HHV-6 Infection Research Articles

Acute Transverse Myelitis in HHV-6 Infection

Acute Transverse Myelitis in HHV-6 Infection

Assessment of human Herpes Virus-8 infection in Iranian cirrhotic patients on the waiting list for liver transplantation: A cross-sectional analysis

BackgroundHuman Herpes Virus 8 (HHV-8) is involved in autoimmunity. However, its association with advanced liver disease has not been fully explained. Herein, the prevalence of HHV-8 viremia was assessed in Iranian liver transplant candidates with a confirmed diagnosis of cirrhosis. MethodsThis cross-sectional study was conducted on 230 patients with cryptogenic cirrhosis, virus-related cirrhosis, and autoimmune hepatitis, as well as 140 healthy blood donors from April 2022 to September 2023. The HHV-8 IgG antibody concentration and viral load were evaluated via ELISA and RT‒PCR, respectively. ResultsAnti-HHV-8 IgG antibodies were detected in 25 cirrhotic patients (10.8 %) and four healthy individuals (2.6 %) (p = 0.022). The majority of the seropositive patients had cryptogenic cirrhosis (20.4 %), followed by autoimmune hepatitis (13.1 %) and virus-related cirrhosis (4.7 %). The seropositivity of HHV-8 IgG antibody was significantly different among the etiologies of liver cirrhosis (p = 0.011). However, HHV-8 genomic DNA was not detected in the sera of the patients or healthy blood donors. ConclusionThe role of HHV-8 infection in the development of posttransplant diseases, together with the higher seroprevalence of HHV-8 antibodies in cirrhotic patients than in healthy individuals, highlights the importance of both primary and latent infections in liver transplantation. Therefore, serological and molecular screening of HHV-8 is highly suggested for liver transplant candidates and organ donors. The possibility of antibody-mediated epitope mimicry in cryptogenic and autoimmune groups with moderate HHV-8 antibody positivity and negative viral loads may account for the development of advanced liver diseases.

Common Cancer-Related Factors and the Risk of Developing Kaposi Sarcoma in Individuals without AIDS: Korea National Health Insurance Services Claims Database.

Backgrounds: Kaposi sarcoma (KS) is a unique form of cancer with epidemiological characteristics distinct from those of other solid cancers. While common risk factors including alcohol consumption, smoking, and metabolic disorders have been well studied in various cancers, their relationship with KS remains unclear. Methods: This study used a cohort approach with adults without AIDS, utilizing data from the National Health Insurance Service in South Korea. This study examined various conventional cancer-related risk factors related to the incidence of KS, including psoriasis. Results: Alcohol consumption, smoking, body mass index, diabetes mellitus, hypertension, hypercholesterolemia, and regular exercise were not significantly associated with the incidence of KS. Additionally, older age and male sex were associated with a higher incidence of KS. KS risk was increased in pathological conditions such as psoriasis and proteinuria, which require immunosuppressive medication. Conclusions: Our study suggests that traditional cancer-related risk factors may not play a significant role in the pathogenesis of KS, unlike other cancers. This, in turn, emphasizes the importance of immunosuppression and HHV-8 infection in the development of KS.

A systematic review and meta-analysis of HHV-6 and mortality after hematopoietic cell transplant.

Human herpesvirus-6B (HHV-6B) reactivation has been associated with non-relapse mortality (NRM) and overall mortality (OM) following allogeneic hematopoietic stem cell transplant (HCT). We performed a systematic review and meta-analysis to better quantify the association. Studies were included if they systematically tested a cohort of HCT recipients for HHV-6 infection or reactivation and described mortality for patients with and without HHV-6B. Random effects models were used to assess the pooled effect of HHV-6B positivity on each outcome of interest. Bayesian aggregation was additionally performed if models included 10 or fewer studies. Eight studies were included in the NRM analysis, which demonstrated a significant association between HHV-6 detection and NRM (pooled effect: 1.84; 95% CI: 1.29-2.62) without significant heterogeneity (I2 = 0.0%, p = 0.55). A Bayesian aggregation of the raw data used to construct the NRM random effects model supported these findings (95% credible interval: 0.15-1.13). Twenty-five studies were included in OM analysis, which showed a significant positive association (pooled effect: 1.37; 95% CI: 1.07-1.76), though considerable heterogeneity was observed (I2 = 36.7%, p < 0.05). HHV-6 detection is associated with NRM and OM following HCT. Randomized trials are warranted to evaluate if preventing or treating HHV-6B reactivation improves outcomes.

