Refinement of treatment strategies in ex vivo T-cell-depleted haploidentical SCT for pediatric patients

Abstract

We evaluated the feasibility of T-cell-depleted haploidentical hematopoietic SCT (HHCT) in pediatric patients. Between July 2008 and January 2013, 28 patients underwent ex vivo T-cell-depleted HHCT; 9 had hematologic malignancy, 18 had nonmalignant hematologic disease, and 1 had refractory neuroblastoma. Twenty-six patients achieved neutrophil engraftment at a median of 11 days (range, 9-15 days). Two patients failed to achieve primary engraftment and five experienced graft rejection after primary engraftment. These seven patients achieved stable engraftment after a second HHCT. The cumulative incidences (CIs) of ⩾ grade II and ⩾ grade III acute GVHD were 33.3% and 14.3%, respectively, and the 1-year CI of extensive chronic GVHD was 11.1%. Four patients died of non-relapse-related causes (two of CMV disease, one of encephalopathy and one of autoimmune hemolytic anemia) and one of leukemia relapse. Non-relapse mortality at 100 days, 1 year and 2 years was 0.0%, 10.7% and 14.3%, respectively. At a median follow-up of 32.8 months (range, 17.0-72.5 months), the 2-year OS was 82.1%. OSs for nonmalignant diseases and malignant diseases were 94.4% and 60.0%, respectively (P = 0.019). Thus, HHCT is a realistic alternative for patients with malignant or nonmalignant diseases who lack a suitable donor.Bone Marrow Transplantation (2015) 50, 225-231; doi:10.1038/bmt.2014.232; published online 13 October 2014 INTRODUCTION Recent advances in haploidentical hematopoietic SCT (HHCT) have improved outcomes and enabled the use of haploidentical relatives as donors for children and adults with diseases that are curable with hematopoietic cell transplantation (HCT).A recently developed transplant strategy using a CD3/CD19-depleted graft instead of CD34 + cell selection has shown improved results. [1][2][3] Depleting CD3 + cells is superior to selecting CD34 + cells in terms of rapid engraftment and immune reconstitution. 2,3 Depletion of CD3 + T cells also has the advantage of increasing the number of natural killer cells, monocytes and other immunomodulating cells. 4 We recently completed our prospective study of in vitro CD3-depleted HHCT for pediatric patients lacking suitable related or unrelated donors. We reported our experience with CD3-depleted HHCT for patients with acquired SAA and patients with graft failure (GF) after allogeneic HCT. 5,6 These patients constitute part of the current patient cohort: of 28 patients in the present cohort, 17 were included in the previous two reports. The purpose of the present study was to assess the efficacy and feasibility of CD3-depleted HHCT in the children and adolescents of our cohort with an additional 11 patients and with an extended follow-up of previously reported cases.

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

“…6,[10][11][12][13][14][15] There have been several reports on HHCT in pediatric patients. 4,5,7,[16][17][18] In our current study, all 42 patients achieved stable engraftment early post transplant at a median of 10 days. No patient experienced graft failure (GF), including late GF.…”

“…7 Our previous study with CD3-depleted HHCT showed a rather high incidence of GF in the early period of the study; therefore, we modified the targeted dose of T cells in different ranges to improve the outcomes. Another practical issue was that the reduction of T cells is less effective with the CD3-depletion method and frequently leads to residual T cells in the graft that exceed the threshold of 5 × 10 4 /kg, requiring immunosuppressive drugs to prevent GvHD.…”

“…Our previous study on HHCT using CD3-depleted grafts showed that 7 out of 28 patients experienced GF. 7 GF can be affected by many factors such as disease, prior therapy, conditioning regimen, T-cell dose, CD34 cell dose and T-cell depletion technique. 3,[19][20][21][22][23] A matched comparison between the present study and our prior study using CD3-depleted grafts is difficult because stem cell dose, proportion of patients with NM and proportion receiving low-dose TBI are somewhat different between the two studies.…”

“…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.…”

Acquired aplastic anemia in Korean children: treatment guidelines from the Bone Marrow Failure Committee of the Korean Society of Pediatric Hematology Oncology

“…In addition, ex vivo T-cell depletion of CD3 cells or even αβ+ T-cells plus B-cell depletion using the CliniMACS ® system (Miltenyi Biotec, Bergisch Gladbach, Germany) has been introduced successfully [44,45]. Most strikingly, Im et al [46] reported excellent survival of 100 % for 12 AA patients after CD3-depleted HSCT in Korean children.…”