Publications by authors named "Ariane Boumendil"

59 Publications

Reliability of the Clinical Frailty Scale in very elderly ICU patients: a prospective European study.

Ann Intensive Care 2021 Feb 3;11(1):22. Epub 2021 Feb 3.

Department of Intensive Care Medicine, Dutch Poisons Information Center (DPIC), University Medical Center, University Utrecht, Utrecht, The Netherlands.

Purpose: Frailty is a valuable predictor for outcome in elderly ICU patients, and has been suggested to be used in various decision-making processes prior to and during an ICU admission. There are many instruments developed to assess frailty, but few of them can be used in emergency situations. In this setting the clinical frailty scale (CFS) is frequently used. The present study is a sub-study within a larger outcome study of elderly ICU patients in Europe (the VIP-2 study) in order to document the reliability of the CFS.

Materials And Methods: From the VIP-2 study, 129 ICUs in 20 countries participated in this sub-study. The patients were acute admissions ≥ 80 years of age and frailty was assessed at admission by two independent observers using the CFS. Information was obtained from the patient, if not feasible, from the family/caregivers or from hospital files. The profession of the rater and source of data were recorded along with the score. Interrater variability was calculated using linear weighted kappa analysis.

Results: 1923 pairs of assessors were included and background data of patients were similar to the whole cohort (n = 3920). We found a very high inter-rater agreement (weighted kappa 0.86), also in subgroup analyses. The agreement when comparing information from family or hospital records was better than using only direct patient information, and pairs of raters from same profession performed better than from different professions.

Conclusions: Overall, we documented a high reliability using CFS in this setting. This frailty score could be used more frequently in elderly ICU patients in order to create a more holistic and realistic impression of the patient´s condition prior to ICU admission.
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http://dx.doi.org/10.1186/s13613-021-00815-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856616PMC
February 2021

Sex-specific outcome disparities in very old patients admitted to intensive care medicine: a propensity matched analysis.

Sci Rep 2020 10 29;10(1):18671. Epub 2020 Oct 29.

Department of Cardiology, Pulmonology and Angiology, University Hospital, Moorenstraße 5, 40225, Duesseldorf, Germany.

Female and male very elderly intensive patients (VIPs) might differ in characteristics and outcomes. We aimed to compare female versus male VIPs in a large, multinational collective of VIPs with regards to outcome and predictors of mortality. In total, 7555 patients were included in this analysis, 3973 (53%) male and 3582 (47%) female patients. The primary endpoint was 30-day-mortality. Baseline characteristics, data on management and geriatric scores including frailty assessed by Clinical Frailty Scale (CFS) were documented. Two propensity scores (for being male) were obtained for consecutive matching, score 1 for baseline characteristics and score 2 for baseline characteristics and ICU management. Male VIPs were younger (83 ± 5 vs. 84 ± 5; p < 0.001), less often frail (CFS > 4; 38% versus 49%; p < 0.001) but evidenced higher SOFA (7 ± 6 versus 6 ± 6 points; p < 0.001) scores. After propensity score matching, no differences in baseline characteristics could be observed. In the paired analysis, the mortality in male VIPs was higher (mean difference 3.34% 95%CI 0.92-5.76%; p = 0.007) compared to females. In both multivariable logistic regression models correcting for propensity score 1 (aOR 1.15 95%CI 1.03-1.27; p = 0.007) and propensity score 2 (aOR 1.15 95%CI 1.04-1.27; p = 0.007) male sex was independently associated with higher odds for 30-day-mortality. Of note, male gender was not associated with ICU mortality (OR 1.08 95%CI 0.98-1.19; p = 0.14). Outcomes of elderly intensive care patients evidenced independent sex differences. Male sex was associated with adverse 30-day-mortality but not ICU-mortality. Further research to identify potential sex-specific risk factors after ICU discharge is warranted.Trial registration: NCT03134807 and NCT03370692; Registered on May 1, 2017 https://clinicaltrials.gov/ct2/show/NCT03370692 .
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http://dx.doi.org/10.1038/s41598-020-74910-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596065PMC
October 2020

Tandem autologous-reduced intensity allogeneic stem cell transplantation in high-risk relapsed Hodgkin lymphoma: a retrospective study of the Lymphoma Working Party-EBMT.

Bone Marrow Transplant 2020 Oct 12. Epub 2020 Oct 12.

Institut Català d'Oncologia (ICO)-Hospitalet, IDIBELL, Universitat de Barcelona, Barcelona, Spain.

Autologous hematopoietic stem cell transplantation (ASCT) is curative for a proportion of patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL). However, there is a small group of patients with high-risk of relapse after ASCT that might benefit from other approaches. We conducted a retrospective analysis on 126 patients treated with tandem ASCT-reduced intensity conditioning (RIC)-allogeneic-SCT and reported to the EBMT registry to analyze the efficacy and safety of this approach. Patients were included if they had received an ASCT followed by a planned RIC-SCT in <6 months without relapse between the procedures. The median time between diagnosis and ASCT was 16 months (2-174). The median number of lines prior to ASCT was two (33% of the patients received >3 lines). Forty-one percent were transplanted with active disease. The median follow-up was 44 months (6-130). Three-year-progression-free survival (PFS), overall survival (OS), incidence of relapse (IR), and non-relapse mortality (NRM) after the tandem were 53% (45-64), 73% (65-81), 34% (24-42), and 13% (8-21), respectively. This is the largest series analyzing the efficacy and safety of a tandem approach in R/R HL. The low NRM and IR with promising PFS and OS suggest that this might be an effective procedure for a high-risk population.
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http://dx.doi.org/10.1038/s41409-020-01075-yDOI Listing
October 2020

The wave of very old people in the intensive care unit-A challenge in decision-making.

J Crit Care 2020 12 10;60:290-293. Epub 2020 Sep 10.

Department of Anaesthesia and Intensive Care, Haukeland University Hospital, Bergen, Norway.

In this paper the authors express the opinion that there is much to be learned about the 80+ year old age group as it relates to critical care and end-of-life matters. We need to learn how to better predict outcome, we need to learn our limitations and deal with uncertainties, we need to better communicate with our elderly patients and their caregivers and we need to engage with our colleagues in Geriatrics. There is a wave of very old people arriving in the intensive care unit and we have much to do to prepare for it and for the ethical, fair and appropriate care of these critically ill, but elderly, patients.
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http://dx.doi.org/10.1016/j.jcrc.2020.08.030DOI Listing
December 2020

Second autologous stem cell transplantation for relapsed/refractory Hodgkin lymphoma after a previous autograft: a study of the lymphoma working party of the EBMT.

Leuk Lymphoma 2020 12 11;61(12):2915-2922. Epub 2020 Jul 11.

Department of Haematology, Institut Catala d'Oncologia, Hospital Duran I Reynals, Barcelona, Spain.

