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