Publications by authors named "Hélène Schoemans"

51 Publications

National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: IIa. The 2020 Clinical Implementation and Early Diagnosis Working Group Report: NIH cGVHD WG2a.

Transplant Cell Ther 2021 Apr 8. Epub 2021 Apr 8.

Division of Stem Cell Transplantation and Cellular Therapy, Dana-Farber Cancer Institute, Boston, MA, USA.

Recognition of the earliest signs and symptoms of chronic graft versus host disease (GVHD) that lead to severe manifestations remains a challenge. The standardization provided by the National Institutes of Health (NIH) 2005 and 2014 consensus projects have helped improve diagnostic accuracy and severity scoring for clinical trials, but utilization of these tools in routine clinical practice is variable. Additionally, when patients meet the NIH diagnostic criteria, many already have significant morbidity and possibly irreversible organ damage. The goals of this early diagnosis project are two fold. First, we provide consensus recommendations regarding implementation of the current NIH diagnostic guidelines into routine transplant care, outside of clinical trials, aiming to enhance early clinical recognition of chronic GVHD. Second, we propose directions for future research efforts to enable discovery of new, early laboratory as well as clinical indicators of chronic GVHD, both globally and for highly morbid organ-specific manifestations. Identification of early features of chronic GVHD that have high positive predictive value for progression to more severe manifestations of the disease could potentially allow for future pre-emptive clinical trials.
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http://dx.doi.org/10.1016/j.jtct.2021.03.033DOI Listing
April 2021

National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: IIb. The 2020 Preemptive Therapy Working Group Report.

Transplant Cell Ther 2021 Apr 6. Epub 2021 Apr 6.

Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.

Background: Chronic graft-versus-host disease (GVHD) commonly occurs after allogeneic hematopoietic cell transplantation (HCT) despite standard prophylactic immune suppression. Intensified universal prophylaxis approaches are effective but risk possible over-treatment and may interfere with the graft-vs-malignancy immune response.

Objectives: We summarize conceptual and practical considerations regarding preemptive therapy of chronic GVHD, namely interventions applied after HCT based on evidence that the risk of developing chronic GVHD is higher than previously appreciated. This risk may be anticipated by clinical factors or risk assignment biomarkers or may be indicated by early signs and symptoms of chronic GVHD that do not fully meet NIH diagnostic criteria. However, truly preemptive, individualized, and targeted chronic GVHD therapies currently do not exist.

Study Design And Results: The goals of this report are to (1) review current knowledge regarding clinical risk factors for chronic GVHD; (2) review what is known about chronic GVHD risk assignment biomarkers; (3) examine how chronic GVHD pathogenesis intersects with available targeted therapeutic agents; and (4) summarize considerations for preemptive therapy for chronic GVHD, emphasizing trial development including trial design and statistical considerations.

Conclusions: We conclude that robust risk assignment models that accurately predict chronic GVHD after HCT and early phase preemptive therapy trials represent the most urgent priorities to advance this novel area of research.
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http://dx.doi.org/10.1016/j.jtct.2021.03.029DOI Listing
April 2021

Addition of Rituximab in Reduced Intensity Conditioning Regimens for B-Cell Malignancies Does Not Influence Transplant Outcomes: EBMT Registry Analyses Following Allogeneic Stem Cell Transplantation for B-Cell Malignancies.

Front Immunol 2020 2;11:613954. Epub 2021 Feb 2.

Department of Hematology, Transplantology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland.

Rituximab (R) is increasingly incorporated in reduced intensity conditioning (RIC) regimens for allogeneic hematopoietic cell transplantation (alloHCT) in patients with B-cell malignancies, not only to improve disease control, but also to prevent graft-versus-host disease (GVHD). There are no randomized prospective data to validate this practice, although single center data and the CIBMTR analysis have shown promising results. We aimed at validation of these findings in a large registry study. We conducted a retrospective analysis using the EBMT registry of 3,803 adult patients with B-cell malignancies undergoing alloHCT (2001-2013) with either rituximab (R-RIC-9%) or non-rituximab (RIC-91%) reduced intensity regimens respectively. Median age and median follow up were 55 years (range 19.1-77.3) and 43.2 months (range 0.3-179.8), respectively. There was no difference in transplant outcomes (R-RIC vs RIC), including 1-year overall survival (69.9% vs 70.7%), 1-year disease-free survival (64.4% vs 62.2%), 1-year non-relapse mortality (21% vs 22%), and day-100 incidence of acute GVHD 2-4° (12% vs 12%). In summary, we found that addition of rituximab in RIC regimens for B-cell malignancies had no significant impact on major transplant outcome variables. Of note, data on chronic GVHD was not available, limiting the conclusions that can be drawn from the present study.
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http://dx.doi.org/10.3389/fimmu.2020.613954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884746PMC
February 2021

Systematic reviews in hematopoietic cell transplantation and cellular therapy: considerations and guidance from the American Society for Transplantation and Cellular Therapy, European Society for Blood and Marrow Transplantation, and the Center for International Blood and Marrow Transplant Research late effects and quality of life working committee.

Bone Marrow Transplant 2021 Apr 29;56(4):786-797. Epub 2021 Jan 29.

Center for International Blood and Marrow Transplant Research, Milwaukee, WI, USA.

Systematic reviews apply rigorous methodologies to address a pre-specified, clearly formulated clinical research question. The conclusion that results is often cited to more robustly inform decision-making by clinicians, third-party payers and managed care organizations about the clinical question of interest. While systematic reviews provide a rigorous standard, they may be unfeasible when the task is to create general disease-focused guidelines comprised of multiple clinical practice questions versus a single major clinical practice question. Collaborating transplantation and cellular therapy societal committees also recognize that the quantity and or quality of reference sources may be insufficient for a meaningful systematic review. As the conduct of systematic reviews has evolved over time in terms of grading systems, reporting requirements and use of technology, here we provide current guidance in methodologies, resources for reviewers, and approaches to overcome challenges in conducting systematic reviews in transplantation and cellular therapy.
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http://dx.doi.org/10.1038/s41409-020-01199-1DOI Listing
April 2021

How much has allogeneic stem cell transplant-related mortality improved since the 1980s? A retrospective analysis from the EBMT.

