Haploidentical HCT using an αβ T-cell-depleted graft with targeted αβ+ cells by add-back after a reduced intensity preparative regimen containing low-dose TBI

Abstract

Between 2012 and 2015, 42 pediatric patients underwent haploidentical hematopoietic cell transplantation using an αβ + T-cell-depleted graft with targeted αβ cells at 1-5 × 10 5 /kg by add-back; 31 had hematologic malignancy (HM), 8 had non-malignant disease (NM) and 3 had solid tumors. All patients received uniform reduced-intensity conditioning with fludarabine, cyclophosphamide, rabbit anti-thymocyte globulin and low-dose TBI. All 42 patients achieved neutrophil engraftment at a median of 10 days. The cumulative incidences (CIs) of ⩾ grade II and ⩾ grade III acute GvHD were 31 ± 7.1% (SE) and 12 ± 5.0%, respectively, and 1-year CI of chronic GvHD was 15 ± 5.8%. One patient died of CMV pneumonia, leading to transplant-related mortality (TRM) of 2.6 ± 2.5%. Sixteen patients relapsed and 11 died of disease. At a median follow-up of 19 months (range, 5-43 months), the estimated 2-year event-free survival for NM and HM were 88 ± 11.7 and 50 ± 10.1%, respectively. Our study demonstrated that haploidentical hematopoietic cell transplantation after ex vivo depletion of αβ + T cells with targeted dose noticeably reduced the graft failure rate and TRM in pediatric patients and could be applied to patients lacking a suitable related or unrelated donor. While αβ + T cells are known to be associated with the initiation of GvHD, γδ + T cells can enhance immune reconstitution and are not implicated in GvHD. 6 Recently, we reported our experience with HHCT using a CD3-depleted graft. 7 Since 2012, we have initiated HHCT using ex vivo depletion of αβ + T cells with targeted αβ cells at 1-5 × 10 5 /kg after add-back. Here, we report our prospective results using αβ-depleted grafts in HHCT for children and adolescents with malignant or non-malignant disease.

Depletion of αβ+ T cells for a haploidentical hematopoietic stem cell transplantation in children

“…Moreover, preliminary reports on the new method of αβ + T cell depletion showed further improved outcomes for T cell‐depleted haploidentical transplants . Since 2012, we have initiated haploidentical HCTs by ex vivo depletion of αβ + T cells and have recently reported our preliminary findings on haploidentical HCTs of αβ + T cell‐depleted grafts …”

“…12,15 Since 2012, we have initiated haploidentical HCTs by ex vivo depletion of ab 1 T cells and have recently reported our preliminary findings on haploidentical HCTs of ab 1 T celldepleted grafts. 16 The establishment of a consistent and reproducible depletion technique is crucial for a successful transplantation of an ex vivo depleted graft. In this study, we evaluated the efficacy of a technique for ex vivo depletion of ab 1 T cells using a biotinylated anti-TCRab monoclonal antibody.…”

Comparable Outcome with a Faster Engraftment of Optimized Haploidentical Hematopoietic Stem Cell Transplantation Compared with Transplantations from Other Donor Types in Pediatric Acquired Aplastic Anemia

“…Although LD-TBI enhanced engraftment, GF can be affected by many factors such as disease, prior therapy, conditioning regimen, cell dose, and T cellÀdepletion technique [13,46]. Multivariate analysis was performed with factors that might influence the engraftment, but no single factor including LD-TBI was found to be important in the present study.…”

“…Sibling donors for bone marrow transplantation were primed with 7.5 mg/kg/day granulocyte colony-stimulating factor as a single evening injection [10][11][12], and bone marrow was harvested under general anesthesia. Peripheral blood stem cells were collected as described previously [7,13]. Ex vivo T cell depletion was conducted with the CliniMACS system (Miltenyi-BioTec, * There is a difference in T cell dose according to the T cellÀdepletion methods; detailed values are described in Table 3.…”

TCR α+β+/CD19+ cell–depleted hematopoietic stem cell transplantation for pediatric patients

“…F I G U R E 1 Rate of acute graft vs host disease at 1 y. Grade II-IV acute GVHD was 20% at 1 y. Grade III-IV acute GVHD was 0% at 1 y Importantly, no patients developed grade III-IV GVHD, and all patients with grade II acute GVHD responded to first-line therapy. Literature suggests satisfactory engraftment can be achieved with CD34 + doses of 3-6 × 10 6 /kg, 27,29,37,39 and given the high doses of CD34 + cells/kg in most products, there may be scope for limiting the amount of donor product delivered to the patient without impacting engraftment.…”