Toxicity Profile According to Etoposide and Cytarabine Dosing in Patients with Lymphoma Receiving Autologous Stem Cell Transplantation Following BEAM Conditioning.

High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is part of the treatment strategy for some patients with high-risk lymphoma by improving survival with an acceptable toxicity profile. Although the BEAM (BCNU, etoposide, cytarabine, and melphalan) intensification regimen is the most used, the optimal dosing for each drug is unclear. Here, we retrospectively compared the outcome of 110 patients receiving higher (400 mg/m2, n = 69) or lower (200 mg/m2, n = 41) etoposide and cytarabine doses in our institution between 2012 and 2019. Patients in the BEAM 200 group experienced less toxicity with reduced fever duration (P < 0.001), number of platelet transfusions (P = 0.008), antibiotic duration (P < 0.001), antifungal therapy (P < 0.001), and mucositis (P < 0.001) whereas length of stay, admission to the intensive care unit, and in-hospital mortality were not different between groups. Progression-free survival (PFS) was non-significantly lower in the BEAM 200 group (36-month PFS, 68% vs. 80%, P = 0.053) whereas OS was similar between the two groups (36-month OS, 87% vs. 91%, respectively, P = 0.12). Albeit a non-significant reduction in PFS, BEAM 200 conditioning intensity was associated with a reduced toxicity profile.

Impact of allogeneic stem cell transplantation comorbidity indexes after haplotransplant using post-transplant cyclophosphamide.

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.

Early Post-Transplantation Serum Ferritin Level Predicts Survival in Recipients of Haploidentical Stem Cell Transplantation Using Post-Transplantation Cyclophosphamide as Graft-versus-Host Disease Prophylaxis.

The negative impact of high serum ferritin level (SFL) before and after allogeneic hematopoietic cell transplantation (allo-HSCT) on outcomes is well recognized. However, it is poorly documented in adults undergoing haploidentical HSCT (haplo-HSCT) with post-transplantation cyclophosphamide (PTCY) for hematologic malignancies. The main objective was to assess the impact of pretransplantation and post-transplantation SFL on overall survival (OS), disease-free survival (DFS), and nonrelapse mortality (NRM) in patients undergoing haplo-HSCT with PTCY. The secondary objective was to identify factors associated with outcomes after transplantation by comparing SFL with other parameters related to the status of patients or donors. This multicentric retrospective study included 223 consecutive patients who underwent haplo-HSCT with PTCY in 4 French centers (Nantes, Angers, Besançon, and Brest) between October 2013 and January 2020. The impact of SFL on OS, DFS, and NRM at different time points was assessed based on receiver operating characteristic curves. With a median follow-up of 37.6 months (interquartile range, 23.5 to 51.0 months), 3-year OS, DFS, and NRM were 48.1 ± 4%, 46.3 ± 4%, and 30.0 ± 3%, respectively. Pretransplantation SFL had no impact on outcomes irrespective of the cutoff tested. Considering patients alive at 3 months post-transplantation, an SFL ≥3500 µg/L at 3 months was statistically significantly associated with worse 3-year OS (32.7 ± 8.7% versus 53.4 ± 7.2%; P = .01) and DFS (30.1 ± 8.2% versus 53.1 ± 7.1%; P = .008), with a trend toward higher NRM (33.2 ± 8.6% versus 17.6 ± 5.4%; P = .10). Similarly, high SFL (≥2700 µg/L) at 6 months post-transplantation was associated with worse 3-year OS (56.1 ± 9.1% versus 79.2 ± 6.0%; P = .02) and DFS (53.6 ± 8.7% versus 74.9 ± 6.2%; P = .01), with a trend toward higher NRM (21.4 ± 7.4% versus 8.2 ± 4.0%; P = .10). In multivariate analysis, high 3-month and 6-month FL remained associated with lower OS and DFS, with a trend toward higher NRM. Pretransplantation SFL appears to have no impact on outcomes in haplo-HSCT with PTCY, in contrast to what is documented in the matched allo-HSCT setting. In contrast, in the haplo-HSCT setting, high SFL early post-transplantation is associated with lower survival and a trend toward higher NRM.