T-cell-replete haploidentical stem cell transplantation using low-dose antithymocyte globulin in children with relapsed or refractory acute leukemia

Abstract

We evaluated the efficacy and toxicity of T-cell-replete haploidentical stem cell transplantation (TCR-haploSCT) using low-dose antithymocyte globulin (ATG) in children with refractory/relapsed (R/R) acute leukemia. From October 2009 to April 2016, 39 consecutive patients with R/R acute leukemia who underwent TCR-haploSCT were included. At the time of TCR-haploSCT, 17 patients were in complete remission (CR), but 22 had active disease. Thirty-three patients received a myeloablative regimen and six received a reduced-intensity conditioning regimen. Graft-versus-host disease (GvHD) prophylaxis comprised tacrolimus, methotrexate, prednisolone, and low-dose ATG (thymoglobulin 2.5 mg/kg). Neutrophil engraftment (> 0.5 × 10/L) was 95% after a median of 13 days. The median follow-up period was 527 days, with mean 3-year overall and disease-free survival rates of 45.1% [standard deviation (SD), ± 8.5%) and 33.8% (SD, ± 7.9%), respectively. The cumulative incidence of acute GvHD was 73.0%, but that of grade III-IV acute GvHD was 34.1%. The 3-year cumulative incidences of relapse and transplant-related mortality were 50.3 and 15.9%, respectively. Age < 10 years at transplantation was associated with a better overall survival in the multivariate analysis. These data suggest that TCR-haploSCT using a low-dose ATG combined with the GvHD prophylaxis described here has a significant anti-leukemic activity, particularly in younger patients.

The Combination of Anti-Thymocyte Globulin and Basiliximab for Haploidentical Hematopoietic Stem Cell Transplantation

“…Fortunately, the incidence of EBV-reactivation and PTLD in our patients was low, and no PTLD-related death occurred. Since the observed high rate of EBV-reactivation and CMV reactivation were predominantly related to the degree of Tcell depletion or impairment [32], it is known that at high concentrations (0.1-1.0 mg/mL), ATG induces lysis of both resting and activated T cells (via human classic complement pathway activation), whereas at low concentrations, it induces apoptosis of activated cells (by Fas/Fas-ligand interaction) while sparing resting cells [33,34]. GVHD prophylaxis using basiliximab and lowdose ATG may be effective by selective elimination of highly activated donor-specific alloreactive T cells, while sparing non-activated T cells.…”

T-cell replete haploidentical stem cell transplantation for children with relapsed or refractory acute leukemia.

“…replication occurs in approximately half of allogeneic HSCT recipients and may cause fever, skin rash, interstitial pneumonia, and encephalitis. 4,5 To date, however, HHV6associated pleurisy has not been recognized as a complication of HSCT. In this report, we describe an adult HSCT recipient who developed HHV6-associated pleurisy after an unrelated cord blood transplantation (CBT).…”

Single-Arm Non-Blinded Multicenter Clinical Trial on T-Cell-Replete Haploidentical Stem Cell Transplantation Using Low-Dose Antithymocyte Globulin for Relapsed and Refractory Pediatric Acute Leukemia

“…In a retrospective study (n = 14) of T-cell-replete haplo transplantation for relapsed/refractory leukemia at the same institution, the overall 3-year survival rate was 79% (AML 67%, ALL 78%), overall 3-year EFS rate was 50% (AML 67%, ALL 52%), and outcome by disease of ALL and AML was almost unchanged [9]. In addition, an analysis in 39 patients with relapsed/refractory leukemia who received haplo transplantation at the same institution with an observation period of 2 years or more showed mean 3-year overall and disease-free survival rates of 45.1% and 33.8%, respectively [10]. The cumulative incidence of acute GVHD was 73.0%, but that of grade III-IV acute GVHD was 34.1%.…”