[Digital eye strain. Functional symptoms and binocular balance analysis in intensive digital users]. / Stress oculaire induit par les écrans. Analyses des symptômes fonctionnels et de l'équilibre binoculaire chez des utilisateurs intensifs.

INTRODUCTION: In almost 50 % of cases, acute or chronic screen exposure is accompanied by symptoms of dry eye or binocular imbalance, known as digital eye strain. This phenomenon is described relatively little in the literature. The goal of this study is to determinate the effects of screen exposure on subjective comfort and binocular balance. PATIENTS AND METHODS: This is a cross-sectional, prospective, monocentric pilot study conducted from August to October 2019. The first part of the study focused on disturbances induced by short-term screen exposure (comparison between morning and evening examinations) between a control group (less than 5hours a day) and an exposed group (more than 5hours a day). The second part investigates the consequences of chronic exposure (screen exposure greater than 5hours a day, 5 days a week for one year) excluding pre-presbyopic and presbyopic patients (over 35 years of age). The study parameters consisted of an ocular discomfort questionnaire and binocular function tests (refraction, phoria, near point of accommodation and convergence, fusional vergence (FV), and binocular amplitude facility (BAF)). RESULTS: Short exposure : 52 participants were included. No significant difference was found between the control group (n=24, mean exposure=2.6 hr) and the exposed group (n=28, mean exposure=6.1 hr) for any of the objective parameters. The ocular discomfort score was highest in the exposed group for the following parameters: near (p=0.04) and intermediate (p=0.02) blurred vision and light sensitivity (p=0.04). Chronic exposure: 35 participants were included. The exposed group (n=12, mean exposure=6.7 hr) showed a decrease in FV (p=0.045) and BAF (p=0.038) compared to the control group (n=23, mean exposure=2.1 hr). DISCUSSION: Binocular balance is disturbed by intensive and chronic use of screens. Special attention must therefore be paid to these patients.

[Medical biostatistics with GMRC Shiny Stats - learning by doing]. / Biostatistiques médicales avec GMRC Shiny Stats ­ un outil de formation par la pratique.

Biostatistics are omnipresent in the scientific and medical literature and are an essential skill for any health student. We have developed a practical training tool - GMRC Shiny stats - an interactive application specifically dedicated to medical data statistical analysis. The application has been designed to provide an analysis workflow corresponding to the usual progression of an experienced statistician during data analysis. The most common statistical analyses can be performed (descriptive statistics, inferences according to frequentist methods, survival analyses, correlation, agreement measurements, etc.). GMRC Shiny stats is intuitive and user-friendly and assists students in choosing the most appropriate statistical tests. With all these functionalities, students can learn statistical analysis by doing. Getting involved in the statistical analysis and processing of their own data is likely to improve their biostatistics skills.

Dialkylcarbamoyl chloride-coated versus alginate dressings after pilonidal sinus excision: a randomized clinical trial (SORKYSA study).

BACKGROUND: Disease of the pilonidal sinus is a common condition that affects mainly young adults. Options for management include excision of the sinus tracts, leaving the wound open to heal by secondary intention. The aim of this study was to compare wound healing with dialkylcarbamoyl chloride (DACC)-coated dressings versus alginate dressings. METHODS: This multicentre trial randomized consecutive patients undergoing surgery for pilonidal disease to postoperative wound care with either DACC-coated or alginate dressings. The primary outcome was the proportion of wounds healed after 75 days. Secondary outcomes were the local status of wounds during the healing process, the quality assessment of the dressings by the patient, and the time needed to return to usual activities. RESULTS: A total of 246 patients were included: 120 in the DACC-coated group and 126 in the alginate group. In per-protocol analysis, there were significantly more patients with completely healed wounds after 75 days in the DACC group than in the alginate group: 78 of 103 (75·7 per cent) versus 58 of 97 (60 per cent) respectively (odds ratio 2·55, 95 per cent c.i. 1·12 to 5·92; P = 0·023). During follow-up, wounds with alginate dressings had more fibrin than those with DACC-coated dressings, but the difference was not significant (P = 0·079). There was no difference between the two arms in patients' assessment of the dressings. CONCLUSION: The number of wounds completely healed at 75 days was significantly higher for DACC-coated compared with alginate dressings. However, the preplanned, clinically significant improvement in healing of 20 per cent was not reached. Registration number: NCT02011802 ( https://clinicaltrials.gov/).

