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Red Cell Biology & its Disorders
Long-term event-free survival, chimerism and fertility outcomes in 234 patients with sickle-cell anemia younger than 30 years after myeloablative conditioning and matched-sibling transplantation in France
Ferrata Storti Foundation
Haematologica 2020 Volume 105(1):91-101
FrançoiseBernaudin,1,2 Jean-HuguesDalle,3 DominiqueBories,4
Regis Peffault de Latour,2 Marie Robin,2 Yves Bertrand,5 Corinne Pondarre,1,5 Jean-Pierre Vannier,6 Benedicte Neven,7 Mathieu Kuentz,8 Sébastien Maury,8 Patrick Lutz,9 Catherine Paillard,9 Karima Yakouben,3 Isabelle Thuret,10 Claire Galambrun,10 Nathalie Dhedin,2,11 Charlotte Jubert,12 Pierre Rohrlich,13 Jacques-Olivier Bay,14 Felipe Suarez,15 Nicole Raus,16 Jean-Paul Vernant,11 Eliane Gluckman,2,17 Catherine Poirot18 and Gérard Socié2 for the Société Française de Greffe de Moelle et de Thérapie Cellulaire
1Referral Center for Sickle Cell Disease, Centre Hospitalier Intercommunal Créteil (CHIC), Université Paris XII, France; 2Hematology, Transplantation, AP-HP Hôpital Saint Louis, Paris, France; 3Pediatric Hematology, Hôpital Robert Debré, Paris, France; 4Molecular Biochemistry, Hôpital Henri Mondor, Creteil, Université Paris XII, Paris, France; 5Institute of Pediatric Hematology and Oncology, Hospices Civils, Lyon, France; 6Pediatric Hematology, Centre Hospitalo-Universitaire Charles Nicolle, Rouen, France; 7Pediatric Immuno- Hematology, Hôpital Necker, Paris, France; 8Hematology, Hôpital Henri Mondor, Université Paris XII, Créteil, France; 9Department of Pediatric Hematology-Oncology, University Hospital Hautepierre, Strasbourg, France; 10Hemato-Pediatrics, La Timone, Marseille, France; 11Hematology, Hôpital la Pitié, Paris, France; 12Hemato-Pediatrics, Hôpital de Bordeaux, France; 13Hematology, Hôpital de Besançon, Besançon, France; 14Hematology, Limoges, France; 15Hematology, Hôpital Necker, Paris, France; 16Data Manager, SFGM-TC; 17Eurocord/Monacord, Hôpital Saint-Louis, Paris, France and Centre Scientifique de Monaco, Monaco and 18Reproductive Biology Hôpital Saint-Louis, Sorbonne University, Paris
ABSTRACT
Allogeneic stem cell transplantation remains the only curative treat- ment for sickle cell anemia (SCA), but the place of myeloablative conditioning in the procedure remains to be defined. The aim of the present study was to analyze long-term outcomes, including chimerism, SCA-related events and biological data (hemoglobin, reticulocytes, HbS%), and fertility in a French series of 234 SCA patients under 30 years of age who, from 1988 to 2012, received a matched-sibling-donor stem cell transplantation following standardized myeloablative conditioning [busul- fan, cyclophosphamide and rabbit anti-thymocyte globulin (ATG)]. Since the first report of the series (1988-2004), 151 new consecutive patients with SCA have been similarly transplanted. Considering death, non- engraftment or rejection (donor cells <5%) as events, the 5-year event-free survival was 97.9% (95% confidence interval: 95.5-100%), confirming, since the year 2000, an at least 95% chance of cure. In the overall cohort (n=234, median follow up 7.9 years), event-free survival was not associat- ed with age, but chronic-graft-versus-host disease (cGvHD) was independ- ently associated with recipient’s age >15 years (hazard ratio=4.37; P=0.002) and lower (5-15 vs. 20 mg/kg) ATG dose (hazard ratio=4.55; P=0.001). At one year, 44% of patients had mixed chimerism (5-95% donor cells), but those prepared with ATG had no graft rejection. No events related to SCA occurred in patients with mixed chimerism, even those with 15-20% donor cells, but hemolytic anemia stigmata were observed with donor cells <50%. Myeloablative transplantation with matched-sibling donor currently has a higher event-free survival (98%) in patients under 30 years of age than that reported for non-myeloablative conditioning (88%). Nevertheless, the risk of cGvHD in older patients and the need to preserve fertility might be indications for a non-myeloablative conditioning.
Correspondence:
FRANÇOISE BERNAUDIN
francoise.bernaudin@chicreteil.fr
Received: December 3, 2018. Accepted: May 15, 2019. Pre-published: May 16, 2019.
doi:10.3324/haematol.2018.213207
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