HLA Haploidentical Bone Marrow Transplant in Patients With Severe Sickle Cell Disease

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 \<55% and tricuspid regurgitation speed\> 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