Resolution of painful trichodysplasia spinulosa with topical cidofovir: case report.

Purpose: Trichodysplasia spinulosa (TS) is a rare, disfiguring skin condition which presents with widespread asymptomatic or pruritic, skin-colored papules with white protruding keratin spiculations in immunocompromised individuals. Due to its rarity, there is little data to guide treatment decisions. The purpose of this article is to report a case of TS that completely resolved after treatment with topical cidofovir.Materials and methods: A 19-year-old immunosuppressed female presented with widespread painful, itchy bumps on the nose and face. Upon examination, there were erythematous papules with hyperkeratinized spicules affecting the central face. Biopsy of the lesions was consistent with TS which was confirmed via PCR analysis. The tenderness of this patient's eruption was highly atypical for TS. Once daily topical application of compounded 1% cidofovir cream was prescribed.Results: The patient's symptoms resolved completely after 4 weeks of therapy with topical cidofovir 1% cream, without reduction of immunosuppression.Conclusions: Topical cidofovir 1% cream may be a valuable treatment for this rare disease.

In Vitro Generation of BK polyomavirus-specific T cells for adoptive cell therapy in refractory cystitis hemorrhagic patients after hematopoietic stem cell transplantation.

INTRODUCTION: BKPyV associated hemorrhagic cystitis (BKPyV-HC) is a major and prevalent outcome of hematopoietic stem cell transplantation (HSCT) with no standard treatment option. Adoptive T cell therapy (ACT) against transplant-associated viruses has shown promising potential. We sought to produce virus-specific T cells (VSTs) against BKPyV with the aim of treating refractory HSCT-associated HC. METHODS: Peripheral blood mononuclear cells (PBMC) from healthy donors were isolated by Ficoll-Hypaque density gradient centrifugation. BKPyV-pulsed, monocyte-derived dendritic cells (mo-DCs) and T cells were co-cultured and expanded over 2-3 weeks with the addition of IL-2. The T cells were examined for various functional assays. RESULTS: Comparison analysis of Carboxyfluorescein diacetate succinimidyl ester (CFSE) indicated that the percentage of proliferated cells were significantly higher in donors (49.62 ± 7.09%) than controls (7.96 ± 4.55%). Furthermore, expanded T cells exhibited specificity to BKPyV antigens by IFN-γ ELISPOT assay. The expanded cells showed cytotoxic function versus human lymphoblastoid cell line (LCL). Final VST products mainly comprised of CD8/CD69 double-positive T cells, which were significantly higher in donors (46.8 ± 7.1%) than controls (16.91 ± 3.40%). CONCLUSION: In this study we demonstrated the feasibility of producing functional BKPyV-specific T cells in healthy donors using BKPyV PepMixes. These functional cells were able to proliferate and produce IFN-γ cytokine in response to BKPyV PepMixes. In addition, these T cells had cytotoxic ability against BKPyV antigen-expressing target cells.

The diagnostic and therapeutic dilemma of the co-existence of BK virus nephropathy with acute rejection - an experience from a single Centre and review of the literature.

INTRODUCTION: BKV nephropathy (BKVN) is one of the major causes of graft loss with the advent of potent immunosuppressive drugs. The literature on the co-existence of acute rejection (AR) and BKVN is scarce. MATERIALS AND METHODS: This is a single-center retrospective analysis, where the allograft biopsies of patients transplanted between 2011 and 2021 were reviewed. The biopsies, which showed evidence of coexistent AR and BKVN, were included. In addition, demographic profiles, clinical presentation, treatment details, response to therapy, and follow-up were analyzed. RESULTS: Out of 1175 live transplants done between January 2011 and March 2021, 49 had BKVN representing 4.17%. Only seven patients (0.59%) had coexistent BKVN with AR. The mean serum creatinine at presentation was 2.3 mg/dl. The mean duration to diagnosis from transplant was seven months (range 3-22 months). All had significant viremia at presentation (17450-4,750,000 copies/ml). All biopsies showed type 1 inclusion bodies with SV40 positivity except one. Coexistent acute T cell-mediated rejection (TCMR) was found in five and acute ABMR in two patients. Three patients received pulse IV methylprednisolone, five received 2 g/kg IVIG, two received plasma exchange as upfront therapies. Maintenance immunosuppression reduction was made in all. Viremia clearance was noted at a mean duration of 3.5 months. However, three patients lost their grafts on follow-up. Four had stable graft function with a mean serum creatinine of 1.54 mg/dl. CONCLUSION: Intensifying immunosuppression to treat AR followed by a reduction in maintenance immunosuppression and IVIG and antiviral therapies seems better strategy and showed good long-term graft survival in patients with coexistent BKVN and AR.

