IVIg therapy in the management of BK virus infections in pediatric kidney transplant patients.

BK virus-associated nephropathy (BKPyVAN) induces kidney allograft dysfunction. Although decreasing immunosuppression is the standard for managing BK virus (BKPyV) infection, this strategy is not always effective. The use of polyvalent immunoglobulins (IVIg) may be of interest in this setting. We performed a retrospective single-center evaluation of the management of BKPyV infection in pediatric kidney transplant patients. Among the 171 patients who underwent transplantation between January 2010 and December 2019, 54 patients were excluded (combined transplant n = 15, follow-up in another center n = 35, early postoperative graft loss n= 4). Thus, 117 patients (120 transplants) were included. Overall, 34 (28%) and 15 (13%) transplant recipients displayed positive BKPyV viruria and viremia, respectively. Three had biopsy-confirmed BKPyVAN. The pre-transplant prevalence of CAKUT and HLA antibodies was higher among BKPyV-positive patients compared to non-infected patients. After the detection of BKPyV replication and/or BKPyVAN, the immunosuppressive regimen was modified in 13 (87%) patients: either by decreasing or changing the calcineurin inhibitors (n = 13) and/or switching from mycophenolate mofetil to mTor inhibitors (n = 10). Starting IVIg therapy was based on graft dysfunction or an increase in the viral load despite reduced immunosuppressive regimen. Seven of 15(46%) patients received IVIg. These patients had a higher viral load (5.4 [5.0-6.8]log vs. 3.5 [3.3-3.8]log). In total, 13 of 15 (86%) achieved viral load reduction, five of seven after IVIg therapy. As long as specific antivirals are not available for the management of BKPyV infections in pediatric kidney transplant patients, polyvalent IVIg may be discussed for the management of severe BKPyV viremia, in combination with decreased immunosuppression.

Adverse events during nursing care procedure in intensive care unit: The PREVENIR study.

OBJECTIVES: Intensive care unit patients undergo several nursing care procedures (NCP) every day. These procedures involve a risk for adverse events (AE). Yet, their prevalence, intensity, and predisposing risk factors remain poorly established. The main objective of the study was to measure the incidence and severity of NCP related AE. DESIGN: This prospective observational multicentre study was conducted in 9 ICUs. All NCP were recorded for four consecutive weeks. For each NCP, the following were collected: patients' baseline characteristics, type of NCP, characteristics of the NCP, AE and therapeutic responses. RESULTS: 5849 NCP occurred in 340 patients. Among the 340 patients included, 292 (85.9%) were affected by at least one AE, and 141 (41.5%) by an SAE during a NCP. Thirty % of NCP were associated with at least one AE: hemodynamic AE in 17.1%, respiratory AE in 13.6%, agitation and pain (3.7% and 3.3%). Eight invasive devices were accidentally removed. Severe Adverse Events (SAE) occurred in 5.5% of NCP. The main risk factor associated with SAE was pain/agitation at the beginning of the NCP. CONCLUSION: AE are frequent during NCP in ICU. We identified several risk factors, some of them preventable, that could be considered for the development of recommendations for the nursing care of critically ill patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT02881645.

Exogenous acquisition of Pseudomonas aeruginosa in intensive care units: a prospective multi-centre study (DYNAPYO study).

BACKGROUND: Pseudomonas aeruginosa remains one of the most common nosocomial pathogens in intensive care units (ICUs). Although exogenous acquisition has been widely documented in outbreaks, its importance is unclear in non-epidemic situations. AIM: To elucidate the role of exogenous origin of P. aeruginosa in ICU patients. METHODS: A chronological analysis of the acquisition of P. aeruginosa was performed using samples collected in 2009 in the DYNAPYO cohort study, during which patients and tap water were screened weekly. Molecular relatedness of P. aeruginosa isolates was investigated by pulsed-field gel electrophoresis. Exogenous acquisition was defined as identification of a P. aeruginosa pulsotype previously isolated from another patient or tap water in the ICU. FINDINGS: The DYNAPYO cohort included 1808 patients (10,402 samples) and 233 water taps (4946 samples). Typing of 1515 isolates from 373 patients and 375 isolates from 81 tap water samples identified 296 pulsotypes. Analysis showed exogenous acquisition in 170 (45.6%) of 373 patients. The pulsotype identified had previously been isolated from another patient and from a tap water sample for 86 and 29 patients, respectively. The results differed according to the ICU. CONCLUSION: Exogenous acquisition of P. aeruginosa could be prevented in half of patients. The overall findings of this survey support the need for studies on routes of transmission and risk assessment approach to better define how to control exogenous acquisition in ICUs.

