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
Françoise Bernaudin,
Jean-Hugues Dalle,
Dominique Bories,
Regis Peffault de Latour,
Marie Robin,
Yves Bertrand,
Corinne Pondarre,
Jean-Pierre Vannier,
Benedicte Neven,
Mathieu Kuentz,
Sébastien Maury,
Patrick Lutz,
Catherine Paillard,
Karima Yakouben,
Isabelle Thuret,
Claire Galambrun,
Nathalie Dhedin,
Charlotte Jubert,
Pierre Rohrlich,
Jacques-Olivier Bay,
Felipe Suarez,
Nicole Raus,
Jean-Paul Vernant,
Eliane Gluckman,
Catherine Poirot,
Gérard Socié,
for the Société Française de Greffe de Moelle et de Thérapie Cellulaire
Affiliations
Françoise Bernaudin
Referral Center for Sickle Cell Disease, Centre Hospitalier Intercommunal Créteil (CHIC), Université Paris XII, France;Hematology, Transplantation, AP-HP Hôpital Saint Louis, Paris, France
Jean-Hugues Dalle
Pediatric Hematology, Hôpital Robert Debré, Paris, France
Dominique Bories
Molecular Biochemistry, Hôpital Henri Mondor, Creteil, Université Paris XII, Paris, France
Regis Peffault de Latour
Hematology, Transplantation, AP-HP Hôpital Saint Louis, Paris, France
Marie Robin
Hematology, Transplantation, AP-HP Hôpital Saint Louis, Paris, France
Yves Bertrand
Institute of Pediatric Hematology and Oncology, Hospices Civils, Lyon, France
Corinne Pondarre
Referral Center for Sickle Cell Disease, Centre Hospitalier Intercommunal Créteil (CHIC), Université Paris XII, France;Institute of Pediatric Hematology and Oncology, Hospices Civils, Lyon, France
Jean-Pierre Vannier
Pediatric Hematology, Centre Hospitalo-Universitaire Charles Nicolle, Rouen, France
Benedicte Neven
Pediatric Immuno-Hematology, Hôpital Necker, Paris, France
Mathieu Kuentz
Hematology, Hôpital Henri Mondor, Université Paris XII, Créteil, France
Sébastien Maury
Hematology, Hôpital Henri Mondor, Université Paris XII, Créteil, France
Patrick Lutz
Department of Pediatric Hematology-Oncology, University Hospital Hautepierre, Strasbourg, France
Catherine Paillard
Department of Pediatric Hematology-Oncology, University Hospital Hautepierre, Strasbourg, France
Karima Yakouben
Pediatric Hematology, Hôpital Robert Debré, Paris, France
Isabelle Thuret
Hemato-Pediatrics, La Timone, Marseille, France
Claire Galambrun
Hemato-Pediatrics, La Timone, Marseille, France
Nathalie Dhedin
Hematology, Transplantation, AP-HP Hôpital Saint Louis, Paris, France;Hematology, Hôpital la Pitié, Paris, France
Charlotte Jubert
Hemato-Pediatrics, Hôpital de Bordeaux, France
Pierre Rohrlich
Hematology, Hôpital de Besançon, Besançon, France
Jacques-Olivier Bay
Hematology, Limoges, France
Felipe Suarez
Hematology, Hôpital Necker, Paris, France
Nicole Raus
Data Manager, SFGM-TC
Jean-Paul Vernant
Hematology, Hôpital la Pitié, Paris, France
Eliane Gluckman
Hematology, Transplantation, AP-HP Hôpital Saint Louis, Paris, France;Eurocord/Monacord, Hôpital Saint-Louis, Paris, France and Centre Scientifique de Monaco, Monaco
Catherine Poirot
Reproductive Biology Hôpital Saint-Louis, Sorbonne University, Paris
Gérard Socié
Hematology, Transplantation, AP-HP Hôpital Saint Louis, Paris, France
for the Société Française de Greffe de Moelle et de Thérapie Cellulaire
Allogeneic stem cell transplantation remains the only curative treatment 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 [busulfan, cyclophosphamide and rabbit antithymocyte 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 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