hla haploidentical bone marrow transplant in patients with severe sickle cell disease

Conditions: Sickle Cell Disease

Summary: multicentric interventional biomedical research phase ii, prospective, non-randomized evaluating a haploidentical marrow transplants after reduced-intensity conditioning and prevention of gvhd based on cyclophosphamide administration post transplantation in patients with severe sickle cell disease.

sickle cell disease is a severe disease with frequent occurrence of painful crises and progressive installation of a multi organ injuries. despite the progress in its management, particularly since the introduction of hydroxycarbamide, the median age of death in sickle cell patients was about 40 years in a recent us study. severe forms resistant to hydroxyurea or cerebral vasculopathy require transfusion programs throughout susceptible to risks of iron overload and alloimmunization. the bone marrow transplantation cures almost 95% of children and adolescents transplant from an hla-identical siblings. in patients without hla-identical donor, interesting results have been reported in haploidentical transplants marrow without ex vivo t cell depletion taken after non myeloablative conditioning regimen and gvhd prevention with cyclophosphamide high dose injection after bone marrow transplant . this approach performed in 14 patients was effective to cure 50% of the patients and 50% have rejected the transplant . no death or severe gvhd were related to the procedure. drephaplo protocol aims to evaluate that approach in a population of sickle cell patients with severe complications of the disease, bringing direct benefit to patients with a cure of the disease in at least half of them.

Eligibility criteria:
inclusion criteria recipient: * age: 13 years-40 years * severe sickle cell with at least one of the following criteria: * stenosing vasculopathy with abnormal mra despite prolonged transfusion program * pah confirmed by right catheterization with mpap\> 25mmhg * systolic ejection fraction \ 2.5m /s at distance from an acute episode * no possibility of blood transfusion or very complicated blood transfusion * report albumin / creatinine\> 30 mg / mmol, confirmed 3 times, away at distance from acute episode and persistent despite hydroxyurea or iec * gfr \<80ml / min /1.73m2 (ckd-epi without ethnic criterion) * previous history of acute liver sequestration with liver failure * acute chest syndrome or vaso-occlusive crises under hydroxyurea * complications of sickle cell transfusion imposing an exchange program with no possible withdrawal beyond a period of one year * not having geno-identical donor, but a haploidentical major donor (parent, sibling, adult child, or hbaa as) * having red and understood the information letter and signed the informed consent * patients affiliated to a social security system (social security or universal medical coverage) exclusion criteria recipient: * patient with a geno-identical donor * performans status: ecog\> 1 * lung disease: fev1 and fvc \<50% predicted, * score of pah nyha≥2 * liver disease with bilirubin\> 50 .mu.mol / l * heart failure defined by nyha≥3 score ejection fraction \<45% or shortening fraction \<24% * anti hla alloimmunization against the donor or against red cell antigens of the donor * serology or hiv viral load positively * patients who for family, social or geographical reasons, do not wish to be regularly monitored in consultation * severe uncontrolled infection at the time of inclusion or graft * pregnant woman (positive beta hcg) or during lactation * incapable adult patient, trust, guardianship, or safeguard justice inclusion criteria donor * age\> 18 years and \<60 years * viral serologic economy allows the graft * no contraindication for general anesthesia * no contraindication the administration of g-csf (the existence of sickle cell trait is not a contraindication) * lack antigens hla recognized by the recipient antibody * hemoglobin s \<50% * when several donors are compatible: choose according to the abo recipient: prefer abo compatibility and major incompatibility and minor incompatibility, and finally major and minor incompatibility. * signature of informed consent * non-inclusion criteria donors: β hcg positive or known pregnancy

Keywords: sickle cell disease haploidentical graft marrow