High CD3+ and CD34+ peripheral blood stem cell grafts content is associated with increased risk of graft-versus-host disease without beneficial effect on disease control after reduced-intensity conditioning allogeneic transplantation from matched unrelated donors for acute myeloid leukemia — an analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

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Abstract

Inconsistent results have been reported regarding the influence of graft composition on the incidence of graft versus host disease (GVHD), disease control and survival after reduced-intensity conditioning (RIC) allogeneic peripheral blood stem cell transplantation (allo-PBSCT). These discrepancies may be at least in part explained by the differences in disease categories, disease status at transplant, donor type and conditioning. The current retrospective EBMT registry study aimed to analyze the impact of CD3+ and CD34+ cells dose on the outcome of RIC allo-PBSCT in patients with acute myelogenous leukemia (AML) in first complete remission, allografted from HLA-matched unrelated donors (10 of 10 match). We included 203 adults. In univariate analysis, patients transplanted with the highest CD3+ and CD34+ doses (above the third quartile cut-off point values, >347 × 10^6/kg and >8.25 × 10^6 /kg, respectively) had an increased incidence of grade III-IV acute (a) GVHD (20% vs. 6%, P = .003 and 18% vs. 7%, P = .02, respectively). There was no association between cellular composition of grafts and transplant-related mortality, AML relapse, incidence of chronic GVHD and survival. Neither engraftment itself nor the kinetics of engraftment were affected by the cell dose. In multivariate analysis, CD3+ and CD34+ doses were the only adverse predicting factors for grade III-IV aGVHD (HR = 3.6; 95%CI: 1.45-9.96, P = .006 and 2.65 (1.07-6.57), P = .04, respectively). These results suggest that careful assessing the CD3+ and CD34+ graft content and tailoring the cell dose infused may help in reducing severe acute GVHD risk without negative impact on the other transplantation outcomes.

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Most cited references 29

Record: found
Abstract: found
Article: not found

Estimation of failure probabilities in the presence of competing risks: new representations of old estimators.

T Gooley, W Leisenring, J. Crowley … (1999)

A topic that has received attention in both the statistical and medical literature is the estimation of the probability of failure for endpoints that are subject to competing risks. Despite this, it is not uncommon to see the complement of the Kaplan-Meier estimate used in this setting and interpreted as the probability of failure. If one desires an estimate that can be interpreted in this way, however, the cumulative incidence estimate is the appropriate tool to use in such situations. We believe the more commonly seen representations of the Kaplan-Meier estimate and the cumulative incidence estimate do not lend themselves to easy explanation and understanding of this interpretation. We present, therefore, a representation of each estimate in a manner not ordinarily seen, each representation utilizing the concept of censored observations being 'redistributed to the right.' We feel these allow a more intuitive understanding of each estimate and therefore an appreciation of why the Kaplan-Meier method is inappropriate for estimation purposes in the presence of competing risks, while the cumulative incidence estimate is appropriate.

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Record: found
Abstract: found
Article: not found

Reduced-intensity conditioning regimen workshop: defining the dose spectrum. Report of a workshop convened by the center for international blood and marrow transplant research.

Marcelo C. Pasquini, James Douglas Rizzo, Brenda M. Sandmaier … (2009)

During the 2006 BMT Tandem Meetings, a workshop was convened by the Center for International Blood and Marrow Transplant Research (CIBMTR) to discuss conditioning regimen intensity and define boundaries of reduced-intensity conditioning (RIC) before hematopoietic cell transplantation (HCT). The goal of the workshop was to determine the acceptance of available RIC definitions in the transplant community. Participants were surveyed regarding their opinions on specific statements on conditioning regimen intensity. Questions covered the "Champlin criteria," as well as operational definitions used in registry studies, exemplified in clinical vignettes. A total of 56 participants, including transplantation physicians, transplant center directors, and transplantation nurses, with a median of 12 years of experience in HCT, answered the survey. Of these, 67% agreed that a RIC regimen should cause reversible myelosuppression when administered without stem cell support, result in low nonhematologic toxicity, and, after transplantation, result in mixed donor-recipient chimerism at the time of first assessment in most patients. Likewise, the majority (71%) agreed or strongly agreed that regimens including < 500 cGy of total body irradiation as a single fraction or 800 cGy in fractionated doses, busulfan dose < 9 mg/kg, melphalan dose <140 mg/m(2), or thiotepa dose < 10 mg/kg should be considered RIC regimens. However, only 32% agreed or strongly agreed that the combination of carmustine, etoposide, cytarabine, and melphalan (BEAM) should be considered a RIC regimen. These results demonstrate that although HCT professionals have not reached a consensus on what constitutes a RIC regimen, most accept currently used criteria and operational definitions. These results support the continued use of current criteria for RIC regimens until a consensus statement can be developed.