Off-the-Shelf Third-Party Virus-Specific T Cell Therapy to Treat JC Polyomavirus Infection in Hematopoietic Stem Cell Transplantation Recipients.

Progressive multifocal leukoencephalopathy (PML) is a progressive and generally fatal demyelinating neurologic disease that occurs in profoundly immunocompromised patients due to infection with the human polyomavirus JC virus (JCPyV). Treatment options are limited and are largely focused on restoring T cell immunity, and outcomes are historically poor. Control of JCPyV in the setting of an immunocompromised patient by adoptive transfer of third-party virus specific T cells (VSTs) has been described in a small number of cases. To investigate treatment response and outcomes in recipients of hematopoietic stem cell transplantation (HSCT) with PML treated with third-party VSTs directed against the BK virus, a highly homologous polyoma virus that shares immunogenic epitopes with JCPyV. A retrospective chart review was performed on 4 patients who received VSTs for the treatment of PML at Cincinnati Children's Hospital Medical Center since 2019. VSTs were administered safely, with no cases of graft-versus-host disease and no infusion reactions. One patient who was treated almost immediately after diagnosis was able to clear JCPyV from blood and cerebrospinal fluid, with resultant stabilization of neurologic decline. IFN-γ enzyme-linked immunospot (ELISpot) analysis demonstrated VSTs in the peripheral blood following infusion. Response was maintained through repeat infusions. Three other patients, all of whom had a longer delay between diagnosis and infusion, exhibited progressive neurologic decline despite varying degrees of improvement in viral load. PML is a rare but often fatal complication following HSCT for which few treatment options are available. BK-directed, JCPyV cross-reactive VSTs are a safe and viable therapeutic option, and prompt administration should be considered once PML is diagnosed. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Quality Is King: Fundamental Insights into Tumor Antigenicity from Virus-Associated Merkel Cell Carcinoma.

Merkel cell carcinoma (MCC) is a rare skin malignancy that is a paradigm cancer for solid tumor immunotherapy. MCCs associated with Merkel cell polyomavirus (virus-positive MCC [VP-MCC]) or chronic UV exposure (virus-negative MCC [VN-MCC]) are anti-PD(L)1 responsive, despite VP-MCC's low mutational burden. This suggests that antigen quality, not merely mutation quantity, dictates immunotherapy responsiveness, and cell-based therapies targeting optimal antigens may be effective. Despite VP-MCC's antigenic homogeneity, diverse T-cell infiltration patterns are observed, implying microenvironment plasticity and multifactorial contributions to immune recognition. Moreover, VP-MCC exemplifies how antitumor adaptive immunity can provide tumor burden biomarkers for early detection and disease monitoring.

Prospective analysis of BKV hemorrhagic cystitis in children and adolescents undergoing hematopoietic cell transplantation.

BK virus is one of the most common causes of hemorrhagic cystitis (HC) in children undergoing hematopoietic cell transplantation (HCT). Viruses can be found in urine and serum samples of immunocompromised patients. Malignant diseases, age, cell source, day of granulocyte reconstitution, conditioning regimen, or use of total body irradiation may play an important role in BKV epidemiology, development of hemorrhagic cystitis course, and outcome. The aim of this study was to evaluate the incidence, clinical course, and risk factors for BKV-HC in children undergoing HCT. A total number of 133 patients who were prospectively tested for BKV colonization/infection were enrolled into this multicenter analysis. Episodes of BKV-HC occurred in 36/133 (27%) enrolled subjects. In a univariate analysis for BKV-HC incidence, the following factors were significant: age >5 years, peripheral blood transplantation, matched unrelated donor (MUD) transplantation, busulfan-cyclophosphamide-melphalan conditioning regimen, and acute myeloblastic leukemia (AML) diagnosis. Presence of acute graft-versus-host disease (aGVHD) in liver and gut GVHD was a significant risk factor of BKV-HC. No BKV-attributed deaths were reported. In multivariate analysis, the incidence of HC was significantly higher in patients with AML, age >5 years, MUD transplants, and children with GVHD. HC is a frequent complication after HCT among children causes prolonged hospitalization but rarely contributes to death. We identified risk factors of BKV-HC development in children, with focus on aGVHD: we concluded that excessive immune reaction connected with GVHD and immunosuppression drugs might play a pivotal role in the development of BKV-HC.