Blood Adv 2020 12;4(24):6283-6290

European Society for Blood and Marrow Transplantation (EBMT) Transplant Complications Working Party, Paris, France.

We performed a study to find out how advances in modern medicine have improved the mortality risk of allogeneic stem cell transplantation. We analyzed major transplantation outcome parameters in adult patients on the European Society for Blood and Marrow Transplantation (EBMT) registry who had hematologic malignancies and had received transplants from matched sibling donors. We performed multivariate analyses using the Cox proportional-hazards model including known risk factors for nonrelapse mortality and a matched-pairs analysis. We identified 38 800 patients who fulfilled the inclusion criteria. Considerable changes in patient characteristics have occurred in the past decades, such as older age, different underlying diseases, and a higher proportion of patients with advanced disease. Major reasons for transplantation-related death in the 1980s were infectious complications and graft-versus-host disease. Nonrelapse mortality, measured at 1 year after transplantation, has decreased over time: 29.7% from 1980 through 1989, 24.4% from 1990 through 1999, 14.8% from 2000 through 2009, and 12.2% from 2010 through 2016. On multivariate analysis, the year of transplantation was associated with reduced nonrelapse mortality (P < .0001; hazard ratio [HR] [95% confidence interval (CI)], 0.8 [0.79-0.82], for 5-year intervals) and decreased overall mortality (P < .0001; HR [95% CI], 0.87 [0.86-0.88]. In the matched-pairs analysis of 3718 patients in each group, nonrelapse mortality at 1 year was 24.4% in the 1990s and 9.5% from 2013 through 2016 (P < .0001; HR [95% CI], 0.39 [0.34-0.43]). Transplantation-related mortality has decreased significantly in the past 40 years. These favorable data facilitate evidence-based treatment decisions on transplantation indications in the context of the availability of novel immunotherapies.
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http://dx.doi.org/10.1182/bloodadvances.2020003418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756984PMC
December 2020

miR-15a-5p and miR-21-5p contribute to chemoresistance in cytogenetically normal acute myeloid leukaemia by targeting PDCD4, ARL2 and BTG2.

J Cell Mol Med 2021 Jan 3;25(1):575-585. Epub 2020 Dec 3.

Department of Hematology, Cliniques Universitaires Saint-Luc, Brussels, Belgium.

Cytarabine and daunorubicin are old drugs commonly used in the treatment of acute myeloid leukaemia (AML). Refractory or relapsed disease because of chemotherapy resistance is a major issue. microRNAs (miRNAs) were incriminated in resistance. This study aimed to identify miRNAs involved in chemoresistance in AML patients and to define their target genes. We focused on cytogenetically normal AML patients with wild-type NPM1 without FLT3-ITD as the treatment of this subset of patients with intermediate-risk cytogenetics is not well established. We analysed baseline AML samples by small RNA sequencing and compared the profile of chemoresistant to chemosensitive AML patients. Among the miRNAs significantly overexpressed in chemoresistant patients, we revealed miR-15a-5p and miR-21-5p as miRNAs with a major role in chemoresistance in AML. We showed that miR-15a-5p and miR-21-5p overexpression decreased apoptosis induced by cytarabine and/or daunorubicin. PDCD4, ARL2 and BTG2 genes were found to be targeted by miR-15a-5p, as well as PDCD4 and BTG2 by miR-21-5p. Inhibition experiments of the three target genes reproduced the functional effect of both miRNAs on chemosensitivity. Our study demonstrates that miR-15a-5p and miR-21-5p are overexpressed in a subgroup of chemoresistant AML patients. Both miRNAs induce chemoresistance by targeting three pro-apoptotic genes PDCD4, ARL2 and BTG2.
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http://dx.doi.org/10.1111/jcmm.16110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810923PMC
January 2021

How to Make an Immune System and a Foreign Host Quickly Cohabit in Peace? The Challenge of Acute Graft--Host Disease Prevention After Allogeneic Hematopoietic Cell Transplantation.

Front Immunol 2020 21;11:583564. Epub 2020 Oct 21.

Laboratory of Hematology, GIGA-I3, GIGA Institute, University of Liège, Liège, Belgium.

Allogeneic hematopoietic cell transplantation (alloHCT) has been used as cellular immunotherapy against hematological cancers for more than six decades. Its therapeutic efficacy relies on the cytoreductive effects of the conditioning regimen but also on potent graft--tumor (GVT) reactions mediated by donor-derived immune cells. However, beneficial GVT effects may be counterbalanced by acute GVHD (aGVHD), a systemic syndrome in which donor immune cells attack healthy tissues of the recipient, resulting in severe inflammatory lesions mainly of the skin, gut, and liver. Despite standard prophylaxis regimens, aGVHD still occurs in approximately 20-50% of alloHCT recipients and remains a leading cause of transplant-related mortality. Over the past two decades, advances in the understanding its pathophysiology have helped to redefine aGVHD reactions and clinical presentations as well as developing novel strategies to optimize its prevention. In this review, we provide a brief overview of current knowledge on aGVHD immunopathology and discuss current approaches and novel strategies being developed and evaluated in clinical trials for aGVHD prevention. Optimal prophylaxis of aGVHD would prevent the development of clinically significant aGVHD, while preserving sufficient immune responsiveness to maintain beneficial GVT effects and immune defenses against pathogens.
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http://dx.doi.org/10.3389/fimmu.2020.583564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609863PMC
October 2020

The Role of Flexible Bronchoscopy in Swab-negative Patients During the SARS-CoV2 Pandemic.

J Bronchology Interv Pulmonol 2020 Nov 3. Epub 2020 Nov 3.

Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department CHROMETA, KU Leuven.

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http://dx.doi.org/10.1097/LBR.0000000000000733DOI Listing
November 2020

Community health status and outcomes after allogeneic hematopoietic cell transplantation in the United States.

Cancer 2021 Feb 21;127(4):609-618. Epub 2020 Oct 21.

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

Background: The association of community factors and outcomes after hematopoietic cell transplantation (HCT) has not been comprehensively described. Using the County Health Rankings and Roadmaps (CHRR) and the Center for International Blood and Marrow Transplant Research (CIBMTR), this study evaluated the impact of community health status on allogeneic HCT outcomes.