The purpose of this study was to analyze the results of second autologous hematopoietic stem cell transplantation (ASCT2) for patients with relapsed/refractory Hodgkin lymphoma (HL) after a first transplantation (ASCT1). Outcomes for 56 patients receiving an ASCT2 registered in the EBMT database were analyzed. The 4-year cumulative incidences of non-relapse mortality and disease relapse/progression were 5% and 67%, respectively. The 4-year overall survival (OS) and progression-free survival (PFS) were 62% and 28%. In univariate analysis, relapse of HL within 12 months of ASCT1 was associated with a worse OS (35% versus 76%,  = 0.01) and PFS (19% versus 29%,  = 0.059). Chemosensitivity at ASCT2 predicted better outcomes (4-year OS 72% versus 29%,  = 0.002; PFS 31% versus 12%,  = 0.015). This series shows that ASCT2 is a safe procedure and a relatively effective option for patients with late relapses after ASCT1 and with chemosensitive disease who are not eligible for an allogeneic transplant.
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http://dx.doi.org/10.1080/10428194.2020.1789624DOI Listing
December 2020

Changes in patients population and characteristics of hematopoietic stem cell transplantation for relapsed/refractory Hodgkin lymphoma: an analysis of the Lymphoma Working Party of the EBMT.

Bone Marrow Transplant 2020 11 15;55(11):2170-2179. Epub 2020 May 15.

Department of Haemato-Oncology, St Bartholomew's Hospital, Barts Health NHS Trust, London, UK.

Indications for autologous (auto-HCT) and allogeneic transplantation (allo-HCT) in relapsed/refractory Hodgkin lymphoma (rrHL) have been long established. The expectation is that long-term outcomes have significantly improved over time with increased experience in these procedures. The objective of this study was to assess whether this is the case and to identify further areas of improvement. A total of 13,639 adult patients receiving an auto-HCT or allo-HCT for rrHL were reported to the European Society for Blood and Marrow Transplantation (EBMT) over a 25-year period. Regarding auto-HCT, recipients are younger, interval between diagnosis and transplant shorter, peripheral blood has become the universal stem cell source and the use of total body irradiation is almost non-existent in recent years. Allo-HCT is currently mostly used as a second transplant; recipients are younger, fitter and less frequently, chemorefractory. Reduced intensity conditioning protocols have vastly replaced myeloablative protocols. Increasing numbers of haplo-HCT have been reported. Both in auto-HCT and allo-HCT, NRM, PFS and OS have significantly improved but relapse remains the main cause of treatment failure. A better selection of patients and improvements in the supportive care has resulted in a reduction in the NRM. Relapse after HCT remains unchanged and further research is needed.
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http://dx.doi.org/10.1038/s41409-020-0929-yDOI Listing
November 2020

Sepsis at ICU admission does not decrease 30-day survival in very old patients: a post-hoc analysis of the VIP1 multinational cohort study.

Ann Intensive Care 2020 May 13;10(1):56. Epub 2020 May 13.

Department of Intensive Care Medicine, Hospital Universitario Sagrat Cor, Viladomat 288, 08029, Barcelona, Spain.

Background: The number of intensive care patients aged ≥ 80 years (Very old Intensive Care Patients; VIPs) is growing. VIPs have high mortality and morbidity and the benefits of ICU admission are frequently questioned. Sepsis incidence has risen in recent years and identification of outcomes is of considerable public importance. We aimed to determine whether VIPs admitted for sepsis had different outcomes than those admitted for other acute reasons and identify potential prognostic factors for 30-day survival.

Results: This prospective study included VIPs with Sequential Organ Failure Assessment (SOFA) scores ≥ 2 acutely admitted to 307 ICUs in 21 European countries. Of 3869 acutely admitted VIPs, 493 (12.7%) [53.8% male, median age 83 (81-86) years] were admitted for sepsis. Sepsis was defined according to clinical criteria; suspected or demonstrated focus of infection and SOFA score ≥ 2 points. Compared to VIPs admitted for other acute reasons, VIPs admitted for sepsis were younger, had a higher SOFA score (9 vs. 7, p < 0.0001), required more vasoactive drugs [82.2% vs. 55.1%, p < 0.0001] and renal replacement therapies [17.4% vs. 9.9%; p < 0.0001], and had more life-sustaining treatment limitations [37.3% vs. 32.1%; p = 0.02]. Frailty was similar in both groups. Unadjusted 30-day survival was not significantly different between the two groups. After adjustment for age, gender, frailty, and SOFA score, sepsis had no impact on 30-day survival [HR 0.99 (95% CI 0.86-1.15), p = 0.917]. Inverse-probability weight (IPW)-adjusted survival curves for the first 30 days after ICU admission were similar for acute septic and non-septic patients [HR: 1.00 (95% CI 0.87-1.17), p = 0.95]. A matched-pair analysis in which patients with sepsis were matched with two control patients of the same gender with the same age, SOFA score, and level of frailty was also performed. A Cox proportional hazard regression model stratified on the matched pairs showed that 30-day survival was similar in both groups [57.2% (95% CI 52.7-60.7) vs. 57.1% (95% CI 53.7-60.1), p = 0.85].

Conclusions: After adjusting for organ dysfunction, sepsis at admission was not independently associated with decreased 30-day survival in this multinational study of 3869 VIPs. Age, frailty, and SOFA score were independently associated with survival.
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http://dx.doi.org/10.1186/s13613-020-00672-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221097PMC
May 2020

Nonmyeloablative Alternative Donor Transplantation for Hodgkin and Non-Hodgkin Lymphoma: From the LWP-EBMT, Eurocord, and CIBMTR.

J Clin Oncol 2020 05 7;38(14):1518-1526. Epub 2020 Feb 7.

Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI.

Purpose: To compare the outcomes of patients with Hodgkin or non-Hodgkin lymphoma undergoing nonmyeloablative haploidentical or unrelated cord blood (UCB) hematopoietic cell transplantation.

Patients And Methods: We retrospectively studied 740 patients with Hodgkin lymphoma (n = 283, 38%) and non-Hodgkin lymphoma (n = 457, 62%) age 18-75 years who received transplantations from 2009 to 2016. Data were reported to the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation, Eurocord, or Center for International Blood and Marrow Transplant Research. Of the 526 patients who received haploidentical transplantation, 68% received bone marrow and 32% received peripheral blood. All patients received a uniform transplantation conditioning regimen (2 Gy of total-body irradiation, cyclophosphamide, and fludarabine) and graft-versus-host disease prophylaxis (calcineurin inhibitor and mycophenolate). In addition, patients who received a haploidentical transplantation received posttransplantation cyclophosphamide.