Concurrent BK polyomavirus, adenovirus and cytomegalovirus infections in a patient treated for chronic lymphocytic leukaemia.

A 58-year-old woman with chronic lymphocytic leukaemia (CLL) presented with 2 weeks of fever and haematuria following chemo-immunotherapy. CT scan showed thickening of her left urethra and bladder, suggesting pyleo-ureteritis with cystitis. The patient was initially treated for suspected bacterial urinary tract infection although repeated blood and urine cultures remained negative. She then received multiple transfusions for chemotherapy-induced pancytopenia while her urinary symptoms did not improve. Due to her immunocompromised status, she was tested for viral infection, which revealed, BK polyomavirus, adenovirus and cytomegalovirus in serum and urine. Cidofovir was initially administered to treat these infections while ganciclovir was used with filgrastim due to neutropenia. The patient subsequently improved. This case represents a diagnostic and therapeutic challenge due to the multiple concurrent viral infections causing haematuria as well as the combined post-chemo-immunotherapy and antiviral myelotoxicity in a CLL patient.

Case Report: Fatal Complications of BK Virus-Hemorrhagic Cystitis and Severe Cytokine Release Syndrome Following BK Virus-Specific T-Cells.

BK virus (BKV)-hemorrhagic cystitis (HC) is a well-known and rarely fatal complication of hematopoietic stem cell transplantation (HSCT). Treatment for BKV-HC is limited, but virus-specific T-cells (VST) represent a promising therapeutic option feasible for use posttransplant. We report on the case of a 16-year-old male with dedicator of cytokinesis 8 (DOCK8) deficiency who underwent haploidentical HSCT complicated by severe BKV-HC, catastrophic renal hemorrhage, and VST-associated cytokine release syndrome (CRS). Gross hematuria refractory to multiple interventions began with initiation of posttransplant cyclophosphamide (PT/Cy). Complete left renal arterial embolization (day +43) was ultimately indicated to control intractable renal hemorrhage. Subsequent infusion of anti-BK VSTs was complicated by CRS and progressive multiorgan failure, with postmortem analysis confirming diagnosis of hepatic sinusoidal obstruction syndrome (SOS). This case illustrates opportunities for improvement in the management of severe BKV-HC posttransplant while highlighting rare and potentially life-threatening complications of BKV-HC and VST therapy.

Virus-specific T-cell therapy to treat BK polyomavirus infection in bone marrow and solid organ transplant recipients.

BK polyomavirus (BKPyV) infection is a major complication of hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT). Treatment options are limited, poorly effective, and have significant toxicities. Cellular therapy using T cells directed against BKPyV is an emerging therapy, and we report efficacy in controlling BKPyV-associated disease in highly immunocompromised patients. Virus-specific T cells (VSTs) against BKPyV were manufactured using either blood from the patient's stem cell donor (donor-derived VSTs) or from unrelated donors (third-party VSTs). VSTs were used to treat BKPyV in 38 HSCT recipients and 3 SOT recipients between June 2017 and December 2019. Overall response rate was 86% in patients treated for BK viremia, 100% in patients treated for hemorrhagic cystitis, and 87% in patients treated for both BK viremia and hemorrhagic cystitis. No infusional toxicity, de novo graft-versus-host disease, or rejection of the organ occurred attributable to the VST infusion. BKPyV-specific immune responses were demonstrated by interferon-γ production by peripheral blood mononuclear cells postinfusion in response to BKPyV antigens. VSTs are a safe and potentially effective strategy to treat BKPyV and associated symptoms in recipients of HSCT and SOT. Cellular therapy should be considered for all patients with BKPyV and underlying immune suppression at risk of complications. This trial was registered at www.clinicaltrials.gov as #NCT02532452.

