High CD3+ and CD34+ peripheral blood stem cell grafts content is associated with increased risk of graft-versus-host disease without beneficial effect on disease control after reduced-intensity conditioning allogeneic transplantation from matched unrelated donors for acute myeloid leukemia — an analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

Abstract

Inconsistent results have been reported regarding the influence of graft composition on the incidence of graft versus host disease (GVHD), disease control and survival after reduced-intensity conditioning (RIC) allogeneic peripheral blood stem cell transplantation (allo-PBSCT). These discrepancies may be at least in part explained by the differences in disease categories, disease status at transplant, donor type and conditioning. The current retrospective EBMT registry study aimed to analyze the impact of CD3+ and CD34+ cells dose on the outcome of RIC allo-PBSCT in patients with acute myelogenous leukemia (AML) in first complete remission, allografted from HLA-matched unrelated donors (10 of 10 match). We included 203 adults. In univariate analysis, patients transplanted with the highest CD3+ and CD34+ doses (above the third quartile cut-off point values, >347 × 10^6/kg and >8.25 × 10^6 /kg, respectively) had an increased incidence of grade III-IV acute (a) GVHD (20% vs. 6%, P = .003 and 18% vs. 7%, P = .02, respectively). There was no association between cellular composition of grafts and transplant-related mortality, AML relapse, incidence of chronic GVHD and survival. Neither engraftment itself nor the kinetics of engraftment were affected by the cell dose. In multivariate analysis, CD3+ and CD34+ doses were the only adverse predicting factors for grade III-IV aGVHD (HR = 3.6; 95%CI: 1.45-9.96, P = .006 and 2.65 (1.07-6.57), P = .04, respectively). These results suggest that careful assessing the CD3+ and CD34+ graft content and tailoring the cell dose infused may help in reducing severe acute GVHD risk without negative impact on the other transplantation outcomes.

Persistent donor derived Vδ4 T cell clones may improve survival for recurrent T cell acute lymphoblastic leukemia after HSCT and DLI

“…Even after undergoing RE3, the OS time of the patient was much longer than expected. The long-term disease remission of this patient and serial DLI treatment after achieving a third CR with persistent cGvHD were signals reflecting that an immune response was mediated by the grafts or the infusion of cells from the donor [12, 13]. However, as we knew, there were also examples that DLI was failed to rescure patients with relapse leukemia after HSCT.…”

RIC versus MAC UCBT in adults with AML: A report from Eurocord, the ALWP and the CTIWP of the EBMT

“…For the purpose of this study, all necessary data were collected according to EBMT and Eurocord guidelines. RIC was defined as use of fludarabine (Flu) associated with < 6 Gy total-body irradiation (TBI), or busulfan ≤ 8 mg/kg, melphalan ≤ 140 mg/m 2 or other nonmyeloablative drugs, as previously reported [14, 35–37]. Specifically, the combination of total body irradiation, cyclophosphamide and fludarabine (TCF regimen) was classified as RIC when the TBI dose was < 6 Gy (most RIC patients were given 2 Gy TBI) and as MAC when the TBI dose was ≥ 6 Gy (most MAC patients were given > 10 Gy TBI).…”

Impact of CD34+ cell dose on reduced intensity conditioning regimen haploidentical hematopoietic stem cell transplantation

“…This finding correlates with data reported in MSD and MUD allo‐SCT from single center reports and from larger retrospective studies done by the EBMT and CIBMTR . The CD34+ cell dose threshold is close to values established in previously published studies . However, the best CD34+ cell dose range to improve transplant outcomes is not defined.…”

“…However, higher CD34+ doses seem to be associated with an increased incidence of GVHD and worse overall survival (OS) . Several studies have evaluated the effect of CD34+ cell dose on the outcome after allo‐SCT and have reported inconsistent results . These discrepancies may be explained by the differences including disease categories, donor type, conditioning regimen, and GVHD prophylaxis.…”