Results: Compared with haploidentical bone marrow and peripheral-blood transplantations and adjusted for age, lymphoma subtype, and disease status, survival was lower after UCB transplantation (hazard ratio [HR], 1.55; = .001; and HR, 1.59; = .005, respectively). Similarly, progression-free survival was lower after UCB transplantations compared with haploidentical bone marrow and peripheral-blood transplantations (HR, 1.44; = .002; and HR, 1.86; < .0001), respectively. The 4-year overall and progression-free survival rates after UCB transplantation were 49% and 36%, respectively, compared with 58% and 46% after haploidentical bone marrow transplantation and 59% and 52% after peripheral-blood transplantation, respectively. Lower survival was attributed to higher transplantation-related mortality after UCB transplantation compared with haploidentical bone marrow and peripheral-blood transplantation (HR, 1.91; = .0001; and HR, 2.27; = .0002, respectively).

Conclusion: When considering HLA-mismatched transplantation for Hodgkin or non-Hodgkin lymphoma, the data support haploidentical related donor transplantation over UCB transplantation.
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http://dx.doi.org/10.1200/JCO.19.02408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7213591PMC
May 2020

The contribution of frailty, cognition, activity of daily life and comorbidities on outcome in acutely admitted patients over 80 years in European ICUs: the VIP2 study.

Intensive Care Med 2020 01 29;46(1):57-69. Epub 2019 Nov 29.

Dep. of Clinical Medicine, University of Bergen, Bergen, Norway.

Purpose: Premorbid conditions affect prognosis of acutely-ill aged patients. Several lines of evidence suggest geriatric syndromes need to be assessed but little is known on their relative effect on the 30-day survival after ICU admission. The primary aim of this study was to describe the prevalence of frailty, cognition decline and activity of daily life in addition to the presence of comorbidity and polypharmacy and to assess their influence on 30-day survival.

Methods: Prospective cohort study with 242 ICUs from 22 countries. Patients 80 years or above acutely admitted over a six months period to an ICU between May 2018 and May 2019 were included. In addition to common patients' characteristics and disease severity, we collected information on specific geriatric syndromes as potential predictive factors for 30-day survival, frailty (Clinical Frailty scale) with a CFS > 4 defining frail patients, cognitive impairment (informant questionnaire on cognitive decline in the elderly (IQCODE) with IQCODE ≥ 3.5 defining cognitive decline, and disability (measured the activity of daily life with the Katz index) with ADL ≤ 4 defining disability. A Principal Component Analysis to identify co-linearity between geriatric syndromes was performed and from this a multivariable model was built with all geriatric information or only one: CFS, IQCODE or ADL. Akaike's information criterion across imputations was used to evaluate the goodness of fit of our models.

Results: We included 3920 patients with a median age of 84 years (IQR: 81-87), 53.3% males). 80% received at least one organ support. The median ICU length of stay was 3.88 days (IQR: 1.83-8). The ICU and 30-day survival were 72.5% and 61.2% respectively. The geriatric conditions were median (IQR): CFS: 4 (3-6); IQCODE: 3.19 (3-3.69); ADL: 6 (4-6); Comorbidity and Polypharmacy score (CPS): 10 (7-14). CFS, ADL and IQCODE were closely correlated. The multivariable analysis identified predictors of 1-month mortality (HR; 95% CI): Age (per 1 year increase): 1.02 (1.-1.03, p = 0.01), ICU admission diagnosis, sequential organ failure assessment score (SOFA) (per point): 1.15 (1.14-1.17, p < 0.0001) and CFS (per point): 1.1 (1.05-1.15, p < 0.001). CFS remained an independent factor after inclusion of life-sustaining treatment limitation in the model.

Conclusion: We confirm that frailty assessment using the CFS is able to predict short-term mortality in elderly patients admitted to ICU. Other geriatric syndromes do not add improvement to the prediction model. Since CFS is easy to measure, it should be routinely collected for all elderly ICU patients in particular in connection to advance care plans, and should be used in decision making.
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http://dx.doi.org/10.1007/s00134-019-05853-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223711PMC
January 2020

Ibrutinib as a salvage therapy after allogeneic HCT for chronic lymphocytic leukemia.

Bone Marrow Transplant 2020 05 7;55(5):884-890. Epub 2019 Nov 7.

Department of Hematology, University Hospital Dresden, Dresden, Germany.

The purpose of our study is to provide information on safety and efficacy of ibrutinib as salvage treatment after allo-HSCT for CLL. A total of 56 patients were included, 36 (64%) males; median age at transplantation was 48 years (range: 35-64) and the median number of treatment lines prior to transplantation was 3 (1-10). The median time between allo-HSCT and Ibrutinib was 30 months (range: 1-140). Overall, 40 (71%) patients responded to Ibrutinib; 23 (41%) PR, and 17 (30%) CR. At time of ibrutinib initiation, ten patients had active chronic GVHD that resolved under Ibrutinib, whilst a single patient developed limited de novo chronic GVHD on Ibrutinib. Fourteen patients discontinued ibrutinib, four because of toxicity and ten because of disease progression. Overall, 14 patients progressed (median PFS = 24 months) among them 10 died. Two-year OS and PFS probabilities were 72% (95% CI: 52-84) and 50% (95% CI: 32-66), respectively. Patients with late relapse after allo-HSCT (≥24 months) had a better PFS after ibrutinib. Our study shows that ibrutinib can be safely administered for CLL relapse after allo-HSCT, with comparable efficacy to non-transplanted patients with high-risk disease.
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http://dx.doi.org/10.1038/s41409-019-0742-7DOI Listing
May 2020

Analysis of data collected in the European Society for Blood and Marrow Transplantation (EBMT) Registry on a cohort of lymphoma patients receiving plerixafor.

Bone Marrow Transplant 2020 03 30;55(3):613-622. Epub 2019 Sep 30.

University of Heidelberg, Heidelberg, Germany.

Plerixafor + granulocyte-colony stimulating factor (G-CSF) is administered to patients with lymphoma who are poor mobilizers of hematopoietic stem cells (HSCs) in Europe. This international, multicenter, non-interventional registry study (NCT01362972) evaluated long-term follow-up of patients with lymphoma who received plerixafor for HSC mobilization versus other mobilization methods. Propensity score matching was conducted to balance baseline characteristics between comparison groups. The following mobilization regimens were compared: G-CSF + plerixafor (G + P) versus G-CSF alone; G + P versus G-CSF + chemotherapy (G + C); and G-CSF + plerixafor + chemotherapy (G + P + C) versus G + C. The primary outcomes were progression-free survival (PFS), overall survival (OS), and cumulative incidence of relapse (CIR). Overall, 313/3749 (8.3%) eligible patients were mobilized with plerixafor-containing regimens. After propensity score matching, 70 versus 36 patients were matched in the G + P versus G-CSF alone cohort, 124 versus 124 in the G + P versus G + C cohort, and 130 versus 130 in the G + P + C versus G + C cohort. For both PFS and OS, the upper bound of confidence interval for the hazard ratio was >1.3 for all comparisons, implying that non-inferiority was not demonstrated. No major differences in PFS, OS, and CIR were observed between the plerixafor and comparison groups.
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http://dx.doi.org/10.1038/s41409-019-0693-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7051902PMC
March 2020

Acute critically ill elderly patients: What about long term caregiver burden?

