Vasculopathie cérébrale après greffe S. VERLHAC Washington 2007

Transcription

1 CEREBRAL VASCULOPATHY OUTCOME AFTER STEM-CELL TRANSPLANTATION FOR SICKLE CELL DISEASE S Verlhac*, F Bernaudin, C Galeotti, M Benkerrou, I Thuret, M de Montalembert, t A Kandem, M Vasile, G Sebag and the SFGM-TC. *Diagnostic Imaging, CHI Creteil, hôpital Robert Debre APHP Paris, France Reference center for sickle cell disease Background Stroke risk in SCD patients % at 8 years in SS/Sb Recurrence rate 67% on standard care % on chronic transfusions TCD detects patients at risk of stroke MRI detects silent infarcts Purpose SCT is the only curative treatment for SCD but early transplant-related neurological toxicity has been reported The aim of the study is to describe the cerebral vasculopathy outcome after SCT 87 consecutive patients transplanted between /988 and /4 (4 F, 47 M) 4 French centers Mean age: 9.5 y ( to years) Median Follow-up : 6 y (range -8 years) 4 Sibling Donors AA (n=4), AS (n=6), AbThal (n=) HLA identical n=8, One mismatched n=4 Stem Cell Source Bone marrow n=74 Cord blood n= BM+CB n= Peripheral blood stem cells n= Myeloablative allogeneic hematopoietic stem cell transplantation Preparation Transfusion/Exchange program to obtain HbS < % Myeloablative conditioning regimen consisting of Busulfan, cyclophosphamide and since 99 rabbit antithymocyte globulin GVHD prophylaxis Ciclosporin A +/- short MTX 5 6

2 56 had a cerebral vasculopathy 6 overt stroke abnormal TCD without stroke with abnormal conventional arteriography or MRA(n=6) or with normal angiography but persistent abnormal TCD despite chronic transfusions (n=4). 5 out of had silent infarcts. silent infarcts with severe anemia and/or cognitive deficiency and normal TCD 7 MRI grading Parenchyma right /left white matter ischemic lesions jonctional infarct territory infarct Atrophy mild intermediate severe 8 Location of lesions on pre-transplant MRI 9 Stroke patients 6 Grey and white matter MCA or ACA territory or jonctional infarct on one side and white matter lesions on the other side uni or bilateral white matter lesions hematoma Normal Non-stroke patients Grey and white matter ACA or MCA territory or jonctional on 5 one side and white matter periventricular lesions on the other side uni or bilateral white matter lesions normal 5 MRA grading Narrowing of each artery from MRA for rmca, lmca, raca, laca, rica, lica normal Questionable or mild stenosis Intermediate stenosis Severe stenosis 4 occlusion Moya absent begining intermediate severe Score 5 Score Arterial lesions on pre-transplant MRA Early neurological complications Score to 5 Location Unilateral lesions n= MCA n=4 ACA n= ICA n= or arteries n=5 Bilateral lesions n= Right ICA, MCA occlusion Left ICA,MCA stenoses, ACA occlusion PRES: Posterior Reversible Encephalopathy Syndrome Seizures Stroke

3 PRES n=7 rate % Seizures n=6 Cortical blindness n=5 Headaches n=4 Coma or confusion n= MRI lesions n=7 Onset of symptoms day- to day 44 Complete resolution including MRI findings Headache, confusion at day 6 post transplant cerebellum, hemispheric bilateral hyperintense lesions Resolution of symtoms in 48 hours. Anomalies resolved on followup MRI months later 4 PRES FLAIR FLAIR : early complications Seizures n=6 Frequent n=6 (4%) Significant risk factors GVHD with Steroids treatment p=. (/6) HTA p <. History of stroke, age and date of transplantation were not significant risk factors Early complications Stroke n= Day after engraftment: fatal intracranial hemorrhage in a 7 year-old patient with infarcts and severe Moya Day: Transient Ischemic Attack in a boy on CSA with a history of stroke 5 6 RESULTS : Long-term outcome No stroke recurrence after day Risk of recurrence 5.6% No first stroke Seizures n=,5,5,5 r.mca pre-sct r.mca post-sct Velocities were significantly reduced (p<.) one year post-transplantation (from,46 ±,4 at baseline to,97 ±,7 m/sec in the right middle cerebral artery and from, ± 49 to,96 ±,9 m/sec in the left MCA). 95% IC r.mca,6,4,,,8 7 8 Pre-SCT Post-SCT

4 Normalization of high velocities in MCA on the opposite side of a MCA occlusion n=4 in 4 patients with normal MRA or mild stenoses Occlusions persisted No more temporal window available n= No normal TCD became abnormal No change of high velocities n= 4 9 Long term outcome of abnormal velocities.5 BD: 5/999,5,5,5 Transfusion Program SCT Jun. r.mca l.mca Oct. Jan. Jan. Jun. Jan. Nov. Sep Transfusions SCT Jul. r.mca l.mca Abnormal TCD at the age of 4. Mild both ICA stenoses on MRA in. No change in. Rapid TCD normalisation following transplantation whereas chronic transfusions had failed to revert to normal velocities. May. Feb. Oct. May. Sep. Nov. Nov.6 Oct.5 Jun.4 : Long term outcome of MRI No change of the MRI score : presct.8 postsct (-6) p =,8 ns No new ischemic lesion in engrafted patients Worsened cerebral atrophy n= girl without history of stroke. MRA unchanged 4 years post-transplant abnormal TCD at.5 years of age left supra-clinoid ICA and ACAs stenosis at conventional angiography. normal parenchyma. Pre-transplantation 4 Post-transplantation 5 4

5 : Long term outcome of MRA : Long term outcome of MRA No change of the MRA score presct 5.47 postsct 5 (-) p=.6 ns n=5 normalization or improvement of mild stenoses n= worsened arterial lesions (ACAs) 5 pre-sct MRA post-sct MRA Pre-transplant years post-transplant No change Pre-transplant RMCA.95 m/sec RACA. m/sec 6 Post-transplant RMCA.47 m/sec R ACA Stroke girl with rmca mild stenosis and raca severe stenosis and occlusion of lmca on pretransplant MRA. years after SCT occlusion of the entire raca with moya while rmca stenosis improved. No stroke occured and MRI remained unchanged. Pre-transplantation year post-transplantation Conclusion Mild improvement of the right and left ACAs and MCAs stenoses No change of both supraclinoid ICA stenoses 7 High risk of early complications Seizures PRES with a slighty higher rate than in others diseases SCT 4.-7.% (Reece 99, Bartynski 4) Effective prevention of A first stroke stroke recurrence Silent infarcts Stabilization of stenoses Normalization of high velocities 8 Conclusion As it was shown that abnormal velocities precede arterial stenoses, it is likely that SCT has prevent constitution of severe stenoses in these children. On the other hand, arterial occlusion and cerebral infarcts did nt change. Even parenchymal atrophy progressed. Transplantation should be proposed earlier before stroke and its sequellae when abnormal velocities are detected by TCD