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Humoral immune-depression following autologous stem cell transplantation is a marker of prolonged response duration in patients with mantle cell lymphoma
Bouard, L., Tessoulin, B., Thieblemont, C., Bouabdallah, K., Gastinne, T., Oberic, L., Carras, S., Delette, C., Casasnovas, O., Dartigeas, C., et al
Haematologica. 2022
Abstract
Rituximab maintenance (RM) after autologous stem cell transplantation (ASCT) is standardof-care for young patients with mantle cell lymphoma (MCL). RM may enhance posttransplantation immune-depression and risk of infections. We compared infection incidence and immune consequences of RM versus observation in transplanted MCL patients. All randomized patients included in the LyMa trial were eligible. The following parameters were collected prospectively: occurrence of fever, infection, hospitalization, neutropenia, hypogammaglobulinemia, CD4 lymphopenia and gamma globulin (Ig) substitution. The post-ASCT period was divided into 4 periods in order to assess the possible effects of RM or ASCT on immune status. Each arm included 120 patients. Concerning infection incidence and all biological parameters, there was no difference between the 2 arms during the first year post-ASCT. After this period, RM patients were more exposed to fever (p=0.03), infections (p=0.001), hypogammaglobulinemia (p=0.0001) and Ig substitution (p.
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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.
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Absence of influence of peripheral blood CD34+ and CD3+ graft cell counts on outcomes after reduced-intensity conditioning transplantation using post-transplant cyclophosphamide
Garnier, A., Guillaume, T., Peterlin, P., Le Bourgeois, A., Mahe, B., Dubruille, V., Blin, N., Touzeau, C., Gastinne, T., Lok, A., et al
Annals of hematology. 2020
Abstract
The influence of peripheral blood stem cell (PBSC) graft cell contents after transplant with post-transplant cyclophosphamide (PTCY) remains unclear. Here, we retrospectively report on a cohort of 77 adults who received a Baltimore-based reduced-intensity conditioning regimen either with fludarabine (n = 40) or clofarabine (n = 37) and PTCY. With a median follow-up of 29.2 months, [2-]year overall (OS), disease-free (DFS), and GVHD/relapse-free survival (GRFS) rates were 62.8%, 51%, and 36.7%, respectively. The incidence of grades [2-]4 acute GVHD was significantly higher in patients transplanted with a haplodonor (n = 56), at 57.1% vs 19% (p = 0.006). PBSC graft cell contents (CD45+, CD34+, and CD3+ cells) had no impact on any outcome. Considering immune reconstitution until 1 year, only monocytes were above the normal range (as early as day + 30) during the first year post-transplant. In multivariate analysis, an older donor (> 45 years) and a high/very high disease risk index were independently associated with lower OS. A higher monocyte count (> median) at day + 90 was also associated with better OS, DFS, and GRFS. Donor/recipient CMV status matching was independently associated with GRFS. In conclusion, our data support the fact that there is no need to manipulate the graft before infusion in the particular context of PBSC/PTCY Baltimore-based allotransplant.
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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.
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FLT3 ligand plasma levels have no impact on outcomes after allotransplant in acute leukemia
Peterlin, P., Gaschet, J., Guillaume, T., Garnier, A., Eveillard, M., Le Bourgeois, A., Cherel, M., Debord, C., Le Bris, Y., Theisen, O., et al
Cytokine. 2019;120:85-87
Abstract
OBJECTIVE This study was designed to assess the impact on outcomes of early soluble Fms-like tyrosine kinase 3 ligand concentrations (sFLc) in patients receiving an allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). METHODS This was a prospective monocentric study including all allo-HSCT patients included in the previous FLAM/FLAL study (Peterlin et al., 2019). Blood samples collected before the start of conditioning then post-transplant were frozen, stored and tested by ELISA. The parameters considered were hematopoietic recoveries, Leukemia Free Survival and Overall Survival, acute and chronic GVHD, grade 3 or 4 acute and/or extensive chronic GVHD-free and relapse-free survival (GRFS). RESULTS Forty-one patients were included, a total of 179 samples were assayed for sFLc. There was no impact of sFLc levels (<=median vs>median) on acute and chronic GVHD incidences, LFS, OS nor GRFS. CONCLUSION At variance with induction results for AML (Peterlin et al., 2019) endogenous sFLc do not appear to be a prognostic marker at the time of or after allo-HSCT. Even though the results are negatives, this is, to the best of our knowledge, the only prospective series specifically addressing the question of sFLc impact after allo-HSCT in acute leukemias.