Face Transplantation: Partial Graft Loss of the First Case 10 Years Later.

Ten years after the first face transplantation, we report the partial loss of this graft. After two episodes of acute rejection (AR) occurred and completely reversed in the first posttransplantation year, at 90 months posttransplantation the patient developed de novo class II donor-specific antibodies, without clinical signs of AR. Some months later, she developed several skin rejection episodes treated with steroid pulses. Despite rapid clinical improvement, some months later the sentinel skin graft underwent necrosis. Microscopic examination showed intimal thickening, thrombosis of the pedicle vessel, and C4d deposits on the endothelium of some dermal vessels of the facial graft. Flow magnetic resonance imaging of the facial graft showed a decrease of the distal right facial artery flow. Three steroid pulses of 500 mg each, followed by intravenous immunoglobulins (2 g/kg), five sessions of plasmapheresis, and three cycles of bortezomib 1.3 mg/m2 , were administered. Despite rescue therapy with eculizumab, necrosis of the lips and the perioral area occurred, which led to surgical removal of the lower lip, labial commissures, and part of the right cheek in May 2015. In January 2016, the patient underwent conventional facial reconstruction because during the retransplantation evaluation a small-cell lung carcinoma was discovered, causing the patient's death in April 2016.

Pharmacokinetic-pharmacodynamic modelling of drug-induced QTc interval prolongation in man: prediction from in vitro human ether-à-go-go-related gene binding and functional inhibition assays and conscious dog studies.

BACKGROUND AND PURPOSE: Functional measures of human ether-à-go-go-related gene (hERG; Kv 11.1) channel inhibition have been prioritized as an in vitro screening tool for candidate molecules. However, it is unclear how these results can be translated to humans. Here, we explore how data on drug binding and functional inhibition in vitro relate to QT prolongation in vivo. Using cisapride, sotalol and moxifloxacin as paradigm compounds, we assessed the relationship between drug concentrations, binding, functional measures and in vivo effects in preclinical species and humans. EXPERIMENTAL APPROACH: Pharmacokinetic-pharmacodynamic modelling was used to characterize the drug effects in hERG functional patch clamp, hERG radio-labelled dofetilide displacement experiments and QT interval in conscious dogs. Data were analysed in parallel to identify potential correlations between pharmacological activity in vitro and in vivo. KEY RESULTS: An Emax model could not be used due to large variability in the functional patch clamp assay. Dofetilide displacement revealed that binding curves are unrelated to the in vivo potency estimates for QTc prolongation in dogs and humans. Mean in vitro potency estimates ranged from 99.9 nM for cisapride to 1030 µM for moxifloxacin. CONCLUSIONS AND IMPLICATIONS: The lack of standardized protocols for in vitro assays leads to significant differences in experimental conditions, making the assessment of in vitro-in vivo correlations unreliable. Identification of an accurate safety window during the screening of candidate molecules requires a quantitative framework that disentangles system- from drug-specific properties under physiological conditions, enabling translation of the results to humans. Similar considerations will be relevant for the comprehensive in vitro pro-arrhythmia assay initiative.

Risk factors and outcome of graft failure after HLA matched and mismatched unrelated donor hematopoietic stem cell transplantation: a study on behalf of SFGM-TC and SFHI.

Graft failure remains a severe complication of hematopoietic stem cell transplantation (HSCT). Several risk factors have already been published. In this study, we re-evaluated them in a large cohort who had the benefit of the recent experience in HSCT (2006-2012). Data from 4684 unrelated donor HSCT from 2006 to 2012 were retrospectively collected from centers belonging to the French Society for Stem Cell Transplantation. Among the 2716 patients for whom HLA typing was available, 103 did not engraft leading to a low rate of no engraftment at 3.8%. In univariate analysis, only type of disease and status of disease at transplant for malignant diseases remained significant risk factors (P=0.04 and P<0.0001, respectively). In multivariate analysis, only status of disease was a significant risk factor (P<0.0001). Among the 61 patients who did not engraft and who were mismatched for 1 HLA class I and/or HLA-DP, 5 donor-specific antibodies (DSAs) were detected but only 1 was clearly involved in graft failure, for the others their role was more questionable. Second HSCT exhibited a protective although not statistically significant effect on OS (hazard ratio=0.57 [0.32-1.02]). In conclusion, only one parameter (disease status before graft) remains risk factor for graft failure in this recent cohort.