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Record: found
Abstract: found
Article: not found

Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients.

(1980)

This study of chronic graft-versus-host disease (GVHD) describes the clinical, pathologic and laboratory features, and the causes of morbidity and mortality in 20 patients who received allogeneic marrow transplants from HLA identical sibling donors. Chronic GVHD is a pleiotrophic syndrome with variability in the time of onset, organ systems involved and rate of progression. The clinical-pathologic features resemble an overlap of several collagen vascular diseases with frequent involvement of the skin, liver, eyes, mouth, upper respiratory tract, esophagus and less frequent involvement of the serosal surfaces, lower gastrointestinal tract and skeletal muscles. Major causes of morbidity are scleroderma with contractures and ulceration, dry eyes and mouth, pulmonary insufficiency and wasting. Chronic GVHD has features of immune dysregulation with elevated levels of eosinophils, circulating autoantibodies, hypergammaglobulinemia and plasmacytosis of viscera and lymph nodes. In this study, three patients had limited chronic GVHD with relatively favorable prognosis characterized by localized skin involvement and/or hepatic disease without chronic aggressive histology. Most patients, however, had extensive disease with a progressive course. Survival was largely determined by the presence or absence of serious recurrent bacterial infections. The over-all severity of disease was best assessed by using the Karnofsky performance rating.

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Author and article information

Journal

Journal ID (nlm-ta): Oncotarget

Journal ID (iso-abbrev): Oncotarget

Journal ID (publisher-id): Oncotarget

Journal ID (publisher-id): ImpactJ

Title: Oncotarget

Publisher: Impact Journals LLC

ISSN (Electronic): 1949-2553

Publication date Collection: 10 May 2016

Publication date (Electronic): 29 March 2016

Volume: 7

Issue: 19

Pages: 27255-27266

Affiliations

¹ Department of Bone Marrow Transplantation and Oncohematology, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Gliwice Branch, Gliwice, Poland

² Clinical Hematology and Cellular Therapy Department, The Acute Leukemia Working Party of the EBMT office, Hopital Saint-Antoine APHP Paris, France

³ INSERM UMRs 938, Paris, France

⁴ Université Pierre et Marie Curie (UPMC, Paris VI), Paris, France

⁵ Klinikum Augsburg, University of Munich, Munich, Germany

⁶ Department of Hematology, Erasmus University medical center Cancer Institute, Rotterdam, The Netherlands

⁷ CHU Nantes, Dept. D'Hematologie, Nantes, France

⁸ Unité de transplantation et de thérapie cellulaire, Institut Paoli Calmettes, Marseille, France

⁹ University Medical Centre, Dept. of Haematology, Utrecht, The Netherlands

¹⁰ CHU Bordeaux, Hôpital Haut-leveque, Pessac, France

¹¹ Hopital A. Michallon, Hématologie Clinique, Pole Cancérologie, Grenoble, France

¹² Nouvel Hopital Civil, Strasbourg, France

¹³ CHU Lapeyronie, Département d'Hématologie Clinique, Montpellier, France

¹⁴ Hôpital de Brabois, Centre Hospitalier Universitaire (CHU) de Nancy, Vandoeuvres les Nancy, France

¹⁵ University Hospital, Dept. of Hematology, Linköping, Sweden

¹⁶ University Hospital Gasthuisberg, Dept. of Hematology, Leuven, Belgium

¹⁷ CHU Morvan, Brest, France

¹⁸ CHRU Limoges, Service d'Hématologie Clinique, Limoges, France

¹⁹ Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel Hashomer, Israel

Author notes

Correspondence to: Tomasz Czerw, tomcmed@ 123456gmail.com

Article

Publisher ID: 8463

DOI: 10.18632/oncotarget.8463

PMC ID: 5053647

PubMed ID: 27036034

SO-VID: bf6549df-641c-469e-b5cd-e7447cf545f5

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

History

Date received : 17 March 2016

Date accepted : 23 March 2016

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