Methods: This study included 18,544 adult allogeneic HCT recipients reported to the CIBMTR by 170 US centers in 2014-2016. Sociodemographic, environmental, and community indicators were derived from the CHRR, an aggregate community risk score was created, and scores were assigned to each patient (patient community risk score [PCS]) and transplant center (center community risk score [CCS]). Higher scores indicated less healthy communities. The impact of PCS and CCS on patient outcomes after allogeneic HCT was studied.

Results: The median age was 55 years (range, 18-83 years). The median PCS was -0.21 (range, -1.37 to 2.10; standard deviation [SD], 0.42), and the median CCS was -0.13 (range, -1.04 to 0.96; SD, 0.40). In multivariable analyses, a higher PCS was associated with inferior survival (hazard ratio [HR] per 1 SD increase, 1.04; 99% CI, 1.00-1.08; P = .0089). Among hematologic malignancies, a tendency toward inferior survival was observed with a higher PCS (HR, 1.04; 99% CI, 1.00-1.08; P = .0102); a higher PCS was associated with higher nonrelapse mortality (NRM; HR, 1.08; 99% CI, 1.02-1.15; P = .0004). CCS was not significantly associated with survival, relapse, or NRM.

Conclusions: Patients residing in counties with a worse community health status have inferior survival as a result of an increased risk of NRM after allogeneic HCT. There was no association between the community health status of the transplant center location and allogeneic HCT outcomes.
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http://dx.doi.org/10.1002/cncr.33232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855526PMC
February 2021

Evaluation of the Cost of Survivorship Care After Allogeneic Hematopoeitic Stem Cell Transplantation-An Analysis of 2 German Transplantation Centers.

Front Public Health 2020 25;8:572470. Epub 2020 Sep 25.

Department of Stem Cell Transplantation, University Hospital Hamburg-Eppendorf, Hamburg, Germany.

The aim of the presented study was to analyze the care expenditure for outpatients after allogeneic hematopoietic stem cell transplantation (alloHSCT) done in accordance with the national, European guidelines and the German Social Law. We performed an analysis of the National and European survivorship care guidelines and in parallel recorded the time expenditure and staff costs separated according to different occupational groups involved in outpatient care at two German transplantation centers [University Hospital Regensburg (UKR) and University Hospital Hamburg-Eppendorf (UKE)]. In addition, we performed a comparison of real costs vs. reimbursed costs according to the standard rating benchmark catalog (EBM), which was supplemented by a survey of German transplantation centers. The results showed that the staff costs are only covered by the EBM for patients without complications during long-term follow-up care-notably, this accounts for 15% of alloHSCT patients. Staff costs for patients requiring treatment of graft-vs.-host disease or relapse of the malignant underlying malignancy exceed to the factor 6.5 (UKR) to 12 (UKE) of the EBM revenue, caused both by the increased duration and frequency of the outpatient visits. As a result of the survey at German transplant centers, 15 out of 18 responding centers reported a lack of cost coverage for follow-up care. Two/15 centers reported that survivorship care is limited to a restricted time, independent of patient's needs, due to a lack of cost reimbursement. The results show that alloHSCT survivorship care of patients requires significant staff resources, which are not covered by the current version of the German EBM catalog. New approaches to finance labor intensive after care of transplant patients are required.
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http://dx.doi.org/10.3389/fpubh.2020.572470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544947PMC
September 2020

Sexual Functioning in Long-Term Survivors of Hematopoietic Cell Transplantation.

Transplant Cell Ther 2021 Jan 29;27(1):80.e1-80.e12. Epub 2020 Sep 29.

Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Psychiatry and Behavioral Science and Department of Medicine, University of Washington School of Medicine, Seattle, Washington.

This investigation characterized sexual activity and sexual function in hematopoietic cell transplantation (HCT) survivors, compared them with norms, and examined factors associated with sexual dysfunction, with the goal of identifying targets for intervention to improve sexual health. Surviving adults from a large transplantation center were asked to complete an annual survey with a core of health questions and a module on sexual activity and function. Participants completed the Sexual Function Questionnaire, Cancer and Treatment Distress form, and Revised Dyadic Adjustment Scale. Clinical data were collected from the transplantation medical database. Multivariate logistic regressions identified factors associated with sexual activity and function. Participating survivors (n = 1742) were a mean of 11.9 years (range, .4 to 43.1 years) after HCT, mean age 57.6 years, and 53% male. Women were more likely than men to report being sexually inactive in the past year (39% versus 27%) and, among those sexually active, to report low sexual function (64% versus 32%). Male and female survivors reported lower rates of sexual activity and function than comparison norms (all P < .01). In regressions, factors associated with being sexually inactive included older age, having <4 years of college education, low performance status, and not being in a committed relationship. Additional factors for men included receipt of nonmyeloablative conditioning and not being employed or in school. Low sexual functioning for men and women was associated with low performance status, and, for women, a committed relationship of lower quality, while for men the association was with older age. Sexual dysfunction is common in both men and women after HCT, regardless of time since treatment. Survivors need routine evaluation and access to multimodal interventions.
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http://dx.doi.org/10.1016/j.bbmt.2020.09.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005503PMC
January 2021

Reduced Calcium Signaling Is Associated With Severe Graft-Versus-Host Disease: Results From Preclinical Models and From a Prospective EBMT Study.

Front Immunol 2020 11;11:1983. Epub 2020 Aug 11.

Department of Hematology, Oncology, and Tumor Immunology, Charité Universitätsmedizin Berlin, Berlin, Germany.