Improved outcome of children transplanted for high-risk leukemia by using a new strategy of cyclosporine-based GVHD prophylaxis.

There is currently a major concern regarding the optimal immunosuppression therapy to be administered after hematopoietic stem cell transplantation (HSCT) to reduce both the toxicity of GvHD and the rate of relapse. We report the outcome of high-risk leukemia children transplanted with a new way of managing cyclosporine (CsA)-based GvHD prophylaxis. A total of 110 HSCT in 109 ALL or AML children who received CsA without mycophenolate or methotrexate in matched related as well as in matched or mismatched unrelated stem cell transplantation were included. CsA dosage regimens were individualized to obtain specific trough blood concentrations values. The incidences of grade I-II and III-IV acute GvHD were 69.1% and 1.8%, respectively, and 8.4% for chronic GvHD. GvHD was neither more frequent nor severe in unrelated than in related HSCT. GvHD occurred in 87% of patients with a mean CsA trough concentration ⩽120 ng/mL versus 43% with concentration >120 ng/mL (P<0.0001). Five-year disease-free survival (DFS) and overall survival were 78% and 83.6%, respectively. DFS was 76.9% for ALL and 80.4% for AML patients. There was no difference in DFS between matched siblings and matched unrelated or mismatched unrelated HSCT. DFS in patients with minimal residual disease (MRD) ⩾10(-3) and in those with MRD <10(-3) before SCT was comparable. Our results indicate that a GvHD prophylaxis regimen based on CsA without mycophenolate or methotrexate is safe and effective whatever the donor compatibility is. These results suggest that GvL effect may be enhanced by this strategy of GvHD prophylaxis.

Suggestive evidence of a role of HLA-DRB4 mismatches in the outcome of allogeneic hematopoietic stem cell transplantation with HLA-10/10-matched unrelated donors: a French-Swiss retrospective study.

We have conducted a retrospective study on 251 patients from three centers in France and Switzerland between 2004 and 2010 with the goal to evaluate the impact of HLA-DRB3/B4/B5 allele mismatching after HLA-10/10-matched unrelated allogeneic hematopoietic stem cell transplantation (HSCT). Fourteen (5.5%) patients receiving HSCT from an HLA-10/10-matched unrelated donor had a mismatched DRB4 donor, 23 (9.5%) patients had a mismatched DRB3 donor and 214 (85%) had a fully matched unrelated donor (HLA-10/10) without DRB3- or DRB4-mismatched donor. We compared the outcomes of 37 patients with a DRB3 or DRB4 mismatch with the rest of the population. The median survival for a patient without DRB3/4 mismatch was 18 months (95% confidence interval (CI), 13-29), for DRB3-mismatched patients 32 months (95% CI, 13-NR) and for DRB4-mismatched patients 7 months (95% CI, 3-NR). The multivariate analysis showed a significant impact of DRB4 mismatching on survival (Hazards ratio (HR)=2.1 (95% CI, 1.01-4.67), P=0.045), acute GvHD (HR=2.66 (95% CI, 0.99-7.09) P=0.05) and on transplant-related mortality (HR=2.8; (95% CI, 1.7-4.4) P=0.024). In the view of an impact of DRB4 locus mismatch on clinical outcome, it would be important to confirm this observation in a prospective study as it may be worth considering DRB4 in the unrelated donor selection.

Is there any impact of HLA-DPB1 disparity in 10/10 HLA-matched unrelated hematopoietic SCT? Results of a French multicentric retrospective study.