Multidisciplinary Treatment, Including Locoregional Chemotherapy, for Merkel-Polyomavirus-Positive Merkel Cell Carcinomas: Perspectives for Patients Exhibiting Oncogenic Alternative Δ exon 6-7 TrkAIII Splicing of Neurotrophin Receptor Tropomyosin-Related Kinase A.

Merkel cell carcinomas (MCCs) are rare, aggressive, cutaneous neuroendocrine tumours, approximately 80% of which are caused by the genomic integration of Merkel cell polyomavirus (MCPyV). MCPyV-positive MCCs carry poor prognosis in approximately 70% of cases, highlighting the need for greater understanding of the oncogenic mechanisms involved in pathogenesis, progression and post-therapeutic relapse, and translation into novel therapeutic strategies. In a previous pilot study, we reported a potential relationship between MCPyV gene expression and oncogenic alternative Δ exon 6-7 TrkAIII splicing in formalin-fixed paraffin-embedded (FFPE) MCC tissues from a 12-patient cohort of >90% MCPyV-positive MCCs, diagnosed at San Salvatore Hospital, L'Aquila, Italy, characterising a new MCC subgroup and unveiling a novel potential MCPyV oncogenic mechanism and therapeutic target. This, however, could not be fully verified due to poor RNA quality and difficulty in protein extraction from FFPE tissues. Here, therefore, we extend our previous observations to confirm the relationship between MCPyV and oncogenic alternative Δ exon 6-7 TrkAIII splicing in fresh, nonfixed, MCPyV-positive MCC metastasis by detecting sequence-verified RT-PCR products, including full-length Δ exon 6-7 TrkAIII, and by Western blot detection of a 100 kDa TrkA protein isoform of identical size to 100 kDa Δ exon 6-7 TrkAIII expressed by stable transfected SH-SY5Y cells. We also report that in three MCC patients submitted for multidisciplinary treatment, including locoregional chemotherapy, MCPyV large T-antigen mRNA expression, Δ exon 6-7 TrkAIII mRNA expression and intracellular indirect immunofluorescence (IF) TrkA and phosphorylation protein isoform(s) immunoreactivity in FFPE tissues were not reduced in postchemotherapeutic-relapsed MCCs compared to pretherapeutic MCCs, extending the possible roles of this novel potential MCPyV oncogenic mechanism from MCC pathogenesis to post-therapeutic relapse and progression. Detection of alternative Δ exon 6-7 TrkAIII splicing in MCC, therefore, not only characterises a new MCPyV-positive MCC subgroup and unveils a novel potential MCPyV oncogenic mechanism but also identifies patients who may benefit from inhibitors of MCPyV T-antigen and/or TrkAIII expression or clinically approved Trk kinase inhibitors such as larotrectinib or entrectinib, which are known to inhibit activated TrkA oncogenes and to elicit durable responses in TrkA-fusion oncogene-driven cancers, supporting the call for a large-scale multicentre clinical study.

Antigenic competition in the generation of multi-virus-specific cell lines for immunotherapy of human cytomegalovirus, polyomavirus BK, Epstein-Barr virus and adenovirus infection in haematopoietic stem cell transplant recipients.

