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1.
20-Year Steady Increase in Survival of Adult Patients with Relapsed Philadelphia-Positive Acute Lymphoblastic Leukemia Post Allogeneic Hematopoietic Cell Transplantation
Bazarbachi, A., Labopin, M., Aljurf, M., Niittyvuopio, R., Balsat, M., Blaise, D., Yakoub-Agha, I., Grassi, A., Reinhardt, H. C., Lenhoff, S., et al
Clinical cancer research : an official journal of the American Association for Cancer Research. 2022
Abstract
PURPOSE Relapse after allogeneic hematopoietic cell transplantation (allo-HCT) remains the first cause of transplant failure in patients with Philadelphia-positive (Ph(+)) acute lymphoblastic leukemia (ALL). In other hematologic malignancies, therapeutic advances resulted in significant improvement over time in survival of patients relapsing after transplant. PATIENTS AND METHODS We compared outcomes at European Society for Blood and Marrow Transplantation (EBMT) participating centers of 899 adult patients with Ph(+) ALL who relapsed between 2000 and 2019 after allo-HCT performed in first complete remission. Median follow-up for alive patients was 56 months. RESULTS Overall, 116 patients relapsed between 2000 and 2004, 225 between 2005 and 2009, 294 between 2010 and 2014, and 264 between 2015 and 2019. Patient and transplant characteristics were similar over the four time periods except for a progressive increase in unrelated donors, peripheral blood stem cells, reduced intensity conditioning, and in vivo T-cell depletion and a progressive decrease in total body irradiation. The 2-year overall survival (OS) after relapse increased from 27.8% for patients relapsing between 2000 and 2004 to 54.8% for 2015 and 2019 (P = 0.001). A second allo-HCT within 2 years after relapse was performed in 13.9% of patients resulting in a 2-year OS of 35.9%. In multivariate analysis, OS from relapse was positively affected by a longer time from transplant to relapse and the year of relapse. CONCLUSIONS We observed a major progressive improvement in OS from posttransplant relapse for patients with Ph(+) ALL over the years, likely multifactorial including transplant-related factors, posttransplant salvage, and improvement in supportive care. These large-scale real-world data can serve as a benchmark for future studies in this setting.
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2.
Metabolic syndrome and cardiovascular disease after haematopoietic cell transplantation (HCT) in adults: an EBMT cross-sectional non-interventional study
Greenfield, D. M., Salooja, N., Peczynski, C., van der Werf, S., Schoemans, H., Hill, K., Cortelezzi, A., Lupo-Stangellini, M., Özkurt, Z. N., Arat, M., et al
Bone marrow transplantation. 2021
Abstract
Metabolic syndrome (MetS) is associated with cardiovascular disease in the general population and is also a potential cardiovascular risk factor in survivors of haematopoietic cell transplantation (HCT). We report an EBMT cross-sectional, multi-centre, non-interventional study of 453 adult HCT patients surviving a minimum of 2 years post-transplant attending routine follow-up HCT and/or late effects clinics in 9 centres. The overall prevalence of MetS was 37.5% rising to 53% in patients >50 years of age at follow-up. There were no differences in rates of MetS between autologous and allogeneic HCT survivors, nor any association with graft-versus-host disease (GvHD) or current immunosuppressant therapy. Notably, there was a significantly higher occurrence of cardiovascular events (CVE, defined as cerebrovascular accident, coronary heart disease or peripheral vascular disease) in those with MetS than in those without MetS (26.7% versus 9%, p?0.001, OR 3.69, 95% CI 2.09-6.54, p?0.001), and, as expected, MetS and CVE were age-related. Unexpectedly, CVE were associated with occurrence of second malignancy. Screening for and management of MetS should be integrated within routine HCT long-term follow-up care for both allogeneic and autologous HCT survivors. Further research is warranted, including randomised controlled trials of interventional strategies and mechanistic studies of cardiovascular risk in HCT survivors.
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3.
