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• refractory versus sensitive disease
status at alloHCT (hazard ratio [HR]
= 10.2 for non-relapse mortality
[NRM; 97.5% CI 3.09-33.4] and 0.49
for relapse incidence [REL; 97.5% CI
0.18-1.32])
• alemtuzumab ex vivo T-cell deple-
tion (HR=5.81 for NRM [97.5% CI
1.79-18.8] and 1.13 for REL [95% CI
0.45-2.84])
TABLE.
Long-Term Outcomes for Patients Receiving AlloHCT
Overall 10-Year Follow-Up
(n=32) Patients Alive and Event-Free at
6-Year Follow-Up (n=32)
Non-relapse mortality 20% (95% CI 15-36) 3.4% (95% CI 0-10)
Relapse incidence 46% (95% CI 43-67) 18% (95% CI 4-32)
Progression-free survival 34% (95% CI 23-44) 79% (95% CI 65-94)
Overall survival 51% (95% CI 40-62) 94% (95% CI 85-100)
alloHCT = allogeneic hematopoietic cell transplantation
For the 59 patients who had sensitive
disease at the time of alloHCT and did
not receive alemtuzumab T-cell depletion,
10-year outcomes were:
• 9% for NRM (95% CI 2-23)
• 51% for REL (95% CI 40-68)
• 41% for PFS (95% CI 27-54)
• 61% for OS (95% CI 47-75)
MRD-negative status at 12 months
post-alloHCT was “highly prognostic
for a reduced relapse risk,” the authors
wrote (25% vs. 80%; p<0.0001). “The
protective effect of MRD negativity at
the 12-month landmark was even more
pronounced if MRD clearance occurred
only after immunosuppression withdrawal,
suggesting effective GVL activity (10-year
REL = 12%),” they added.
Thirty-nine patients relapsed during
follow-up, and no relapses occurred after
10 years post-alloHCT. Five of the relapses
occurred late (from 2011 to present), but
all five patients were alive at a median
of 28 months (range = 4-62 months)
after the relapse event. Three patients
who relapsed achieved sustained disease
control with ibrutinib, “[reflecting] the
improved rescue options with ibrutinib
and other pathway inhibitors that are
available,” the authors wrote.
Earl ier results from the CLL3X study
indicated that GVL activity is strongly
associated with the development of
chronic GVHD, and the researchers
reported a six-year GVHD- and relapse-
free survival of 8 percent (95% CI 2-14)
for the entire patient cohort. “However, it
has to be taken into account that chronic
GVHD is characterized by a large variance
in clinical appearance and severity, and –
most importantly – can calm down over
time,” the authors wrote. Chronic GVHD
and quality of life were not formally
studied in this analysis.
The study is limited by its non-
randomized design and limited number
of patients with long-term follow-up.
Because of the inclusion of only patients
≤65 years old, the results may not be gen-
eralizable to the full CLL population. ●
Dr. Krämer reported honoraria from
Medical Specialties Distributors and travel
grants from Gilead.
REFERENCE
Krämer I, Stilgenbauer S, Dietrich S, et al. Allogeneic hematopoietic
cell transplantation for high-risk CLL: 10-year follow-up of the GCLLSG
CLL3X trial. Blood. 2017 July 17. [Epub ahead of print]
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