1.
Impact of allogeneic stem cell transplantation comorbidity indexes after haplotransplant using post-transplant cyclophosphamide
Jullien, M., Orvain, C., Berceanu, A., Couturier, M. A., Guillaume, T., Peterlin, P., Garnier, A., Le Bourgeois, A., Klemencie, M., Schmidt, A., et al
Cancer medicine. 2021
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Abstract
BACKGROUND Three different scoring systems have been developed to assess pre-transplant comorbidity in allogeneic hematopoietic stem cell transplantation (Allo-HSCT): the Hematopoietic Cell Transplantation-Specific Comorbidity Index, the Comorbidity/Age index, and the Augmented Comorbidity/Age index. All were devised to predict overall survival (OS) and disease-free survival (DFS) survivals and non-relapse mortality (NRM) in patients receiving HLA-matched Allo-HSCT, but their performance has scarcely been studied in the haploidentical Allo-HSCT setting with post-transplant cyclophosphamide, a procedure in constant expansion worldwide. METHODS To address this issue, their impact on survivals and NRM was examined in a cohort of 223 patients treated with haploidentical Allo-HSCT in four different centers. RESULTS With a median follow-up of 35.6 months, 3-year OS, DFS, and NRM were 48.1% ± 4%, 46.3% ± 4%, and 30.0% ± 3%, respectively. No impact was found for any of the three comorbidity scores in univariate analysis. In multivariate analyses, the only three factors associated with lower OS were DRI (p < 0.001), an older age of recipients (=55 years old, p = 0.02) and of donors (=40 years old, p = 0.005). Older donor age was also associated with lower DFS and higher NRM. CONCLUSION The comorbidity scores do not predict survivals nor NRM in haploidentical Allo-HSCT with PTCY, suggesting that pre-transplant comorbidities should not be a contra-indication to this procedure.
PICO Summary
Population
Patients from four European centres who underwent haploidentical transplantation with post-transplant cyclophosphamide (n=223)
Intervention
Use of three comorbidity scores for each patient: 1) Hematopoietic Cell Transplantation-Specific Comorbidity Index
Comparison
2) Comorbidity/Age index, and 3) the Augmented Comorbidity/Age index
Outcome
With a median follow-up of 35.6 months, 3-year overall survival (OS), disease free survival (DFS), and non-relapse mortality (NRM) were 48.1% ± 4%, 46.3% ± 4%, and 30.0% ± 3%, respectively. No impact was found for any of the three comorbidity scores in univariate analysis. In multivariate analyses, the only three factors associated with lower OS were disease risk index, an older age of recipients (>/=55 years old) and of donors (>/=40 years old). Older donor age was also associated with lower DFS and higher NRM.
2.
Grade 2 acute GVHD is a factor of good prognosis in patients receiving peripheral blood stem cells haplo-transplant with post-transplant cyclophosphamide
Chevallier, P., Berceanu, A., Peterlin, P., Garnier, A., Le Bourgeois, A., Imbert, B. M., Daguindau, E., Mahé, B., Dubruille, V., Blin, N., et al
Acta oncologica (Stockholm, Sweden). 2020;:1-9
Abstract
BACKGROUND The impact of acute graft versus host disease (GVHD) on survivals for patients receiving a haploidentical allogeneic stem-cell transplant (Allo-SCT) with peripheral blood stem-cells (PBSC) complemented by post-transplant cyclophosphamide (PTCY) is ill-known. MATERIAL AND METHODS This retrospective study included 131 patients who received a PBSC haplograft in order to precise the impact of acute GVHD on outcomes. There were 78 males and 53 females and the median age for the whole cohort was 59 years (range: 20-71). Thirty-five patients were allografted for a lymphoid disease and 96 for a myeloid malignancy, including 67 patients with acute myeloid leukemia (AML). RESULTS The cumulative incidence (CI) of day 100 grade 2-4 and 3-4 acute GVHD was 43.4 + 4.6% and 16.7 + 3.4%, respectively. The 2-year CI of moderate/severe chronic GVHD was 10.1 + 2.8%. The only factor affecting the occurrence of GVHD was GVHD prophylaxis. Indeed, CI of day 100 grade 2-4 (but not grade 3-4) acute GVHD was significantly reduced when adding anti-thymoglobulin (ATG) to PTCY. However, in multivariate analysis, grade 2 acute GVHD was significantly associated with better disease-free (HR: 0.36; 95%CI: 0.19-0.69, p = .002) and overall (HR: 0.35; 95%CI: 0.1-0.70, p = .003) survivals. The same results were observed when considering only AML patients. CONCLUSION Acute grade 2 GVHD is a factor of good prognosis after PBSC haplotransplant with PTCY. Further and larger studies are needed to clarify the complex question of GVHD prophylaxis in the setting of haplo-transplant, especially that of combining ATG and PTCY.
3.
Clofarabine-based reduced intensity conditioning regimen with peripheral blood stem cell graft and post-transplant cyclophosphamide in adults with myeloid malignancies
Chevallier, P., Peterlin, P., Garnier, A., Le Bourgeois, A., Mahe, B., Dubruille, V., Blin, N., Touzeau, C., Gastinne, T., Lok, A., et al
Oncotarget. 2018;9(71):33528-33535
Abstract
Background: The Baltimore reduced-intensity conditioning (RIC) regimen using high-dose post-transplant cyclophosphamide (PTCY) is considered as a standard of care for haploidentical allogeneic stem cell transplantation (allo-SCT). However, it is associated with relatively low survivals and high incidence of relapse, especially when considering myeloid malignancies. Results: This retrospective study included 36 adults (males n = 18; median age: 60.5 years old; haplodonors n = 27; matched donors n = 8) with myeloid malignancies transplanted between March 2014 and March 2017 at the University Hospital of Nantes. Very encouraging results were observed with a 18-month overall survival (OS), disease-free survival (DFS) and relapse incidence (RI) of 72% +/- 7.5%, 63.8 +/- 8%, and 25 +/- 6% respectively, and a GVHD relapse-free survival (GRFS) of 52.6 +/- 8%. In univariate analysis, there were no differences regarding 18-month survivals between patients allografted: i) for acute myeloid leukemia vs myelodysplastic syndrome (OS 70 +/- 11% vs 69.2 +/- 13%, p = 0.3; DFS 64.7 +/- 11% vs 61.5 +/- 13%, p = 0.65), or ii) with haplo-identical vs other donors (OS: 66.2 +/- 9% vs 88.8 +/- 10.4%, p = 0.16; DFS 59 +/- 9.5% vs 77.8%, p = 0.6). Conclusion: The "Clo-Baltimore regimen" is safe and feasible and provides good survivals for patients with myeloid malignancies and haplo-donors. Methods: Here, we report a variant of the Baltimore regimen, where 1) fludarabine was replaced by clofarabine, 2) bone marrow was replaced by peripheral blood stem cells, and 3) tacrolimus was replaced by cyclosporine, in a "Clo-Baltimore regimen".