Clinical Efficacy of the HIV Protease Inhibitor Indinavir in Combination with Chemotherapy for Advanced Classic Kaposi Sarcoma Treatment: A Single-Arm, Phase II Trial in the Elderly.

This phase-2 trial showed that the HIV protease inhibitor indinavir may boost and extend the duration of the effects of chemotherapy in elderly with advanced progressive classic Kaposi sarcoma, without additional toxicity. Further, the amelioration of the immune status seen in responders suggests a better control of HHV-8 infection and tumor-cell killing. Thus, indinavir combined with chemotherapy may represent an important tool for the clinical management of classic Kaposi sarcoma in elderly patients.

Assessment of Nurse's Knowledge toward Human Herpes Virus 6 HHV-6 Infection in NICU

Background: The infant contracted Herpes Simplex Virus (HSV) during the process of being born. The worldwide occurrence of NH is approximately 10 cases per 100,000 births, and it is associated with substantial risks of illness and death. Objective: To evaluate nurses' level of understanding regarding HHV-6 infection in the neonatal intensive care unit (NICU) for newborn infants. The study employed a descriptive research design methodology to achieve its objective. A representative sample of 50 nurses currently employed in neonatal critical care units. Tool I: An Arabic-language structured interview questionnaire. The study encompassed many demographic factors of nurses, such as gender, age, educational attainment, years of experience in the Neonatal Intensive Care Unit (NICU), completion of training on HHV-6 infection, and the source of information. The second tool, the knowledge assessment sheet, focused on HHV-6 infection. The findings indicate that the study included exclusively female nurses, comprising 46.0% of the sample, while males accounted for 54%. Furthermore, the educational background of the participants primarily consisted of graduates from nursing institutes and colleges, with each group representing a substantial proportion of 34%. Conclusion: Our findings indicate that we have chosen to dismiss the null hypothesis, which posits that there is no correlation between the demographic attributes of nurses and their degree of understanding regarding herpes virus type 6 infection. Instead, we have opted to embrace the alternative hypothesis. Recommendations: Provide nurses with a thorough knowledge of the viral causes and risk factors linked to HSV type 6 infections in pregnant women.

Molecular detection and genotyping of human herpes virus 8 in blood donors in Congo.

Human herpesvirus 8 (HHV8) is rarely studied in Congo, despite its prevalence in Africa. Among healthy individuals, HHV-8 does not always lead to a life-threatening infection; however, in immunocompromised individuals, it could lead to more severe disease. The distribution of HHV-8 genotypes varies depending on ethnicity and geographic region. A prospective cross-sectional study included 265 samples from healthy blood donors from the National Blood Transfusion Center in Brazzaville, with an average age of 35 years, with extremes ranging from 18 to 60 years. After DNA extraction, a nested PCR was carried out for molecular detection, followed by genotyping by amplification of specific primers. In this study, 4.9% were positive for molecular detection of HHV-8 DNA. All HHV-8 positive DNA samples that were subjected to genotyping by amplification with specific primers allowing discrimination of two major genotypes (A and B). Genotype A was identified in 5 (1.9%) samples and genotype B in 2 (0.7%) samples, indicating that both genotypes were predominant. The remaining viral DNA samples not identified as the major genotypes were classified as «indeterminate» and consisted of 6 (2.3%) samples. The results of the study suggest that Congo is an area where HHV-8 infection is endemic.

The Eruptive Fevers at Sixes and Sevens.

