Survival and predictors of death in people with HIV-associated lymphoma compared to those with a diagnosis of lymphoma in general population

Cingolani, Antonella; Lepri, Alessandro Cozzi; Teofili, Luciana; Galli, Laura; Mazzotta, Valentina; Baldin, Gianmaria; Hohaus, Stefan; Bandera, Alessandra; Alba, Lucia; Galizzi, Nadia; Castagna, Antonella; Monforte, Antonella d’Arminio; Antinori, Andrea

doi:10.1371/journal.pone.0186549

Cited by 34 publications

(34 citation statements)

References 25 publications

(24 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These findings may serve to explain why primary refractory rates up to 70% are observed in HIV(+) DLBCL patients treated with chemotherapy alone . Although the standard of care is rituximab in conjunction with chemotherapy, the findings reported here may still be relevant given that just 54% of HIV(+) Non‐Hodgkin lymphoma (majority DLBCL) patients report using rituximab, leaving a substantial proportion of HIV(+) patients receiving chemotherapy alone …”

Section: Discussionmentioning

confidence: 76%

Enhanced DNA repair and genomic stability identify a novel HIV‐related diffuse large B‐cell lymphoma signature

Maguire

Chen

Wisner

et al. 2019

Intl Journal of Cancer

View full text Add to dashboard Cite

Diffuse large B‐cell lymphoma (DLBCL) is up to 17‐fold more likely to occur, follows a more aggressive clinical course and frequently presents at advanced stages in HIV infected (+) individuals compared to HIV negative (−) individuals. However, the molecular pathology underpinning the clinical features of DLBCL in HIV(+) patients relative to the general population is poorly understood. We performed a retrospective study examining the transcriptional, genomic and protein expression differences between HIV(+) and HIV(−) germinal center B‐cell (GCB) DLBCL cases using digital gene expression analysis, array comparative genomic hybridization (CGH) and immunohistochemistry (IHC). Genes associated with cell cycle progression (CCNA2, CCNB1, CDC25A, E2F1), DNA replication (MCM2, MCM4, MCM7) and DNA damage repair, including eight Fanconi anemia genes (FANCA, FANCD1/BRCA2, FANCE, FANCG, FANCR/RAD51, FANCS/BRCA1, FANCT/UBE2T, FANCV/MAD2L2), were significantly increased in HIV(+) GCB‐DLBCL tumors compared to HIV(−) tumors. In contrast, genes associated with cell cycle inhibition (CDKN1A, CDKN1B) as well as apoptosis regulating BCL2 family members (BCL2, BAX, BIM, BMF, PUMA) were significantly decreased in the HIV(+) cohort. BCL2 IHC confirmed this expression. Array CGH data revealed that HIV(+) GCB‐DLBCL tumors have fewer copy number variations than their HIV(−) counterparts, indicating enhanced genomic stability. Together, the results show that HIV(+) GCB‐DLBCL is a distinct molecular malignancy from HIV(−) GCB‐DLBCL; with an increased proliferative capacity, confirmed by Ki67 IHC staining, and enhanced genomic stability, the latter of which is likely related to the enhanced expression of DNA repair genes.

show abstract

Section: Discussionmentioning

confidence: 76%

Enhanced DNA repair and genomic stability identify a novel HIV‐related diffuse large B‐cell lymphoma signature

Maguire

Chen

Wisner

et al. 2019

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…The introduction of HAART has significantly improved survival rates for ADCs, nevertheless, HIV infection seems to remain a factor increasing the risk of death in patients with ADCs. The overall survival of HIV‐infected patients with NHLs and cervical cancer is significantly lower than in HIV‐negative population …”

Section: Hiv and Cancer Treatment In The Haart Eramentioning

confidence: 98%

“…In the HAART era, survival rates for HLs and anal cancer improved considerably . The overall 3‐year survival of HIV‐infected patients with HLs is significantly lower than in HIV‐negative population, which might be due to treatment disparities . For solid tumors, such as lung, liver, anal cancer 5‐year survival is comparable to that in general population …”

Section: Hiv and Cancer Treatment In The Haart Eramentioning

confidence: 99%

“…The overall survival of HIV-infected patients with NHLs and cervical cancer is significantly lower than in HIV-negative population. 57,58 ADCs give better responses to treatment with the HAART + chemotherapy/radiotherapy combination rather than HAART alone or chemotherapy/radiotherapy alone, 59-63 therefore, HAART use is recommended for patients with ADCs. 14 No difference was found between PI-based HAART vs. other regimens in treatment outcomes of Kaposi's sarcoma 64 and NHL 65,66 in a combination with chemotherapy.…”