Adoptive transfer of multivirus-specific T cell lines (MVST) is an advanced tool for immunotherapy of virus infections after hematopoietic stem cell transplantation (HSCT). Their preparation includes activation of donor virus-specific T cells by the mixture of oligopeptides derived from immunodominant antigens of several most harmful viruses, i.e. human cytomegalovirus (HCMV), polyomavirus BK (BKV), Epstein-Barr virus (EBV) and adenovirus (ADV). The aim of our study was to find out whether antigenic competition may have an impact on the expansion of virus-specific T cells. MVST from several heathy blood donors were generated using a pulse of overlapping oligopeptides (PepMixes™, derived from the IE1 and pp65 CMV antigens, VP1 and LTAG BKV antigens, BZLF1 and EBNA1 proteins of EBV and hexon protein from ADV) and short time culture in the presence of IL-7 and IL-4. The amount of virus-specific T cells in MVST was measured by ELISPOT and flow cytometry after re-stimulation with individual antigens. To evaluate antigenic competition, MVST were expanded either with a complete set of antigens or with the mixture lacking some of them. MVST expanded with the antigen mixture including CMV antigens contained a lower proportion of the T cells of other antigen specificities. A similar inhibitory effect was not apparent for EBV-derived peptides. The competitive effect of CMV antigens was most pronounced in MVST from CMV-seropositive donors and was mediated by both IE1 and pp65-derived peptides. Antigenic competition did not influence the phenotype of either CMV- or BKV-specific T cells. Both T cell populations had an effector memory phenotype (CD45RO+, CD27-, CCR7-). However, CMV-specific T cells preferentially consist of CD8+ while in BKV-specific T cells, the CD4+ phenotype predominated. Modification of the MVST manufacture protocol to prevent antigenic competition may increase the efficacy of MVST in therapy of BKV infections in HSCT recipients.

T-cell adoptive immunotherapy for BK nephropathy in renal transplantation.

INTRODUCTION: BK virus (BKPyV) nephropathy occurs in 1%-10% of kidney transplant recipients, with suboptimal therapeutic options. CASE: A 54-year-old woman received a transplant in March 2017. BKPyV was detected at 1.5 × 102  copies/mL within a month, necessitating halving of mycophenolate and addition of leflunomide. Allograft histology in December showed polyomavirus nephropathy treated with intravenous immunoglobulin and cessation of mycophenolate. In February 2018, cidofovir and ciprofloxacin were commenced. In April, tacrolimus was reduced while introducing everolimus. A second graft biopsy in August showed increasing polyoma virus infection and a subsequent biopsy in September for worsening renal function showed 30% of tubular reactivity for simian virus 40 (SV40). Allogeneic BKPyV-reactive T cells were generated from the patient's daughter and infused over 10 sessions starting late September. The fourth allograft biopsy in November 2018 demonstrated involvement of BKPyV in 50% of tubules. Allograft function continued to decline, requiring hemodialysis from December 2018. Allograft nephrectomy after 6 months showed <1% SV40 in preserved tubules and 80% interstitial fibrosis. DISCUSSION: We conclude that the T-cell adoptive immunotherapy reduced BKPyV load significantly despite extensive infection, but attendant fibrosis and tubular atrophy led to graft failure. Early intervention with T-cell therapy may prove efficacious in BKPyV nephropathy.

Update on the Management of BK Virus Infection.

The BK polyomavirus was isolated in 1971; it has been a significant risk factor for both graft dysfunction and failure in renal transplant recipients. So far, no specific treatment option has been available for effective treatment or prophylaxis for BK virus infections. Although the use of heavy immunosuppression has been the main risk factor for BK virus infection, other risk factors are equally important, including elderly recipients, prior rejection episodes, male sex, human leukocyte antigen mismatching, prolonged cold ischemia time, pretransplant BK virus serostatus, and ureteral stenting. Regular follow-up for BK virus infections according to each institution's policy has been, so far, effective in detecting patients with BK virus viremia and consequently preventing allograft loss. The mainstay of management continues to be reduction of immunosuppression. However, newer options are providing new insights, such as cellular immunotherapy. In this review, we will address the diagnosis, screening, new diagnostic tools, and updated management of BK virus infections.

BK virus infection in allogeneic hematopoietic cell transplantation: An update on pathogenesis, immune responses, diagnosis and treatments.

In hematopoietic cell transplantation (HCT) patients, BK polyomavirus (BKPyV) infection results in significant morbidity mainly due to hemorrhagic cystitis (HC). Despite increased knowledge acquired over recent decades, no treatment has shown effectiveness in the management of organ damage in HCT allografts. This review summarizes the current knowledge on BKPyV, from the virus constitution to the pathophysiology and immune-related mechanisms. We next focus on BKPyV-induced HC in HCT to discuss the benefit of monitoring BKPyV viruria and viremia in the management of patients. At last, we review currently used therapeutics, along with future promising therapies to propose clinical and practical guidelines and further interesting research areas.

