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A Primed Neutrophil Subset Predicts the Risk of Bloodstream Infections in Allo-HSCT Patients: A Prospective Study
Elebyary, O., Fine, N., Sun, C., Saha, S. T., Robinson, S., Mojdami, Z. D., Khoury, N., Watson, E., Coburn, B., Lipton, J. H., et al
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2023
Abstract
BACKGROUND Bloodstream infections (BSI) are the most common infectious complications in patients receiving allogeneic hematopoietic stem-cell transplants (allo-HSCT). Polymorphonuclear neutrophils (PMN) are quantified to monitor the susceptibility to BSIs, however, their degree of activation is not. We previously identified a population of primed PMNs (pPMN) with distinct markers of activation representing ∼10% of PMNs in the circulation. In this study, we investigate whether susceptibility to BSIs is related to the proportion of pPMN rather than strictly PMN counts. METHODS In this prospective observational study, we used flow cytometry to assess pPMNs in blood and oral rinse samples collected from patients receiving an allo-HSCT over the course of their treatment. We used the proportion of pPMNs in the blood on day five post-transplant to categorize patients into a high- or a low-pPMN group (> or <10% pPMNs). These groups were then used as a predictor of BSIs. RESULTS A total of 76 patients were enrolled in the study with 36 in the high-pPMN group and 40 in the low-pPMN group. Patients in the low-pPMN group had lower expression of PMN activation and recruitment markers and displayed a delay in PMN repopulation of the oral cavity after the transplant. These patients were more susceptible to BSI compared to patients in the high-pPMN group with an odds ratio of 6.5 (95% CI= 2.110-25.07, P= 0.002). CONCLUSION In patients receiving an allo-HSCT, having less than 10% pPMNs early in the post-transplant phase can be an independent predictor of BSI in allo-HSCT patients.
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Improved outcome of patients with graft-versus-host disease after allogeneic hematopoietic cell transplantation for hematologic malignancies over time: an EBMT mega-file study
Greinix, H. T., Eikema, D. J., Koster, L., Penack, O., Yakoub-Agha, I., Montoto, S., Chabannon, C., Styczynski, J., Nagler, A., Robin, M., et al
Haematologica. 2021
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Editor's Choice
Abstract
Acute graft-versus-host disease (aGvHD) remains a major threat to successful outcome after allogeneic hematopoietic cell transplantation. Advances in prophylaxis and supportive care have taken place over the years. The aim of this study is to test whether incidence and mortality of aGvHD have been reduced over time. 102 557 patients with a median age of 47.6 years with malignancies after first allogeneic sibling or unrelated donor (URD) transplant were studied in the following periods: 1990-1995, 1996-2000, 2001-2005, 2006-2010, 2011-2015. Findings: 100-day-incidences of aGvHD grades II-IV decreased from 40%, to 38%, 32%, 29% and 28% over calendar time (p.
PICO Summary
Population
Patients undergoing first allogeneic sibling or unrelated donor transplant (URD) between 1990 and 2015 (n=102 557)
Intervention
Registry data study assessing incidence of acute GvHD (aGvHD)
Comparison
Patients were compared in the following time periods: 1990-1995, 1996-2000, 2001-2005, 2006-2010, 2011-2015
Outcome
In multivariate analysis URD, not in CR at transplant or untreated, and female donor for male recipient were associated with increased risk whereas use of ATG/alemtuzumab decreased aGvHD incidence. Median follow-up was 214, 169, 127, 81 and 30 months for periods analyzed. 3-year-survival after aGvHD grades II-IV increased significantly from 38% to 40%, 43%, 44%, and 45%. In multivariate analysis URD, not in CR at transplant, peripheral blood as stem cell source, female donor for male recipient, and use of ATG/alemtuzumab were associated with increased mortality whereas reduced-intensity conditioning with lower one. Mortality increased with increasing patients‘ age but decreased in the recent cohorts.
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Long-term outcome of patients receiving haematopoietic allogeneic stem cell transplantation as first transplant for high-risk Hodgkin lymphoma: a retrospective analysis from the Lymphoma Working Party-EBMT
Gutiérrez-García, G., Martínez, C., Boumendil, A., Finel, H., Malladi, R., Afanasyev, B., Tsoulkani, A., Wilson, K. M. O., Bloor, A., Nikoloudis, M., et al
British journal of haematology. 2021
Abstract
We analysed long-term outcome of patients receiving haematopoietic allogeneic stem cell transplantation (allo-HSCT) as a first transplant for high-risk Hodgkin lymphoma (HL). One hundred and ninety patients were included in this study, 63% of them had previously received brentuximab vedotin and/or checkpoint inhibitors. Seventy patients (37%) received an unrelated donor allo-HSCT, 99 (51%) had myeloablative conditioning (MAC) and 60% had in?vivo T-cell/depleted grafts (TCD). The 100-day cumulative incidence (CI) of grade II-IV acute graft-versus-host disease (GVHD) was 25% and the 3-year CI of chronic GVHD was 38%. The 3-year CI of non-relapse mortality (NRM) and relapse rate were 21% and 38% respectively. After a median follow-up of 58?months, 3-year overall survival (OS) and progression-free survival (PFS) were 58% and 41% respectively. Multivariate analysis showed that, in comparison to reduced-intensity conditioning regimens with or without TCD, MAC using TCD had similar NRM and a lower risk of relapse leading to significantly better OS and PFS. MAC without TCD was associated with higher NRM and worse survival outcomes. These results suggest that in patients with high-risk HL and candidates of allo-HSCT, a MAC strategy with TCD might be the best option.