ANTECEDENTES: El sinus pilonidal es una afección común que afecta principalmente a adultos jóvenes. Las opciones de tratamiento incluyen la escisión de los trayectos del sinus, dejando la herida abierta para cicatrizar por segunda intención. El objetivo de este estudio fue comparar la cicatrización de heridas con apósitos recubiertos con cloruro de diaquilcarbamoilo (dialkylcarbamoyl chloride, DACC) en comparación con apósitos de alginato. MÉTODOS: En este ensayo multicéntrico se asignó al azar a pacientes consecutivos sometidos a cirugía por sinus pilonidal a uno de los dos brazos: cuidado postoperatorio de heridas con apósitos recubiertos con DACC o con alginato. El criterio de valoración principal fue la proporción de heridas curadas después de 75 días. Los criterios de valoración secundarios fueron el estado local de las heridas durante el proceso de curación, la evaluación de la calidad de los apósitos por parte del paciente y el tiempo necesario para volver a la actividad profesional. RESULTADOS: Se incluyeron un total de 246 pacientes: 120 en el grupo de apósitos recubiertos de DACC y 126 en el grupo de alginato. En el análisis por protocolo, hubo significativamente más pacientes con heridas completamente curadas después de 75 días en el grupo DACC que en el grupo de alginato: 78 de 103 (75,7%) y 58 de 97 (59,7%) respectivamente (razón de oportunidades, odds ratio, OR = 2,55; (1,12; 5,92); P = 0,02)). Durante el seguimiento, las heridas recubiertas con apósitos de alginato tenían más fibrina que las recubiertos con DACC, pero la diferencia no fue significativa (P = 0,08). No hubo diferencias entre los dos brazos en la evaluación realizada por los pacientes de los apósitos. CONCLUSIÓN: El número de heridas completamente curadas a los 75 días fue significativamente mayor con los apósitos recubiertos con DACC en comparación con los apósitos de alginato. Sin embargo, no se alcanzó la mejoría clínicamente significativa preestablecida de una curación del 20%.

[Multidrug-resistant tuberculosis: A management problem that weighs heavily on the University Hospitals of Strasbourg]. / Tuberculose multirésistante : une prise en charge qui pèse lourd aux hôpitaux universitaires de Strasbourg.

INTRODUCTION: Multidrug-resistant tuberculosis (MDR-TB) is a major public health problem with great regional disparities. The aim of this study was to describe the epidemiological, clinical, and therapeutics aspects of MDR-TB in Alsace, France. PATIENTS AND METHODS: A 10 years retrospective study, conducted for the years 2006 to 2016, of all MDR-TB cases diagnosed in Alsace and particularly in Strasbourg University Hospitals. RESULTS: We included 22 patients with MDR-TB of whom 90% originated from Eastern Europe, 13.6% had extensively-resistant strains, and 41% reported previously treated tuberculosis. Clinically, 86,4% had a pulmonary form of tuberculosis. The mean length of antibiotic treatment was 21 months with several changes of drugs because of severe side effects. The mean follow-up was 48 months, during which time 2 patients were lost from contact and the 20 remaining patients were cured. CONCLUSIONS: Management of MDR-TB is a real social and medical challenge. Our study shows that the therapeutic protocols used in the management of these patients lead to an unusually high rate of success despite the occurrence of several, sometimes severe, side effects.

Pre- and post-transplant quantification of measurable ('minimal') residual disease via multiparameter flow cytometry in adult acute myeloid leukemia.

Measurable ('minimal') residual disease (MRD) before or after hematopoietic cell transplantation (HCT) identifies adults with AML at risk of poor outcomes. Here, we studied whether peri-transplant MRD dynamics can refine risk assessment. We analyzed 279 adults receiving myeloablative allogeneic HCT in first or second remission who survived at least 35 days and underwent 10-color multiparametric flow cytometry (MFC) analyses of marrow aspirates before and 28±7 days after transplantation. MFC-detectable MRD before (n=63) or after (n=16) transplantation identified patients with high relapse risk and poor survival. Forty-nine patients cleared MRD with HCT conditioning, whereas two patients developed new evidence of disease. The 214 MRD(neg)/MRD(neg) patients had excellent outcomes, whereas both MRD(neg)/MRD(pos) patients died within 100 days following transplantation. For patients with pre-HCT MRD, outcomes were poor regardless of post-HCT MRD status, although survival beyond 3 years was only observed among the 58 patients with decreasing but not the seven patients with increasing peri-HCT MRD levels. In multivariable models, pre-HCT but not post-HCT MRD was independently associated with overall survival and risk of relapse. These data indicate that MRD(pos) patients before transplantation have a high relapse risk regardless of whether or not they clear MFC-detectable disease with conditioning and should be considered for pre-emptive therapeutic strategies.

The association between donor and recipient statin use and infections after allogeneic hematopoietic cell transplantation.

