Values of Hematopoietic Cell Transplantation-Specific Comorbidity Index, Comorbidity/Age Index and Augmented Comorbidity/Age Index in Recipients of Haploidentical Stem Cell Transplantation Using Ptcy As Gvhd Prophylaxis: A Retrospective Study of 223 Cases
Authors: Jullien Maxime , François Sylvie , Berceanu Ana , Couturier Marie-Anne , Guillaume Thierry , Peterlin Pierre , Garnier Alice , Le Bourgeois Amandine , Klemencie Marion , Schmidt Aline , Hunault Mathilde , Daguindau Etienne , Deconinck Eric , Guillerm Gaelle , Giltat Aurelien , Orvain Corentin , Thepot Sylvain , Le Gouill Steven , Bene Marie C , Chevallier Patrice 
Published: November 2020

Introduction: Pre-transplant comorbidities, which may impact the success of allogeneic stem cell transplantation (AlloSCT) can be appreciated through 3 different scoring systems. The Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) allows to predict non-relapse mortality (NRM) and survival (Sorror, Blood 2005). Its prognostic value was further augmented by the addition of donor age (&lt; vs ≥40 yo) (Comorbidity/Age index, C/AI, Sorror, JCO 2014) then of pre-transplant ferritin (&lt; or &gt;2500 µg/L) and albumin (&lt;3 g/dL vs 3-3.5 g/dL vs &gt;3.5g/dL) serum levels as well as platelet count (&lt; vs &gt;100 109/L) (Augmented Comorbidity/Age index, AC/AI, Elsawy, BBMT 2019). The performance of these 3 scores has not been evaluated in haploASCT using post-transplant cyclophosphamide (PTCY), a procedure in constant expansion worldwide.
Material and Methods: We studied retrospectively the impact on non-relapse mortality (NRM), overall (OS) and disease-free (DFS) survival of the 3 comorbidity scores on a cohort of 223 patients (pts) having received a haploSCT with PTCY. All pts had pre-transplant ferritin and albumin levels and platelet counts available. These parameters were evaluated at the time of the pre-transplant check-up or just before conditioning (median from transplant: 20 days, range: 4-49).
Results: Pts were recruited in 4 French centers (Nantes n=127; Angers n=45; Besançon n=29, Brest n=22). They had received haploSCT between October 2013 and January 2020. There were 136 males and 87 females with a median age of 55 yo (16-71, &gt;40 years n=172). The majority of pts had a myeloid disease (n=157) and received a reduced intensity regimen (n=161, myeloablative n=30; sequential n=32). Respectively, 132 and 91 pts had low/intermediate and high/very-high Disease-Risk Index (DRI). All pts received PTCY, cyclosporine and mycophenolate mofetyl as graft versus host disease (GVHD) prophylaxis. Donors had a median age of 40.8 years (19.4-71.7). Median HCT-CI, C/AI and AC/AI scores were 2 (0-8), 3 (0-9) and 3 (0-11), respectively. The HCT-CI score was &lt;2 in 139 patients, CA/I was &lt;3, 3-4 and &gt;5 in 110, 83 and 30 pts, respectively, while the AC/AI score was &lt;4 in 112 cases.
With a median follow-up for alive patients of 35.6 months (6-77), 3-year OS, DFS and NRM were 47.8+3%, 46+3% and 29.4+6%, respectively.
In univariate analysis, better 3-year OS and DFS were associated with lymphoid diseases (OS: 60.4+6% vs 42.3+4%, p=0.02; DFS: 56.2+6% vs 41.6+4%, p=0.04), low/intermediate DRI (OS: 59.1+4% vs 30.1+7%, p&lt;0.001; DFS: 56.3+4% vs 31.1+5% p&lt;0.001), donor age &lt;40 years (OS: 58.1+4% vs 36.2+5% p=0.004; DFS: 55.4+4% vs 35.7+4% p=0.01), and albumin level (&lt;3g/dL OS: 33.3+12% vs 3-3.5g/dL 46.1+8% vs &gt;3.5g/dL 50.1+4%, p=0.03; &lt;3g/dL DFS: 30+12% vs 3-3.5g/dL 44.5+8% vs &gt;3.5g/dL 47.4+3%, p=0.05). OS and DFS were not impacted by ferritin levels, platelet count, recipient age, gender, nor any of the 3 comorbidity scores. A lower 3-year NRM was observed in younger pts (&lt;55 yo) (21.8% vs 36.8%, p=0.02) and in those with a younger donor (&lt;40 yo) (20.5% vs 39.2%, p=0.003). NRM was not associated with gender, type of disease, DRI, ferritin, albumin, platelet counts nor any of the 3 comorbidity scores.
In multivariate analysis, each comorbidity score was compared to DRI, donor and patient age, type of disease and pre-transplant albumin levels. DRI and donor age remained associated with OS and DFS. This was also the case for recipient age, except when considering a high C/AI index score. Finally, an older age of recipients and donors remained associated with higher NRM.
Conclusion: HCT-CI, C/AI and AC/AI do not to predict survivals nor NRM in haploSCT with PTCY, suggesting that pre-transplant comorbidities should not be a contra-indication to this procedure. As donor age is the only factor predicting survivals and NRM in this series, while multiple donors are generally available in the haploSCT setting, the selection of a younger donor should be the rule whenever possible for all patients.

Disclosures
Hunault: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Diachi: Membership on an entity's Board of Directors or advisory committees; Jansen: Honoraria; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees. Deconinck:ImmunoGen: Consultancy, Research Funding; Stemline: Consultancy. Thepot:astellas: Honoraria; novartis: Honoraria; sanofi: Honoraria; celgene: Honoraria. Le Gouill:Loxo Oncology at Lilly: Consultancy; Roche Genentech, Janssen-Cilag and Abbvie, Celgene, Jazz pharmaceutical, Gilead-kite, Loxo, Daiichi-Sankyo and Servier: Honoraria. Chevallier:Incyte Corporation: Honoraria.