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Encouraging outcomes after autoHCT in patients with ALL

Presented by
Prof. Sebastian Giebel, Maria Skłodowska-Curie National Research Institute of Oncology, Poland
ASH 2020
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. 62nd ASH Annual Meeting, 5-8 December 2020. Abstract 614.

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