J Crit Care 2019 12 28;54:180-184. Epub 2019 Aug 28.

Department of Critical Care, Saint Antoine Hospital, Assistance Publique Hôpitaux de Paris (APHP), Paris, France.

Purpose: Acute critical illness induce a high caregivers burden in the young population, however data in the older population are lacking. The objectives of this study were to evaluate caregiver burden in a critically ill old population and to assess factors associated with mild to severe burden level.

Materials And Methods: All patients from two participating centers of the ICE-CUB 2 trial were included in the study. Inclusion criteria were an age ≥75, at least one critical condition and preserved functional status. The primary endpoint was a Zarit Burden Interview (ZBI) ≥ 21 at 6 months.

Results: One hundred ninety-one patients (median age 86 [81-89] years) were included. Median caregiver ZBI at 6 months was 13 [5-27]. In the multivariate analysis, factors significantly associated with moderate to severe burden were the 6-month ADL decrease (OR: 1.3, p = .049) and the 6-month mental component of the quality of life score (OR: 0.94, p = .0009). In contrast, age, ICU admission and length of hospital stay were not associated with moderate to severe load.

Conclusion: In our study, functional status and mental health at 6 months were associated with mild to severe burden unlike age and admission in ICU.
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http://dx.doi.org/10.1016/j.jcrc.2019.08.028DOI Listing
December 2019

Influence of donor type, stem cell source and conditioning on outcomes after haploidentical transplant for lymphoma - a LWP-EBMT study.

Br J Haematol 2020 03 9;188(5):745-756. Epub 2019 Sep 9.

ICO - Hospital Duran i Reynals, Barcelona, Spain.

Haploidentical stem cell transplantation (haploSCT) is becoming a major transplant modality for lymphoma. To assess the effects of donor characteristics, stem cell source and conditioning on outcomes, we identified 474 adults with Hodgkin (HL; 240), peripheral T-cell (PTCL; 88), diffuse large B-cell (77), mantle cell (40) or follicular lymphoma (FL; 29), who received haploSCT with post-transplant cyclophosphamide. Median follow-up of alive patients was 32 months. On multivariate analysis, acute graft-versus-host disease (GVHD) grade 2-4 was lower with offspring donors or bone marrow cells, whereas extensive chronic GVHD was higher in partial response at haploSCT or when using sisters, haploidentical donors beyond first degree, or female donors in male patients. Progression-free survival (PFS) was better for FL, HL and PTCL, whereas overall survival (OS) was better for HL and PTCL. Complete remission at haploSCT improved PFS and OS whereas these were negatively affected by cytomegalovirus donor positive/recipient positive status. No other donor characteristics (age, gender, human leucocyte antigen mismatch, ABO incompatibility) affected PFS or OS except use of haploidentical donors beyond first degree, which negatively affected OS. PFS and OS are mostly influenced by disease status and lymphoma subtype, supporting the use of any first degree haploidentical family member as a donor.
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http://dx.doi.org/10.1111/bjh.16182DOI Listing
March 2020

Trends in the use of hematopoietic stem cell transplantation for adults with acute lymphoblastic leukemia in Europe: a report from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT).

Ann Hematol 2019 Oct 7;98(10):2389-2398. Epub 2019 Aug 7.

EBMT Acute Leukemia Working Party Office, Hospital Saint-Antoine, 84 Rue du Faubourg Saint-Antoine, 75012, Paris, France.

Hematopoietic stem cell transplantation (HSCT) is considered an effective way to prevent relapse in adults with acute lymphoblastic leukemia (ALL). This study aimed to assess general trends in the use of various types of HSCTs performed between 2001 and 2015 in Europe, based on data reported to the European Society for Blood and Marrow Transplantation registry. We also evaluated HSCT rates with respect to ALL incidence in selected countries. Altogether, 15,346 first allogeneic (n = 13,460) or autologous (n = 1886) HSCTs were performed in the study period. Comparing 2013-2015 and 2001-2003, the number of allogeneic HSCTs performed in first complete remission increased by 136%, most prominently for transplantations from unrelated (272%) and mismatched related donors (339%). The number of HSCTs from matched sibling donors increased by 42%, while the total number of autologous HSCTs decreased by 70%. Increased use of allogeneic HSCT was stronger for Philadelphia chromosome (Ph)-positive (166%) than for Ph-negative ALL (38%) and for patients aged > 55 years (599%) than for younger adults (59%). The proportion of allogeneic HSCT with reduced-intensity conditioning (RIC) increased from 6 to 27%. The age-standardized rates of allogeneic HSCT per ALL incidence varied strongly among countries. Our analysis showed a continued trend toward increased allogeneic HSCT use for adults with ALL, which may be attributed to increasing availability of unrelated donors, wider use of RIC regimens, and improving efficacy of pretransplant therapy, including tyrosine kinase inhibitors for Ph-positive ALL. Allogeneic HSCT remains a major tool in the fight against ALL in adults.
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http://dx.doi.org/10.1007/s00277-019-03771-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733814PMC
October 2019

Leukemia relapse following unmanipulated haploidentical transplantation: a risk factor analysis on behalf of the ALWP of the EBMT.

J Hematol Oncol 2019 07 4;12(1):68. Epub 2019 Jul 4.

Hematology and Bone Marrow Transplantation Division, Chaim Sheba Medical Center, Tel-Hashomer, Israel.

Background: As information on incidence, risk factors, and outcome of acute leukemia (AL) relapse after unmanipulated haploidentical stem cell transplantation (haplo-SCT) is scarce, a retrospective registry study was performed by the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

Methods: Among 1652 transplants performed for lymphoblastic and myeloid AL between 2007 and 2014, 587 patients (acute lymphoblastic leukemia (ALL) 131, acute myeloid leukemia (AML) 456) with detailed information were analyzed aiming to identify risk factors for post-transplant relapse and for overall survival (OS) after relapse.

Results: The cumulative incidence of relapse at 3 years was 44% (35-53%) for ALL and 32% (27-36%) for AML (p = 0.023). In ALL, risk factors for relapse were disease status different from the first complete remission (CR1) at haplo-SCT (CR2 vs CR1: HR 2.85, p = 0.011; advanced vs CR1: HR 14.28, p < 0.0001) and male donor gender (HR 3.64, p = 0.0002), while in AML, risk factors were advanced disease at haplo-SCT (advanced vs CR1: HR 3.95, p < 0.0001) and comorbidities (HCT-CI) ≥ 3 (HR 1.75, p = 0.014). Transplants performed in more recent years were associated with lower relapse incidence (RI) in AML, but not in ALL (HR 0.91, p = 0.042). After relapse, median follow-up was 13 months (mos). OS at 1-year post relapse was 18%. Prognostic factors for superior OS after relapse were remission at time of haplo-SCT (CR vs advanced: HR 0.71, p = 0.028), time from transplant to relapse (≥ 5 mos vs < 5 mos: HR 0.530, p < 0.0001), and bone marrow as a stem cell source (peripheral blood (PB) vs bone marrow (BM): HR 1.473, p = 0.016).