Despite its involvement in various immune functions, including the allogeneic activation of T-lymphocytes, the relevance of calcium (Ca) for GVHD pathobiology is largely unknown. To elucidate a potential association between Caand GVHD, we analyzed Ca-sensing G-protein coupled receptor 6a (GPRC6a) signaling in preclinical GVHD models and conducted a prospective EBMT study on Ca serum levels prior alloSCT including 363 matched sibling allogeneic peripheral blood stem cell transplantations (alloSCTs). In experimental models, we found decreased expression during intestinal GVHD. GPRC6a deficient alloSCT recipients had higher clinical and histopathological GVHD scores leading to increased mortality. As possible underlying mechanism, we found increased antigen presentation potential in GPRC6a alloSCT recipients demonstrated by higher proliferation rates of T-lymphocytes. In patients with low Ca serum levels (≤median 2.2 mmol/l) before alloSCT, we found a higher incidence of acute GVHD grades II-IV (HR = 2.3 Cl = 1.45-3.85 = 0.0006), severe acute GVHD grades III-IV (HR = 3.3 CI = 1.59-7.14, = 0.002) and extensive chronic GVHD (HR = 2.0 Cl = 1.04-3.85 = 0.04). In conclusion, experimental and clinical data suggest an association of reduced Ca signaling with increased severity of GVHD. Future areas of interest include the in depth analysis of involved molecular pathways and the investigation of Ca signaling as a therapeutic target during GVHD.
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http://dx.doi.org/10.3389/fimmu.2020.01983DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431962PMC
August 2020

Risk Factors for Graft-versus-Host Disease in Haploidentical Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide.

Biol Blood Marrow Transplant 2020 08 17;26(8):1459-1468. Epub 2020 May 17.

Blood & Marrow Transplant Program, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio. Electronic address:

Post-transplant cyclophosphamide (PTCy) has significantly increased the successful use of haploidentical donors with a relatively low incidence of graft-versus-host disease (GVHD). Given its increasing use, we sought to determine risk factors for GVHD after haploidentical hematopoietic cell transplantation (haplo-HCT) using PTCy. Data from the Center for International Blood and Marrow Transplant Research on adult patients with acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or chronic myeloid leukemia who underwent PTCy-based haplo-HCT (2013 to 2016) were analyzed and categorized into 4 groups based on myeloablative (MA) or reduced-intensity conditioning (RIC) and bone marrow (BM) or peripheral blood (PB) graft source. In total, 646 patients were identified (MA-BM = 79, MA-PB = 183, RIC-BM = 192, RIC-PB = 192). The incidence of grade 2 to 4 acute GVHD at 6 months was highest in MA-PB (44%), followed by RIC-PB (36%), MA-BM (36%), and RIC-BM (30%) (P = .002). The incidence of chronic GVHD at 1 year was 40%, 34%, 24%, and 20%, respectively (P < .001). In multivariable analysis, there was no impact of stem cell source or conditioning regimen on grade 2 to 4 acute GVHD; however, older donor age (30 to 49 versus <29 years) was significantly associated with higher rates of grade 2 to 4 acute GVHD (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.11 to 2.12; P = .01). In contrast, PB compared to BM as a stem cell source was a significant risk factor for the development of chronic GVHD (HR, 1.70; 95% CI, 1.11 to 2.62; P = .01) in the RIC setting. There were no differences in relapse or overall survival between groups. Donor age and graft source are risk factors for acute and chronic GVHD, respectively, after PTCy-based haplo-HCT. Our results indicate that in RIC haplo-HCT, the risk of chronic GVHD is higher with PB stem cells, without any difference in relapse or overall survival.
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http://dx.doi.org/10.1016/j.bbmt.2020.05.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391266PMC
August 2020

Composite GRFS and CRFS Outcomes After Adult Alternative Donor HCT.

J Clin Oncol 2020 06 4;38(18):2062-2076. Epub 2020 May 4.

University of Minnesota, Minneapolis, MN.

Purpose: There is no consensus on the best choice of an alternative donor (umbilical cord blood [UCB], haploidentical, one-antigen mismatched [7/8]-bone marrow [BM], or 7/8-peripheral blood [PB]) for hematopoietic cell transplantation (HCT) for patients lacking an HLA-matched related or unrelated donor.

Methods: We report composite end points of graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) and chronic GVHD (cGVHD)-free relapse-free survival (CRFS) in 2,198 patients who underwent UCB (n = 838), haploidentical (n = 159), 7/8-BM (n = 241), or 7/8-PB (n = 960) HCT. All groups were divided by myeloablative conditioning (MAC) intensity or reduced intensity conditioning (RIC), except haploidentical group in which most received RIC. To account for multiple testing, < .0071 in multivariable analysis and < .00025 in direct pairwise comparisons were considered statistically significant.

Results: In multivariable analysis, haploidentical group had the best GRFS, CRFS, and overall survival (OS). In the direct pairwise comparison of other groups, among those who received MAC, there was no difference in GRFS or CRFS among UCB, 7/8-BM, and 7/8-PB with serotherapy (alemtuzumab or antithymocyte globulin) groups. In contrast, the 7/8-PB without serotherapy group had significantly inferior GRFS, higher cGVHD, and a trend toward worse CRFS (hazard ratio [HR], 1.38; 95% CI, 1.13 to 1.69; = .002) than the 7/8-BM group and higher cGVHD and trend toward inferior CRFS (HR, 1.36; 95% CI, 1.14 to 1.63; = .0006) than the UCB group. Among patients with RIC, all groups had significantly inferior GRFS and CRFS compared with the haploidentical group.

Conclusion: Recognizing the limitations of a registry retrospective analysis and the possibility of center selection bias in choosing donors, our data support the use of UCB, 7/8-BM, or 7/8-PB (with serotherapy) grafts for patients undergoing MAC HCT and haploidentical grafts for patients undergoing RIC HCT. The haploidentical group had the best GRFS, CRFS, and OS of all groups.
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http://dx.doi.org/10.1200/JCO.19.00396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7302955PMC
June 2020

Use of chimerism analysis after allogeneic stem cell transplantation: Belgian guidelines and review of the current literature.

Acta Clin Belg 2020 May 2:1-9. Epub 2020 May 2.

Department of Hematology, University Hospital, Ghent University, Ghent, Belgium.

Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment option in both adult and pediatric patients with malignant and non-malignant hematological diseases.  Chimerism analysis, which determines the donor or recipient origin of hematopoietic cells in HSCT recipients, is an essential aspect of post-HSCT follow-up. To review the current literature and develop Belgian consensus guidelines for the use of chimerism analysis in the standard of care after allogeneic HSCT.: Non-systematic review of the literature in consultancy with the members of the BHS transplantation committee.: Clinical application with regards to prediction of graft failure or relapse as well as cell source are reviewed. A consensus guideline on the use of chimerism analysis after HSCT is presented.: Monitoring of the dynamics or kinetics of a patient's chimerism status by serial analysis at fixed time points, as well as on suspicion of relapse or graft failure, is needed to monitor engraftment levels, as well as disease control and possible relapse.
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http://dx.doi.org/10.1080/17843286.2020.1754635DOI Listing
May 2020

Association of Serum Ferritin Levels Before Start of Conditioning With Mortality After alloSCT - A Prospective, Non-interventional Study of the EBMT Transplant Complications Working Party.

Front Immunol 2020 15;11:586. Epub 2020 Apr 15.

Department of Hematology and Oncology, Medical University of Warsaw, Warsaw, Poland.

Elevated serum ferritin levels occur due to iron overload or during inflammation and macrophage activation. A correlation of high serum ferritin levels with increased mortality after alloSCT has been suggested by several retrospective analyses as well as by two smaller prospective studies. This prospective multicentric study aimed to study the association of ferritin serum levels before start of conditioning with alloSCT outcome. Patients with acute leukemia, lymphoma or MDS receiving a matched sibling alloSCT for the first time were considered for inclusion, regardless of conditioning. A comparison of outcomes between patients with high and low ferritin level was performed using univariate analysis and multivariate analysis using cause-specific Cox model. Twenty centers reported data on 298 alloSCT recipients. The ferritin cut off point was determined at 1500 μg/l (median of measured ferritin levels). In alloSCT recipients with ferritin levels above cut off measured before the start of conditioning, overall survival (HR = 2.5, CI = 1.5-4.1, = 0.0005) and progression-free survival (HR = 2.4, CI = 1.6-3.8, < 0.0001) were inferior. Excess mortality in the high ferritin group was due to both higher relapse incidence (HR = 2.2, CI = 1.2-3.8, = 0.007) and increased non-relapse mortality (NRM) (HR = 3.1, CI = 1.5-6.4, = 0.002). NRM was driven by significantly higher infection-related mortality in the high ferritin group (HR = 3.9, CI = 1.6-9.7, = 0.003). Acute and chronic GVHD incidence or severity were not associated to serum ferritin levels. We conclude that ferritin levels can serve as routine laboratory biomarker for mortality risk assessment before alloSCT.
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http://dx.doi.org/10.3389/fimmu.2020.00586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7174614PMC
March 2021

Diagnosis and Management of Secondary HLH/MAS Following HSCT and CAR-T Cell Therapy in Adults; A Review of the Literature and a Survey of Practice Within EBMT Centres on Behalf of the Autoimmune Diseases Working Party (ADWP) and Transplant Complications Working Party (TCWP).

Front Immunol 2020 31;11:524. Epub 2020 Mar 31.

Department of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom.

Secondary haemophagocytic lymphohistiocytosis (sHLH) or Macrophage Activation Syndrome (MAS) is a life-threatening hyperinflammatory syndrome that can occur in patients with severe infections, malignancy or autoimmune diseases. It is also a rare complication of haematopoetic stem cell transplantation (HSCT), with a high mortality. It may be associated with graft vs. host disease in the allogeneic HSCT setting. It is also reported following CAR-T cell therapy, but differentiation from cytokine release syndrome (CRS) is challenging. Here, we summarise the literature and present results of a survey of current awareness and practice in EBMT-affiliated centres of sHLH/MAS following HSCT and CAR-T cell therapy. An online questionnaire was sent to the principal investigators of all EBMT member transplant centres treating adult patients (18 years and over) inviting them to provide information regarding: number of cases of sHLH/MAS seen in their centre over 3 years (2016-2018 inclusive); screening strategies and use of existing diagnostic/classification criteria and treatment protocols. 114/472 centres from 24 different countries responded (24%). We report estimated rates of sHLH/MAS of 1.09% (95% CI = 0.89-1.30) following allogeneic HSCT, 0.15% (95% CI = 0.09-5.89) following autologous HSCT and 3.48% (95% CI = 0.95-6.01) following CAR-T cell therapy. A majority of centres (70%) did not use a standard screening protocol. Serum ferritin was the most commonly used screening marker at 78% of centres, followed by soluble IL-2 receptor (24%), triglycerides (15%), and fibrinogen (11%). There was significant variation in definition of "clinically significant" serum ferritin levels ranging from 500 to 10,000 μg/mL. The most commonly used criteria to support diagnosis were HLH-2004 (43%) and the H score (15%). Eighty percent of responders reported using no standard management protocol, but reported using combinations of corticosteroids, chemotherapeutic agents, cytokine blockade, and monoclonal antibodies. There is a remarkable lack of consistency between EBMT centres in the approach to screening, diagnosis and management. Further research in this field is needed to raise awareness of and inform harmonised, evidence-based approaches to the recognition and treatment of sHLH/MAS following HSCT/CAR-T cell therapy.
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http://dx.doi.org/10.3389/fimmu.2020.00524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7137396PMC
March 2021

Systematic Review of Patient-Reported Outcome Measures in Graft-versus-Host Disease.

Biol Blood Marrow Transplant 2020 05 3;26(5):e113-e127. Epub 2020 Feb 3.

Department of Dermatology, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom.

Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality after allogeneic stem cell transplantation. These patients face a unique challenge due to the complexity of GVHD and the toxicity of treatments received. GVHD has significant impact on quality of life (QOL), but this is not routinely evaluated formally. Despite the availability of patient-reported outcome measures (PROMs) to assess QOL, there is currently no consensus regarding the optimal PROMs that should be used to evaluate the impact of GVHD. We undertook a systematic review to determine the current evidence for the use of PROMs in assessment of QOL, symptom burden, and disease severity of patients with GVHD. A comprehensive systematic review based on the COSMIN guidelines was conducted to identify studies using PROMs (including those for QOL and symptom burden) in acute and chronic GVHD (cGVHD) patients. The following databases were searched: OVID Medline, AMED, CINAHL, Embase, PROQOLID, ProQuest, PsychINFO, and Social Sciences Citation Index from inception to May 2018. Hand searches updated the search to December 2018. Articles were screened by 2 independent reviewers, with discrepancies resolved by a third independent reviewer. Included articles were critically appraised using the COSMIN Risk of Bias tool, and relevant data on measurement properties for the included PROMs were extracted from within the target population. A total of 4545 articles were identified, and 64 articles reporting on 27 PROMs were included in this review. PROMs were separated into 5 groups; generic patient-reported measures (n = 7), cancer-specific measures (n = 4), bone marrow transplant-specific measures (n = 2), cGVHD-specific measures (n = 4), and dimension-specific measures (n = 10). Three PROMs (Human Activity Profile, Lee Symptom Scale, National Institutes of Health Eleven Point Scale) had evidence to support strong reliability (including internal consistency), responsiveness, and aspects of validity within the cGVHD population. Only 5 included PROMs were used in patients with acute GVHD. This review summarizes the current evidence regarding the use of 27 included PROMs in the context of GVHD. The choice of the most optimal PROM depends on the clinical or research context of use. Future research should comprehensively validate these tools in the GVHD population, including the testing and possible development of a PROM for use in acute GVHD, which remains a current critical gap in the existing literature.
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http://dx.doi.org/10.1016/j.bbmt.2020.01.022DOI Listing
May 2020

Prophylaxis and management of graft versus host disease after stem-cell transplantation for haematological malignancies: updated consensus recommendations of the European Society for Blood and Marrow Transplantation.

Lancet Haematol 2020 Feb;7(2):e157-e167

Department of Hematology, Oncology and Internal Medicine, Medical University of Warsaw, Poland.

Graft-versus-host disease (GVHD) is a major factor contributing to mortality and morbidity after allogeneic stem-cell transplantation. Because of the small number of results from well designed, large-scale, clinical studies there is considerable variability in the prevention and treatment of GVHD worldwide. In 2014, to standardise treatment approaches the European Society of Blood and Marrow Transplantation published recommendations on the management of GVHD in the setting of HLA-identical sibling or unrelated donor transplantation in adult patients with haematological malignancies. Here we update these recommendations including the results of study published after 2014. Evidence was searched in three steps: first, a widespread scan of published trials, meta-analyses, and systematic reviews; second, expert opinion was added for specific issues following several rounds of debate; and third, a refined search to target debated or rapidly updating issues. On the basis of this evidence and the 2014 recommendations, five members of the EBMT Transplant Complications Working Party created 38 statements on GVHD prophylaxis, drug management, and treatment of acute and chronic GVHD. Subsequently, they created the EBMT GVHD management recommendation expert panel by recruiting 20 experts with expertise in GVHD management. An email-based, two-round Delphi panel approach was used to manage the consensus. Modified National Comprehensive Cancer Network categories for evidence and consensus were applied to the approved statements. We reached 100% consensus for 29 recommendations and 95% consensus for nine recommendations. Key updates to these recommendations include a broader use of rabbit anti-T-cell globulin; lower steroid doses for the management of grade 2 acute GVHD with isolated skin or upper gastrointestinal tract manifestations; fluticasone, azithromycin, and montelukast should be used for bronchiolitis obliterans syndrome; and the addition of newer treatment options for resteroid-refractory acute and chronic GVHD. In addition, we discuss specific aspects of GVHD prophylaxis and management in the setting of haploidentical transplantation and in paediatric patients, but no formal recommendations on those procedures have been provided in this Review. The European Society of Blood and Marrow Transplantation proposes to use these recommendations as a basis for the routine management of GVHD during stem-cell transplantation.
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http://dx.doi.org/10.1016/S2352-3026(19)30256-XDOI Listing
February 2020

Predictors of Loss to Follow-Up Among Pediatric and Adult Hematopoietic Cell Transplantation Survivors: A Report from the Center for International Blood and Marrow Transplant Research.

Biol Blood Marrow Transplant 2020 03 11;26(3):553-561. Epub 2019 Nov 11.

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

Follow-up is integral for hematopoietic cell transplantation (HCT) care to ensure surveillance and intervention for complications. We characterized the incidence of and predictors for being lost to follow-up. Two-year survivors of first allogeneic HCT (10,367 adults and 3865 children) or autologous HCT (7291 adults and 467 children) for malignant/nonmalignant disorders between 2002 and 2013 reported to the Center for International Blood and Marrow Transplant Research were selected. The cumulative incidence of being lost to follow-up (defined as having missed 2 consecutive follow-up reporting periods) was calculated. Marginal Cox models (adjusted for center effect) were fit to evaluate predictors. The 10-year cumulative incidence of being lost to follow-up was 13% (95% confidence interval [CI], 12% to 14%) in adult allogeneic HCT survivors, 15% (95% CI, 14% to 16%) in adult autologous HCT survivors, 25% (95% CI, 24% to 27%) in pediatric allogeneic HCT survivors, and 24% (95% CI, 20% to 29%) in pediatric autologous HCT survivors. Factors associated with being lost to follow-up include younger age, nonmalignant disease, public/no insurance (reference: private), residence farther from the tranplantation center, and being unmarried in adult allogeneic HCT survivors; older age and testicular/germ cell tumor (reference: non-Hodgkin lymphoma) in adult autologous HCT survivors; older age, public/no insurance (reference: private), and nonmalignant disease in pediatric allogeneic HCT survivors; and older age in pediatric autologous HCT survivors. Follow-up focusing on minimizing attrition in high-risk groups is needed to ensure surveillance for late effects.
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http://dx.doi.org/10.1016/j.bbmt.2019.11.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367505PMC
March 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

Association of uric acid levels before start of conditioning with mortality after allogeneic hematopoietic stem cell transplantation - a prospective, non-interventional study of the EBMT Transplant Complication Working Party.

Haematologica 2020 07 10;105(7):1977-1983. Epub 2019 Oct 10.

Medical University of Warsaw, Warsaw, Poland.

