Outcome of transplantation for standard‐risk leukaemia with grafts depleted of lymphocytes after conditioning with an intensified regimen

Abstract

Summary.One hundred and eighty-one consecutive patients with standard-risk leukaemia were transplanted with HLAidentical sibling grafts depleted of lymphocytes using counterflow centrifugation. In 116 patients, standard conditioning was intensified by the addition of anthracyclines.Multivariate analysis revealed significantly more acute GVHD 5 grade 2 and a trend towards more chronic GVHD in patients conditioned with the addition of anthracyclines. For all patients the risk for chronic GVHD, but not for acute GVHD, increased with a higher number of T cells in the graft. The projected 5-year probability of relapse was significantly lower in the group of patients conditioned with anthracyclines; 26% versus 52% (P ¼ 0 . 015). In multivariate analysis the addition of anthracyclines to the conditioning regimen was the only significant factor contributing to a lower probability of relapse. The projected 5-year probability of leukaemia-free survival [LFS] in the patients conditioned with and without the addition of anthracyclines was 56% and 36%, respectively (P ¼ 0 . 004). In multivariate analysis the addition of anthracyclines to the conditioning regimen correlated significantly with a lower number of mixed chimaeras in patients at 6 and 12 months after BMT. Mixed chimaerism at 6 months after transplantation did not significantly correlate with a higher incidence of relapse in further follow-up. In contrast, mixed chimaerism at 12 months after BMT was significantly associated with higher relapse rate.We conclude that the addition of anthracyclines to the conditioning regimen improves outcome of BMT using Tcell-depleted grafts.

Autologous stem cell transplantation for elderly patients with acute myeloid leukaemia conditioned with continuous infusion idarubicin and busulphan

“…Such a regimen was specifically designed for AML, with the aim of reducing relapse rate which, differently from toxicity, remains substantially unmodified in patients autografted with PBSC. The choice of high-dose IDA, given as c.i., was supported by previous data demonstrating a significant reduction in relapse rate for patients treated with IDA-BuCy or IDA-total body irradiation (TBI)-Cy group when compared with historical controls conditioned with classical regimens, such as BuCy or TBI-Cy [37][38][39][40]. Furthermore, the uniqueness of the regimen used in our series lies with the specific increase of the dose of IDA, which was given as c.i.…”

NOD2 polymorphisms predict severe acute graft-versus-host and treatment-related mortality in T-cell-depleted haematopoietic stem cell transplantation

“…The most important is the higher overall incidence of aGVHD (grade II/IV, 32.1 vs 10%), which probably relates to the use of idarubicin-containing regimen, as this induces more MBI and aGVHD. 20 Furthermore, the use of partially T-celldepleted grafts, with a mean of 0.5 Â 10 6 CD3 þ T cells per kg, contributes to the higher incidence of aGVHD in our patients. There was also a higher allele frequency of NOD2 polymorphisms in our cohort (9.7 vs 5.1%).…”

“…Idarubicin was used in this conditioning regimen to reduce the risk of relapse in the setting of T-cell-depleted HSCT. 20 Partial T-celldepletion was achieved by counterflow elutriation, CD34 selection or CD3/CD19 depletion. On day 0, all patients were given a graft containing 3.0 Â 10 6 CD34 þ cells per kg (range 0.8-11.4; BM or PBSC) and 0.5 Â 10 6 CD3 þ cells per kg (range 0.3-0.7) achieved by dosed T-cell add back.…”

Addition of ATG to the conditioning regimen is a major determinant for outcome after transplantation with partially lymphocyte-depleted grafts from voluntary unrelated donors

“…We could not exclude an association between the conditioning with the addition of ATG and the use of partially lymphocyte-depleted grafts on this fatal course and decided to use our standard conditioning regimen for HLAidentical SIBS with or without the addition of idarubicin. 13 However, this regimen was disappointing in transplants with grafts from voluntary unrelated donors, since five of 12 patients (42%) suffered from take failure or rejection. In a modification of Soiffer et al, 14 conditioning was changed to TBI, TLI, and cyclophosphamide.…”