BK virus encephalitis and end-stage renal disease in a child with hematopoietic stem cell transplantation.

BK virus encephalitis after HSCT is uncommon. Several reports of native kidney BKVN in patients with HSCT, hematologic malignancies, human immunodeficiency virus infection, and non-renal solid organ transplantation have been described. However, an uncommon combination of BK encephalitis and ESRD of native kidneys secondary to BK virus in a child with HSCT has not been described. We report a 10-year-old boy who presented with a gradually rising serum creatinine during treatment for severe autoimmune hemolytic anemia, which he developed 9 months after receiving an allogeneic HSCT for aplastic anemia. There was no proteinuria or hematuria present. Serum BK virus load was 5 × 106  copies/mL. A renal biopsy showed evidence of BKVN. He developed fever, seizures, and confusion, and the (CSF) showed significant presence of the BK virus (1 × 106  copies/mL) along with biochemical evidence of viral encephalitis. Cerebrospinal fluid cultures were negative. Despite significant clinical symptoms and presence of BK virus in CSF, the magnetic resonance brain imaging findings were minimal. With reduction of immunosuppression, there was resolution of BK encephalitis but BKVN remained resistant to multiple anti-BK virus agents, including leflunomide and cidofovir. He eventually became dialysis-dependent and, 6 years later, received a renal transplant from his mother. This case illustrates that BK virus in severely immunocompromised HSCT recipient may lead to BK encephalitis and BKVN of native kidneys, even without hemorrhagic cystitis, leading to ESRD. Knowledge of such is important for appropriate timely evaluation and management.

Effects of intravenous immunoglobulin therapy and Fc gamma receptor polymorphisms on BK virus nephropathy in kidney transplant recipients.

BACKGROUND: BK virus nephropathy (BKVN) is a major complication in kidney transplant patients. This study aimed to investigate the efficacy of intravenous immunoglobulin (IVIG) therapy against persistent BKVN and to evaluate the association between persistent BKVN and Fc gamma receptor (FcγR) single nucleotide polymorphisms (SNPs). METHODS: A total of 86 patients out of 279 kidney recipients with BKVN were investigated in a single-center retrospective study. The majority of 86 patients were Hispanic and Asian (69.8% and 17.4%). Patients were treated with adjunctive IVIG or standard therapy (controls). Subgroup analysis was performed between IVIG responders and non-responders. BK virus copy number and serum creatinine (SCr) were measured to evaluate the impact of IVIG. We analyzed the association between the response to IVIG and genotype at FcγR3A (rs396991) and FcγR2A (rs1801274) SNPs. RESULTS: Viral load in IVIG non-responders was significantly higher than in responders at the time of diagnosis (219 271.8 vs 29 816.3 copies/mL, P = .015) and after 6 months of IVIG use (12 789.5 vs 1369.5 copies/mL, P < .001). However, analyses SNP of FcγR2A (OR = 0.807, CI = 0.435-1.496 P = .495) and FcγR3A (OR = 0.997, CI = 0.505-1.970, P = .993) SNPs showed no significant differences between the 2 groups. CONCLUSION: IVIG appears to lower BK DNA viral load significantly in patients with persistent BKVN. However, no associations were identified between BKVN and FcγR2A or FcγR3A SNPs.

Effects and long-term follow-up of using umbilical cord blood-derived mesenchymal stromal cells in pediatric patients with severe BK virus-associated late-onset hemorrhagic cystitis after unrelated cord blood transplantation.

This is a retrospective study to evaluate the efficacy and safety of umbilical cord blood-derived mesenchymal stromal cells (MSCs) for the treatment of pediatric patients with severe BK virus-associated late-onset hemorrhagic cystitis (BKV-HC) after unrelated cord blood transplantation (UCBT). Thirteen pediatric patients with severe BKV-HC from December 2013 to December 2015 were treated with MSCs. The number of MSCs transfused in each session was 1 × 106 /kg once a week until the symptoms improved. The median follow-up time was 1432 (89-2080) days. The median frequency of MSC infusion was 2 (1-3), with eight cured cases and five effective cases; the total efficacy rate was 100%. The copy number of urine BKV DNA was 4.43 (0.36-56.9) ×108 /mL before MSC infusion and 2.67 (0-56.3) ×108 /mL after MSC infusion; the difference was not significant (P = .219). There were no significant differences in the overall survival, disease-free survival, and the incidence of relapse and acute and chronic graft-versus-host disease between the MSC infusion group and non-MSC infusion group. There was also no significant difference in the cytomegalovirus, Epstein-Barr virus (EBV), and fungal and bacterial infection rates between the two groups. Although umbilical cord blood-derived MSCs do not reduce the number of BKV DNA copies in the urine, the cells have a high efficacy rate and minimal side effects in treating severe BKV-HC after UCBT among pediatric patients. MSCs do not affect the rates of relapse, long-term infection, or survival of patients with leukemia.

