Characteristics and outcomes of KSHV-associated multicentric Castleman disease with or without other KSHV diseases

Ramaswami, Ramya; Lurain, Kathryn; Polizzotto, Mark N.; Ekwede, Irene; Waldon, Kirsta; Steinberg, Seth M.; Mangusan, Ralph; Widell, Anaida; Rupert, Adam; George, Jomy; Gonçalves, Priscila; Marshall, Vickie; Whitby, Denise; Wang, Hao Wei; Pittaluga, Stefania; Jaffe, Elaine S.; Little, Richard F.; Uldrick, Thomas S.; Yarchoan, Robert

doi:10.1182/bloodadvances.2020004058

Cited by 42 publications

(47 citation statements)

References 39 publications

(57 reference statements)

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“…Thus, additional studies are necessary to evaluate the effect of MT treatment at a long time of treatment (at least 24 weeks) to confirm if this scheme has a positive effect on the HHV-8 VL in KS/HIV patients. In fact, VGC as a complementary therapy in KS/HIV controls the viral replication of HHV-8 [ 33 ]. Therefore, we consider it necessary to understand host immune responses during VGC on cell subpopulations that play a fundamental antiviral role as NK and NKT and not solely the effect on HHV-8 VL.…”

Section: Discussionmentioning

confidence: 99%

“…They were followed up at 12 weeks and divided depending on the received scheme treatment, CT, and MT for this study. The median age for the CT group was 32 (26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45) years and 34 (27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41) years for MT group.…”

Section: Baseline Clinic Characteristics Of Study Populationsmentioning

confidence: 99%

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Valganciclovir as Add-On Therapy Modifies the Frequency of NK and NKT Cell Subpopulations in Disseminated Kaposi Sarcoma Patients

Flores‐González

Ramón‐Luing

Ocaña-Guzmán

et al. 2022

Cancers

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Human herpesvirus-8 infection (HHV-8) is the causative agent of Kaposi sarcoma (KS) and is highly prevalent among people living with HIV (KS/HIV). It has been reported that valganciclovir (VGC) reduces HHV-8 replication in KS/HIV patients. However, currently it is unclear if VGC modifies the frequency and induces changes in markers of immune regulation of immune cells necessary to eliminate HHV8-infected cells, such as Natural Killer (NK) and NK T cells (NKT). This study evaluated the effect of VGC used as antiviral HHV8 therapy in KS patients on the frequency of NK and NKT subpopulations based on the CD27 and CD57 expression, and the immunosenescence markers, PD-1 and KLRG1. Twenty KS/HIV patients were followed-up at baseline (W0), 4 (W4), and 12 weeks (W12) of the study protocol. Among them, 10 patients received a conventional treatment scheme (CT), solely antiretroviral therapy (ART), and 10 patients received a modified treatment regime (MT), including VGC plus ART. In both groups, bleomycin/vincristine was administrated according to the treating physician’s decision. The soluble levels of IL-15, PD-L1, PD-L2, and E-cadherin were quantified across the follow-up. Our results showed that the higher IL-15 levels and lower NK frequencies cells in KS/HIV patients reach almost normal values with both treatments regimes at W12. CD27+ NK and NKT cell frequencies increased since W4 on KS/HIV patients with MT. Furthermore, PD-1 expression decreased while KLRG1 increased on NK and NKT subpopulations at W12, and it is accompanied by increased PD-L1 plasma level since W4. Our study highlights the disruption of NK and NKT subpopulations in patients with KS/HIV and explores VGC treatment’s contribution to immune reconstitution during the first weeks of treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Baseline Clinic Characteristics Of Study Populationsmentioning

confidence: 99%

Valganciclovir as Add-On Therapy Modifies the Frequency of NK and NKT Cell Subpopulations in Disseminated Kaposi Sarcoma Patients

Flores‐González

Ramón‐Luing

Ocaña-Guzmán

et al. 2022

Cancers

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“…Therefore, the considerable heterogeneity between skin and GI samples may also be related to the underlying clinical characteristics and concurrent KSHV-associated process. In the presence of other KSHV-associated processes, elevated inflammatory cytokines (IL-1, IL-6 and IL-10) are notably high in the circulation(3, 26, 27). Skin KS lesions had higher IL-6 and IL-10 gene expression compared to normal tissue.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional analysis identifies overlapping and tissue-distinct profiles between Kaposi sarcoma tumors of the skin and gastrointestinal tract

