Myeloablative Bone Marrow Transplantation in Young Adults with Sickle Cell Disease: the French Experience
Authors: Kuentz Mathieu , Robin Marie , Dhedin Nathalie , Pautas Cécile , Tour Regis Peffaut De La , Rohrlich Pierre , Bordigoni Pierre , Socié Gérard , Cordonnier Catherine , Bernaudin Francoise 
Published: October 2019

Abstract
Abstract 3516
Allogeneic Bone Marrow Transplantation (ABMT) is currently the only curative treatment for sickle cell disease (SCD). However, in adult patients, myeloablative conditioning is usually considered as excessively toxic and non-myeloablative procedures have resulted in high rejection rates or frequent mixed chimerism. In these mixed chimeras, erythropoiesis is usually of donor origin, but the long-term stability of this chimerism remains unknown. In this context, we report the French experience of myeloablative ABMT in young adults, using a preparative regimen previously successful in children (Bernaudin et al. Blood 2007).

Patients and Methods:
Twelve SCD patients,8 males and 4 females, 16 to 28 years old (mean 20,6) were transplanted with an HLA identical sibling between 1999 and 2009 in five french centers. These patients were listed in the French BMT registry (SFGM-TC). All patients received the same BU-CY +ATG (varying dosage) preparative regimen and Cyclosporine and Methotrexate for GVHD prophylaxis. Reason for transplant included a stroke history in 4 patients, asymptomatic pulmonary hypertension (TRV: 2.9m/s) in 1 patient, and frequent vasoocclusive crisis and/or acute chest syndrome in all the others. Before transplant, 10 patients had received numerous transfusions (>20 units) and none had received Hydroxyurea. Erythrocyte immunisation was present in 1 patient. The donors were AA in 7 cases and AS in 5. Eight donors were seropositive for CMV and 4 had a major ABO incompatibility with the recipient. The median follow-up of surviving patients is currently 36 months (range 9–120).

Results:
All patients engrafted (mean time for PMN > 0.5×109/L: 23days) and no rejection was observed. A patient who had successful engraftment but previous severe CNS vasculopathy and moya-moya, had a massive intracerebral haemorrhage at day 32 after transplant and died. Early toxicity included also a sub-dural haemorrhage successfully evacuated in a patient without any previous cerebral vasculopathy. Other early complications included seizures, viral pericarditis, bacteriemia and CMV reactivations, but no veno occlusive disease was observed. Four patients had acute GVHD grade II that responded to Prednisone treatment. Two patients had limited chronic GVHD, one with severe peripheral thrombocytopenia; however, both episodes resolved and the patients do not currently receive any immunosuppression. Only one death was observed, resulting in an overall survival and disease-free survival of 92% at 3 years. All survivors have the Hb electrophoretic profile of their donor and a normal Hb level. DNA-chimerism was characterized as full-donor. All patients have a normal quality of life, except for the sequelae of previous CNS disease in two patients and residual migraine after hematoma evacuation in one patient.

Conclusion:
This experience demonstrates that myeloablative allogenic BMT is feasible in selected young adults with SCD: The overall results are similar to those obtained in younger children. Early regimen-related toxicity does not appear to be increased as compared to BU-CY regimen used for other disease,but the early transplantation course has been more complicated in these patients than in younger children. Patients with severe CNS disease require special care. Of note, only one patient with significant renal involvement was included in this study. Acute and chronic GVHD have been moderate and easy to manage in these patients younger than 30 with an HLA identical sibling. A stable long-term full chimerism and cure has been achieved in all survivors. These results should encourage physicians to perform HLA typing in all young adults with SCD and their family in order to identify as early as possible potential candidates for transplantation. Although this experience is limited, it suggests that SCT could be proposed to young adults who had non-severe disease during childhood but developed severe criteria during adulthood such as a tricuspid regurgitant jet velocity at least 2.5 m/second.
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Disclosures:
No relevant conflicts of interest to declare.