Allogeneic stem cell transplantation in therapy-related myelodysplasia after autologous transplantation for lymphoma: a retrospective study of the SFGM-TC
Jaimes-Albornoz, D., Mannone, L., Nguyen-Quoc, S., Chalandon, Y., Chevallier, P., Mohty, M., Meunier, M., Robin, M., Ledoux, M. P., Guillerm, G., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019
Abstract
Therapy-related myelodysplastic syndrome (t-MDS) after autologous stem-cell transplantation (ASCT) is a rare complication with no curative option. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be considered for eligible patients and has been understudied in t-MDS. We report 47 consecutive patients with t-MDS after an ASCT who underwent allo-HSCT with a median age of 58 years (range: 30-71) at transplantation and a median follow-up of 22 months (range: 0.7-107). The median overall survival (OS) was 6.9 months (95% confidence interval, 0-19). OS rates were 45% (29-60%) and 30% (15-45%) at 1 and 3 years after transplantation, respectively. On univariate analysis prior therapy for t-MDS before allo-HSCT (p=0.02) and mismatched donors (p=0.004) were associated with poor OS. Three-year non-relapse mortality (NRM) and relapse rates were 44% (25-63%) and 41% (22-61%), respectively. Mismatched donors (p<0.001) were associated with higher NRM and a high-risk MDS (p=0.008) with a higher relapse risk. On multivariate analysis HLA mismatch was associated with higher NRM (HR 6.21; 95% CI 1.63-23.62; p=0.007). In conclusion, our results suggest that one third of the patients who develop t-MDS after an ASCT for lymphoma are cured after an allo-HSCT. The use of mismatched donors with standard GVHD prophylaxis should be avoided in such indication for allo-HSCT. It will be worth to see if the implementation of CY post-transplantation will improve the outcome with mismatched donors.
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4.
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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5.
Metabolic syndrome and cardiovascular disease following hematopoietic cell transplantation: screening and preventive practice recommendations from CIBMTR and EBMT. [Review]
DeFilipp, Z., Duarte, R. F., Snowden, J. A., Majhail, N. S., Greenfield, D. M., Miranda, J. L., Arat, M., Baker, K. S., Burns, L. J., Duncan, C. N., et al
Bone Marrow Transplantation. 2017;52(2):173-182
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Abstract
Metabolic syndrome (MetS) is a constellation of cardiovascular risk factors that increases the risk of cardiovascular disease, diabetes mellitus and all cause mortality. Long-term survivors of hematopoietic cell transplantation (HCT) have a substantial risk of developing MetS and cardiovascular disease, with the estimated prevalence of MetS being 31-49% among HCT recipients. Although MetS has not yet been proven to impact cardiovascular risk after HCT, an understanding of the incidence and risk factors for MetS in HCT recipients can provide the foundation to evaluate screening guidelines and develop interventions that may mitigate cardiovascular-related mortality. A working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal of reviewing literature and recommend practices appropriate to HCT recipients. Here we deliver consensus recommendations to help clinicians provide screening and preventive care for MetS and cardiovascular disease among HCT recipients. All HCT survivors should be advised of the risks of MetS and encouraged to undergo recommended screening based on their predisposition and ongoing risk factors. The authors declare no conflict of interest.