Conclusions: Risk factors for relapse after haploidentical transplantation were disease specific. Longer OS after relapse was achieved in particular by patients both in CR at haplo-SCT and relapsing more than 5 months after transplant (1-year OS 33%).
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http://dx.doi.org/10.1186/s13045-019-0751-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6610936PMC
July 2019

Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Patients Age >69 Years with Acute Myelogenous Leukemia: On Behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

Biol Blood Marrow Transplant 2019 10 7;25(10):1975-1983. Epub 2019 Jun 7.

European Society for Blood and Marrow Transplantation, Paris study office/CEREST-TC, Paris, France; Hematology Division and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel-Hashomer, Israel.

Reduced-intensity conditioning (RIC) allows for the use of allogeneic hematopoietic stem cell transplantation (HSCT) in older patients with acute myelogenous leukemia (AML). We compared outcomes between 713 patients age ≥70 years and 16,161 patients age 50 to 69 years who underwent HSCT between 2004 and 2014. A higher proportion of the older patients were male and had secondary AML, active disease, a peripheral blood stem cell graft, a matched unrelated donor, an RIC regimen, and a lower Karnofsky Performance Status (KPS) score (P< .001). In multivariate analysis, the incidences of acute and chronic graft-versus-host disease and relapse were similar in the 2 age groups. Nonrelapse mortality at 2 years was 34% (95% confidence interval [CI], 31% to 38%) in patients age ≥70 years and 24% (95% CI, 25% to 32%) in those age 50 to 69 years (P< .001). Survival at 2 years in the 2 groups was 38% (95% CI, 34% to 42%) and 50% (95% CI, 49% to 50%), respectively (P< .001). In patients with active disease, the corresponding percentages were 35% (95% CI, 29% to 41%) in those age ≥70 years and 33% (95% CI, 31% to 34%) in those age <70 years (P = .36). In patients age ≥70 years, a KPS score of ≥80% was associated with improved survival (hazard ratio, 1.53; 95% CI, 1.14 to 2.06; P = .003). In summary, patients age ≥70 years had worse outcomes, except for those with active AML.
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http://dx.doi.org/10.1016/j.bbmt.2019.05.037DOI Listing
October 2019

A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention.

J Crit Care 2019 08 2;52:141-148. Epub 2019 May 2.

Department of Clinical Medecine,University of Bergen, Department of Anaestesia and Intensive Care, Haukeland University Hospital, Bergen, Norway. Electronic address:

Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (≥80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.

Methods: In total, 5063 VIPs were included in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.

Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 ± 5 vs 7 ± 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).

Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery.

Trial Registration: NCT03134807. Registered 1st May 2017.
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http://dx.doi.org/10.1016/j.jcrc.2019.04.020DOI Listing
August 2019

Cumulative Prognostic Score Predicting Mortality in Patients Older Than 80 Years Admitted to the ICU.

J Am Geriatr Soc 2019 06 12;67(6):1263-1267. Epub 2019 Apr 12.

Assistance Publique - Hôpitaux de Paris, Hôpital Saint-Antoine, Service de Réanimation Médicale, Paris, France.

Objectives: To develop a scoring system model that predicts mortality within 30 days of admission of patients older than 80 years admitted to intensive care units (ICUs).

Design: Prospective cohort study.

Setting: A total of 306 ICUs from 24 European countries.

Participants: Older adults admitted to European ICUs (N = 3730; median age = 84 years [interquartile range = 81-87 y]; 51.8% male).

Measurements: Overall, 24 variables available during ICU admission were included as potential predictive variables. Multivariable logistic regression was used to identify independent predictors of 30-day mortality. Model sensitivity, specificity, and accuracy were evaluated with receiver operating characteristic curves.

Results: The 30-day-mortality was 1562 (41.9%). In multivariable analysis, these variables were selected as independent predictors of mortality: age, sex, ICU admission diagnosis, Clinical Frailty Scale, Sequential Organ Failure Score, invasive mechanical ventilation, and renal replacement therapy. The discrimination, accuracy, and calibration of the model were good: the area under the curve for a score of 10 or higher was .80, and the Brier score was .18. At a cut point of 10 or higher (75% of all patients), the model predicts 30-day mortality in 91.1% of all patients who die.

Conclusion: A predictive model of cumulative events predicts 30-day mortality in patients older than 80 years admitted to ICUs. Future studies should include other potential predictor variables including functional status, presence of advance care plans, and assessment of each patient's decision-making capacity.
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http://dx.doi.org/10.1111/jgs.15888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6850576PMC
June 2019

Autologous stem cell transplantation for HIV-associated lymphoma in the antiretroviral and rituximab era: a retrospective study by the EBMT Lymphoma Working Party.

Bone Marrow Transplant 2019 10 25;54(10):1625-1631. Epub 2019 Feb 25.

University Hospital of Heidelberg, Heidelberg, Germany.

The present study aimed at describing the outcome of patients with HIV-associated lymphomas following autologous hematopoietic stem cell transplantation (autoHCT) in the rituximab and combined antiretroviral therapy (cART) era. Eligible for this retrospective study were HIV-positive patients with lymphoma who received autoHCT between 2007 and 2013. A total of 118 patients were included with a median age of 45 years (range 24-66). Underlying diagnoses were diffuse large B cell lymphoma in 47%, Hodgkin lymphoma in 24%, Burkitt lymphoma in 18%, and plasmablastic lymphoma in 7% of patients. Disease status at autoHCT was complete remission in 44%, partial remission (PR) in 38%, and less than PR in 18% of the patients. With a median follow-up of 4 years, 3-year non-relapse mortality, incidence of relapse, progression-free survival (PFS) and overall survival (OS) were 10%, 27%, 63% and 66%, respectively. By multivariate analysis, disease status less than PR but not CD4+ cell count at the time of autoHCT was a significant predictor of unfavorable PFS and OS. In conclusion, in the era of cART and chemoimmunotherapy, the outcome of autoHCT for HIV-related lymphoma is driven by lymphoma-dependent risk factors rather than by characteristics of the HIV infection.
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http://dx.doi.org/10.1038/s41409-019-0480-xDOI Listing
October 2019

PTCy-based haploidentical vs matched related or unrelated donor reduced-intensity conditioning transplant for DLBCL.

Blood Adv 2019 02;3(3):360-369

Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI.

