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Allogeneic hematopoietic stem cell transplantation is the only potentially curative therapy for high-risk acute myeloid leukemia. In the absence of an HLA-matched related or unrelated donor (MRD or MUD), the best alternative donor source remains controversial. Umbilical cord blood and haploidentical donors offer a time advantage when considering the duration from treatment indication to transplantation. This retrospective multicenter study of a French registry compares overall survival for alternative donor transplants in the 18 months following decision to transplant in the absence of a MRD between four groups of transplanted patients: MUD (control); HLA-mismatched MUD (mMUD); umbilical cord blood (UCB); and haploidentical (haplo). Between March 2012 and July 2016, 1302 patients were transplanted with MUD (n=803), mMUD (n=219), UCB (n=153) and haplo (n=127) donors. Multivariate analyses were conducted for overall survival 18 months after registration, overall survival after transplant, and transplant-related mortality, with adjustment for the several variables. After adjustment, the type of donor did not influence any of the three endpoints. Our results confirmed the significant negative impact of a longer time interval between registration and transplant: HR=1.04 [1.02–1.06] (p

In many healthcare settings, benchmarking for complex procedures has become a mandatory requirement by competent authorities, regulators, payers and patients to assure clinical performance, cost-effectiveness and safe care of patients. In several countries inside and outside Europe, benchmarking systems have been established for haematopoietic stem cell transplantation (HSCT), but access is not universal. As benchmarking is now integrated into the FACT-JACIE standards, the EBMT and JACIE established a Clinical Outcomes Group (COG) to develop and introduce a universal system accessible across EBMT members. Established systems from seven European countries (United Kingdom, Italy, Belgium, France, Germany, Spain, Switzerland), USA and Australia were appraised, revealing similarities in process, but wide variations in selection criteria and statistical methods. In tandem, the COG developed the first phase of a bespoke risk-adapted international benchmarking model for one-year survival following allogeneic and autologous HSCT based on current capabilities within the EBMT registry core dataset. Data completeness, which has a critical impact on validity of centre comparisons, is also assessed. Ongoing development will include further scientific validation of the model, incorporation of further variables (when appropriate) alongside implementation of systems for clinically meaningful interpretation and governance aiming to maximise acceptance to centres, clinicians, payers and patients across EBMT., The project was supported by funding from EBMT

In many healthcare settings, benchmarking for complex procedures has become a mandatory requirement by competent authorities, regulators, payers and patients to assure clinical performance, cost-effectiveness and safe care of patients. In several countries inside and outside Europe, benchmarking systems have been established for haematopoietic stem cell transplantation (HSCT), but access is not universal. As benchmarking is now integrated into the FACT-JACIE standards, the EBMT and JACIE established a Clinical Outcomes Group (COG) to develop and introduce a universal system accessible across EBMT members. Established systems from seven European countries (United Kingdom, Italy, Belgium, France, Germany, Spain, Switzerland), USA and Australia were appraised, revealing similarities in process, but wide variations in selection criteria and statistical methods. In tandem, the COG developed the first phase of a bespoke risk-adapted international benchmarking model for one-year survival following allogeneic and autologous HSCT based on current capabilities within the EBMT registry core dataset. Data completeness, which has a critical impact on validity of centre comparisons, is also assessed. Ongoing development will include further scientific validation of the model, incorporation of further variables (when appropriate) alongside implementation of systems for clinically meaningful interpretation and governance aiming to maximise acceptance to centres, clinicians, payers and patients across EBMT.

Statistical modeling methods have had increasing use in drug disposition studies, both to estimate pharmacokinetic parameters and to develop regression models that relate these parameter estimates to patient characteristics. These methods are particularly flexible as they allow non-linearity and sparse within-patient information. In the past few years, multiple analysis methods have become available, but there is a lack of systematic comparisons of their estimates on the same data sets. Two simulated data sets were therefore developed by the Population Modeling Workgroup of the Biopharmaceutical Section of the American Statistical Association. We analysed these data sets using seven population modeling programs, some of which contain multiple analysis methods. Although each data set represents a single replicate from a given model and data collection design, the results suggest that the behaviour of some methods differs from that of the others.

Purpose To investigate the influence of donor type (human leukocyte antigen [HLA] -identical sibling donor versus HLA-A–, HLA-B–, HLA-Cw–, HLA-DRB1–, and HLA-DQB1–identical unrelated donors, or so-called 10/10) on the outcome of patients who underwent allogeneic stem-cell transplantation (alloSCT), adjusting for other prognostic factors, in patients with standard-risk hematologic malignancy. Patients and Methods Between March 2000 and January 2003, we prospectively investigated the outcome of 236 consecutive patients with standard-risk malignancy from 12 French centers. Fifty-five patients underwent alloSCT from an unrelated HLA-identical donor at the allelic level, whereas 181 patients received an alloSCT from an HLA-identical sibling. Diagnoses included acute leukemia (n = 175), chronic myeloid leukemia (n = 43), and myelodysplastic syndrome (MDS; n = 18). All patients received unmodified marrow graft following myeloablative conditioning with cyclophosphamide and total-body irradiation. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and short-course methotrexate in all patients. Results In multivariable analysis, overall survival and transplantation-related mortality were adversely influenced by recipient cytomegalovirus (CMV) -positive serology, age of donor older than 37 years, and the occurrence of acute grade ≥ II GVHD. Event-free survival rates were lower for patients with recipient CMV-positive serology. Acute grades II to IV GVHD rates were higher for patients with chronic myeloid leukemia (CML). No factor was found to influence either relapse or acute grades III to IV GVHD. The effect of donor type was nonsignificant for all criteria. Conclusion In patients with standard-risk malignancy, transplantation from unrelated HLA-allellically matched donors led to outcomes similar to those from HLA-identical sibling donors.

We evaluated the effect of individual and collective factors on the outcome of allogeneic haematopoietic stem cell transplantation (HSCT) at 35 French centres. Individual factors included patient and transplantation characteristics. Collective factors were related to the period and centre in which HSCT was performed. Two centre factors were studied: centre experience (ie number of HSCT performed during the study period) and the type of centre (paediatric or adult). All patients receiving a first allogeneic HSCT in France between 1st January 1993 and 31st December 1997 were included in the study. The follow-up period ended on 31st December 1997. The final sample included 2756 subjects. We analysed overall survival (OS) and transplant-related mortality (TRM). Prognostic factors were identified by univariate and multivariate analysis, using Cox models. We found that centre experience had no significant effect on outcome. However, survival rates, whether determined on the basis of OS or TRM, were significantly higher in paediatric centres than in adult centres. Residual heterogeneity was found between adult centres. Survival rates were significantly higher for HSCT performed after 1st January 1996 than for those performed before this date.