Diagnostics, treatment, and immune response in BK polyomavirus infection after pediatric kidney transplantation.

After pediatric kidney transplantation BK polyomavirus (BKPyV) infections are associated with an increased risk of graft loss by BKPyV-associated nephropathy (BkPyVAN). However, suitable prognostic markers for the individual outcome of BKPyV infections are missing and the management of therapeutic interventions remains a challenge to the success of pediatric kidney transplantation. This review gives an overview on current diagnostic and therapeutic strategies in the field of BKPyV infections after pediatric kidney transplantation. Methods determining the individual immune response to BKPyV are described and their usability is discussed. There is growing evidence that BKPyV-specific T cells (BKPyV-Tvis) may serve as prognostic markers in order to steer immunosuppressive therapy in pediatric kidney recipients with BKPyV viremia in future. Prospective randomized trials in viremic kidney recipients comparing Tvis-steered therapeutic intervention with standard reduction of immunosuppression are needed before implementation of BKPyV-Tvis monitoring in routine care of BKPyV infections.

BK polyomavirus-specific antibody and T-cell responses in kidney transplantation: update.

PURPOSE OF REVIEW: BK polyomavirus (BKPyV) has emerged as a significant cause of premature graft failure after kidney transplantation. Without effective antiviral drugs, treatment is based on reducing immunosuppression to regain immune control over BKPyV replication. The paradigm of high-level viruria/decoy cells, BKPyV-DNAemia, and proven nephropathy permits early interventions. Here, we review recent findings about BKPyV-specific antibody and T-cell responses and their potential role in risk stratification, immune monitoring, and therapy. RECENT FINDING: Kidney transplant recipients having low or undetectable BKPyV-specific IgG immunoglobulin G (IgG) are higher risk for developing BKPyV-DNAemia if the donor has high BKPyV-specific IgG. This observation has been extended to neutralizing antibodies. Immunosuppression, impaired activation, proliferation, and exhaustion of BKPyV-specific T cells may increase the risk of developing BKPyV-DNAemia and nephropathy. Clearance of BKPyV-DNAemia was correlated with high CD8 T cell responses to human leukocyte antigen (HLA)-types presenting BKPyV-encoded immunodominant 9mers. For clinical translation, these data need to be assessed in appropriately designed clinical studies, as outlined in recent guidelines on BKPyV in kidney transplantation. SUMMARY: Evaluation of BKPyV-specific immune responses in recipient and donor may help to stratify the risk of BKPyV-DNAemia, nephropathy, and graft loss. Future efforts need to evaluate clinical translation, vaccines, and immunotherapy to control BKPyV replication.

Trichodysplasia spinulosa mimicking lichen nitidus in a renal transplant patient.

Trichodysplasia spinulosa (TS) is a rare cutaneous condition associated with the TSPyV and characterized by skin-colored, folliculocentric papules with keratin spicule formation. TS is seen almost exclusively in immunosuppressed individuals, often presenting in patients with a history of solid organ transplantation or chemotherapy for a lymphoreticular malignancy. We report a case of widespread TS in a 9-year-old girl with a history of renal transplantation complicated by BK viremia, which is also caused by a polyomavirus, BKPyV. The clinical presentation of TS in this case morphologically resembled the more common, harmless skin condition known as "lichen nitidus," and was more extensive than expected for TS, creating a diagnostic challenge. This case illustrates an important presentation of severe TS of which transplant teams, oncologists, primary care providers, and dermatologists should be aware.