Section: Aids-defining Cancersmentioning

confidence: 99%

See 1 more Smart Citation

HIV‐1, HAART and cancer: A complex relationship

Шмакова

Germini

Vassetzky

2019

Intl Journal of Cancer

View full text Add to dashboard Cite

HIV infected people are at higher risk of developing cancer, although it is globally diminished in the era of highly active antiretroviral treatment (HAART). Recently, antioncogenic properties of some HAART drugs were discovered. We discuss the role of HAART in the prevention and improvement of treatment outcomes of cancers in HIV‐infected people. We describe different trends in HAART–cancer relationships: cancer‐predisposing as well as cancer‐preventing. We cover the roles of particular drug regimens in cancer prevention. We also describe the causes of cancer treatment with HAART drugs in HIV‐negative people, including ongoing clinical studies that may directly point to a possible independent anti‐oncogenic activity of HAART drugs. We conclude that despite potent antioncogenic activities of every class of HAART drugs reported in preclinical models, the evidence to date indicates that their independent clinical impact in HIV‐infected people is limited. Improved cancer prevention strategies besides HAART are needed to reduce HIV‐cancer‐related mortality.

show abstract

“…However, with the burden of AIDS-related lymphoma in SSA, and no current standard-of-care in this setting, future trials should focus on moving care toward accepted standards for resourced settings, where HIV infection may no longer be an independent predictor or death, once risk score and receipt of rituximab are taken into account. 33 Establishing the safety of rituximab in PLWH has been important, as will be ensuring access to this drug, including in the United States, where it is less commonly offered to PLWH. 34 …”

Section: Future Directionsmentioning

confidence: 99%

Evolving Paradigms in HIV Malignancies: Review of Ongoing Clinical Trials

Ignacio¹,

Lin²,

Rajdev³

et al. 2018

J Natl Compr Canc Netw

View full text Add to dashboard Cite

This review highlights current interventional clinical trials for HIV-associated malignancies (HIVAMs), with emphasis on 4 mechanistic areas: immunomodulatory therapies and gene therapies, including immune checkpoint inhibitors; cytotoxic therapies; novel tumor-targeted and virally targeted therapies in both AIDS-defining and non–AIDS-defining cancers (NADC); and other screening or topical/ablative interventions. A search on ClinicalTrials.gov located 35 trials, including 12 immunomodulatory or gene therapy trials, 6 cytotoxic therapy trials, 10 trials of therapies with tumor or viral molecular targets, and 7 trials evaluating screening interventions or topical or ablative therapies. Study drugs, mechanisms, and outcomes of interest, including future directions, are discussed. Targeted therapies and immunotherapies address not only the tumor but underlying viral oncogens, including possible benefits on HIV-specific immunologic control. The resulting science from the trials listed in this review will provide important translational breakthroughs for people living with HIV (PLWH) and cancer. We highlight disease-specific challenges that could be addressed in future studies, including testing the safety and efficacy of cutting-edge immunotherapy and targeted treatments used in the general cancer population, and improving gaps in knowledge and practice for cancer screening and its treatment, especially in low-resource regions. Additional important considerations include identification of novel therapies for virally mediated tumors that disproportionally present in PLWH, how to treat persons with HIVAM and advanced immunosuppression, and how to comanage both diseases in antiretroviral therapy–naïve persons and those receiving care in settings where supportive therapies for hematologic toxicities and infections are limited. Current and future clinical trials should address needs of both resource-replete and -limited regions, as well as cancers that are uncommon in or respond differently to HIV-negative populations (eg, Kaposi sarcoma or anal cancer), in addition to an increased focus on NADCs not traditionally linked with HIV, such as lung or gastrointestinal tumors.

show abstract

Survival and predictors of death in people with HIV-associated lymphoma compared to those with a diagnosis of lymphoma in general population

Cited by 34 publications

References 25 publications

Enhanced DNA repair and genomic stability identify a novel HIV‐related diffuse large B‐cell lymphoma signature

Enhanced DNA repair and genomic stability identify a novel HIV‐related diffuse large B‐cell lymphoma signature

HIV‐1, HAART and cancer: A complex relationship

Evolving Paradigms in HIV Malignancies: Review of Ongoing Clinical Trials

Contact Info

Product

Resources

About