TCR alpha/beta and B-cell depleted haploidentical haematopoietic stem cell transplantation in severe aplastic anaemia in children: a case report
Background: Allogeneic haematopoietic stem-cell transplantation (AHSCT) from matched sibling donor (MSD) is the therapy of choice for children with severe aplastic anemia (SAA), although graft-versus-host disease (GvHD) or graft rejection remain the major concerns. Children with SAA who lack a MSD and fail to respond to immunosuppressive (IS) treatment should be considered for alternative donor such as from manipulated haploidentical parents. We present a case of child with SAA complicated with lung aspergillosis, treated with haploidentical HSCT (HHCST) with TCR alpha/beta (TCR-a/b) and B cell depletion. Methods: A 4-year-old female with SAA not responded to IS treatment, presented persistent fever due to lung aspergillosis. In the absence of MSD and prompt available alternative donor, she was subjected to HHCST TCRa/b and B depleted cell from maternal PBSC, using immunomagnetic separation with CliniMACS System (Miltenyi Biotec). Depletion of a/b T cells was 4.5 log. The recovery of CD34+ was 74.6%.The number of infused CD34+,TCRa/b,TCRgamma/delta(TCRg/d) and CD20+ was 11.6X10(6)/kg, 25,092/Kg, 2.57X10(6)/kg, 38,596/kg respectively. Myeloablative conditioning regimen (MCR) included thiotepa (TT) and cyclophosphamide (Cy). IS prophylaxis consisted of rabbit antithymocyte globulin (rATG) and ciclosporin (CsA) (1 mg/Kg i.v. from day -6 to day -1). Despite initial engraftment of absolute neutrophilis count (ANC) and platelets (PLTs) (day +12 and +15 respectively), graft rejection occurred at day +20. After 38 days, a second HHCST TCRa/b and B depleted cell from paternal PBSC was performed. Depletion of a/b T cells was 3.85 log. The recovery of CD34+ was 88.6%. The number of infused CD34+, TCRa/b, TCRg/d and CD20+ was 19.3X10(6)/ kg, 94,313/Kg, 5.9X10(6)/kg, 106,000/kg respectively. MCR included TT, Cy and total nodal irradiation. rATG and CsA (3 mg/Kg i.v. from day -6) were used as IS prophylaxis. Results: Stable ANC and PLTs engraftment occurred from day +14, with clinical and radiological improvement. Mild acute GvHD on the gut occurred at day +30, with complete response to CsA that is gradually tapering. CMV reactivation was controlled with antiviral therapy. Five months later, our patient is still in good clinical conditions with complete donor engraftment and immune reconstitution. Conclusion: HHCST TCRa/b and B depleted cell is feasible in patients with SAA, due to quick engraftment, reduction of GvHD without impairing pathogen-speci64257; c immunity and prompt availability of the donor.
Full conference title:
Annual Meeting of the EBMT, 38th