Posterior Reversible Encephalopathy Syndrome in Beta Thalassemia Major Transplants: A Single Center Experience
Authors: Mathew Amrith , Philip Chepsy C , John M Joseph 
Published: October 2019

Background: Posterior reversible encephalopathy syndrome (PRES) is a neurological syndrome characterized by clinical finding of hypertension, seizures, behavioral changes and altered vision, coupled with MRI abnormalities, known to occur after hematopoietic stem cell transplantation, potentially associated with calcineurin inhibitors. There is limited literature on the clinical and radiological findings in patients with PRES undergoing transplant for beta thalassemia major.

Method: A Retrospective analysis of the incidence and characteristics of PRES was performed on transplants done between November 2008 and May 2015. This study assessed the frequency, etiology, clinical and imaging characteristics in patients undergoing stem cell transplantation for beta thalassemia major.

Results: A total of 88 bone marrow transplants (BMT) were performed for various indications and among them 39 transplants were for patients with thalassemia major. The median age among the beta thalassemia group was 9 years (range 2-18). Two different regimens were used for thalassemia. Table: 1 Cyclosporine A (CSA) and short course methotrexate were used as graft versus host disease (GVHD) prophylaxis in all allogeneic transplants.

A total of 6 (6.7%) patients developed PRES. Two (4%) were among non-thalassemia transplants and 4 (10%) were among thalassemia transplants. (p= 0.276).

Among the beta thalassemia transplants, 2 (7%) of them underwent matched related donor (MRD) and 2 (22%) had matched unrelated donor (MUD) transplants. All patients who developed PRES belonged to either Pesaro class II or III risk group. Table 1.

High blood pressure recordings above 95th centile were noted in all the patients prior to the onset of seizure and all of them (100%) complained about persisting head ache. Two patients (50%) had visual hallucinations and one of them had transient loss of vision with no ophthalmic findings.

MRI changes were seen among 3 patients (75%). Of the patients who had radiological findings, T2 hyper-intensive white matter changes were present in frontal 1 (25%), parietal 3 (75%), occipital 3 (75%), and thalamus 1 (25%). Abnormalities were bilateral all in all patients who had MRI findings, but not necessarily symmetrical. None of the patients had hemorrhage or grey matter changes. The etiological factor for 3 (75%) patients was calcineurin inhibitor (CNI), CSA and the symptoms reverted on discontinuation of CSA. An increased level of CSA was noted only in on patient with a level of 358µg/L (range 131 - 358µg/L). One patient had the seizure with MRI changes following stem cell product infusion.

The occurrence of PRES was not associated with previous history of seizures in any of the patients. Time to PRES ranged between 53 to 60 days in patients on calcineurin inhibitors. All patients made a complete recovery within 24-48 hours and were continued on antiepileptics. However, one patient died after status-epilepticus and brain stem injury while on tapering doses of leviteracetam at 6 months post-transplant.

Conclusion: It is important to promptly recognize this syndrome based on the post-transplant day, clinical history of head ache, hypertension, visual abnormalities and MRI findings. Early imaging, withdrawal of calcineurin inhibitors, tight blood pressure control and initiation of anticonvulsants in high risk thalassemia transplants may be helpful reducing the incidence. By analyzing larger databases it may be helpful to develop diagnostic criteria and scoring for early diagnosis and intervention.

Table 1. Transplant indications, types and risk stratification and conditioning regimens. Variable n (%) Total transplants 88 (100) Non Thalassemia 49 (56) Thalassaemia Class I Class II Class III MRD MUD 39 (44) 3 (8) 9(23) 27 (69) 30 (77) 9 (23) Conditioning regimen for thalassemia N = 39 Thiotepa, Treosulfan and Fludarabine 36 (92) Busulphan, Cyclophosphamide, ATG 3 (8) PRES N=6 Non-Thalassemia Thalassemia 2 (6.7%) 4 (10%) p=0.276 Etiology among thalassemia transplantsCNI Stem cell product infusion N=4 3 (75%) 1 (25%)

Disclosures

No relevant conflicts of interest to declare.