Sixth Disease (roseola infantum) and its primary causative agent, HHV-6, share names that numerically concur. This article examines and answers the question of whether that correspondence is by design or coincidental by briefly reviewing the history and nomenclature of the HHV viruses and the classic febrile rashes of childhood while highlighting some clinical and microbiologic features of HHV-6 infection.

Clinical and virological problems of sudden exanthema in children

The problem of sudden exanthema/children’s roseola, an infection caused by HHV 6, is very relevant in our country. Domestic and foreign experts are actively studying the structure of the virus, the features of clinical forms and course options, methods for diagnosing infection, co-infection with other herpes viruses. It has been established that the immediate environment plays a leading role in the spread of infection. A review of recent data on sudden exanthema makes it clear why healthcare professionals retain such an unusual name for herpesvirus type 6 infection. The underdiagnosis of this disease in our country is associated with a lack of knowledge and alertness on the part of doctors and medical personnel. Although modern clinical and laboratory criteria for diagnosing HHV-6 infection make it possible to quite convincingly diagnose the disease with a fairly high degree of certainty. If desired. The advantage is the use of a technique for detecting virus DNA in plasma and other body media, in combination with serological research methods. The article presents modern recommendations for the treatment and prevention of sudden exanthema

Mendelian randomization analysis suggests no associations of human herpes viruses with amyotrophic lateral sclerosis.

The causal associations between infections with human herpes viruses (HHVs) and amyotrophic lateral sclerosis (ALS) has been disputed. This study investigated the causal associations between herpes simplex virus (HSV), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), HHV-6, and HHV-7 infections and ALS through a bidirectional Mendelian randomization (MR) method. The genome-wide association studies (GWAS) database were analyzed by inverse variance weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode methods. MR-Egger intercept test, MR-PRESSO test, Cochran's Q test, funnel plots, and leaveone-out analysis were used to verify the validity and robustness of the MR results. In the forward MR analysis of the IVW, genetically predicted HSV infections [odds ratio (OR) = 0.9917; 95% confidence interval (CI): 0.9685-1.0154; p = 0.4886], HSV keratitis and keratoconjunctivitis (OR = 0.9897; 95% CI: 0.9739-1.0059; p = 0.2107), anogenital HSV infection (OR = 1.0062; 95% CI: 0.9826-1.0304; p = 0.6081), VZV IgG (OR = 1.0003; 95% CI: 0.9849-1.0160; p = 0.9659), EBV IgG (OR = 0.9509; 95% CI: 0.8879-1.0183; p = 0.1497), CMV (OR = 0.9481; 95% CI: 0.8680-1.0357; p = 0.2374), HHV-6 IgG (OR = 0.9884; 95% CI: 0.9486-1.0298; p = 0.5765) and HHV-7 IgG (OR = 0.9991; 95% CI: 0.9693-1.0299; p = 0.9557) were not causally associated with ALS. The reverse MR analysis of the IVW revealed comparable findings, indicating no link between HHVs infections and ALS. The reliability and validity of the findings were verified by the sensitivity analysis. According to the MR study, there is no evidence of causal associations between genetically predicted HHVs (HSV, VZV, EBV, CMV, HHV-6, and HHV-7) and ALS.

A Parallel Comparison of the Safety and Efficacy of Allogeneic Hematopoietic Stem Cell Transplantation for Refractory and Relapsed T-ALL/Lbl Patients Who Achieved Complete Remission with CD7 CAR-T Versus Patients Who Achieved First Complete Remission with Chemotherapy before Transplantation

