acute promyelocytic leukemia. Proc Natl Acad Sci U S A. (2004) 101:5328–35. doi: 10.1073/pnas.0400053101
6
HuJLiuYFWuCFXuFShenZXZhuYMet al. Long-term efficacy and safety of all-trans retinoic acid/arsenic trioxide-based therapy in newly diagnosed acute promyelocytic leukemia. Proc Natl Acad Sci U S A. (2009) 106:3342–7. doi: 10.1073/pnas.0813280106
7
CalvoRRiberaJMBattleMSanchoJMGranadaIFloresAet al. Acute promyelocytic leukemia in a HIV seropositive patient. Leukemia lymphoma. (1997) 26:621–4. doi: 10.3109/10428199709050899
8
SuttonLGuénelPTanguyMLRioBDhedinNCasassusPet al. Acute myeloid leukaemia in human immunodeficiency virus-infected adults: epidemiology, treatment feasibility and outcome. Br J haematology. (2001) 112:900–8. doi: 10.1046/j.1365-2141.2001.02661.x
9
KudvaGCMaliekelKRichartJMBatanianJRGrossoLESokol-AndersonMet al. Acute promyelocytic leukemia and HIV-1 infection: case report and review of the literature. Am J Hematol. (2004) 77:287–90. doi: 10.1002/ajh.20192
10
De VitaSDe MatteisSLaurentiLSorà FTarnaniMCingolaniAet al. Acute promyelocytic leukemia in an HIV-infected patient: a case report. Am J Hematol. (2006) 81:300.
11
BobanARadmanIZadroRDubravcicKMareticTCivljakRet al. Acute promyelocytic leukemia after whole brain irradiation of primary brain lymphoma in an HIV-infected patient. Eur J Med Res. (2009) 14:42–3. doi: 10.1186/2047-783X-14-1-42
12
MalikALevineRL. The first case report of APL (ACUTE PROMYELOCYTIC LEUKEMIA) in an HIV positive patient on (Highly active antiretroviral therapy) treated with ARSENIC TRIOXIDE. Blood. (2009) 114:4166–6. doi: 10.1182/blood.V114.22.4166.4166
13
DrilonADGamboaEOKoolaeeRGoelA. Acute promyelocytic leukemia in HIV-infected adults: a case report and review of therapeutic considerations. Clin lymphoma myeloma leukemia. (2010) 10:E47–52. doi: 10.3816/CLML.2010.n.075
14
KunitomiAHasegawaYLmamuraJYokomakuYTokunagaTMiyataYet al. Acute promyelocytic leukemia and HIV: case reports and a review of the literature. Internal Med (Tokyo Japan). (2019) 58:2387–91. doi: 10.2169/internalmedicine.1662-18
15
Mendes-de-AlmeidaDPFernandezTSLovatelVLda RochaMMGomesBEMonte-MórBCRet al. Acute promyelocytic leukemia in a long-standing HIV-positive patient: Case report and literature review. Leukemia Res Rep. (2022) 18:100339. doi: 10.1016/j.lrr.2022.100339
16
MahmoudAGhrewatiMKaniaBNaseerMKapoorAMichaelP. Aleukemic acute promyelocytic leukemia: how concomitant HIV, hepatitis C, and chronic alcohol use disorder may have hidden an underlying Malignancy. Am J Case Rep. (2023) 24:e938086. doi:Â 10.12659/AJCR.938086
17
WuJLuADZhangLPZuoYXJiaYP. Study of clinical outcome and prognosis in pediatric core binding factor-acute myeloid leukemia. Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi. (2019) 40:52–7.
18
SemmelMMachoACoulaudDAlilecheAPlaisanceSAguilarJet al. Effect of retinoic acid on HL-60 cells infected with human immunodeficiency virus type 1. Blood. (1994) 84:2480–8. doi: 10.1182/blood.V84.8.2480.2480
19
MaedaYYamaguchiTHijikataYMoritaYTanakaMHiraseCet al. All-trans retinoic acid attacks reverse transcriptase resulting in inhibition of HIV-1 replication. Hematol (Amsterdam Netherlands). (2007) 12:263–6.
20
YangQFengFLiPPanEWuCHeYet al. Arsenic trioxide impacts viral latency and delays viral rebound after termination of ART in chronically SIV-Infected macaques. Advanced Sci (Weinheim Baden-Wurttemberg Germany). (2019) 6:1900319. doi:Â 10.1002/advs.201900319
Summary
Keywords
acute promyelocytic leukemia (APL), acquired immunodeficiency syndrome (AIDS), all-trans retinoic acid (ATRA), arsenic trioxide (ATO), PML-RARA fusion gene
Citation
Ai C, Shentu J, Xu H, Xia Y and Duan S (2025) Co-occurrence of AIDS and acute promyelocytic leukemia: a case report and review of the literature. Front. Hematol. 4:1527938. doi: 10.3389/frhem.2025.1527938
Received
14 November 2024
Accepted
26 June 2025
Published
15 July 2025
Volume
4 - 2025
Edited by
Stefano Molica, Hull University Teaching Hospitals NHS Trust, United Kingdom
Reviewed by
Raffaele Palmieri, University of Rome Tor Vergata, Italy
Daniela P. Mendes-de-Almeida, Oswaldo Cruz Foundation (Fiocruz), Brazil
Updates
Copyright
© 2025 Ai, Shentu, Xu, Xia and Duan.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Yongming Xia, xym20246@163.com; Shiwei Duan, duansw@hzcu.edu.cn
†These authors have contributed equally to this work
Disclaimer
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.