This study retrospectively compared long-term outcomes of nonmyeloablative/reduced intensity conditioning (NMC/RIC) allogeneic hematopoietic cell transplantation (allo-HCT) from a haploidentical family donor (haplo-HCT) using posttransplant cyclophosphamide (PTCy) with those of matched sibling donor (MSD) and matched unrelated donor (MUD) with or without T-cell depletion (TCD+/TCD-) in patients with relapsed diffuse large B-cell lymphoma (DLBCL). Adult patients with DLBCL who had undergone their first NMC/RIC allo-HCT between 2008 and 2015 were included. Recipients of haplo-HCT were limited to those receiving graft-versus-host disease (GVHD) prophylaxis with PTCy. GVHD prophylaxis in MSD was limited to calcineurin inhibitor (CNI)-based approaches without in vivo TCD, while MUD recipients received CNI-based prophylaxis with or without TCD. Outcome analyses for overall survival (OS) and progression-free survival (PFS), nonrelapse mortality (NRM), and disease relapse/progression were calculated. A total of 1438 patients (haplo, 132; MSD, 525; MUD TCD+, 403; and MUD TCD-, 378) were included. Patients with haplo donors were significantly older, had a better performance status and had more frequently received total body irradiation-based conditioning regimens and bone marrow grafts than MSD and MUD TCD+ or TCD-. 3-year OS, PFS, NRM and relapse/progression incidence after haplo-HCT was 46%, 38%, 22%, and 41%, respectively, and not significantly different from outcomes of matched donor transplants on multivariate analyses. Haplo-HCT was associated with a lower cumulative incidence of chronic GVHD compared with MSD, MUD TCD+/TCD-. NMC/RIC haplo-HCT with PTCy seems to be a valuable alternative for patients with DLBCL considered for allo-HCT but lacking a matched donor.
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http://dx.doi.org/10.1182/bloodadvances.2018027748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6373757PMC
February 2019

Unmanipulated haploidentical versus HLA-matched sibling allogeneic hematopoietic stem cell transplantation in relapsed/refractory acute myeloid leukemia: a retrospective study on behalf of the ALWP of the EBMT.

Bone Marrow Transplant 2019 09 4;54(9):1499-1510. Epub 2019 Feb 4.

Acute Leukemia Working Party of EBMT, Paris, France.

Refractory or relapsed acute myeloid leukemia (R/R-AML) has poor prognosis. Allogeneic hematopoietic stem-cell transplantation (HSCT) may provide cure in this scenario. We compared outcomes of HSCT from HLA-identical (HLA-id, n = 1654) sibling or haploidentical (Haplo, n = 389) donors in patients with R/R-AML, performed during the period 2007-2015. The Haplo group included patients receiving an unmanipulated graft (post-transplant cyclophosphamide, n = 278; in vivo T-cell depletion, n = 95; or both, n = 16). Median age at HSCT was 52 (range 18-74) years. Median follow-up was 16 and 22 months for HLA-id sibling and Haplo recipients, respectively (p = 0.11). Compared to MSD, Haplo HSCT were performed more recently (2013 vs 2011, p < 0.01), at longer interval from diagnosis (7 vs 5 months, p < 0.01), more frequently using bone marrow as stem cell source (47% vs 8%, p < 0.01) and with a reduced intensity conditioning regimen (50% vs 43%, p = 0.03). Engraftment was higher (93% vs 83%, p < 0.01) in HLA-id sibling. In multivariate analysis, Haplo HSCT was associated with lower GVHD/relapse-free survival, inferior LFS and OS and higher NRM, mainly due to a higher rate of infections (41% vs 25%, p < 0.01). For R/R-AML, HLA-id sibling donors remain the gold standard, when available, due to higher mortality in Haplo without significant gain in disease control.
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http://dx.doi.org/10.1038/s41409-019-0459-7DOI Listing
September 2019

Brentuximab vedotin for recurrent Hodgkin lymphoma after allogeneic hematopoietic stem cell transplantation: A report from the EBMT Lymphoma Working Party.

Cancer 2019 01 23;125(1):90-98. Epub 2018 Oct 23.

Department of Haematology, Catala Oncology Institute, Barcelona, Spain.

Background: The treatment of patients with Hodgkin lymphoma (HL) who develop disease progression after undergoing allogeneic stem cell transplantation (allo-SCT) remains challenging.

Methods: The authors assessed outcomes in 184 adult patients with HL who developed disease recurrence or progression after a matched related or unrelated allo-SCT at European Society for Blood and Marrow Transplantation-participating centers between 2010 and 2014.

Results: Eighty patients who received brentuximab vedotin (BV) salvage therapy were compared with 104 patients who did not. Patients in the BV group were younger (median age of 30 years vs 34 years) and were more likely to receive pretransplant BV (65% vs 46%) or posttransplant donor lymphocyte infusion (66% vs 33%). The 2 groups otherwise were comparable. Patients in the BV group received a median of 6 doses of posttransplant BV, resulting in a complete remission rate of 29%, a partial response rate of 45%, and a stable disease rate of 26%. Response to BV after allo-SCT did not appear to be affected by receipt of pretransplant BV. Despite a longer median follow-up for surviving patients in the BV group (33 months vs 23 months; P<.001), approximately 34% of the original BV cohort were alive and in CR at the time of last follow-up versus 18% in the group that did not receive BV (P=.003). The use of BV before donor lymphocyte infusion was found to be associated with the highest probability of being alive and in CR (40%) at the time of last follow-up. Salvage BV appeared to have no effect on chronic graft-versus-host disease or 1-year overall survival from the time of disease recurrence after allo-SCT (76% vs 67%).

Conclusions: BV is a safe and effective salvage therapy for patients with HL who develop disease recurrence or progression after undergoing allo-SCT, even after prior exposure to BV.
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http://dx.doi.org/10.1002/cncr.31755DOI Listing
January 2019

The Impact of Advanced Patient Age on Mortality after Allogeneic Hematopoietic Cell Transplantation for Non-Hodgkin Lymphoma: A Retrospective Study by the European Society for Blood and Marrow Transplantation Lymphoma Working Party.

Biol Blood Marrow Transplant 2019 01 13;25(1):86-93. Epub 2018 Sep 13.

Medical Clinic V, University of Heidelberg, Heidelberg, Germany.