Introduction We have developed a fratricide-resistant CD7 CAR-T cells from bulk T cells transduced with CD7 CAR without gene editing or additional gene transfer, named naturally selected CD7 CAR-T (NS7CAR-T). NS7 CAR-T therapy has shown a robust complete remission (CR) rate in patients with refractory or relapsed (R/R) T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma (T-ALL/LBL). Nonetheless, the risk of relapse remains a challenge post-CD7 CAR-T therapy alone, suggesting the potential benefits of consolidation allogeneic hematopoietic stem cell transplantation (allo-HSCT). The question remains whether CD7 CAR-T therapy could increase the incidence of post-transplant complications. Here we conduct a parallel study to compare the safety and efficacy of allo-HSCT in R/R T-ALL/LBL patients who achieved CR with NS7 CAR-T therapy vs those who reached first CR (CR1) using chemotherapy prior to transplantation. Methods Between November 2020 and January 2023, a total of 223 consecutive patients with T-ALL/LBL who underwent allo-HSCT at our center were retrospectively analyzed. Patients who met the following criteria were included in this parallel study: 1) underwent the first allo-HSCT in our hospital, 2) achieved CR before transplantation either from NS7CAR-T therapy or CR1 from chemotherapy (Fig. 1). A total of 139 patients met the criteria for analysis and underwent allo-HSCT after achieving CR either from NS7CAR-T therapy (n=43) or chemotherapy (CR1=96). The median patient age at the time of transplantation was 15 years (range: 1-51 years). The median follow-up time was 370 days (2-941 days). CD7 CAR-T patients were from two clinical trials registered at www.clinicaltrials.gov NCT04572308, NCT04916860. Transplant donor types included sibling identical (n=12), haploidentical (n=110), and unrelated donors (n=17). We used total body irradiation (TBI)-based conditioning regimens (n=128) or Busulfan/Melphalan-based regimens (n=11). To prevent graft-versus-host disease (GVHD), we used ATG along with a short-term regimen combining methotrexate, cyclosporine/tacrolimus, and mycophenolate mofetil. Results The characteristics of patients from both groups are detailed in Table 1. The median interval between CD7 CAR-T treatment and transplantation was 59 (39-131) days. Within the CAR-T group, 16 patients had primary refractory disease, 18 had relapsed disease and 9 in minimal residual disease (MRD)-positive status in bone marrow before CD7 CAR-T therapy. Prior to CAR-T therapy, 55.8% (24 patients) had extramedullary lesions. In comparing the CAR-T and chemotherapy CR1 groups, we observed no significant differences in long-term efficacy post-allo-HSCT. The 2-year leukemia-free survival (LFS) rates were 64.9 (95% CI, 49.1-79.2)% and 69.8 (95% CI, 59.0-79.6)% (p=0.340); the 2-year overall survival (OS) rates were 64.1 (95%CI, 48.0-78.6)% and 71.8 (95%CI, 60.5-81.9)% (p=0.107); the 2-year relapse incidence (RI) rates were 9.3 (95%CI, 3.7-23.7)% and 11.5 (95%CI, 6.4-20.7)% (p=0.873); and the 2-year non-relapsed mortality (NRM) rates were 28.3 (95% CI, 16.9-47.4)% and 21.6 (95% CI, 13.9-33.4)% (p=0.244), for the CD7 CAR-T and non-CAR-T groups, respectively. The incidence of all grades of acute GVHD (aGVHD) 37.2 (95%CI, 25.2-54.9)% vs. 42.1 (95%CI, 33.3-53.3)% did not significantly differ between the CAR-T and non-CAR-T groups. A trend toward an increased rate but no P significance was observed in Grade 3-4 aGVHD incidence of 20.93 (95%CI, 11.7-37.4)% vs. 9.5 (95%CI, 5.1-17.6)% (p=0.139). One-year incidences of moderate to severe chronic GVHD (cGVHD) were 12.2 (95%CI, 5.4-28.0)% and 18.0 (95%CI, 11.5-28.0)% (p=0.357) in the CD7CAR-T and non-CAR-T groups, respectively (Table 2). No statistically significant differences were detected in the occurrences of transplant-associated thrombotic microangiopathy (TA-TMA), CMV, EBV, and HHV-6 infections between the two groups. Upon analyzing, we found that r/r patients who received allo-HSCT after achieving remission with NS7 CAR-T had a similar OS to CR1 patients (Fig. 2). Conclusions Our parallel study showed that T-ALL/LBL patients, who achieved CR via CD7 CAR-T therapy followed by a consolidation allo-HSCT, had similar favorable OS and LFS compared to patients who underwent allo-HSCT in the CR1 state induced by chemotherapy. This was achieved without increasing the incidence of GVHD, infections, or TA-TMA.

