Clinical Management of Posterior Reversible Encephalopathy Syndrome after Allogeneic Hematopoietic Stem Cell Transplantation: A Case Series and Review of the Literature

Abstract

Background: Posterior reversible encephalopathy syndrome (PRES) is a rare but serious complication after allogeneic hematopoietic stem cell transplantation (alloHSCT). Among others, calcineurin inhibitors (CNI) for prophylaxis of graft-versus-host disease (GvHD) may promote the development of PRES, but the pathomechanism is still controversial. Discontinuation of CNI facilitates remission of symptoms but might contribute to the unfavorable prognosis of PRES due to an elevated incidence of GvHD. Methods: This is a case series of 7 patients with PRES from a retrospective analysis of 146 consecutive patients who received alloHSCT for hematologic malignancies. Results: At the onset of PRES, all patients presented a systemic infection, while no influence was seen for underlying disease, conditioning regimen, donor type, or GvHD. Discontinuation of CNI and control of the blood pressure reversed neurological symptoms in 6 patients, while 1 patient died from septic multiorgan failure. After bridging with prednisolone and/or mycophenolic acid, replacement of CNI by the mammalian target of rapamycin (mTOR) inhibitor everolimus effectively prevented severe GvHD without recurrence of PRES. Conclusions: A systemic infection/inflammation may be an important cause of PRES. Prophylaxis of GvHD by the mTOR inhibitor everolimus in case of PRES after alloHSCT demonstrated promising results but needs to be validated in larger cohorts.

Posterior Reversible Encephalopathy Syndrome after Hematopoietic Cell Transplantation in Children with Hemoglobinopathies

“…In fact, in a recent study 30 adult patients with SCD were given single-agent GVHD prophylaxis with sirolimus following nonmyeloablative conditioning, and none developed GVHD [35]. Furthermore, 7 patients with PRES after myeloablative transplantation for hematologic malignancies were successfully treated with everolimus [36]. All SCD patients in the present study were on oral valproic acid anticonvulsant prophylaxis before PRES onset, yet 12 of them developed seizures.…”

Neurocognitive dysfunction in hematopoietic cell transplant recipients: expert review from the late effects and Quality of Life Working Committee of the CIBMTR and complications and Quality of Life Working Party of the EBMT

“…116 PRES occurring in the first 100 days after allogeneic HCT is associated with neurocognitive dysfunction 116 and requires careful management strategies. 117 Identification of PRES and tight control of hypertension as well as a careful search for and removal of the etiologic agent remains a mainstay of management. For example, sirolimus, cyclosporine or tacrolimus have been associated with PRES and may be withdrawn if they are felt to be contributing to the development of PRES.…”

Etiologies, Cerebral Vasomotion, and Endothelial Dysfunction in the Pathophysiology of Posterior Reversible Encephalopathy Syndrome in Pediatric Patients

“…32 Less commonly, PRES in ALL patients occurs during the consolidation phase of chemotherapeutic treatment, maintenance chemotherapy, or prophylactic cranial irradiation. 27,[232][233][234] Developing a strategy to determine which patients with hematologic malignancy will most likely develop PRES has remained elusive. Thus, the identification of such risk factors may prove instructive and accordingly provide us with predictive power in this regard.…”