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Measurable residual disease status and outcome of transplant in acute myeloid leukemia in second complete remission: a study by the acute leukemia working party of the EBMT
Gilleece, M. H., Shimoni, A., Labopin, M., Robinson, S., Beelen, D., Socié, G., Unal, A., Ganser, A., Vitek, A., Sengeloev, H., et al
Blood cancer journal. 2021;11(5):88
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Editor's Choice
Abstract
Measurable residual disease (MRD) prior to hematopoietic cell transplant (HCT) for acute myeloid leukemia (AML) in first complete morphological remission (CR1) is an independent predictor of outcome, but few studies address CR2. This analysis by the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation registry assessed HCT outcomes by declared MRD status in a cohort of 1042 adult patients with AML CR2 at HCT. Patients were transplanted 2006-2016 from human leukocyte antigen (HLA) matched siblings (n?=?719) or HLA 10/10 matched unrelated donors (n?=?293). Conditioning was myeloablative (n?=?610) or reduced-intensity (n?=?432) and 566 patients (54%) had in-vivo T cell depletion. At HCT, 749 patients (72%) were MRD negative (MRD NEG) and 293 (28%) were MRD positive (MRD POS). Time from diagnosis to HCT was longer in MRD NEG than MRD POS patients (18 vs. 16 months (P?0.001). Two-year relapse rates were 24% (95% CI, 21-28) and 40% (95% CI, 34-46) in MRD NEG and MRD POS groups (P?0.001), respectively. Leukemia-free survival (LFS) was 57% (53-61) and 46% (40-52%), respectively (P?=?0.001), but there was no difference in terms of overall survival. Prognostic factors for relapse and LFS were MRD NEG status, good risk cytogenetics, and longer time from diagnosis to HCT. In-vivo T cell depletion predicted relapse.
PICO Summary
Population
Patients with AML who were transplanted in second complete remission (CR2) at transplant (n=1042)
Intervention
Patients who were minimal disease negative (MRD NEG, n=749)
Comparison
Patients who were minimal disease positive (MRD POS, n=293)
Outcome
Time from diagnosis to HCT was longer in MRD NEG than MRD POS patients (18 vs. 16 months). Two-year relapse rates were 24% and 40% in MRD NEG and MRD POS groups, respectively. Leukemia-free survival (LFS) was 57% and 46%, respectively, but there was no difference in terms of overall survival. Prognostic factors for relapse and LFS were MRD NEG status, good risk cytogenetics, and longer time from diagnosis to HCT. In-vivo T cell depletion predicted relapse.
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Impact of detectable measurable residual disease on umbilical cord blood transplantation
Baron, F., Labopin, M., Ruggeri, A., Sierra, J., Robinson, S., Labussiere-Wallet, H., Potter, M., Ribera, J. M., Deconinck, E., Rambaldi, A., et al
American journal of hematology. 2020
Abstract
The impact of measurable residual disease (MRD) on cord blood transplantation (CBT) outcomes has remained debated. To address this issue, we assessed the impact of measurable MRD at CBT on outcomes in large cohort of patients with acute leukemia. Inclusion criteria included adult patients with acute myeloid (AML) or acute lymphoblastic leukemia (ALL), CBT as first allo-HCT in first or second complete remission (CR) at transplantation, and known MRD status at the time of CBT. Data from 506 patients were included in the analysis. Among them, 317 patients had AML and 189 had ALL. Positive MRD was reported in 169 (33%) patients while the remaining 337 patients were MRD negative at CBT. At 2 years, relapse incidence was 18% in patients with MRD negativity versus 33% in those with MRD positivity at transplantation (P<0.001). Two-year leukemia-free survival (LFS) and overall survival (OS) were 57% and 60%, respectively, in MRD negative patients, versus 38% (P<0.001) and 48% (P=0.004), respectively, in those with MRD positivity. There was no interaction between the impact of MRD on OS and LFS and diagnosis (i.e. ALL versus AML), single or double CBT, and reduced-intensity or myeloablative conditioning. On multivariate analysis, MRD positivity was associated with a higher risk of relapse (HR=1.8, P=0.003), comparable non-relapse mortality (P=0.44), worse LFS (HR=1.4, P=0.008) and a trend towards worse OS (HR=1.3, P=0.065). In conclusion, these data suggest that novel strategies that are aiming to achieve MRD negativity at CBT are needed for leukemic patients with positive MRD pre-CBT. This article is protected by copyright. All rights reserved.