Haploidentical SCT in children: an update and future perspectives

Abstract

Transplantation of haploidentical stem cells has become a well-established approach, which makes a potential donor available for almost all patients. This review focuses on current results and new strategies, especially in pediatric patients with malignant diseases. CD34 þ positive selection was the most common procedure for graft manipulation in the past years, whereas T and B cell depletion is a promising new method. GVHD could herewith be effectively reduced and primary engraftment was reported in 83-100% of patients after transplantation of high stem cell doses. For patients with ALL in remission, diseasefree survival at 3 years ranged between 22 and 48%. TRM, mainly because of viral infections, was improved by the use of reduced-intensity conditioning (which helped to speed up T cell recovery) and by close monitoring of viral loads and prophylactic/preemptive therapy. The role of donor-derived Ag-specific T cells against viral and fungal antigens is currently under investigation. Patients with active disease at the time of transplantation had a poor outcome and several attempts to improve these results are currently evaluated, such as co-infusion of natural killer cells, co-transplantation of MSC, use of new antileukemic drugs and post-transplant immunotherapy.

The impact of T-cell depletion techniques on the outcome after haploidentical hematopoietic SCT

“…Over the years, a wealth of studies has led to a variety of different transplantation techniques with regard to patient selection, TCD, conditioning regimens, stem cell numbers as well as many other factors, and its complexity has been highlighted by a number of recent reviews. [2][3][4][5][6]10,13,15,16 In reality, however, transplant centers generally choose one transplant technique according to the feasibility in their institution and continue with this technique with slight modifications. Nevertheless, although direct comparisons of different TCD are sparse, studies in haploidentical HSCT generally consider them as comparable.…”

“…Three patients had grade III acute GVHD (4%), whereas none had grade IV acute GVHD. The median time to onset of acute grade II-IV GVHD was 19 days (range, 9-79) and cumulative incidence of grade II-IV GVHD at day 100 was 15% (95% CI, [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] (Figure 1). Patients with in vivo TCD had a higher incidence of grade II-IV GVHD compared with in vitro TCD (cumulative incidence at day 100: 31 vs 9%, P ¼ 0.045).…”

Invariant NKT Cell Reconstitution in Pediatric Leukemia Patients Given HLA-Haploidentical Stem Cell Transplantation Defines Distinct CD4+ and CD4− Subset Dynamics and Correlates with Remission State

“…The rapid NK cell recovery can partially compensate for the prolonged T cell deficiency in providing a GVL effect, which occurs when donor NK cells are alloreactive toward the HLA-disparate patient (10)(11)(12). T lymphocytes account for the long-lasting protection against infectious pathogens and leukemia cells, and reconstitute in pediatric hHSCT recipients essentially via a thymusdependent pathway, which recapitulates T cell ontogeny and is very efficient in children, where the thymus is still functional (8,13).…”

“…The presence of allogeneic MHC barriers between donor and recipient of haploidentical HSCT (hHSCT) requires almost complete elimination of donor T cells from the graft, to prevent graft-versus-host disease (GVHD). This results in a state of profound post-hHSCT immunodeficiency of the recipients, which lasts until the immune system is newly generated from donor hematopoietic stem cells (HSCs), and predisposes patients both to life-threatening infections and to leukemia relapse, the leading causes of death in this approach (7,8). A deeper understanding of the reconstitution dynamics of all the components of the immune system after hHSCT is hence instrumental to optimize the control of infections, leukemia recurrence, and GVHD.…”

Reduced‐intensity allogeneic stem cell transplantation for children with neuroblastoma who failed tandem autologous stem cell transplantation

“…HaploSCT has proven to be feasible and to involve acceptable toxicity in children with hematologic malignancies [33,34]. Although reports concerning haploSCT for NB are still limited, a potential GVT effect has been suggested with low toxicity [12,13,29,30].…”