We retrospectively analyzed the impact of HLA-DPB1 mismatches in a large cohort of 1342 French patients who underwent 10/10 HLA-matched unrelated HSCT. A significant impact of HLA-DPB1 allelic mismatches (2 vs 0) was observed in severe acute GVHD (aGVHDIII-IV) (risk ratio (RR)=1.73, confidence interval (CI) 95% 1.09-2.73, P=0.019) without impact on OS, TRM, relapse and chronic GVHD (cGVHD). According to the T-cell epitope 3 (TCE3)/TCE4 HLA-DPB1 disparity algorithm, 37.6% and 58.4% pairs had nonpermissive HLA-DPB1, respectively. TCE3 and TCE4 disparities had no statistical impact on OS, TRM, relapse, aGVHD and cGVHD. When TCE3/TCE4 disparities were analyzed in the graft-vs-host or host-vs-graft (HVG) direction, only a significant impact of TCE4 nonpermissive disparities in the HVG direction was observed on relapse (RR=1.34, CI 95% 1.00-1.80, P=0.048). In conclusion, this French retrospective study shows an adverse prognosis of HLA-DPB1 mismatches (2 vs 0) on severe aGVHD and of nonpermissive TCE4 HVG disparities on relapse after HLA-matched 10/10 unrelated HSCT.

Resolution of HLA-B*44:02:01G, -DRB1*14:01:01G and -DQB1*03:01:01G reveals a high allelic variability among 12 European populations.

Within the framework of the EU-funded HLA-NET action, an analysis of three G-group alleles, HLA-B*44:02:01G, DRB1*14:01:01G and DQB1*03:01:01G, was undertaken in 12 European populations. Ambiguities were resolved by polymerase chain reaction-sequence-specific amplification (PCR-SSP) or PCR-sequence-based typing (PCR-SBT) in a total of 5095 individuals. The results of the DRB1*14:01/14:54 ambiguity showed high relative ratios (24-53%) of DRB1*14:01 in Bulgarians, Croatians, Greeks, Italians and Slovenians, contrasting with low ratios (6-13%) in Austrians, Finnish, French, Hungarians, Norwegians and Swiss. Resolution of the B*44:02/44:27 ambiguity showed that B*44:27 had a high relative ratio in Slovenians (25.5%) and Bulgarians (37%) and low in French and Swiss (0.02-1%), and was not observed in Greeks and Italians. The highest relative ratio of DQB1*03:19 was found in Portuguese (11%), by contrast with low ratios (0-3%) in the other five populations. Analysis of the A, B, DRB1 phenotypes and family-derived haplotypes in 1719 and 403 individuals positive for either HLA-B*44:02G or DRB1*14:01G ambiguities, respectively, showed some preferential associations, such as A*26∼DRB1*14:01, B*35∼DRB1*14:01, B*38∼DRB1*14:01 and B*44:27∼DRB1*16. Because these ambiguities are located outside the peptide-binding site, they may not be recognized by alloreactive T-cells. However, because of strong linkage disequilibrium (LD), the DRB1*14:01 vs DRB1*14:54 and the B*44:02 vs B*44:27 mismatches are associated to DRB3-, and C-mismatches, respectively. These results are informative for algorithms searching unrelated hematopoietic stem cell donors. For B*44:27-positive patients, searches are expected to be more successful when requesting donors from Southeastern-European ancestry. Furthermore, the introduction of human leukocyte antigen (HLA)-typing strategies that allow resolving exon 4 (for class I) and exon 3 (for class II) polymorphisms can be expected to contribute significantly to population genetics studies.

[Impact of anti-HLA antibodies on outcomes of allogeneic stem cell transplantation: a report by the SFGM-TC]. / Impact des anticorps anti-HLA sur le devenir de l'allogreffe de cellules souches hématopoïétiques : un rapport par la SFGM-TC.

The role of anti-HLA antibodies in allogeneic stem cell transplantation setting is still unclear. In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC) set up its fourth annual series of workshops which brought together practitioners from all of its member centers. These workshops took place in September 2013 in Lille. This article offers the recommendations of the group that considered the impact that have anti-HLA antibodies on outcomes in allogeneic stem cell transplantation.

The transcription intermediary factor 1ß coactivates the androgen receptor.

The androgen receptor (AR) is a ligand-inducible transcription factor. Its transcription activation domain consists of the two transcription activation units called Tau-1 and Tau- 5. Tau-5 interacts with p160 coactivators like the transcription intermediary factor 2 (TIF2), which in their turn recruit histone modifiers and chromatin-remodelling complexes. The mechanism of action of Tau-1, however, remains elusive. Here, we demonstrate that transcription intermediary factor 1ß (TIF1ß) can induce the activity of the AR up to five fold when tested in vitro. Although there is no evidence for direct interactions between TIF1ß and AR, mutation studies show that the activity of TIF1ß depends on the integrity of Tau-1 in AR on the one hand, and the so-called tripartite motif domain in TIF1ß on the other. Surprisingly, the coactivation by TIF1ß via Tau-1 seems additive rather than cooperative with the AR coactivation by TIF2. Some mutations naturally occurring in androgen-insensitivity syndrome patients that reside in Tau-1 seem to impair the TIF1ß coactivation of the AR, indicating that TIF1ß could also be relevant for the in vivo androgen response in humans. Moreover, since TIF1ß is well expressed in prostate cancer cells, its functional interaction with androgen signalling could in the long run be a therapeutic target for this disease.