Recent studies have reported that statin use may be associated with improved outcomes in patients with sepsis or respiratory viral infections. In the setting of allogeneic hematopoietic cell transplantation (HCT), it has been shown that donor and recipient statin use is associated with reduced risks of GVHD. We assessed in retrospective analysis whether donor or recipient statin use impacts infection risk after allogeneic HCT (n=1191). Although recipient statin use was associated with the increased incidence of Gram-negative bacteremia (adjusted hazard ratio (aHR) 2.22, (95% confidence interval (CI) 1.2-4.2), P=0.01) without affecting mortality, donor statin use was associated with an increased incidence of respiratory viral infections in recipients (aHR 2.84 (95% CI 1.3-6.0), P=0.007). The overall incidence of invasive fungal infections and CMV reactivation and CMV disease were not impacted by recipient or donor statin use. In conclusion, this study suggests that recipient or donor statin use may be associated with an increased incidence of some infections without adversely affecting mortality.

Prognostic factors and outcomes of severe gastrointestinal GVHD after allogeneic hematopoietic cell transplantation.

We hypothesized that clinical risk factors could be identified within 2 weeks of onset of severe (stage 3 or 4) acute gut GVHD for identifying a patient population with a very poor outcome. Among 1462 patients who had allogeneic hematopoietic cell transplantation (HCT) between January 2000 and December 2005, 116 (7.9%) developed stage 3-4 gut GVHD. The median time for onset of stage 3-4 gut GVHD was 35 (4-135) days after allogeneic HCT. Eighty-five of the 116 patients (73%) had corticosteroid resistance before or within 2 weeks after the onset of stage 3-4 gut GVHD. Significant risk factors for mortality included corticosteroid resistance (hazards ratio (HR)=2.93; P=0.0005), age >18 years (HR=4.95; P=0.0004), increased serum bilirubin (HR 2.53; P=0.0001) and overt gastrointestinal bleeding (HR 2.88; P=0.0004). Among patients with stage 3-4 gut GVHD, the subgroup with 0, 1 or 2 risk factors had a favorable prognosis, whereas the subgroup with 3 or 4 risk factors had a dismal prognosis. This information should be considered in designing future studies of severe gut GVHD and in counseling patients about prognosis.

Steroid-sparing effect of extracorporeal photopheresis in the therapy of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

INTRODUCTION: Steroid-refractory graft-versus-host disease (GVHD) remains a challenging therapeutic problem after allogeneic hematopoietic stem cell transplantation (HSCT). The aim of this study was to evaluate the clinical effect of extracorporeal photopheresis (ECP), and its impact on intensivity of immunosuppresive therapy in allogeneic HSCT patients. PATIENTS AND METHODS: In this study 443 Therakos ECP procedures were performed in 21 patients after allogeneic HSCT with acute (aGVHD, 8 patients) or chronic (cGVHD, 13 patients) therapy-refractory GVHD. The median age at ECP onset was 20.5 years (range, 10-55). Venous access was provided by a nontunelized central venous catheter (12 patients) or 9.6-French portacath (9 patients). RESULTS: In the cGVHD group 9/13 patients were improved with a 4-year overall survival rate of 67.7%. ECP led to steroid discontinuation in 6 and substantial dose reduction in 5 patients. The prednisone dose equivalent per kilogram body weight decreased from 0.32 mg to 0.07 mg after therapy. Therapy of aGVHD led to complete or partial symptom remission in 3/9 subjects. The change in steroid dose in the aGVHD group was not significant, there were no long-term survivors. Portacath access was well tolerated and provided adequate blood flow rates. CONCLUSIONS: The ECP therapy significantly reduced the rates of remissions with steroid discontinuation among cGVHD but not aGVHD patients. Rare ECP-related complications were either catheter related or anticoagulation induced during ECP procedures. Photopheresis was a safe, effective method to treat steroid-resistant cGVHD.

Benign inflammatory pseudotumour of the parotid gland: a case report and literature review.

We describe a rare case of benign inflammatory pseudotumour of the parotid gland. The literature concerning this condition is discussed.

Patient satisfaction with conventional and nurse-led telephone follow-up after nasal septal surgery.

The need to bring down costs while maintaining a high standard of care has led to the expansion in the role of nurses in recent years. We present results of an audit of patient satisfaction with conventional and nurse-led telephone follow-up after nasal septal surgery. Our results indicate that patient satisfaction with nurse-led telephone follow-up is significantly higher than conventional follow-up (p=0.001, two-tailed). More patients in the conventional follow-up group felt that a follow-up appointment with an ENT doctor was essential compared with the patients in the nurse-led telephone follow-up group (p<0.001, two-tailed). We conclude that nurse-led telephone follow-up avoids unnecessary outpatient appointments, while identifying patients who require further care. It makes more appointment slots available for patients with pressing clinical problems and has the potential to reduce outpatient access times in the NHS.

Identification of 6-furfuryladenine (kinetin) in human urine.