Ramaswami

Tagawa

Mahesh

et al. 2022

Preprint

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Kaposi sarcoma (KS), caused by Kaposi sarcoma herpesvirus (KSHV), is a multicentric tumor characterized by abnormal vasculature and proliferation of KSHV-infected spindle cells. KS commonly involves the skin but in severe cases KS can also involve the gastrointestinal tract (GI). Here, we sought to compare the cellular and KSHV gene expression signatures of skin and GI KS lesions. Skin and GI KS were compared to normal matched samples using bulk RNA sequencing.Twenty-two paired samples of KS and normal tissue were obtained (skin (10 pairs) and GI (12 pairs)) from 19 patients with KS of whom 17 had concurrent HIV infection. Seven paired samples were from patients who had received prior KS therapy. Three patients provided both skin and GI samples at the same timepoint. These analyses identified 370 differentially expressed genes unique to cutaneous KS and 58 DEGs unique to GI KS compared to normal skin or GI tissues. Twenty-six differentially expressed genes overlapped between skin and GI KS, which included FLT4, which encodes for a VEGF-C and VEGF-D receptor, and STC1. KSHV infection of primary lymphatic endothelial cells (LECs) resulted in increased angiogenesis, and repression of STC1 or FLT4 inhibited angiogenesis. The analyses of KSHV expression from KS lesions identified certain lytic genes, specifically ORF75, that were consistently expressed, and these expression patterns differed from laboratory infection of LECs with KSHV and KSHV gene expression in PEL cell lines. This study demonstrates that complex patterns of gene expression are found in KS tissue that differ from the canonical latent/lytic programs seen in KSHV cell lines and also demonstrates differences in viral gene and clinically relevant host gene expression in skin and GI KS that may offer insights into the pathogenesis of these forms of KS.

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“…Consideration must be given to HIV status, as many patients diagnosed with PEL are HIV positive. Ramaswami and team highlight that PEL associated with the oftenunderdiagnosed multicentral Castleman's disease led to a clinically significant reduction in overall survival from 71% at 10 years to a 5-year OS of 38% [67]. Patients with AIDS-NHL should be treated with full-dose chemotherapy regimens and concurrent antiretroviral therapy (ART) in a multidisciplinary team inclusive of a hematologist and an HIV specialist.…”

Section: Hiv-positive Pelmentioning

confidence: 99%

“…However, higher-than-normal circulating inflammatory markers (specifically IL-6, IL-10, and viral IL-6), as well as increased HHV8 viral loads, are often found in patients with concurrent PEL and KSHV-MCD, which confer a worse prognosis [69,70]. NCCN guidelines recommend treatment of KSHV-MCD with rituximab-based regimens; however, it is recommended that patients with concurrent PEL receive cytotoxic chemotherapy in addition to these rituximab-based regimens [3,67]. Rituximab has been shown to downregulate inflammatory cytokines as well as work synergistically with common topoisomerase inhibitors and other antineoplastic agents [71,72].…”

Section: Hiv-positive Pelmentioning

confidence: 99%

Primary Effusion Lymphoma: A Clinicopathologic Perspective

Gathers

Galloway

Kelemen

et al. 2022

Cancers

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Primary effusion lymphoma (PEL) is a rare, aggressive B-cell lymphoma that usually localizes to serous body cavities to subsequently form effusions in the absence of a discrete mass. Although some tumors can develop in extracavitary locations, the areas most often affected include the peritoneum, pleural space, and the pericardium. PEL is associated with the presence of human herpesvirus 8 (HHV8), also called the Kaposi sarcoma-associated herpesvirus (KSHV), with some variability in transformation potential suggested by frequent coinfection with the Epstein-Barr virus (EBV) (~80%), although the nature of the oncogenesis is unclear. Most patients suffering with this disease are to some degree immunocompromised (e.g., Human immunodeficiency virus (HIV) infection or post-solid organ transplantation) and, even with aggressive treatment, prognosis remains poor. There is no definitive guideline for the treatment of PEL, although CHOP-like regimens (cyclophosphamide, doxorubicin, vincristine, and prednisone) are frequently prescribed and, given the rarity of this disease, therapeutic focus is being redirected to personalized and targeted approaches in the experimental realm. Current clinical trials include the combination of lenalidomide and rituximab into the EPOCH regimen and the treatment of individuals with relapsed/refractory EBV-associated disease with tabelecleucel.

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Characteristics and outcomes of KSHV-associated multicentric Castleman disease with or without other KSHV diseases

Cited by 42 publications

References 39 publications

Valganciclovir as Add-On Therapy Modifies the Frequency of NK and NKT Cell Subpopulations in Disseminated Kaposi Sarcoma Patients

Valganciclovir as Add-On Therapy Modifies the Frequency of NK and NKT Cell Subpopulations in Disseminated Kaposi Sarcoma Patients

Transcriptional analysis identifies overlapping and tissue-distinct profiles between Kaposi sarcoma tumors of the skin and gastrointestinal tract

Primary Effusion Lymphoma: A Clinicopathologic Perspective

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