BKV‐specific T cells in the treatment of severe refractory haemorrhagic cystitis after HLA‐haploidentical haematopoietic cell transplantation

Pello, Óscar M.; Innes, Andrew; Bradshaw, Anne; Finn, Sally-Anne; Uddin, Shab; Bray, Emma P; Olavarría, Eduardo; Apperley, Jane F.; Pavlů, Jiří

doi:10.1111/ejh.12848

Cited by 37 publications

(22 citation statements)

References 3 publications

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“…However, he has had no recurrence of BK viremia with only minimal immunosuppression and after receiving BK virus‐specific T‐cell infusion. Hence, in addition to the reduced immunosuppression and trial of antiviral agents (cidofovir, leflunomide, quinolones) in selected cases, 43 BK virus‐specific T cells may emerge as a safe and effective approach to treat severe, drug‐refractory BK infections 44,45 . Whether the usage of the virus‐specific T cells in the HSCT recipients to prevent BK nephropathy is an effective approach needs to be studied further.…”

Section: Discussionmentioning

confidence: 99%

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

Bush

Johns

Betty

et al. 2020

Pediatric Transplantation

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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.

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Section: Discussionmentioning

confidence: 99%

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

Bush

Johns

Betty

et al. 2020

Pediatric Transplantation

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“…Polyoma-specific VST are being developed to combat these viruses. A single case report describes the successful use of BK VSTs, after which the patient had complete resolution of HC without bystander organ toxicity, GVHD, or graft rejection ( 74 ). It is now clear that the platforms developed for ex vivo selected and expanded VSTs are readily adaptable to many other viruses that complicate immune deficient states, and future developments include developing VST to target an array of viruses including VZV, HHV, and even HIV ( 16 , 75 – 79 ).…”

Section: Results Of Vsts In Clinical Usementioning

confidence: 99%

Virus-Specific T Cells for the Immunocompromised Patient

Houghtelin

Bollard

2017

Front. Immunol.

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While progress has been made in the treatment of both hematologic cancers and solid tumors, chemorefractory or relapsed disease often portends a dismal prognosis, and salvage chemotherapy or radiation expose patients to intolerable toxicities and may not be effective. Hematopoietic stem cell transplant offers the promise of cure for many patients, and while mismatched, unrelated or haploidentical donors are increasingly available, the recipients are at higher risk of severe immunosuppression and immune dysregulation due to graft versus host disease. Viral infections remain a primary cause of severe morbidity and mortality in this patient population. Again, many therapeutic options for viral disease are toxic, may be ineffective or generate resistance, or fail to convey long-term protection. Adoptive cell therapy with virus-specific T cells (VSTs) is a targeted therapy that is efficacious and has minimal toxicity in immunocompromised patients with CMV and EBV infections in particular. Products have since been generated specific for multiple viral antigens (multi-VST), which are not only effective but also confer protection in 70–90% of recipients when used as prophylaxis. Notably, these products can be generated from either virus-naive or virus-experienced autologous or allogeneic sources, including partially matched HLA-matched third-party donors. Obstacles to effective VST treatment are donor availability and product generation time. Banking of third-party VST is an attractive way to overcome these constraints and provide products on an as-needed basis. Other developments include epitope discovery to broaden the number of viral antigens targets in a single product, the optimization of VST generation from naive donor sources, and the modification of VSTs to enhance persistence and efficacy in vivo.

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“…Cell therapy has been employed also for the treatment of other infections, such as polyomaviruses and HHV6. Although very preliminary, initial experiences with BKPyV-specific cells are promising ( 36 , 69 ), as 13 of 14 patients treated for BKV-associated hemorrhagic cystitis within a clinical trial of third-party banked multivirus-specific T cell therapy in allogeneic HSCT experienced complete resolution of gross hematuria within 1–2 months ( 36 ). Of the two patients treated for virus-related nephropathy, one responded to treatment by ameliorating renal function.…”

Section: Cell Therapy For Infections After Hsctmentioning

confidence: 99%

Harnessing T Cells to Control Infections After Allogeneic Hematopoietic Stem Cell Transplantation

Basso¹,

Compagno²,

Zelini³

et al. 2020

Front. Immunol.

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Dramatic progress in the outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT) from alternative sources in pediatric patients has been registered over the past decade, providing a chance to cure children and adolescents in need of a transplant. Despite these advances, transplant-related mortality due to infectious complications remains a major problem, principally reflecting the inability of the depressed host immune system to limit infection replication and dissemination. In addition, development of multiple infections, a common occurrence after high-risk allo-HSCT, has important implications for overall survival. Prophylactic and preemptive pharmacotherapy is limited by toxicity and, to some extent, by lack of efficacy in breakthrough infections. T-cell reconstitution is a key requirement for effective infection control after HSCT. Consequently, T-cell immunotherapeutic strategies to boost pathogen-specific immunity may complement or represent an alternative to drug treatments. Pioneering proof of principle studies demonstrated that the administration of donor-derived T cells directed to human herpesviruses, on the basis of viral DNA monitoring, could effectively restore specific immunity and confer protection against viral infections. Since then, the field has evolved with implementation of techniques able to hasten production, allow for selection of specific cell subsets, and target multiple pathogens. This review provides a brief overview of current cellular therapeutic strategies to prevent or treat pathogen-related complications after HSCT, research carried out to increase efficacy and safety, including T-cell production for treatment of infections in patients with virus-naïve donors, results from clinical trials, and future developments to widen adoptive T-cell therapy access in the HSCT setting.

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BKV‐specific T cells in the treatment of severe refractory haemorrhagic cystitis after HLA‐haploidentical haematopoietic cell transplantation

Abstract: Our observations suggest that use of products enriched with BKV-specific T cells generated using this system is safe and efficient in HLA-haploidentical HCT where BKV cystitis can be a serious complication.

Cited by 37 publications

References 3 publications

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

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

Virus-Specific T Cells for the Immunocompromised Patient

Harnessing T Cells to Control Infections After Allogeneic Hematopoietic Stem Cell Transplantation

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