Page 100 - 2021_07-Haematologica-web

O. Tournilhac et al.
The 3-year cumulative incidence of relapse was 29.6% (95% CI: 17.3-47.7) (Figure 1). Salvage therapy was deliv- ered in patients who relapsed after donor engraftment; eight patients received ibrutinib; six of them are still in remission at the last follow-up (32 to 52 months) while two had a transient response followed by progression with Richter transformation. (Table 2).
Minimal residual disease (MRD) status at 12 months and MRD kinetics after hematopoietic stem cell transplantation
At M12, 27 patients achieved MRDneg status, including 23 patients with an undetectable MRD (MRD < limit of detection), seven patients remained MRDpos, eight patients were not evaluable because either early toxic death (n=4) or other reason including graft rejection (n=2), Eppstein- Barr virus-induced lymproliferation (n=1) and early relapse (n=1). Thus, at M12, MRDneg status was achieved in 64% (27 of 42) if we consider all patients and in 77% (27of 35) if we take into consideration all 34 patients assessed at this time point and the patient who experi- enced a clinical relapse at 1 month (and thus not subject to systematic MRD assessment but considered as failure) versus 14.2% before transplantation. Most patients remained MRDpos early after transplantation and progres- sively translated to MRDneg within the first 6 months post- transplantation. (Figure 2). Nine of the 13 (69%) D90
MRDpos patients who had no significant GvHD but who had an early CsA withdrawal according to the protocol, managed to reach a MRDneg status.
For the 39 patients who engrafted and were alive after M1, MRD kinetics followed four distinctive patterns. (Figure 3). The pattern A (n=6) is constituted of the pre- transplantation MRDneg patients. Two of these patients relapsed, one at 12 and one at 19 months. The pattern B (n=11) comprised the patients who converted from pre- transplantation MRDpos to post-transplantation MRDneg status within 3 months without any immune-interven- tion. One pattern-B patient with M12 MRD close to the positivity threshold relapsed at 13 months. The pattern C (n=15) is constituted of the patients with pre-trans- plantation MRDpos who remained MRDpos during the first 3 months but became MRDneg either after CsA tapering and withdrawal (n=12) or after cGvHD (n=3). Two pat- tern-C patients relapsed at 23 and 34 months. The pat- tern D (n=7) comprised the patients with a pre-trans- plantation MRDpos status who remained MRDpos despite cGvHD (n=1) or immune-intervention including CsA tapering and withdrawal (n=6) followed by DLI for five of them. Progression was observed in five pattern-D patients including three Richter transformations, each occurring within the first 13 months. The outcome of all four panels is represented in the Online Supplementary Table S3.
AB
CD
Figure 1. Post-transplant outcome of the 42 chronic lymphocytic leukemia transplanted patients. Kaplan-Meier estimates of (A) overall survival, (B) progression- free survival. Calculated probability of (C) non relapse mortality and (D) cumulative incidence of relapse after hematopoietic stem cell transplantation.
1870
haematologica | 2021; 106(7)