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

Abstract

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.

Endovesical instillation of Cidofovir in the treatment of BK polyomavirus hemorrhagic cystitis after allogeneic hematopoietic cell transplantation

“…[23,24] However, efficacy of such a therapy has to be balanced with risks of potential immune-mediated side effects (such GVHD, immune reconstitution syndrome, cytokine release syndrome) and elevated health care costs. [23,25] The main adverse event of EV cidofovir in our patients was bladder spasms and/or pain. Such discomfort was similarly reported in about 30% of cases in other case series.…”

An expert consensus on prevention, diagnosis and management of hemorrhagic cystitis in pediatric hematopoietic cell transplantation, on behalf of the Infectious Disease and Hematopoietic Cell Transplant Working groups of Italian Pediatric Hematology Oncolo-gy Association (AIEOP)

“…Phase-2 studies based on third-party or donor-derived T-lymphocytes demonstrated satisfactory response rates in absence of infusion toxicity and with 1 reported onset of grade 2 skin GvHD (33,34), but a 16-year old HCT patient due to DOCK8 de ciency complicated by HC and high BKPyV viremia suffered from signi cant cytokine release syndrome (35). 9) Adoptive cell therapy is an area of investigation and future research.…”

BK viral infection: A review of management and treatment

“…It is worth noting that rare but serious adverse effects of VST, including cytokine release syndrome, diffuse alveolar damage, hepatic sinusoidal obstruction syndrome, multi-organ failure[ 53 ], and GVHD[ 52 ] have been reported in literature. Other potential logistical limitations of VST include the need for donor immunity to the viral target, as well significant cost, labor, time, and regulatory burden for manufacturing the therapy[ 52 , 54 ].…”