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

Centre Hospitalier Intercommunal Creteil25 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

OTHER

Masking

NONE

Enrollment

Conditions

Sickle Cell Disease

Interventions

bone marrow transplantBIOLOGICAL

haploidentical bone marrow transplant

Eligibility

Sex: ALLMin age: 13 YearsMax age: 40 Years

Medical Language ↔ Plain English

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

Locations (7)

CHU Henri-Mondor

Créteil, France

intercommunal hospital of Créteil

Créteil, France

CHU La Timone

Marseille, France

Hospital Necker

Paris, France

Outcomes

Primary Outcomes

Survival rate

Survival without sickle cell survival rate (electrophoresis of hemoglobin similar to that from the donor, that is to say a percentage of HbS not exceeding 10% of that of distance donor transfusions and that of a stable manner and without GvHDc other than mild

Time frame: 2 years

Secondary Outcomes

Survival rate

Time frame: 1 year

haematologic reconstitution

defined as a neutrophil count\> 500 / mm3 and platelets\> 20000 / mm3, for three consecutive days.

Time frame: 2 years

Chimerism

Chimerism in the peripheral blood of the total population and the CD3 + population with the techniques usually employed by the centers

Time frame: at month 1

Chimerism

Chimerism in the peripheral blood of the total population and the CD3 + population with the techniques usually employed by the centers

Time frame: at month 2

Chimerism

Chimerism in the peripheral blood of the total population and the CD3 + population with the techniques usually employed by the centers

Time frame: at month 3

Chimerism

Chimerism in the peripheral blood of the total population and the CD3 + population with the techniques usually employed by the centers

Data from ClinicalTrials.gov

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