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Allograft and preemptive immuneintervention in CLL
Impact of minimal residual disease on outcome
In Mantel-Byar analysis, evaluating MRD as a time- dependent variable, achievement of the MRDneg status regardless of the time point, was predictive of an improved PFS, Hazard ratio (HR) 0.18 (range, 0.06-0.60), P=0.005, and OS, HR 0.18 (range, 0.03-0.98), P=0.047 along with a reduction of CIR, HR 0.14 (range, 0.04- 0.539, P=0.004. (Figure 4).
Chimerism evaluation
The chimerism analyzed on unselected blood cells had no impact on outcome. Conversely T-cell donor engraft- ment (≥95% donor T cells) tended to be associated with higher PFS, HR 0.16 (range, 0.02-1.37), P=0.09, and lower
relapse risk, HR 0.16 (range, 0.02-1.22) P=0.08 but had no impact on OS, P=0.18.
Discussion
Since the first descriptions, allogeneic HSCT has long been the only curative treatment for CLL. Its development has benefited greatly from the advent of reduced-intensity conditioning that can be proposed until the age of 70. The availability of new alternative therapies, including both BCR and BCL-2 inhibitors have in high-risk patients taken the place of allogeneic HSCT and delayed this strategy until later in the management of the disease. Consequently, the
Table 2. Treatment and follow-up of patients in relapse after hematopoietic stem cell transplantation.
Pt# T1 T2
Relapse treatment
Ibrutinib (M13-ongoing)
DLI(1), failure followed by ibrutinib (M36-ongoing)
DLI(3) followed by Ibrutinib (M18 - ongoing)
Ibrutinib (M34 - ongoing)
DLI(2) response, followed by ruxolitinib (ongoing) for GvHD RCHOP, with initial PR, RDHAP, irradiation
°Ibrutinib (M15-M45) with initial PR then PD*, RDHAC °Ibrutinib (M13-M24) with initial PR then PD*, RCHOP Ibrutinib (M13-ongoing)
Ibrutinib (M10-ongoing)
Last FU
29+
52+
48+
42+
36+
35
47
43
32+
41+
Status
PR, MRDpos
CR, MRDneg CR, MRDneg CR, MRDneg CR, MRDneg PD*
PD*
PD*
CR, MRDneg
PR, MRDpos
35
2 8 19 29 13 4 15 28
18
12 13
19 34 12 15 34 34 23 23 11* 19 1 6 12 12 12 13
9 10
Pt#: patient number ; ASCT: allogenic hematopoietic stem cell transplantation; T1: time from ASCT to relapse (months) ; T2: time from ASCT to relapse treatment (months) ; CR: complete response ; PR: partial response ; PD: progressive disease ; *: Richter transformation ; DLI: donor lymphocytes infusion (number) ; R-CHOP: rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone ; R-DHAC: rituximab, dexamethasone, cytarabine, carboplatinum; GvHD: graft versus host disease; FU: follow-up; M13: 13 months; M15: 15 months; M24: 24 months; M34: 34 months; M45: 45 months. , ° Patients#4 and #15 had received preemptive DLI before relapse treatment as part of the immune-intervention as per study protocol.
Figure 2. Post-transplantation minimal residual disease evaluation. At 12 months (M12), 27 of 42 (64%) patients were minimal residual disease negative (MRDneg),
), 8 of 42 (19%) patients were not evaluable because either prior early toxic death (n=4) and 4 of 42 patients (9.5%) or other reasons including graft rejection (n=2), Eppstein-Barr virus lymproliferation (n=1) and early relapse (n=1).
7 of 42 (17%) patients remained MRD positive (MRD
pos
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