Angioimmunoblastic T-cell lymphoma and Kaposi sarcoma: A fortuitous collision?

Follicular helper T-cell (TFH) lymphoma of the angioimmunoblastic-type (AITL), one of the most prevalent T-cell lymphomas, typically encompasses proliferation of high endothelial venules and Epstein-Barr virus-positive immunoblasts, but neither infection with HHV8 nor association with Kaposi's sarcoma (KS) have been described. The aims of this study are to characterise the association between AITL and HHV8 infection or KS. Three male patients aged 49-76 years, HIV-negative, with concurrent nodal involvement by AITL and KS, were identified from our files and carefully studied. Two patients originated from countries where endemic KS occurs, including one with cutaneous KS. The lymphomas featured abundant vessels, expanded follicular dendritic cells and neoplastic TFH cells [PD1+ (three of three), ICOS+ (three of three), CXCL13+ (three of three), CD10+ (two of three), BCL6 (two of three)] but lacked EBV+ immunoblasts. The foci of KS consisted of subcapsular proliferations of ERG+, CD31+ and/or CD34+ , HHV8+ spindle cells. High-throughput sequencing showed AITL-associated mutations in TET2 (three of three), RHOA (G17V) (three of three) and IDH2 (R172) (two of three), which were absent in the microdissected KS component in two cases. Relapses in two patients consisted of AITL, without evidence of KS. No evidence of HHV8 infection was found in a control group of 23 AITL cases. Concurrent nodal involvement by AITL and KS is rare and identification of both neoplastic components may pose diagnostic challenges. The question of whether the association between AITL and KS may be fortuitous or could reflect the underlying immune dysfunction in AITL remains open.

Haploidentical Aß T Cell Depleted HSCT Represents an Alternative Treatment Option in Pediatric and Adult Patients with Sickle Cell Disease (SCD)

Background: Sickle cell disease (SCD) is the most prevalent inherited hemoglobinopathy worldwide, which is associated with considerable morbidity and early mortality. Although HSCT with a MD offers a curative treatment option with an excellent 2-y OS of 95%, availability of MDs is limited and therefore haploidentical HSCT is increasingly explored. Here we update our in vitro T-depleted haploidentical HSCT approach, which is currently explored in a multicenter international trial (NCT04201210). Methods: 29 pts with SCD or SCD-ß Thal (median age: 18 years; range: 2-32) received either a CD3 +/CD19 + (n=9) or aß/CD19 + (n=20) T-haplo-HSCT and were compared with 20 SCD-pts receiving a BM graft from a MSD (median age: 23 years; range: 9-39) at our center. Indication for T-haplo HSCT pts included severe or moderate SCD related complications such as recurrent pain crisis (&amp;gt;5/year), acute chest syndrome, neurological events, osteonecrosis or nephropathy, transfusion-refractory allo-immunization. After exchange transfusion, almost identical conditioning regimens consisting of treosulfan, thiotepa, fludarabine (FTT) and ATG-Grafalon were applied in almost all pts, with the only difference in the timing of ATG (upfront in T-haplo-HSCT, prior to day 0 in MSD-HSCT). Immunosuppression (IST) was maintained for a minimum of 180 days consisting of calcineurin inhibitors (mainly tacrolimus) and MMF. Results: The OS and DFS for MSD and T-haplo-HSCT was 95% and 83%, respectively (Table 1). The median follow-up was 49 months for MSD (range 5-118) and 67 months for T-haplo-HSCT (range 0.5-135). Neutrophil engraftment was achieved after a median of 29 days for MSD pts and 17 days for T-haplo-HSCT with a median of 2.8 x 10 8 TNC/kg (range: 0.65-4.11) and 12 x 10 6 CD3 +/CD19 + or ab/CD19 + depleted CD34 + cells/kg (range: 4.8-49.2), respectively. One pt received two T-haplo HSCT due to primary graft failure after HHV6 infection with effective engraftment after the second transplantation. One pt required a stem cell boost of the same donor with slow subsequent engraftment and one pt died of infectious complications after the fourth T-haplo HSCT. A mixed chimerism &amp;lt;80% was observed in 1/20 MSD-HSCT (median 94.9%; range 40.5-100%) and in 2/29 T-haplo-HSCT pts (median 97.8%; range: 35.7 -100%). No severe cases of &amp;gt;°III aGVD was observed in both populations. MSD pts reached T cell counts &amp;gt;200/µl on day +62 (median; range: 24-293) and T-haplo-HSCT pts on day +136 (median; range: 25-758). Viral reactivation occurred both in T-haplo HSCT (20/29) and in MSD-BMT (9/20). However, one pt in the T-haplo group developed kidney failure after prolonged BKV infection and four of the T-haplo pts died of complications associated with severe CMV or HHV6 infections that were accompanied by hyperinflammation, macrophage activation and acute respiratory distress despite antiviral and anti-inflammatory treatment. One pt of the MSD group died of late treatment related toxicity in combination with preexisting SCD comorbidity. The last fatality occurred in 2020 with now 16 additional pts being transplanted safely, not least also because of a consistent letermovir prophylaxis. Overall, the treosulfan-based conditioning regimen was well tolerated with only one VOD/SOS and one CNS infarction being observed in this high-risk population. 4/20 pts in the MSD group and none in the T-haplo group developed PRES early after conditioning. Conclusions: The safety and efficacy data of this pilot series of T-haplo-HSCT in SCD reveal that T-haplo-HSCT in advanced stage pediatric and adult SCD patients lacking a MSD is feasible. However, diligent viral monitoring and early treatment of viral reactivation, in particular HHV6 is mandatory as otherwise fatal infections may develop.

