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Influence of donor type (sibling vs matched-unrelated donor vs haplo-identical donor) on outcomes after clofarabine-based reduced-intensity conditioning allograft for myeloid malignancies
Bouard, L., Guillaume, T., Peterlin, P., Garnier, A., Le Bourgeois, A., Duquenne, A., Mahe, B., Dubruille, V., Blin, N., Touzeau, C., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019
Abstract
Clofarabine-based reduced-intensity conditioning (RIC) regimens are well-established schedules for allograft in patients with myeloid malignancies. A retrospective study was conducted including all adults allografted in our department with such a regimen and disease with the aim to assess whether or not the donor type (matched sibling (MSD), unrelated (MUD), or haploidentical (haplo)) impacted outcomes. Between October 2009 and February 2018, 118 patients met the inclusion criteria. Thirty-six, 55 and 27 patients respectively received a graft from a MSD, MUD or haplo donor. Peripheral blood stem cells (PBSC) were the source of graft for all patients. The median age of the whole cohort was 62 years old (range: 20-73) and the median follow-up was 31 months (range: 4.5-106). All patients engrafted except 1 haplo recipient. Neutrophils (>0.5 10(9)/L) and platelets (50 10(9)/L) recoveries were significantly delayed in the haplo-group (p=0.0003; and p<0.0001) compared to MSD and MUD. Acute grade 2-4 or 3-4 graft versus host disease (GVHD) incidences were similar between the three groups as well as the incidence of moderate or severe chronic GVHD. Also, similar 2-year overall survival (OS, 64.7% vs 73.9% vs 60.2%, p=0.39), disease-free survival (DFS, 57.7% vs 70.9% vs and 53.6%, p=0.1) and GVHD-relapse free survival (37.9% vs 54.3% vs 38.9%, p=0.23) were observed between MSD vs MUD vs haplo groups. The same was true when considering only acute myeloid leukemia (AML) cases. In multivariate analysis, the type of donor remained independent of outcomes in this series while myelodysplastic syndrome (vs AML), high disease-risk index and older donor (>=50 years) were associated with lower OS and DFS. These data suggest that haplo-identical donors are an acceptable alternative for patients receiving a clofarabine-based RIC PBSC allograft for myeloid malignancies who lack a MSD or a MUD.
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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".
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Late Complications and Quality of Life after Reduced-Intensity Conditioning Allogeneic Stem Cell Transplantation
Clavert, A., Peric, Z., Brissot, E., Malard, F., Guillaume, T., Delaunay, J., Dubruille, V., Le Gouill, S., Mahe, B., Gastinne, T., et al
Biology of Blood & Marrow Transplantation. 2017;23(1):140-146
Abstract
Late complications (LC) and quality of life (QOL) were analyzed in 110 adult patients who underwent reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (allo-SCT) and were alive for more than 2 years after allo-SCT. Overall survival of these patients was 93% (95% confidence interval [CI], 88% to 99%) and 81% (95% CI, 71% to 94%) at 5 and 10 years, respectively. The primary cause of death was a recurrence of primary malignancy. With a median follow-up of 4.6 years (range, 2 to 12.1), chronic graft-versus-host disease (cGVHD) was the most prevalent late effect, with a cumulative incidence of 66% (95% CI, 57% to 74%) at 10 years. Cardiovascular complications were the most prevalent LC with a cumulative incidence of 47% (95% CI, 35% to 59%), followed by pulmonary complications with a cumulative incidence of 33% (95% CI, 21% to 46%) and renal impairment with a cumulative incidence of 34% (95% CI, 25% to 43%) at 10 years. Secondary malignancies occurred with a cumulative incidence of 11% (95% CI, 5% to 20%) at 10 years. In this series, 61 patients (55%) responded to QOL survey. With the use of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 and Functional Assessment of Cancer Therapy-Bone Marrow Transplant questionnaires, most of the patients reported good to excellent QOL and patients with cGVHD had significantly lower QOL than patients without cGVHD. In conclusion, QOL after RIC is comparable to that seen after myeloablative conditioning, while the natural history of LC after RIC appears to be different from that described in the standard myeloablative setting, warranting further research in this field. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
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Allogeneic stem cell transplantation for patients with mantle cell lymphoma who failed autologous stem cell transplantation: a national survey of the SFGM-TC
Tessoulin, B., Ceballos, P., Chevallier, P., Blaise, D., Tournilhac, O., Gauthier, J., Maillard, N., Tabrizi, R., Choquet, S., Carras, S., et al
Bone Marrow Transplantation. 2016;51(9):1184-90
Abstract
Poly-chemotherapy plus rituximab followed by autologous stem cell transplantation (auto-SCT) is standard care for untreated young patients with mantle cell lymphoma (MCL). Despite this intensive treatment, transplant patients remain highly susceptible to relapse over time. The French SFGM-TC performed a national survey on reduced-intensity conditioning allogeneic stem cell transplantation (RIC-allo-SCT) for fit relapsed/refractory patients who failed after auto-SCT (n=106). Median times of relapse after auto-SCT, and from auto-SCT to RIC-allo-SCT were 28 months and 3.6 years, respectively. Sixty per cent of patients received at least three lines of treatment before RIC-allo-SCT. Conditioning regimens for RIC-allo-SCT were heterogeneous. Twenty patients experienced grade III/IV aGvHD, extensive cGvHD was reported in 28 cases. Median follow-up after RIC-allo-SCT was 45 months. Median PFS after RIC-allo-SCT was 30.1 months and median overall survival was 62 months. Treatment-related mortality (TRM) at 1 year and 3 years were estimated at 28% and 32%, respectively. A total of 52 patients died; major causes of death were related to toxicity (n=34) and MCL (n=11). Patients in good response before RIC-allo-SCT experienced a better PFS and OS. Our work highlights the need for new RIC-allo-SCT MCL-tailored approaches to reduce TRM, and early and late relapse.