16th IHIW: international histocompatibility working group in hematopoietic cell transplantation.

The International Histocompatibility Working Group is a collaborative international effort to understand the HLA and non-HLA genetics of the transplantation barrier. The Working Group is comprised of experts in the fields of histocompatibility and immunogenetics, hematopoietic cell transplantation and outcomes research. Data for 25 855 unrelated donor transplants were submitted in support of research studies for the 16th International Histocompatibility Workshop. Active investigation is in progress in seven key areas: the impact of HLA matching, role of race and ethnicity, identification of permissible HLA mismatches, haplotype-associated determinants, minor histocompatibility antigens, immune response genes and KIR genetics. New hypotheses for the 16th workshop were developed for immunogenetic studies in cord blood and haploidentical-related donor transplantation.

Pretransplant HLA mistyping in diagnostic samples of acute myeloid leukemia patients due to acquired uniparental disomy.

Although acquired uniparental disomy (aUPD) has been reported in relapse acute myeloid leukemia (AML), pretransplant aUPD involving chromosome 6 is poorly documented. Such events could be of interest because loss of heterozygosity (LOH) resulting from aUPD in leukemic cells may lead to erroneous results if HLA typing for hematopoietic stem cell donor searches is performed on blood samples drawn during blastic crisis. We report here six AML patients whose HLA typing was performed on DNA extracted from peripheral blood obtained at diagnosis. We observed LOH involving the entire HLA region (three patients), HLA-A, B, C (two patients) and HLA-A only (one patient). An array-comparative genomic hybridization showed that copy number was neutral for all loci, thus revealing partial aUPD of chromosome 6p21. When HLA typing was performed on remission blood samples both haplotypes were detected. A 3-4% LOH incidence was estimated in AML patients with high blast counts. Based on DNA mixing experiments, we determined by PCR sequence-specific oligonucleotide hybridization on microbeads arrays a detection threshold for HLA-A, B, DRB1 heterozygosity in blood samples with <80% blasts. Because aUPD may be partial, any homozygous HLA result should be confirmed by a second typing performed on buccal swabs or on blood samples from the patient in remission.

[Chimerism analysis after allogeneic haematopoietic stem cell transplantation. Interest of cell sorting: general review]. / Étude de chimérisme post-greffe de cellules souches hématopoïétiques. Intérêt du tri cellulaire : revue générale.

Haematopoietic stem cells transplantation, widely used these last decades, represent the ultimate treatment resource for patients with haematological malignancies. Long range success of this treatment is particularly affected by relapse of the initial disease, graft rejection or graft versus host disease. Chimerism analysis after transplantation had been used since several years to document engraftment, to determine the risk of relapse and to adapt therapy promptly when necessary. Usefulness of this analysis for the outcome of transplanted patients, as well as the impact of using high sensitive techniques coupled with specific cell populations sorted have been demonstrated by retrospective studies. Follow-up of chimerism would allow to operate efficiently before the onset of clinical signs in leukaemic patients with high risk of relapse and to control the expression of minimal residual disease when specific molecular markers could not be monitored.

[Monitoring of chimerism in myeloid cells sorting of transplanted patients with acute myeloid leukaemia: a study from Lyon (France)]. / Suivi de chimérisme des populations cellulaires myéloïdes chez des patients allogreffés atteints de leucémie aiguë myéloïde : étude lyonnaise.