Neither Conditioning Chemotherapy Nor GvHD-Prophylaxis: CD7 CAR-T Treatment Bridging to Haplo-HSCT

BACKGROUND: Relapsed/refractory (R/R) acute leukemia patients ineligible for allo-HSCT have poor prognosis. CAR-T therapy has shown promising therapeutic outcomes for these patients, but simultaneously confers the risk of pancytopenia and potential tumor relapse. Bridging CAR-T therapy with allo-HSCT has the potential to restore hematopoiesis and consolidate long-term efficacy. However, GvHD remains a major impediment, and the myeloablative conditioning regimen eradicates residual CAR-T cells and compromises CAR-mediated antitumor function. Furthermore, the implementation of conditioning regimen and GvHD-prophylaxis could lead to severe toxicities. Novel strategies are therefore warranted to preserve CAR-T cells, enhance antitumor potency and minimize complications. METHODS: In this study, we presented 10 patients (enrolled between November 2021 and June 2023) with R/R CD7-positive acute leukemia who proceeded directly to haploidentical HSCT (haplo-HSCT) after CAR-T therapy. All patients received allogeneic CD7 CAR-T therapy, manufactured from either haploidentical donors (n=8) in a phase I clinical trial of donor-derived CAR-T cells (NCT04599556) or (n=1) universal CD7 CAR-T cells (RD13-02) therapy (NCT05716113) or as a compassionate use program after the end of a phase I clinical trial of universal CD7 CAR-T cells (RD13-01) (NCT04538599). CAR-T cell doses were at 2´10 6(haploidentical donor, n=8), 4´10 6 (RD13-02, n=1) or 5´10 6 (RD13-01, n=1) cells/kg. After achieving complete remission with incomplete hematological recovery (CRi), all patients underwent haplo-HSCT without conditioning regimen or GvHD prophylaxis. The primary end point was efficacy, safety, hematopoiesis recovery, and donor chimerism. RESULTS: All patients relapsed from multiple lines of chemotherapy or immunotherapy (median, 7; range, 4-13), were ineligible for allo-HSCT and received palliative care. After CAR-T infusion, 9 patients achieved MRD-negative CRi, and 1 achieved MRD-positive CRi, on day 15 after CD7 CAR-T therapy. 9 patients developed grade 1-2 cytokine release syndrome, and no neurological toxicity was reported. All patients exhibited grade 4 pancytopenia and bone marrow hypocellularity and were directly bridging to haplo-HSCT. The median time from CAR-T infusion to haplo-HSCT was 19 (range, 15-89) days. One patient died of HHV6 infection in central nervous system on day 13 after haplo-HSCT and was not evaluable for the following safety and efficacy. 3 patients experienced short-term grade II acute GvHD, which was resolved completely after low dose steroid, anti-TNF-α or ruxolitinib therapy. One patient developed PTLD at 2.1 months post-HSCT. In 9 evaluable patients, 8 showed full donor chimerism at 1-month post-HSCT, and 1 showed autologous hematopoiesis recovery. At a median follow-up of 10.2 (range, 2.2-20.7) months after CAR-T therapy, 6 patients remained in MRD-negative CR with normal hematopoiesis (including the patient with autologous hematopoietic recovery), 1 had CD7-negative relapse at 5.6 months, 1 developed CD7-negative relapse at 4.3 months and died at 4.8 months, and 1 died from septic shocks at 3.7 months. OS, PFS, NRM, and CIR at 1 year were 64.3% (95% CI, 38.5%-100%), 51.4% (95% CI, 26.2%-100%), 22.9% and 25.7%, respectively. Peripheral normal T cells in 8/10 of patients remained CD7-negative at the last follow-up, illustrating a well-maintained CAR-T function post-HSCT. CONCLUSIONS: Our findings demonstrate a novel strategy to simultaneously achieve CAR-T persistence and complete HSC engraftment, while reducing the risks of GvHD, providing valuable insights into combining cellular therapy with allo-HSCT for the treatment of R/R acute leukemia patients ineligible for conventional allo-HSCT.