More than 60% of patients with non-Hodgkin lymphoma (NHL) are age >60 years at presentation. The purpose of this study was to compare the potential risks and benefits of allogeneic hematopoietic cell transplantation (alloHCT) in elderly patients with NHL with younger patients in a large sample, also taking into account comorbidity information. All patients age ≥18 years who had undergone alloHCT from a matched sibling or unrelated donor for NHL between 2003 and 2013 and were registered with the European Society for Blood and Marrow Transplantation were eligible for the study. The primary study endpoint was 1-year nonrelapse mortality (NRM). A total of 3919 patients were eligible and were categorized by age: young (Y), 18 to 50 y (n = 1772); middle age (MA), 51 to 65 y (n = 1967); or old (O), 66 to 77 y (n = 180). Follicular lymphoma was present in 37% of the patients; diffuse large B cell lymphoma, in 30%; mantle cell lymphoma, in 21%, and peripheral T cell lymphoma, in 11%. At the time of alloHCT, 85% of the patients were chemosensitive and 15% were chemorefractory. With a median follow-up of 4.5 years in survivors, NRM at 1 year was 13% for the Y group. 20% for the MA group, and 33% for the O group (P <.001), whereas relapse incidence and overall survival (OS) at 3 years in the 3 groups were 30%, 31%, and 28% (P = .355) and 60%, 54%, and 38% (P <.001), respectively. Multivariable adjustment for confounders, including sex, NHL subset, time from diagnosis, chemosensitivity, donor, and conditioning, confirmed older age as a significant predictor for NRM and OS, but not for relapse risk. Although comorbidity was a significant predictor of NRM in a subset analysis restricted to the 979 patients with comorbidity information available, age retained its significant impact on NRM. In conclusion, our data show that alloHCT in patients age >65 y provides similar NHL control as seen in younger patients but is associated with a higher NRM that is not fully explained by comorbidity. Thus, although alloHCT is feasible and effective in very old patients, the increased NRM risk must be taken into account when assessing the indication for alloHCT for NHL in this age group.
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http://dx.doi.org/10.1016/j.bbmt.2018.08.025DOI Listing
January 2019

Conditioning intensity in secondary AML with prior myelodysplastic syndrome/myeloproliferative disorders: an EBMT ALWP study.

Blood Adv 2018 08;2(16):2127-2135

European Blood and Marrow Transplant Paris Study Office/CEREST-TC, Paris, France.

Patients with secondary AML (sAML) with antecedent myelodysplastic syndrome (MDS) or myeloproliferative neoplasms (MPNs) tend to have high-risk disease based on the older age of patients, high-risk cytogenetics, and higher number of prior treatments. Allogeneic hematopoietic cell transplant (HCT) is the only potentially curative therapy available. Eight hundred and two adults with sAML and prior MDS/MPN who received a first HCT between 2000 and 2016 were included in the European Society for Blood and Marrow Transplant (EBMT) Acute Leukemia Working Party (ALWP) study. Median age of the cohort was 59.6 years (range, 18.6-78.6 years). Myeloablative conditioning (MAC) was given to 40% of patients, and 60% received reduced-intensity conditioning (RIC). Overall, the 2-year cumulative incidence of relapse (RI) was 37%, leukemia-free survival (LFS) was 40%, overall survival (OS) was 46%, nonrelapse mortality (NRM) was 23%, and chronic graft-versus-host disease (cGVHD) was 39%. In univariate analysis, a statistical difference between conditioning regimens 6 months after HCT in favor of the MAC group was noted with regard to RI (hazard ratio [HR], 1.47; = .03), LFS (HR, 1.43; = .01), and OS (HR, 1.55; < .05). There was no difference in the cumulative incidence of NRM (HR, 1.38; = .15). This effect was similarly seen in multivariate analysis (MVA): cumulative incidence of relapse (HR, 1.79; < .05), LFS (HR, 1.43; = .02), and OS (HR, 1.53; = .005) with no difference in NRM (HR, 1; = .98). This EBMT ALWP analysis suggests that long-term survival can be achieved in patients with sAML with antecedent MDS/MPN and that MAC is a suitable conditioning regimen in patients with sAML.
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http://dx.doi.org/10.1182/bloodadvances.2018019976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6113606PMC
August 2018

Correction to: Withholding or withdrawing of life-sustaining therapy in older adults (≥ 80 years) admitted to the intensive care unit.

Intensive Care Med 2018 09;44(9):1598-1601

Department of Intensive Care, University Medical Center, University Utrecht, Utrecht, The Netherlands.

In the original publication Dr Patrick Meybohm of the Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, Frankfurt University Hospital, Frankfurt, Germany was inadvertently omitted from the list of investigators.
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http://dx.doi.org/10.1007/s00134-018-5312-8DOI Listing
September 2018

High-dose therapy and autologous stem cell transplantation in marginal zone lymphomas: a retrospective study by the EBMT Lymphoma Working Party and FIL-GITMO.

Br J Haematol 2018 09 9;182(6):807-815. Epub 2018 Jul 9.

Ospedale degli Infermi, Biella, Italy.

The role of autologous stem cell transplantation (ASCT) in patients with marginal zone lymphoma (MZL) is debatable. This study investigated the outcome and prognostic factors affecting the outcome of patients undergoing ASCT for MZL. Eligible patients had non-transformed nodal, extra-nodal (MALT) or splenic MZL (SMZL), aged ≥18 years, who underwent a first ASCT between1994 and 2013 and were reported to the European Society for Blood and Marrow Transplantation, Fondazione Italiana Linfomi or Gruppo Italiano Trapianto Di Midollo Osseo registries. The study included 199 patients, [111 MALT lymphoma, 55 nodal MZL (NMZL) and 33 SMZL]. Median age at transplantation was 56 years. The median number of prior therapies was 2 (range 1-8), including rituximab in 71%. 95% had chemosensitive disease. 89% received a chemotherapy-based high-dose regimen. There were no significant differences in patient and transplant characteristics between the 3 histological subtypes except for a lower percentage of patients previously treated with rituximab in the MALT sub-group and more transplants performed in recent years in the other sub-groups. After a median follow-up of 5 years, 5-year cumulative incidence of relapse/progression and non-relapse mortality were 38% and 9%, respectively. Five-year event-free survival (EFS) and overall survival (OS) were 53% and 73%, respectively. Five-year cumulative incidence of second malignancies was 6%. Multivariate analysis revealed age ≥65 years was associated with a shorter EFS and OS. In addition, patients with SMZL had a shorter OS than those with MALT. ASCT may provide clinical benefit in MZL patients who have failed multiple lines of chemoimmunotherapy.
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http://dx.doi.org/10.1111/bjh.15454DOI Listing
September 2018

High-dose therapy with BEAC conditioning compared to BEAM conditioning prior to autologous stem cell transplantation for non-Hodgkin lymphoma: no differences in toxicity or outcome. A matched-control study of the EBMT-Lymphoma Working Party.

Bone Marrow Transplant 2018 12 8;53(12):1553-1559. Epub 2018 Jun 8.

St Bartholomew's Hospital, Bart's Health NHS Trust, London, UK.

