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Haematologica. 2019 May 16. pii: haematol.2018.213207. doi: 10.3324/haematol.2018.213207. [Epub ahead of print]

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.

Author information

1
Centre Hospitalier Intercommunal Creteil (CHIC), Université Paris XII, France; francoise.bernaudin@chicreteil.fr.
2
Dept. of Pediatric Hematology, Hopital Robert Debré, Paris, France.
3
Dept. of Molecular Biochemistry, Hopital Henri Mondor, Creteil, Université Paris XII, France.
4
Dept. of Hematology, Transplantation, AP-HP Hôpital Saint Louis, Paris, France.
5
Institute of Pediatric Hematology and Oncology, Hospices Civils, Lyon, France.
6
Referral Center for Sickle Cell Disease, Centre Hospitalier Intercommunal Creteil (CHIC), France.
7
Dept. of Pediatric Hematology, Centre Hospitalo-Universitaire Charles Nicolle, Rouen, France.
8
Dept. of Pediatric Immuno-Hematology, Hôpital Necker, Paris, France.
9
Dept. of Hematology, Hopital Henri Mondor, Université Paris XII, Creteil, France.
10
Dept. of Pediatric Hematology-Oncology, University Hospital Hautepierre, Strasbourg, France.
11
Dept. of Pediatric Hematology, Hôpital Robert Debré, Paris, France.
12
Dept. of Hemato-Pediatrics, La Timone, Marseille, France.
13
Dept. of Hematology, Transplantation, Hôpital Saint Louis, Paris, France.
14
Dept. of Hemato-Pediatrics, Hôpital de Bordeaux, France.
15
Dept. of Hematology, Hôpital de Besançon, Besançon, France.
16
Dept. of Hematology, Limoges, France.
17
Dept. of Hematology, Hôpital Necker, Paris, France.
18
Data Manager, SFGM-TC.
19
Dept. of Hematology, Hôpital la Pitié, Paris, France.
20
St-Louis Hospital, Paris, France.
21
Dept. of Reproductive Biology Hôpital Saint-Louis, Sorbonne University, Paris, France.

Abstract

Allogeneic stem cell transplantation remains the only curative treatment for sickle-cell anemia, but the place of myeloablative conditioning remains to be defined. The aim of the present study was to analyze long-term outcomes, including chimerism, sickle-cell anemia-related events and biological data (hemoglobin, reticulocytes, HbS%), and fertility, in a French series of 234 SCA-patients younger than 30 years who received (1988-2012) a matched-sibling-donor stem cell transplantation following standardized myeloablative conditioning (Busulfan, Cyclophosphamide and rabbit anti-thymocyte globulin). Since the first report of the series (1988-2004), 151 new consecutive patients with sickle-cell anemia were 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 at least 95% chance of cure since year 2000. In the overall cohort (n=234, median follow-up of 7.9 years), event-free survival was not associated with age, but chronic-graft-vs-host disease was independently associated with recipien's age>15 (hazard ratio=4.37,P=0.002) and lower (5-15 vs 20 mg/kg) anti-thymocyte globulin 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 anti-thymocyte globulin had no graft rejection. No events related to sickle cell anemia occurred in patients with mixed chimerism, even those with 15-20% donor cells, but hemolytic anemia stigmata were observed with donor cells<50%. Currently, myeloablative transplantation with matched-sibling donor has a higher event-free survival (98%) in patients younger than 30 than that reported for non-myeloablative conditioning (88%). Nevertheless, the risk of chronic graft-vs-host disease in older patients and need for fertility preservation might be indications in patients older than 15 for a non-myeloablative conditioning.

KEYWORDS:

Hemoglobinopathies; Stem Cell Transplantation; chimerism; fertility; myeloablative conditioning

PMID:
31097628
DOI:
10.3324/haematol.2018.213207
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