Uric acid is a danger signal contributing to inflammation. Its relevance to allogeneic stem cell transplantation (alloSCT) derives from preclinical models where the depletion of uric acid led to improved survival and reduced graft--host disease (GvHD). In a clinical pilot trial, peri-transplant uric acid depletion reduced acute GvHD incidence. This prospective international multicenter study aimed to investigate the association of uric acid serum levels before start of conditioning with alloSCT outcome. We included patients with acute leukemia, lymphoma or myelodysplastic syndrome receiving a first matched sibling alloSCT from peripheral blood, regardless of conditioning. We compared outcomes between patients with high and low uric acid levels with univariate- and multivariate analysis using a cause-specific Cox model. Twenty centers from 10 countries reported data on 366 alloSCT recipients. There were no significant differences in terms of baseline comorbidity and disease stage between the high- and low uric acid group. Patients with uric acid levels above median measured before start of conditioning did not significantly differ from the remaining in terms of acute GvHD grades II-IV incidence (Hazard ratio [HR] 1.5, 95% Confidence interval [CI]: 1.0-2.4, =0.08). However, they had significantly shorter overall survival (HR 2.8, 95% CI: 1.7-4.7, <0.0001) and progression free survival (HR 1.6, 95% CI: 1.1-2.4, =0.025). Non-relapse mortality was significantly increased in alloSCT recipients with high uric acid levels (HR 2.7, 95% CI: 1.4-5.0, =0.003). Finally, the incidence of relapse after alloSCT was increased in patients with higher uric acid levels (HR 1.6, 95% CI: 1.0-2.5, =0.04). We conclude that high uric acid levels before the start of conditioning correlate with increased mortality after alloSCT.
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http://dx.doi.org/10.3324/haematol.2019.228668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327652PMC
July 2020

A Conceptual Framework and Key Research Questions in Educational Needs of Blood and Marrow Transplantation Patients, Caregivers, and Families.

Biol Blood Marrow Transplant 2019 07 20;25(7):1416-1423. Epub 2019 Feb 20.

Nebraska Medicine, Omaha, Nebraska.

Patient, caregiver, and family education and support was 1 of 6 key areas of interest identified by the National Marrow Donor Program/Be The Match 2-year project to prioritize patient-centered outcomes research (PCOR) goals for the blood and marrow transplantation (BMT) community. PCOR focuses on research to help patients and their caregivers make informed decisions about health care. Therefore, each area of interest was assigned to a working group with broad representation, including patients, caregivers, and clinicians. Each working group was charged with identifying gaps in knowledge and making priority recommendations for critical research to fill those gaps. The report from this working group presents a conceptual framework to address gaps in knowledge regarding patient and caregiver education in BMT and recommendations for priority research questions on this topic.
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http://dx.doi.org/10.1016/j.bbmt.2019.02.017DOI Listing
July 2019

Phenotypical diversity of airway morphology in chronic lung graft vs. host disease after stem cell transplantation.

Mod Pathol 2019 06 5;32(6):817-829. Epub 2019 Feb 5.

Lung Transplant Unit, Department of Chronic diseases, Metabolism and Aging, KU Leuven, Leuven, Belgium.

Pulmonary graft vs. host disease is a diverse and underestimated complication following allogenic hematopoietic stem cell transplantation. We aimed to compare the airway architecture with chronic lung allograft dysfunction post lung transplantation. Inflated explant lungs from graft vs. host disease patients were compared with lungs with chronic lung allograft dysfunction following lung transplantation, and control lungs using a combination of CT, microCT, and histology (n = 6 per group) and pathology in the (small) airways was further quantified and analyzed. Following allogenic hematopoietic stem cell transplantation, three patients presented as bronchiolitis obliterans syndrome and three patients showed interstitial changes and restriction. The CT analysis demonstrated a strong similarity between bronchiolitis obliterans syndrome after lung transplantation and post allogenic hematopoietic stem cell transplantation, evidenced by severe ( > 50%) airway obstruction from generation 9, with 70.8% of the airways ending in obstruction. Further analysis indicated that the airways either collapsed or accumulated matrix along a segment of the airway. In patients with restriction and interstitial changes following allogenic hematopoietic stem cell transplantation, the degree of airway obstruction was lower compared with bronchiolitis obliterans syndrome post allogenic hematopoietic stem cell transplantation, but similar to restrictive allograft syndrome post lung transplantation, showing a lower proportion of airway obstruction (20-35%), decreased number of terminal bronchioles per lung (p < 0.01), and parenchymal fibrosis. We observed similarities in the airway and parenchymal morphometric changes in lung graft vs. host disease and with chronic lung allograft dysfunction following lung transplantation, suggesting similar pathophysiological mechanisms.
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http://dx.doi.org/10.1038/s41379-019-0203-2DOI Listing
June 2019

Role of Physical Therapy before and after Hematopoietic Stem Cell Transplantation: White Paper Report.

Biol Blood Marrow Transplant 2019 06 15;25(6):e191-e198. Epub 2019 Jan 15.

Physical Therapy Association for Graft Versus Host Disease, Swindon, United Kingdom; Oncology Centre, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia; Department of Medicine, Mayo Clinic, Rochester, Minnesota.

Hematopoietic stem cell transplantation (HSCT) patients can suffer from various musculoskeletal problems resulting in long-term functional incapacity. Physical therapy (PT), as a part of the healthcare team, has been historically advocated for regaining functional capacity and improving quality of life post-HSCT. Because of the nature of this condition and the burden of post-transplant complications, this patient group requires a unique approach toward their rehabilitation that takes into account their complex musculoskeletal presentation ranging from fascia, muscle, tendons, bones, and ligaments. However, to our knowledge there is no universal standardized PT protocol or pathway to help guide rehab specialists to achieve optimal gains for this patient group, and anecdotal evidence suggests that these patients do not always receive the PT care they require. Hence, in collaboration with the Transplant Complications Working Party of the European Society for Blood and Marrow Transplantation, the Survivorship Special Interest Group of the American Society of Blood and Marrow Transplantation, and the Quality of Life Committee of the Eastern Mediterranean Blood and Marrow Transplantation, herein the Physical Therapy Association for Graft Versus Host Disease provides a brief review on role of PT in mitigating musculoskeletal complications in HSCT patients and makes evidence-based recommendations for incorporation of PT into routine HSCT care.
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http://dx.doi.org/10.1016/j.bbmt.2019.01.018DOI Listing
June 2019

Ocular graft-versus-host disease after hematopoietic cell transplantation: Expert review from the Late Effects and Quality of Life Working Committee of the CIBMTR and Transplant Complications Working Party of the EBMT.