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Lymphocyte expansion after unrelated cord blood allogeneic stem cell transplantation in adults
Le Bris, Y., Guillaume, T., Menard, A., Illiaquer, M., Martin, J., Malard, S., Duquesne, A., Peterlin, P., Debord, C., Robillard, N., et al
Bone Marrow Transplantation. 2017;52(6):854-858
Abstract
Limited information is available regarding the incidence and features of lymphocyte expansions after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Large granular lymphocytes (LGL) expansions have been reported after bone marrow or peripheral blood, but not after unrelated cord blood (UCB) allo-HSCT, associated with indolent clinical courses and favorable outcomes. Here, we considered 85 recipients of UCB allo-HSCT to more broadly define the impact of lymphocytosis, not limited to LGL. Sustained lymphocytosis was observed in 21 (25%) patients at a median onset of 12.6 months and with a median duration of 12 months. Immunophenotypic analysis showed predominantly CD8+ T and/or polyclonal B-cell expansions. Three patients only had monoclonal T-cell expansion. CMV reactivation was significantly more frequent in the group of patients with lymphocytosis (76% vs 28%, P=0.0001), but was not associated with survival. Conversely, 2-year disease-free survival and overall survival were significantly higher for lymphocytosis patients (85% vs 55%, P=0.01 and 85% vs 63%, P=0.03, respectively). In conclusion, expansion of T or B lymphocytes after UCB allo-HSCT in adults is not a rare event. Although occurring relatively late after transplant, this feature is predictive of a better outcome for the patients.
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The impact of allogeneic-hematopoietic stem cell transplantation on patients' and close relatives' quality of life and relationships
Polomeni, A., Lapusan, S., Bompoint, C., Rubio, M. T., Mohty, M.
European Journal of Oncology Nursing. 2016;21:248-56
Abstract
PURPOSE Although evidence suggests considerable disruption to families, the impact of allo-Hematopoietic Stem Cell Transplantation (HSCT) on patients' partners and close relatives has not been sufficiently explored. The present mixed-methods study aimed to enlighten allo-HSCT effects on patients' and close relatives' quality of life (QOL) and their relationships. METHODS Patients who received allo-HSCT between 2007 and 2010 (N = 58) and their close relatives (parents, partners and/or adult children) were asked to respond to an anonymous questionnaire including socio-demographic data, Likert-scale of the impact of HSCT on sexual, couple, family, professional and social life, as well as on perceived support. QOL of patients and close relatives was evaluated (by the FACT-BMT and by WHO-QOL-bref) as were the adjustments of the couples (patients/partners by the DAS). In-depth interviews were performed with patients and partners who consented to this proposition. RESULTS Patients (N = 28) and close relatives (N = 48) reported fatigue, sleep and sexual problems, emotional distress and relationship difficulties. Patients were mainly concerned with << being a burden >> to their close relatives. Close relatives' main concerns were changes in marital and family dynamics, disruptions in daily routine tasks and the responsibility for being the main provider of physical and emotional care. These difficulties increased after HSCT - notably when patients have to face the long-term consequences of the procedure. CONCLUSION HSCT has a negative impact on patients' partners and other close relatives' QOL. Data on this topic is still scarce and this study might pave the way for future research in this field and notably guide psychosocial interventions. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Metabolic Syndrome and Cardiovascular Disease after Hematopoietic Cell Transplantation: Screening and Preventive Practice Recommendations from the CIBMTR and EBMT
DeFilipp, Z., Duarte, R. F., Snowden, J. A., Majhail, N. S., Greenfield, D. M., Miranda, J. L., Arat, M., Baker, K. S., Burns, L. J., Duncan, C. N., et al
Biology of Blood & Marrow Transplantation. 2016;22(8):1493-503
Abstract
Metabolic syndrome (MetS) is a constellation of cardiovascular risk factors that increases the risk of cardiovascular disease, diabetes mellitus, and all-cause mortality. Long-term survivors of hematopoietic cell transplantation (HCT) have a substantial risk of developing MetS and cardiovascular disease, with an estimated prevalence of MetS of 31% to 49% among HCT recipients. Although MetS has not yet been proven to impact cardiovascular risk after HCT, an understanding of the incidence and risk factors for MetS in HCT recipients can provide the foundation to evaluate screening guidelines and develop interventions that may mitigate cardiovascular-related mortality. A working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal to review literature and recommend practices appropriate to HCT recipients. Here we deliver consensus recommendations to help clinicians provide screening and preventive care for MetS and cardiovascular disease among HCT recipients. All HCT survivors should be advised of the risks of MetS and encouraged to undergo recommended screening based on their predisposition and ongoing risk factors. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.