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3300 Absence of Influence of the Pre-Transplant Immune Status of Recipients on Survivals and Gvhd after Allogeneic Stem Cell Transplantation: A Retrospective Study of 195 Cases

Program: Oral and Poster Abstracts
Session: 721. Clinical Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Transplant Toxicities: Poster III
Hematology Disease Topics & Pathways:
Biological, Adult, bone marrow, Therapies, Biological Processes, Study Population, transplantation, immune mechanism
Monday, December 7, 2020, 7:00 AM-3:30 PM

Baptiste Le Calvez1*, Thierry Guillaume, MD, PhD2*, Pierre Peterlin, MD2,3*, Alice Garnier, MD4,5*, Amandine Le Bourgeois, MD6*, Marie Audrain, MD, PhD7*, Marion Eveillard2,8*, Thomas Dejoie9*, Béatrice Mahé, MD10*, Viviane Dubruille11*, Nicolas Blin, MD6*, Cyrille Touzeau12*, Thomas Gastinne, MD6*, Anne Lok13*, Benoit Tessoulin, MD, PhD6,14*, Sophie Vantyghem6*, Steven Le Gouill, MD, PhD15,16, Philippe Moreau17,18*, Marie C Bene, PharmSci, PhD2,8* and Patrice Chevalier, MD, PhD19*

1Service d'hématologie, CHU de Nantes, Nantes, France
2CRCINA, INSERM, CNRS, Université d'Angers, Université de Nantes, Nantes, France
3Clinical Hematology, HOPITAL HOTEL DIEU ET HME, NANTES CEDEX 1, France
4Service d’Hématologie, CHU Nantes, Nantes, France., Nantes, France
5Department of Hematology, Nantes University Hospital, Nantes, France
6Clinical Hematology, Nantes University Hospital, Nantes, France
7Immunology, Nantes University Hospital, Nantes, FRA
8Hematology Biology, Nantes University Hospital, Nantes, France
9university hospital, Nantes, France
10CHU Nantes Hôtel-Dieu, Nantes, France
11CHU De Nantes, Nantes, FRA
12Hematology Clinic, University Hospital Hôtel-Dieu, Nantes, France
13Clinical Hematology, Nantes University Hospital, Nantes, FRA
14CRCINA, INSERM 1232, CNRS, Université d'Angers, Université de Nantes, Nantes, France
15CRCINA, INSERM, CNRS, Angers University and Nantes University, Nantes, France
16Service d’hématologie clinique du CHU de Nantes, INSERM CRCINA Nantes-Angers, NeXT Université de Nantes, Nantes, France
17Université de Nantes, INSERM UMR 892, CNRS UMR 6299, Nantes, France
18Department of Hematology, University Hospital of Nantes, Nantes, France
19Department of Hematology and Cell Therapy, CHU Nantes, Nantes, France

Introduction: While many publications have studied immune reconstitution after allogeneic stem cell transplantation (allo-SCT), data exploring whether the pre-transplant immune status (IS) of the recipients has any impact after this procedure are still lacking.

Material and Methods: Since May 2017, in our department, the IS of allo-SCT recipients has been systematically investigated at the time of pre-graft check-up. Data of this monocentric retrospective study on post-allo-SCT outcomes are reported here. Information was retrieved from complete blood counts (CBC) in terms of lymphocytes (normal range [NR] 1.5-4x109/L) and monocytes (NR: 0.15-0.9 x109/L). Classical multiparameter flow cytometry and a double platform were used to assess absolute counts of lymphocyte subsets, i.e. CD3+ (NR: 0.9-1.8 x109/L), CD4+ (NR: 0.5-1.2 x109/L), CD8+ (NR: 0.3-0.7 x109/L), CD19+ (NR: 0.1-0.4 x109/L) and CD56+ (NR: 0.1-0.4 x109/L). All patients also benefited from standard serum electrophoresis allowing to appreciate their global level of immunoglobulins (Ig) (NR: 8-13.6 g/L). The impact of pre-graft immune parameters was investigated for overall (OS) and disease-free (DFS) survivals as well as acute and chronic graft-versus-host disease (GVHD) incidence.

Results: Between May 2017 and December 2019, 195 consecutive adults were checked for immune status before allo-SCT. They were 117 males and 78 females at a median age of 59 years-old (range: 23-71). The median follow-up for the whole cohort was 21.7 months (range: 5.77-37.5). The majority of patients had a myeloid disease (n=141) and received a reduced intensity (RIC) regimen (n=149, myeloablative [MAC] n=23; sequential n=23). The disease-risk index was low/intermediate and high/very-high for respectively 91 and 104 patients. GVHD prophylaxis included anti-thymocytes globulins (ATG) for 102, post-transplant cyclophosphamide (PTCy) for 54 and both ATG+PTCy for 39. Donors were siblings in 39 cases, matched-unrelated (MUD) in 86, haplo-identical in 66 and 9/10 mis-matched in 4. The IS was evaluated at a median of 20 days (range: 8-72) before allo-SCT. Except for monocytes (median: 0.48 x109/L, range: 0-26), all median immune cell populations were lower than the NR before allo-SCT: lymphocytes (0.84 x109/L, range: 0-8.4), CD3+ (0.7 x109/L, range: 0-3.5), CD4+ (0.37 x109/L, range: 0-2.37), CD8+ (0.25 x109/L, range: 0-2.56), CD19+ (0.005 x109/L, range: 0-0.56), CD56+ (0.097 x109/L, range: 0-0.77). Conversely, the Ig median level was in the NR (8.6 g/L, range: 1.4-28). The percentages of patients with immune cells and Ig above the lowest NR were as follows: lymphocytes: 14.8%, monocytes: 80%, CD3: 37.4%, CD4: 37.4%, CD8: 38.9%, CD19: 16.4%, CD56: 47.6%, Ig: 56.7%. Only 5 patients (2.5%) had a fully normal IS before transplant. Considering the whole cohort, 2-year OS and DFS were 55.6+3% and 50.4+3%, respectively, while incidences of day 100 grade 2-4 and 3-4 acute GVHD and 2-year moderate/severe chronic GVHD were 34.7%, 19.4% and 19.8%, respectively.

The comparison of survivals between patients partitioned using either the median of the NR values for immune cells and Ig, showed no difference between subgroups. Similarly, IS had no impact on the incidence of acute nor chronic GVHD. Finally, no difference either was seen according to the conditioning regimen (RIC) or GVHD prophylaxis (ATG, PTCY or both).

Conclusion: As expected, almost all pre-ASCT patients present with immune depression. However, pre-transplant IS does not appear to impact survival nor GVHD. This suggests that there is no need to decrease or replace immunosuppressive treatments commonly used in recipients before allo-SCT in the hope to provide better outcomes.

Disclosures: Touzeau: Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Le Gouill: Roche Genentech, Janssen-Cilag and Abbvie, Celgene, Jazz pharmaceutical, Gilead-kite, Loxo, Daiichi-Sankyo and Servier: Honoraria; Loxo Oncology at Lilly: Consultancy. Moreau: Sanofi: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Novartis: Honoraria; Takeda: Honoraria; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria.

*signifies non-member of ASH