Bone Marrow Transplant 2019 05 7;54(5):662-673. Epub 2018 Dec 7.

Department of Ophthalmology, University Clinical Hospital Zagreb, Zagreb, Croatia.

Ocular graft-versus-host disease (GVHD) occurs in more than half of patients who develop chronic GVHD after allogeneic hematopoietic cell transplantation (HCT), causing prolonged morbidity, which affects activities of daily living and quality of life. Here we provide an expert review of ocular GVHD in a collaboration between transplant physicians and ophthalmologists through the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and the Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation. Recent updates in ocular GVHD, regarding pathophysiology, preclinical models, risk factors, prevention, screening, diagnosis, response criteria, evaluation measures, and treatment are discussed in this review. Ocular GVHD has at least three biological processes: lacrimal gland dysfunction, meibomian gland dysfunction, and corneoconjunctival inflammation. Preclinical models have found several novel pathogenic mechanisms, including renin angiotensin system and endoplasmic reticulum stress signaling that can be targeted by therapeutic agents. Many studies have identified reliable tests for establishing diagnosis and response assessment of ocular GVHD. Efficacy of systemic and topical treatment for ocular GVHD is summarized. It is important for all health professionals taking care of HCT recipients to have adequate knowledge of ocular GVHD for optimal care.
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http://dx.doi.org/10.1038/s41409-018-0340-0DOI Listing
May 2019

Voriconazole-Induced Periostitis After Allogeneic Stem Cell Transplantation.

Clin Nucl Med 2019 Feb;44(2):159-160

From the Departments of Nuclear Medicine and Molecular Imaging, and.

A 34-year-old man with history of Hodgkin lymphoma presented 7 months after allogeneic stem cell transplantation with an unexplained severe musculoskeletal pain syndrome. A Tc-MDP bone SPECTCT showed multiple foci with moderate to intense bone uptake across the axial and appendicular skeleton consistent with periostitis. The patient had been on voriconazole daily for 4 months to treat an Aspergillus pneumonia, and in the absence of other causes, a drug-induced periostitis was suspected. Voriconazole was changed to posaconazole with complete resolution of the musculoskeletal symptoms within 3 weeks.
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http://dx.doi.org/10.1097/RLU.0000000000002383DOI Listing
February 2019

Ocular Graft-versus-Host Disease after Hematopoietic Cell Transplantation: Expert Review from the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation.

Biol Blood Marrow Transplant 2019 02 24;25(2):e46-e54. Epub 2018 Nov 24.

Department of Ophthalmology, University Clinical Hospital Zagreb, Zagreb, Croatia.

Ocular graft-versus-host disease (GVHD) occurs in more than one-half of patients who develop chronic GVHD after allogeneic hematopoietic cell transplantation (HCT), causing prolonged morbidity that affects activities of daily living and quality of life. Here we provide an expert review of ocular GVHD in a collaboration between transplantation physicians and ophthalmologists through the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and the Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation. Recent updates in ocular GVHD regarding pathophysiology, preclinical models, risk factors, prevention, screening, diagnosis, response criteria, evaluation measures, and treatment are discussed. Ocular GVHD involves at least 3 biological processes: lacrimal gland dysfunction, meibomian gland dysfunction, and corneoconjunctival inflammation. Preclinical models have identified several novel pathogenic mechanisms, including the renin angiotensin system and endoplasmic reticulum stress signaling, which can be targeted by therapeutic agents. Numerous studies have identified reliable tests for establishing diagnosis and response assessment of ocular GVHD. The efficacy of systemic and topical treatment for ocular GVHD is summarized. It is important that all health professionals caring for HCT recipients have adequate knowledge of ocular GVHD to provide optimal care.
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http://dx.doi.org/10.1016/j.bbmt.2018.11.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6362842PMC
February 2019

Characteristics of Late Fatal Infections after Allogeneic Hematopoietic Cell Transplantation.

Biol Blood Marrow Transplant 2019 02 2;25(2):362-368. Epub 2018 Oct 2.

Division of Hematology/Oncology, University Florida College of Medicine, Gainesville, Florida.

We analyzed late fatal infections (LFIs) in allogeneic stem cell transplantation (HCT) recipients reported to the Center for International Blood and Marrow Transplant Research. We analyzed the incidence, infection types, and risk factors contributing to LFI in 10,336 adult and 5088 pediatric subjects surviving for ≥2 years after first HCT without relapse. Among 2245 adult and 377 pediatric patients who died, infections were a primary or contributory cause of death in 687 (31%) and 110 (29%), respectively. At 12 years post-HCT, the cumulative incidence of LFIs was 6.4% (95% confidence interval [CI], 5.8% to 7.0%) in adults, compared with 1.8% (95% CI, 1.4% to 2.3%) in pediatric subjects; P < .001). In adults, the 2 most significant risks for developing LFI were increasing age (20 to 39, 40 to 54, and ≥55 years versus 18 to 19 years) with hazard ratios (HRs) of 3.12 (95% CI, 1.33 to 7.32), 3.86 (95% CI, 1.66 to 8.95), and 5.49 (95% CI, 2.32 to 12.99) and a history of chronic graft-versus-host disease GVHD (cGVHD) with ongoing immunosuppression at 2 years post-HCT compared with no history of GVHD with (HR, 3.87; 95% CI, 2.59 to 5.78). In pediatric subjects, the 3 most significant risks for developing LFI were a history of cGVHD with ongoing immunosuppression (HR, 9.49; 95% CI, 4.39 to 20.51) or without ongoing immunosuppression (HR, 2.7; 95% CI, 1.05 to 7.43) at 2 years post-HCT compared with no history of GVHD, diagnosis of inherited abnormalities of erythrocyte function compared with diagnosis of acute myelogenous leukemia (HR, 2.30; 95% CI, 1.19 to 4.42), and age >10 years (HR, 1.92; 95% CI, 1.15 to 3.2). This study emphasizes the importance of continued vigilance for late infections after HCT and institution of support strategies aimed at decreasing the risk of cGVHD.
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http://dx.doi.org/10.1016/j.bbmt.2018.09.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6339825PMC
February 2019