Encouraging outcomes after autoHCT in patients with ALL

Results of autologous haematopoietic cell transplantation (autoHCT) for patients with acute lymphoblastic leukaemia (ALL) aged >55 years in first complete remission and with measurable residual disease (MRD)-negativity pre-transplant are encouraging. This option may be a valuable alternative to reduced-intensity conditioning (RIC)-allogeneic HCT and is associated with improved overall survival (OS) compared with transplantations from HLA-matched unrelated donors [1].

Patients with ALL aged >55 years treated with conventional-dose chemotherapy have poor outcomes. Due to the frequent presence of comorbidities, many patients are ineligible for myeloablative allogeneic HCT (alloHCT). The role of autoHCT and RIC-alloHCT is not well-established. The goal of this study was to analyse results of these transplant options and to identify factors affecting outcome.

Prof. Sebastian Giebel (Maria Skłodowska-Curie National Research Institute of Oncology, Poland) et al. evaluated 560 ALL patients in first complete remission after treatment with RIC-alloHCT (n=418) or autoHCT (n=142). Among allogeneic donors, 50% were HLA-matched sibling donors (MSD) and 50% were 8/8 matched unrelated donors (MUD).

The engraftment rate was 99% after RIC-alloHCT and 96% after autoHCT (P=0.01). Median time to neutrophil recovery was 16 days and 12 days, respectively (P<0.001). With a median follow-up of 57 months, the probabilities of leukaemia-free survival (LFS) at 5 years were 39% versus 34% (P=0.11) and the probabilities of OS at 5 years were 45% versus 42% (P=0.23), respectively. The incidence of relapse was 41% versus 51% (P=0.22) and the incidence of non-relapse mortality was 25% versus 10% (P=0.001), respectively [1].

In a multivariate model, using autoHCT as reference, the risk of non-relapse mortality was increased for MSD-alloHCT (HR 2.1, P=0.02) and MUD-alloHCT (HR 3.08, P<0.001). For MUD-alloHCT, this translated into a decreased chance of LFS (HR 1.55, P=0.01) and OS (HR 1.62, P=0.008). For MSD-alloHCT, there was a tendency towards decreased LFS (HR 1.31, P=0.11) and OS (HR 1.29, P=0.15) when compared with autoHCT.

Among other prognostic factors, the risk of relapse was decreased for Philadelphia chromosome-positive ALL compared with Philadelphia chromosome-negative B-ALL (HR 0.7, P=0.04) which was accompanied by improved OS (HR 0.74, P=0.04). Finally, the risk of relapse was increased for patients with detectable MRD (HR 1.38, P=0.04) without significant effect on survival.

These study results require verification in prospective trials in the context of currently available novel agents and technologies, including blinatumomab, inotuzumab ozogamicin, and CAR T cells, concluded Prof. Giebel.

1. Giebel S, et al. Comparison of Reduced Intensity Conditioning - Allogeneic HCT and Autologous HCT for Elderly Patients with Acute Lymphoblastic Leukemia. an Analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. 62^nd ASH Annual Meeting, 5-8 December 2020. Abstract 614.

Posted on 18 February 202122 February 2021