Sequential chemotherapy followed by reduced‐intensity conditioning and allogeneic haematopoietic stem cell transplantation in adult patients with relapse or refractory acute myeloid leukaemia: a survey from the Acute Leukaemia Working Party of EBMT

Abstract

This study analysed the outcome of 267 patients with relapse/refractory acute myeloid leukaemia (AML) who received sequential chemotherapy including fludarabine, cytarabine and amsacrine followed by reduced-intensity conditioning (RIC) and allogeneic haematopoietic stem cell transplantation (HSCT). The transplants in 77 patients were from matched sibling donors (MSDs) and those in 190 patients were from matched unrelated donors. Most patients (94·3%) were given anti-T-cell antibodies. The incidence of acute graft-versus-host disease (GVHD) of grades II-IV was 32·1% and that of chronic GVHD was 30·2%. The 3-year probability of non-relapse mortality (NRM) was 25·9%, that of relapse was 48·5%, that of GVHD-free and relapse-free survival (GRFS) was 17·8% and that of leukaemia-free survival (LFS) was 25·6%. In multivariate analysis, unrelated donor recipients more frequently had acute GVHD of grades II-IV [hazard ratio (HR) = 1·98, P = 0·017] and suffered less relapses (HR = 0·62, P = 0·01) than MSD recipients. Treatment with anti-T-cell antibodies reduced NRM (HR = 0·35, P = 0·01) and improved survival (HR = 0·49, P = 0·01), GRFS (HR = 0·37, P = 0·0004) and LFS (HR = 0·46, P = 0·005). Thus, sequential chemotherapy followed by RIC HSCT and use of anti-T-cell antibodies seems promising in patients with refractory AML.

Durable graft‐versus‐leukaemia effects without donor lymphocyte infusions – results of a phase II study of sequential T‐replete allogeneic transplantation for high‐risk acute myeloid leukaemia and myelodysplasia

“…Although direct comparison of outcomes from our study with those of other early AHST or sequential transplant approaches is not possible, the 2‐year OS of transplanted patients (39 ± 15%) we report is comparable to outcomes reported by the SAL study group of early AHST (Stolzel et al , ; Schetelig et al , ) and to both individual reports of different individual sequential strategies using either FLAMSA (FLAG + amsacrine) or clofarabine‐based chemotherapy followed by cyclophosphamide and low dose total body iradiation (Schmid et al , ) or busulphan‐based RIC platforms (Schneidawind et al , ; Mohty et al , ), and to the pooled outcome data from a recently published registry‐based survey by the European Society for Blood and Marrow Transplantation (EBMT) of patients with AML treated with sequential chemotherapy and AHST (Ringden et al , ). In the latter series, the authors report that the 3‐year OS of patients treated with T‐cell depleted approaches was superior to that of those who received T‐cell replete transplants (31% vs. 20%).…”

Haploidentical versus HLA-matched sibling transplantation for refractory acute leukemia undergoing sequential intensified conditioning followed by DLI: an analysis from two prospective data

“…The causes of death included relapse (n = 69), infectious diseases (n = 41), GVHD (n = 21), sinusoidal obstruction syndrome (n = 1), thrombotic microangiopathy (n = 1), multiple organs failure (n = 2), primary graft failure (n = 1), and unknown (n = 1) ( Table 3). The 5-year cumulative incidence of NRM was 31% (95% CI, [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] and 23% (95% CI,16-30; p = .114) (Fig. 3a) in HID and MSD groups, respectively.…”

“…Subgroup analysis showed that 5-year OS for AML, ALL, and ALAL was 50% (95% CI, 43-57), 43% (95% CI, 36-51), and 40% (95% CI, 27-53) in HID group, respectively, and 44% (95% CI, 38-51), 38% (95% CI, [31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46], and 40% (95% CI, 25-56) in MSD group, respectively, and there was no difference between two groups for each underlying disease (p = .947 for AML; p = .798 for ALL; p = .927 for ALAL).…”

Reduced Relapse Incidence with FLAMSA–RIC Compared with Busulfan/Fludarabine for Acute Myelogenous Leukemia Patients in First or Second Complete Remission: A Study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

“…FLAMSA-RIC was originally developed for relapsed/refractory disease, where it showed promising efficacy with 2-year leukemia-free survival (LFS) and overall survival (OS) rates of 40% and 42%, respectively [5]. A more recent registry study on 267 patients showed a GVHD-free relapse-free survival (GRFS) rate at 3 years of 17.8% and an LFS of 25.6% [6]. In addition, FLAMSA has also been used with encouraging results in high-risk AML patients in CR1 and in AML patients with complex karyotype transplanted as soon as possible following FLAMSA-RIC irrespective of response [7,8].…”