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

Bone Marrow Transplantation HLA Haploidentical After a Reduced Intensity Conditioning and Prevention of GvHD Based on Post-transplant Cyclophosphamide Administration 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