Page 61 - 2020_01-Haematologica-web

Donor lymphocyte infusion in haplo-HCT
continued from the previous page
Study
T-cell depleted haplo-HCT
Yan et al. (2016)57*#
Yan et al. (2017)32*
Ma et al. (2017)34*
Gao et al. (2018)54*
Zeidan et al. (2014)28+
Ghiso et al. (2015)29+
Jaiswal et al. (2016)56$
Goldsmith et al. (2017)30+
Cauchois et al. (2018)67+
N of patients Diagnosis (prospective/ retrospective)
47 AML=25 (haplo=31) ALL=22
(prospective)
100 AML=59 (haplo=62) ALL=41
(prospective)
36 AML/ALL/ (retrospective) MDS/CML
31 AML=21 (retrospective) ALL=5 CML=2
Other=3
40 AML=16 (retrospective) ALL=3 CML=1
Indication for DLI
Pre-emptive=47 (MRD)
Prophylactic=100
Therapeutic=36
Prophylactic=31
Therapeutic=35 Pre-emptive=5 (MRD+/MC)
Treatments before DLI
CT=100%
CT=0%
CT/TKI =100%
CT=0%
CT/RT= 70%
CT/RT= 100%
CT=0%
CD3+ dose/kg
1.5-6.4x107
1.8-6.6x107
NA
0.4-6.9x107
1x105 to 1x108
1x103 to 1x107
9.2-110x107
N. of DLI (median)
1-4
Disease response
NA
Rate of GvHD
aGvHD =19% (grade 3-4=6%) cGvHD=79% (≥moderate=66%)
Survival
1-yr DFS=71% 1-yr NRM=9% 1-yr OS=78%
Notes
Post-DLI-GvHD ppx=100%
NA NA Haplo-HCT, Haplo-HCT, Post-DLI-GvHD
NA
1
1-4(1)
CR=56%
NA
aGvHD =47% (grade 3-4=10%) cGvHD=63% (≥moderate=59%)
Grade 3-4 aGvHD=25%) Extensive cGvHD=36%
aGvHD=58% (Grade 3-4=7%) cGvHD=39%
3-yr DFS=51% 3-yr NRM=18% 3-yr OS=49%
3-yr DFS=11% 3-yr OS=14%
2-yr RFS=32% 2-yr NRM=33% 2-yr
ppx=100%
Post-DLI-GvHD ppx=100%
Post-DLI-GvHD ppx=100%
(Mod-severe=29%) OS=40%
CR=30%
(MRD=75%, (grade3-4=15%)
8/12 responders (67%)alive, in CR at 17.5 months
aGvHD=25%
42 (retrospective)
21 (prospective)
21 (retrospective)
36 (retrospective)
Therapeutic=22 Pre-emptive=20
AML=21 Prophylactic=21
CR=36% =45%
NA
CR=32%
NA
aGvHD=33%
(grade 3-4=5%) response=4m(2-10),
Lymphoma=11 Other=9
AML=22
ALL=9
HL=10 (MRD)
1-6
(mean-2.5) CR in MRD
Leukemia, median
Relapse=26%)
cGvHD=8% (extensive=5%)
MM=1
median survival =7m(1-15)
HL, median response =9m(3-28), median survival =18m(4-34)
cGvHD=0%
Cum incident aGvHD =31% cGvHD=41%
aGvHD=33% (grade 3-4=5%) cGvHD=26% (extensive=0%)
AML/MDS=16 Therapeutic=19 ALL=2 Pre-emptive=2(MC)
CML=2 Lymphoma=11 Other=9
AML/MDS=25 Prophylactic=36 ALL=2
Lymphoma=6
Other=3
CT=76% 0.01-3x107
1-3
1-5
1-3
1.5-yr PFS=62% 1.5-yr CIR=21% 1.5-yr OS=71%
Hematologic relapse, 4-m RFS=8% 4-m OS=29% EM relapse, 4-m RFS=43% 4-m OS=71%
Post-DLI-GvHD ppx=100%
PBSC haplo-HCT
PBSC graft=31
CT=0%
0.1-2.5x106
1-yr CI of mod-severe 1-yr PFS=83%
GvHD=33%
1-yr NRM=9% 1-yr OS=76%
N: number; AML: acute myeloid leukemia; ALL: acute lymphoblastic leukemia; CML: chronic myeloid leukemia; MDS: myelodyslastic syndromes; MMUD: mismatched unrelated donor; GvHD ppx: graft-versus-host disease prophylaxis; aGvHD: acute GvHD; cGvHD: chronic GvHD; OS: overall survival; DFS: disease-free survival; PFS: progression-free survival; NRM: non-relapse mortality; CT: chemotherapy; TKI: tyrosine kinase inhibitor; MRD: minimal residual disease; MC: mixed-chimerism; NA: not available; RT: radiation therapy; PBSC: peripheral blood stem cell; EM: extra-medullary relapse; RFS: relapse-free survival; haplo-HCT: haploidentical-hematopoietic cell transplant; matched: HLA-matched allo-HCT; MUD: HLA-matched unrelated donor; Treg: regulatory T-cell; Tcon: con- ventional T-cells; CI: cumulative incidence; yr: year; m: months; NA: not available. *Granulocyte colony-stimulating factor (GCSF)-anti-thymocyte globulin (ATG)-based protocol and G-CSF-primed peripheral blood progenitor cell (GBPC). $Haplo-HCT with post-transplant cyclophosphamide (PTCy) and GBPC. +Haplo-HCT with PTCy and standard donor-lymphocyte infusion (DLI). #Patients had salvage chemotherapy + therapeutic DLI for hematologic relapse, followed by pre-emptive DLI for persistent minimal residual disease (MRD). pt: patient; mod: moderate; cum: cumulative; HL: Hodgkin lymphoma.
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