Lymphedema and Kaposi sarcoma: A narrative review

Kaposi sarcoma (KS), due to HHV-8 infection is classified in 4 subtypes: epidemic, endemic, HIV-related and iatrogenic essentially after organ transplant. Lymphedema is a complication of KS. We reviewed the interactions between HHV-8 infection and lymphedema according an analysis of the literature. HHV-8 can infect different types of cells, among them a privileged tropism for lymphatic endothelial cells. It induces multi-centric endothelial proliferation leading to the occlusion of lymphatic vascular lumen. Lymphatic obstruction progressively lead to the blockage of lymphatic drainage, lymph stasis and lymphedema. Lymphedema mostly involved the lower limb affected by KS. It can then develop simultaneously or after the appearance of KS lesions but also be the first sign of KS, a long time before KS skin lesion onset. Lymphedema diagnosis is clinical and lymphoscintigraphy can confirm it if necessary. Lymphedema may be associated with active lesions of KS or non-evolutive, with only cicatricial lesions. KS should be treated according to the KS subtype, aggressive form, with local or systemic treatments associating with causal treatment, such as HIV infection or reducing immuno-suppressive drugs in transplant patients. In most of the cases, KS treatment may slightly reduce (or not) lymphedema volume which remains a chronic disease. Lymphedema management should be associated in order to reduce the volume and then stabilizing it. Low-stretch bandage, elastic garments and skin care are the cornerstone of treatment. Lymphedema is a frequent complication of KS, and may reveal KS or occurs throughout its course. Association of KS and lymphedema must be known because lymphedema is a chronic disease affecting the quality of life. Beyond the treatment of KS, its management must be specific including a long follow-up to optimize the patient's observance required to maintain the best lymphedema control.

Un bambino che ha messo la sesta

The case of a 3-month-old infant presenting with fever, rash and hyporeactivity is described. A diagnosis of left parapharyngeal abscess as one of the complications of HHV-6 infection was finally made.