Chimerism analysis after allogeneic haematopoietic stem cell transplantation has been used to document engraftment and to adapt therapy promptly. The aim of this study was to document engraftment and to detect as soon as possible relapse in patients with acute myeloid leukaemia who underwent stem cell transplantation. Real-time quantitative polymerase chain reaction is a highly sensitive and reproducible technology. It is useful in some disease to target selected sub-populations in order to have an earlier detection of relapse on cell fractions. In the acute myeloid leukaemia (n=65), analysis of the chimerism on whole peripheral blood cells and bone marrow cells, CD3+ cells, specific myeloid CD33+ cells (from blood) and CD34+ cells (from bone marrow) is of importance. After transplant, 25 patients relapsed (38%), three massively, with chimerism detection in whole blood and bone marrow and 22 insidiously following two different schemes (GRI and GRII). In GRI, (n=13): chimerism of CD33+ and CD34+ cellular fractions allowed an early detection of relapse in 100% of cases undetected in whole cells whereas in GRII (n=9): myeloid cells could identified relapse in 89% of cases when whole blood cells and CD3+ cells expressed a mixed chimerism. This study highlighted the importance of sub-cellular population chimerism documentation enable to ascertain a stable engraftment and to detect early relapse. The selection of sub-cellular population studied with high sensitive technology allows a rapid and efficient intervention before the onset of clinical signs in patient with acute myeloid leukaemia and could improve the patient's follow-up.

Evolution of an incompatibility group IncA/C plasmid harboring blaCMY-16 and qnrA6 genes and its transfer through three clones of Providencia stuartii during a two-year outbreak in a Tunisian burn unit.

During a 2-year period in 2005 and 2006, 64 multidrug-resistant Providencia stuartii isolates, including 58 strains from 58 patients and 6 strains obtained from the same tracheal aspirator, were collected in a burn unit of a Tunisian hospital. They divided into four antibiotypes (ATB1 to ATB4) and three SmaI pulsotypes (PsA to PsC), including 49 strains belonging to clone PsA (48 of ATB1 and 1 of ATB4), 11 strains to clone PsB (7 of ATB2 and 4 of ATB3), and 4 strains to clone PsC (ATB3). All strains, except for the PsA/ATB4 isolate, were highly resistant to broad-spectrum cephalosporins due to the production of the plasmid-mediated CMY-16 ß-lactamase. In addition, the 15 strains of ATB2 and ATB3 exhibited decreased quinolone susceptibility associated with QnrA6. Most strains (ATB1 and ATB3) were gentamicin resistant, related to an AAC(6')-Ib' enzyme. All these genes were located on a conjugative plasmid belonging to the incompatibility group IncA/C(2) of 195, 175, or 100 kb. Despite differences in size and in number of resistance determinants, they derived from the same plasmid, as demonstrated by similar profiles in plasmid restriction analysis and strictly homologous sequences of repAIncA/C(2), unusual antibiotic resistance genes (e.g., aphA-6), and their genetic environments. Further investigation suggested that deletions, acquisition of the ISCR1 insertion sequence, and integron cassette mobility accounted for these variations. Thus, this outbreak was due to both the spread of three clonal strains and the dissemination of a single IncA/C(2) plasmid which underwent a remarkable evolution during the epidemic period.

The impact of HLA matching on long-term transplant outcome after allogeneic hematopoietic stem cell transplantation for CLL: a retrospective study from the EBMT registry.

We analyzed 368 chronic lymphocytic leukemia patients who underwent allogeneic hematopoietic stem cell transplantation reported to the EBMT registry between 1995 and 2007. There were 198 human leukocyte antigen (HLA)-identical siblings; among unrelated transplants, 31 were well matched in high resolution ('well matched' unrelated donor, WMUD), and 139 were mismatched (MM), including 30 matched in low resolution; 266 patients (72%) received reduced-intensity conditioning and 102 (28%) received standard. According to the EBMT risk score, 11% were in scores 1-3, 23% in score 4, 40% in score 5, 22% in score 6 and 4% in score 7. There was no difference in overall survival (OS) at 5 years between HLA-identical siblings (55% (48-64)) and WMUD (59% (41-84)), P=0.82. In contrast, OS was significantly worse for MM (37% (29-48) P=0.005) due to a significant excess of transplant-related mortality. Also OS worsened significantly when EBMT risk score increased. HLA matching had no significant impact on relapse (siblings: 24% (21-27); WMUD: 35% (26-44), P=0.11 and MM: 21% (18-24), P=0.81); alemtuzumab T-cell depletion and stem cell source (peripheral blood) were associated with an increased risk. Our findings support the use of WMUD as equivalent alternative to HLA-matched sibling donors for allogeneic HSCT in CLL, and justify the application of EBMT risk score in this disease.