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Haploidentical peripheral blood stem cells reduces the risk of relapse compared to bone marrow in patients with Hodgkin lymphoma. Luca Castagna, MD Institut Paoli Calmettes, Marseille Humanitas Research Hospital, Milan Background

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Haploidentical peripheral blood stem cells reduces the risk of relapse compared to bone marrow in patients with Hodgkin lymphoma.

Luca Castagna, MD Institut Paoli Calmettes, Marseille Humanitas Research Hospital, Milan

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Background

Haploidentical transplantation is effective alternative in

HL patients without HLA identical donor

In retrospective studies, the relapse risk in HL patients

seems to be lower after haploidentical transplantation with PT-Cy

In the original platform, BM is used as preferred stem

cell source

The use of PBSC enhances the risk of GVHD

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Allo-SCT program in lymphoma patients Marseille-Milan

2010-2017

308 HL 109 NHL 199 DLBCL 60 MCL 40 PTCL 60 FL 39

91 analyzed BM 53 PBSC 38

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Patient characteristics

Characteristics All N N° patients 91 (100) Median Age 31 (18-68) Gender M F 52 (57%) 39 (43%) Previous SCT No Yes 12 (13%) 79 (79%) Disease status pre-Allo CR PR SD/PD 58 (64%) 23 (25%) 10 (11%) Conditioning regimens NMAC RIC 68 (75%) 23 (25%) HCT-CI 0-2 ≥ 3 51 (56%) 40 (44%) CMV serostatus Neg/Neg Others 79 (87%) 12 (13%) Sex mismatch Others Female→ Male 74 (81%) 17 (19%)

Median follow-up: 23 months (1-103)

BM PBSC p N N 53 (58%) 38 (42%) 31 (19-66) 33 (19-68) 0.609 26 (49%) 27 (51%) 26 (68%) 12 (32%) 0.066 4 (8%) 49 (92%) 8 (21%) 30 (79%) 0.060 33 (62%) 14 (26%) 6 (11%) 25 (66%) 9 (24%) 4 (11%) 0.941 33 (62%) 20 (38%) 35 (92%) 3 (8%) 0.001 37 (70%) 16 (30%) 14 (37%) 24 (63%) 0.002 44 (83%) 9 (17%) 35 (92%) 3 (8%) 0.206 46 (87%) 7 (13%) 28 (74%) 10 (26%) 0.114

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50 100 150 0.0 0.2 0.4 0.6 0.8 1.0 Cumulative incidence BM PBSC All 180 28% 21% p=0.3

2-4 aGVHD

50 100 150 0.0 0.2 0.4 0.6 0.8 1.0 Cumulative incidence BM PBSC All 180 Days post Haplo-SCT 4% 3% p=0.8

3-4 aGVHD

Results: aGVHD

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Results: moderate/severe cGVHD

Days post Haplo-SCT 200 400 600 0.0 0.2 0.4 0.6 0.8 1.0 Cumulative incidence Days post Haplo-SCT BM PBSC All 730 9% 6% p=0.6

Moderate/severe cGVHD

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Results: OS and PFS

200 400 600 800 1000 0.0 0.2 0.4 0.6 0.8 1.0 Probability 200 400 600 800 1000 0.0 0.2 0.4 0.6 0.8 1.0 Probability PR SD/PD CR 63% 15% 77% p=<0.0001 Days post Haplo-SCT

2-yOS

200 400 600 800 1000 0.0 0.2 0.4 0.6 0.8 1.0 Probability BM PBSC Days post Haplo-SCT Days post Haplo-SCT 62% 74% p=0.1 66% 58%

200 400 600 800 1000 0.0 0.2 0.4 0.6 0.8 1.0 Probability

Days post Haplo-SCT

200 400 600 800 1000 0.0 0.2 0.4 0.6 0.8 1.0 Probability

BM PBSC Days post Haplo-SCT 62% 55%

200 400 600 800 1000 0.0 0.2 0.4 0.6 0.8 1.0 Probability CR PR PD/SD

Days post Haplo-SCT 69% 54% 10%

2-y PFS

p=0.1 p=0.001

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2-y RI

200 400 600 800 1000 0.0 0.2 0.4 0.6 0.8 1.0 Cumulative incidence Days post Haplo-SCT 22% 200 400 600 800 1000 0.0 0.2 0.4 0.6 0.8 1.0 Cumulative incidence CR PR SD/PD Days post Haplo-SCT 11% 36% p=0.0005 50%

200 400 600 0.0 0.2 0.4 0.6 0.8 1.0 Relapse.Day Cumulative incidence BM PBSC

25% 18%

Results: relapse incidence

p=0.3

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Multivariate analysis

Characteristics Relapse p OS p PFS p NRM p Disease status CR PR SD/PD 1 5.11 (1.74-15.0) 35.6 (7.8-161.3) 0.003 <0.00001 1 1.92 (0.78-4.71) 7.97 (3.23-19.63) 0.1 <0.0001 1 1.88 (0.85-4.16) 8.93 (3.66-21.7) 0.1 <0.0001 1 0.42 (0.09-1.9) 5.36 (1.53-18.77) 0.2 0.009 Graft Source BM PBSC 1 0.28 (0.09-0.84) 0.024 1 0.33 (0.14-0.79) 0.014 1 0.43 (0.20-0.91) 0.028 HCT-CI 0-2 ≥3 1 2.84 (1.30-6.20) 0.009 1 1.91 (0.95-3.81) 0.066 1 2.59 (0.98-6.84) 0.053 Conditioning NMA RIC 1 0.33 (0.98-1.15) 0.08

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Conclusions

Haploidentical transplantation with PT Cy is effective in

HL patients

The use of PBSC reduced the risk of relapse compared

to BM

On the other hand, PBSC did not enhance the risk of

acute and chronic GVHD

Finally, as expected the disease status plays a major

role in the outcome.

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Univariate analysis

2y-Relapse p 2y-OS p 2y-PFS p 2y-NRM p 2y-GRFS p Disease status CR PR SD/PD 11% 36 50% <0.001 77 63 15 <0.001 69 55 10 < 0.001 20 9 40 0.026 60 46 10 <0.001 Conditioning NMA RIC 23 18 0.707 71 53 0.160 61 56 0.274 16 26 0.112 53 47 0.247 Graft Source BM PBSC 25% 18% 0.333 62 74 0.076 56 62 0.125 20 20 0.460 48 54 0.141 Previous SCT No Yes 25 21 0.461 56 69 0.532 60 59 0.988 15 20 0.421 50 51 0.780 CMV Others Neg/Pos 21 27 0.696 67 83 0.256 58 65 0.657 21 8 0.309 50 56 0.634 Sex mismatch No F→M 21 25 0.820 67 71 0.583 60 53 0.876 19 21 0.749 52 47 0.704 Sex Female Male 24 21 0.654 66 68 0.757 60 57 0.763 17 21 0.972 52 50 0.756 HCT-CI 0-2 ≥3 25 19 0.583 74 57 0.173 65 50 0.277 10 32 0.054 57 42 0.349