Clinical and virological features of HHV-6 infection among children in Saint Petersburg

Clinical and virological features of HHV-6 infection among children in Saint Petersburg

DP19 Two patients with Kaposi sarcoma from the 2-week-wait clinic

Abstract We present two cases of Kaposi sarcoma (KS) in HIV-negative men who have sex with men (MSM) with no coexisting immunosuppressive treatment or conditions. They both presented with suspicious lesions on lower extremities, with no other mucocutaneous involvement. The initial clinical presentation of both patients was atypical, with uncharacteristic aspects of lesions on clinical examination and dermoscopy, which prompted further investigations. Skin biopsies were performed for both patients. Both cases had similar histological findings in keeping with KS: slit-like vascular spaces within the dermis, proliferation of capillary blood vessels with associated inflammatory infiltrate with lymphocytes and plasma cells and focal aggregates of spindle cells. Immunohistochemistry revealed endothelial cells displaying positive staining for human herpesvirus (HHV)-8. Immunodeficiency screening revealed no abnormalities, and repeat HIV screening was negative in both patients. These cases present an interesting occurrence of an increasingly encountered new subtype of KS seen in HIV-seronegative immunocompetent MSM. In addition to the four established variants of KS, this is an emerging variant that arises mostly in middle-aged MSM. HHV-8 has been identified as the aetiological agent in KS; indeed, the viral infection precedes the development of the disease. The fifth subtype is increasingly recognized: nonepidemic KS in MSM who are HIV-negative and have no other causes for immunodeficiency, as seen in our two cases. This subtype has been reported in the literature since the 1980s in this specific population. The clinical presentation resembles classic KS, with predominantly cutaneous involvement of the lower limbs, running a similar indolent course. There is a strong connection between HHV-8 infection and the development of KS; however, in countries where there is a low prevalence of the virus, in the general population, there is increased detection in the MSM group. Correlating the high detection rate of HHV-8 in MSM with its role in the development in KS, immunocompetent MSM are at risk of developing the condition. However, this subtype carries an overall good prognosis, with an indolent course and good response to similar therapeutic options used in the classic subtype.

HHV6, non solo sesta malattia

The authors describe the case of a 2-year-old girl who developed a leukoencephalitis during a HHV6 infection (sixth disease).

HHV-7 Encephalitis: The Rare Infection and Its Outcome on a Child (P11-10.006)

<h3>Objective:</h3> The primary aims of this study were to relate HHV-7 infection with clinical manifestations of encephalitis, transient hip synovitis and hepatic changes in childhood and to evidence the effectiveness of early diagnosis and treatment in patients with encephalitis. <h3>Background:</h3> A 2-year-old male patient reported persistent high fever, coughing and rhinorrhea starting 1 week ago. They sought outpatient pediatric care and was prescribed ceftriaxone and prednisolone, with no satisfactory response. The symptoms evolved to vomiting and dehydration. During the physical exam, he showed irritation, with constant cervical stiffness and hyperextension, photophobia, and convergent strabismus. On arrival, he had been taking ceftriaxone, acyclovir and desloratadine. Laboratory tests were very altered in leukocytes, platelets, PCR, AST, ALT and GGT. During the ophthalmologic examination, a paresis of cranial nerve VI on the right was identified as secondary to a probable meningitis. After 21 days of treatment with acyclovir, the patient had a good prognosis, however, he had claudication upon movement of the left hip. <h3>Design/Methods:</h3> NA <h3>Results:</h3> The CSF results were colorless, cloudy, pH 8, Glucose 58, Leukocytes 40, Proteins 81. To confirm this observation, the molecular panel detected the presence of HHV-7. The imaging tests helped and added to the results of the blood count and CSF. Cranial MRI showed a hyperintensity in the FLAIR sequence of the perimesencephalic subarachnoid space and small accumulation of liquid. In addition, the abdomen CT found a bit of fluid in the hip region. <h3>Conclusions:</h3> Encephalitis is an inflammation of the brain parenchyma that leads to neurological dysfunction caused by infection or autoimmunity. In this occasion, the patient had a rare case of HHV-7 encephalitis. Basically, the treatment was carried out with acyclovir and ketoprofen, obtaining a progressive improvement of the clinical picture. Consequently, further research on the complications of HHV-7 is essential to develop a good characterization of this disease. <b>Disclosure:</b> Mr. Andrade has nothing to disclose. Miss MARQUES has nothing to disclose. Dr. Mota has nothing to disclose.