The 46th Annual Meeting of the European Society for Blood and Marrow Transplantation, 29 August - 01 September 2020, pp.448-449
Background: Primary immunodeficiency syndromes (PIDs) are associated with high mortality and morbidity in childhood. Therefore early diagnosis and treatment are crucial. Allogeneic hematopoietic stem cell transplantation (HSCT) is used as a therapeutic option for primary immunodeficiency syndromes and HSCT at a younger age was found to increase survival rates. The best outcomes have been achieved with HLA-matched donors, but when a matched donor is not available, a haploidentical HSCT with αβ T cell depletion can be done with low rates of graft failure and graft-versus-host disease, when urgent HSCT is needed. Here, we share our preliminary results on TCR αβ depleted haploidentical transplantation in patients with PIDs.
Methods: Twenty-four patients (median age, 1.4 years; range, .3 to 10.9) received 27 HSCTs from haploidentical donors (father n:10 mother n:17) after TCR αβ depletion. Most patients (74.1%) received reduced-toxicity myeloablative conditioning consisting of treosulfan (n=13) or busulfan (n=6), fludarabine and thiotepa. One patient with severe combined immunodeficiency (SCID) did not receive any conditioning. All conditioned patients received antihuman T-lymphocyte immunoglobulin. Fourteen patients received rituximab to reduce the risk of EBV-related posttransplantation lymphoproliferative disease. Mesenchymal stem cell was infused at day -1 and +5 to suppress alloreactive donor anti-host T-cell responses and to use their ability to promote angiogenesis and support microenvironment, which facilitate engraftment. Graft versus host disease (GVHD) prophylaxis consisted of cyclosporine in 10 patients, CSA +mycophenolate mofetil in 16 patients. All patients received immunoglobulin replacement until complete immune reconstitution. Immune reconstitution was monitored post-transplant monthly until complete reconstitution. The median duration of follow-up was 7 months (range, 1-56 months).
Results: Patients were transplanted with a median of 7.51x106 /kg (range, 2.49 to 19) CD34 cells, and the median number of TCR αβ cells in the graft was 0.2x106 /kg (range, 0 to 4.97). The median times to neutrophil, platelet and lymphocyte engraftment were 12 days (range, 10 to 72), 20 days (range, 11 to 66) and 30 days (range, 12 to 71). Acute GVHD were observed in 8 patients (grade I-II n=2 and grade III-IV n=6). Chronic GVHD was observed in only one patient. Preliminary data on immune reconstitution were very encouraging. Immunophenotypic analysis reveals a progressive increase in lymphocyte subset counts from day +30 through later posttransplantation time points. Patients had lymphocyte more than 1000 cells/mL, median on day 48 (range, 1-56 months). Eighteen patients (66.7%) had viral reactivation/infection post-transplant; 12/18 had one viral reactivation/infection, 6/18 had multiple viral reactivations/infections. Graft failure was observed in 8 patients. Two patients were successfully retransplanted with different rescue protocols. Probabilities of overall survival were 81.5% at day 100, 70.8% at one year and at five years. The cumulative incidences of transplant related mortality were 18% at day 100, 25.9% at one year and at five year.
Conclusions: We conclude that use of TCR αβ depleted
haploidentical transplantation ensures a high engraftment
rate; good immune reconstitution; low incidence of significant aGvHD, and acceptable posttransplantation morbidity in children with a range of PIDs and should be considered in children with PIDs lacking an HLA-matched
donor, when urgent HSCT is indicated.