Cerebral Arterial Velocities in SCA-Children with Abnormal Doppler Are Reduced and Normalized More Frequently after Transplantation Than after Transfusion Program (French National Trial 'Drepagreffe' AP-HP N°: NCT 01340404)
| Autor: | Annie Kamdem, Florence Missud, Gisèle Elana, Maryse Etienne-Julian, Camille Runel, Regis Peffault Delatour, Cécile Arnaud, Corinne Pondarré, Jean-Hugues Dalle, Claire Galambrun, Gérard Socié, Monique Elmaleh, Laurence Lutz, Charlotte Jubert, Françoise Bernaudin, Isabelle Thuret, Corinne Guitton, Bénédicte Neven, Valentine Brousse, Catherine Paillard, Eleonore Petras, Suzanne Verlhac |
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| Rok vydání: | 2014 |
| Předmět: |
Hemolytic anemia
medicine.medical_specialty Thymoglobulin business.industry Surrogate endpoint Immunology Cell Biology Hematology medicine.disease Biochemistry Gastroenterology Surgery Transplantation medicine.anatomical_structure medicine.artery Internal medicine medicine Internal carotid artery business Stroke Hemorrhagic cystitis Artery |
| Zdroj: | Blood. 124:561-561 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.v124.21.561.561 |
| Popis: | Background : Evidence-based practices have shown that transfusion program (TP) is beneficial to SCA-patients with abnormally high velocities by Doppler; however, TP cannot be stopped safely, except following HSCT. No prospective trial has to date compared the extent of cerebral vasculopathy following TP or HSCT. The premise of the French National Trial “Drepagreffe” is that cerebral velocities will be reduced to a greater extent after HSCT than under TP. Patients and Methods : We present here preliminary results from this prospective trial with 2 arms (TP/HSCT), defined by the random-availability of a genoidentical donor. Inclusion criteria were SCA (SS/Sb0) children younger than 15 years with a history of abnormal cerebral arterial velocities (TAMMX ≥ 200 cm/sec), placed on long-term transfusion programs, with at least one non-SCA sibling and parents accepting HLA-typing and HSCT if a genoidentical donor was available. Transplanted patients received as conditioning regimen Busilvex-CY 200 mg/kg and 20 mg/kg rabbit Thymoglobulin with CSA and short MTX or MMF for GVHD prophylaxis. In the TP arm, HbS% was maintained at < 30% with Hb 9-11g/dL. At enrollment and 12 months post-enrollment, blood screening, Doppler, cerebral MRI/MRA were performed along with cognitive performance testing, the latter done in parallel in the control sibling. Primary endpoint was the significantly greater reduction of velocities in the HSCT than in the TP arm. Among the various secondary endpoints, Doppler normalization defined by velocities < 170 cm/s in all arteries was to occur more often after HSCT than on TP. Results: SCA-children (n=67; 36F-31M) from 10 French SCA-centers were enrolled between 12/2010 and 6/2013 at the mean (SD) age of 7.6 (3.1) years. History of stroke was present in 6 patients (4 in HSCT and 2 in TP) and 1 TIA in HSCT arm. At TP initiation, velocities≥200/cm/sec were found in middle (n=50), anterior (n=11) and internal carotid arteries (n=30) as abnormal velocities were observed in more than one artery in several patients. Mean (SD) maximum velocities were 219 (26) cm/s (range: 200-333). At enrollment all patients were on TP and paired analysis showed that mean(SD) maximum velocities had significantly decreased (p Conclusions: This prospective national trial comparing TP vs. HSCT in SCA-patients with a history of abnormal velocities shows for the first time that HSCT repeatedly and significantly results in a greater decrease in velocities than TP, and has very little toxicity. These preliminary results are encouraging and suggest that suppression of host SCA-erythropoiesis by HSCT is the treatment of choice for SCA-children with abnormal-TCD and genoidentical donor. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Bernaudin: Novartis: Research Funding. |
| Databáze: | OpenAIRE |
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