A recent shortage of melphalan has prompted the use of alternatives to BEAM (BCNU, Etoposide, Cytarabine, Melphalan) conditioning for autologous stem cell transplantion (ASCT). The BEAC (BCNU, Etoposide, Cytarabine, Cyclophosphamide) regimen has been employed as a conditioning regimen in lymphoma patients. However, there have been recent concerns about the toxicity of BEAC. We conducted a retrospective analysis of the EBMT database comparing the outcome of patients conditioned using BEAC with a matched cohort of patients conditioned with BEAM. In the BEAC cohort (n = 383), 25 patients died from non-relapse mortality (NRM) events (32% owing to MOF or cardiac toxicity). In the BEAM cohort (n = 766) there were 34 NRM events (23% owing to MOF or cardiac toxicity). The 1-year cumulative incidence of NRM was 4% in the BEAC cohort and 3% in the BEAM group (p = ns). The 2-year relapse/progression rate was 32% with BEAC and 33% with BEAM (p = ns). At 2 years the progression-free survival (PFS) and overall survival (OS) were 63% and 78% for BEAC and 63% and 77% for BEAM-conditioned patients (p = ns for PFS and OS). The toxicity observed with BEAC conditioning as measured by NRM was similar to that seen with BEAM. The outcomes following BEAC were similar to those seen with BEAM, suggesting that BEAC is a safe conditioning regimen.
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http://dx.doi.org/10.1038/s41409-018-0196-3DOI Listing
December 2018

Withholding or withdrawing of life-sustaining therapy in older adults (≥ 80 years) admitted to the intensive care unit.

Intensive Care Med 2018 07 17;44(7):1027-1038. Epub 2018 May 17.

Department of Intensive Care, University Medical Center, University Utrecht, Utrecht, The Netherlands.

Purpose: To document and analyse the decision to withhold or withdraw life-sustaining treatment (LST) in a population of very old patients admitted to the ICU.

Methods: This prospective study included intensive care patients aged ≥ 80 years in 309 ICUs from 21 European countries with 30-day mortality follow-up.

Results: LST limitation was identified in 1356/5021 (27.2%) of patients: 15% had a withholding decision and 12.2% a withdrawal decision (including those with a previous withholding decision). Patients with LST limitation were older, more frail, more severely ill and less frequently electively admitted. Patients with withdrawal of LST were more frequently male and had a longer ICU length of stay. The ICU and 30-day mortality were, respectively, 29.1 and 53.1% in the withholding group and 82.2% and 93.1% in the withdrawal group. LST was less frequently limited in eastern and southern European countries than in northern Europe. The patient-independent factors associated with LST limitation were: acute ICU admission (OR 5.77, 95% CI 4.32-7.7), Clinical Frailty Scale (CFS) score (OR 2.08, 95% CI 1.78-2.42), increased age (each 5 years of increase in age had a OR of 1.22 (95% CI 1.12-1.34) and SOFA score [OR of 1.07 (95% CI 1.05-1.09 per point)]. The frequency of LST limitation was higher in countries with high GDP and was lower in religious countries.

Conclusions: The most important patient variables associated with the instigation of LST limitation were acute admission, frailty, age, admission SOFA score and country.

Trial Registration: ClinicalTrials.gov (ID: NTC03134807).
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http://dx.doi.org/10.1007/s00134-018-5196-7DOI Listing
July 2018

Ibrutinib for bridging to allogeneic hematopoietic cell transplantation in patients with chronic lymphocytic leukemia or mantle cell lymphoma: a study by the EBMT Chronic Malignancies and Lymphoma Working Parties.

Bone Marrow Transplant 2019 01 4;54(1):44-52. Epub 2018 May 4.

EBMT Chronic Malignancies Working Party, Leiden, Netherlands.

The aim of this retrospective study was to investigate the safety and efficacy of allogeneic hematopoietic cell transplantation (alloHCT) in patients pre-treated with ibrutinib. Eligible were patients aged >18 years allotransplanted for chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL) after prior exposure to ibrutinib who were registered with the EBMT registry. Seventy patients (CLL 48, MCL 22) were included. At the time of alloHCT, 73% of the patients were ibrutinib responsive. All patients except one engrafted, and acute GVHD grade 2-4 (3-4) was observed in 49% (12%) of 68 evaluable patients. The cumulative incidence of chronic GVHD was 54% 1 year after transplant. In the CLL group, 12-month non-relapse mortality, relapse incidence (RI), progression-free survival (PFS), and overall survival (OS) were 10, 30, 60, and 72%, respectively, and in the MCL group 5, 19, 76, and 86%, respectively. Pre-transplant ibrutinib failure and poor performance status predicted inferior RI, PFS and OS in the CLL group. In conclusion, ibrutinib does not affect the safety of a subsequent alloHCT. While the relatively high post-transplant relapse risk in ibrutinib-exposed patients with CLL deserves further study, in patients with MCL consolidating disease responses to ibrutinib with alloHCT seems to be a promising option.
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http://dx.doi.org/10.1038/s41409-018-0207-4DOI Listing
January 2019

Transplant Outcomes for Secondary Acute Myeloid Leukemia: Acute Leukemia Working Party of the European Society for Blood and Bone Marrow Transplantation Study.

Biol Blood Marrow Transplant 2018 07 17;24(7):1406-1414. Epub 2018 Apr 17.

EBMT Paris study office/CEREST-TC, Paris, France; Hematology Division, Chaim Sheba Medical Center, Tel Hashomer, Israel.

Secondary acute myeloid leukemia (sAML) has been associated with inferior outcomes compared with de novo AML. Little is known about patient risk factors and outcomes in sAML after allogeneic hematopoietic stem cell transplantation (HCT); thus, this large systemic analysis of the European Society for Blood and Bone Marrow Transplantation registry was performed. This study included 4997 patients with sAML who received HCT from 2000 to 2016. In univariate analysis the 2-year cumulative incidence of chronic graft-versus-host disease (GVHD), relapse, and nonrelapse mortality (NRM) were 33.5% (95% confidence interval [CI], 32% to 34.9%), 33.7% (95% CI, 32.3% to 35.1%), and 27.5% (95% CI, 26.1% to 28.7%), respectively. Overall survival (OS), leukemia-free survival (LFS), and GVHD-free, relapse-free survival (GRFS) at 2 years were 44.5% (95% CI, 43% to 46%), 38.8% (95% CI, 37.4% to 40.3%), and 27.2% (95% CI, 25.9% to 28.6%), respectively. In multivariate analysis, patients receiving myeloablative regimens had decreased relapse (hazard ratio, .859; 95% CI, .761 to .97; P = .01), higher NRM (hazard ratio, 1.175; 95% CI, 1.03 to 1.341; P = .02), and no differences in OS, LFS, and GRFS compared with patients receiving reduced-intensity conditioning regimens. Active disease, adverse cytogenetics, older age, Karnofsky performance status (≤80%), ex vivo T cell depletion, other malignant hematologic diseases, and patient cytomegalovirus seropositivity were associated with inferior OS and LFS. These variables should be considered in patients with sAML in need of HCT, and further study regarding the impact of conditioning regimens on relapse is needed.
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http://dx.doi.org/10.1016/j.bbmt.2018.04.008DOI Listing
July 2018