A Trial of Plerixafor/G-CSF as Additional Agents for Conditioning Before TCR Alpha/Beta Depleted HSCT in WAS Patients

A Trial of Plerixafor With G-CSF as Additional Agents in Conditioning Regimen for Prevention of Graft Failure After Transplantation With TCR Alpha/Beta Grafts Depletion in Patients With Wiskott-Aldrich Syndrome.

Treatment Study to assess of safety and efficiency of conditioning with Plerixafor and G-CSF as additional agents for prevention of graft failure after transplantation with TCR alpha/beta grafts depletion in patient with Wiskott-Aldrich syndrome.

Severe graft dysfunction, such as the degree of donor chimerism predominantly in the myeloid compartment is one of major problem in patients with Wiskott-Aldrich syndrome (WAS), especially after hematopoietic stem cell transplantation (HSCT) from alternative donor. It often leads to the development of severe thrombocytopenia or even transplants rejection. In this study the hypothesis is that the use of plerixafor and G-CSF as additional agents in conditioning regimen would offers advantages due to lowing risk of mixed chimerism after HSCT. This effect is based on the fact that simultaneous use of plerixafor with G-CSF is efficient in inducing stem cell release and opening of bone marrow (BM) niches. Moreover, stem cell release probably leads to liberation of host stem cells from the anti-apoptotic effects of the BM stroma for the more powerful effect of chemotherapy.

In this study, the investigators use TCR alpha/beta grafts depletion of the grafts as basic technology for HSCT from haploidentical and unrelated donors approved in Institution.

Thus, the purpose of this study is to evaluate the safety and efficiency of myeloablative conditioning with Plerixafor and G-CSF as additional agents for prevention of graft failure after transplantation with TCR alpha/beta grafts depletion in patients with Wiskott-Aldrich syndrome.

Inclusion Criteria:

• Patients aged ≥ 1 months and < 19 years
• Patients diagnosed with Wiskott-Aldrich syndrome eligible for an allogeneic transplantation and lacking a related HLA-matched donor
• Lansky/Karnofsky score > 40, WHO > 4
• Signed written informed consent

Exclusion Criteria:

• Dysfunction of liver (ALT/AST > 5 times normal value, or bilirubin > 3 times normal value), or of renal function (creatinine clearance < 30 ml / min)
• Severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive heart failure or left ventricular ejection fraction <40%)
• Serious concurrent uncontrolled medical disorder
• Lack of parents' informed consent.