In contrast to the current view of kinetin (K, N(6)-furfuryladenine) as an unnatural and synthetic cytokinin, recently it has been identified in plant DNA and plant extract. Here we describe identification of K in human urine using chromatography/mass-spectrometry analysis for the first time. The amount of kinetin in urine taken from unhealthy patients lung carcinoma was established to be 0.5 ng in 20 ml and a 100-fold reduced amount in healthy subjects. Since this rare base is a potential source of structural constrains it has to be removed from DNA by enzymatic DNA-repair reactions. It seems that the presence of kinetin in human is linked to oxidative damage processes.

Graft-versus-host disease and donor-directed hemagglutinin titers after ABO-mismatched related and unrelated marrow allografts: evidence for a graft-versus-plasma cell effect.

The gradual disappearance of host antidonor isohemagglutinins after major ABO-mismatched hematopoietic stem cell (HSC) allografts has been attributed to the gradual destruction of host plasma cells by graft-versus-host effects. To corroborate this hypothesis, we retrospectively analyzed results from 383 major or major/minor ABO-mismatched unrelated and related HSC allografts performed between 1983 and 1998. All patients were conditioned by high-dose pretransplant therapy and given methotrexate/cyclosporine for graft-versus-host disease (GvHD) prophylaxis. Of the 383 patients, 155 had HLA-matched related and 228 had unrelated grafts. We asked whether unrelated recipients experienced a more rapid disappearance of isohemagglutinins than related recipients, and whether, within the groups of related and unrelated recipients, the titer disappeared faster in patients with GvHD than in those without GvHD. The median time to reach undetectable antidonor IgG and IgM titers was significantly shorter in unrelated recipients (46 versus 61 days; P =.016). In addition, related recipients with GvHD had a 2. 2-fold increased likelihood (1.12-4.39,95% CI; P =.02) of reaching undetectable titers within 100 days than patients without GvHD. The persistence of antidonor isohemagglutinins led to significantly increased red blood cell (RBC) transfusion requirements in the ABO-mismatched related patients compared with ABO-matched counterparts. However, time to neutrophil and platelet engraftment, incidence of GvHD, and survival were not influenced by ABO incompatibility. In conclusion, our results corroborate the hypothesis that the rate of disappearance of antidonor isohemagglutinins after ABO-mismatched allogeneic HSC grafts is influenced by the degree of genetic disparity between donor and recipient, suggesting a graft-versus-plasma cell effect.

Haemopoietic reconstitution by donor-derived myelodysplastic progenitor cells after haemopoietic stem cell transplantation.

A 50-year-old woman who was retrospectively diagnosed with an early asymptomatic myelodysplastic syndrome (MDS) served as a haemopoietic stem cell donor for her HLA-identical sister who had chemotherapy-refractory non-Hodgkin's lymphoma. The MDS of the donor was classified as refractory anaemia (RA) and cytogenetically characterized by deletion of the long arm of chromosome 20 [del(20q)]. Donor cell engraftment in marrow and peripheral blood was analysed over a period of 5 months after transplant using conventional cytogenetics, fluorescence in situ hybridization, and variable number of tandem repeats. Neutrophil counts >0.5 x 109/l and platelet counts >20 x 109/l were reached promptly on days 12 and 24, respectively. Throughout the period of observation the percentage of cells with the del(20q) abnormality in the recipient's marrow and peripheral blood was comparable to the proportion of these cells in the donor. These data indicate that the abnormal clone was capable of homing to the marrow, proliferating, differentiating, and therefore contributing to haemopoiesis in a relatively efficient manner. This implies that MDS progenitor cells may not have homing and growth deficiencies, a finding that has particular relevance for autologous transplantation in MDS patients where tumour cells potentially contaminate the graft.

Production of interleukin-10 by granulocyte colony-stimulating factor-mobilized blood products: a mechanism for monocyte-mediated suppression of T-cell proliferation.

Previous reports showed that granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood mononuclear cells (G-PBMC) are hyporesponsive to alloantigen compared with control PBMC. In the current study, neutralizing antibodies to interleukin-10 (IL-10) increased the proliferative response of G-PBMC to alloantigen by 50. 14% (+/- 12.79%; n = 8), whereas the proliferative response of control PBMC was not affected. The inhibition of OKT3-stimulated CD4 cell proliferation by G-PBMC-derived CD14(+) cells could also be abrogated by the addition of IL-10 neutralizing antibodies. Further, IL-10 levels correlated with the number of CD14 cells in these cultures. Constitutive IL-10 mRNA levels detected by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) were 10-fold higher in G-PBMC compared with control PBMC. This translated into significantly higher IL-10 levels after 24-hour lipopolysaccharide (LPS) stimulation of G-PBMC compared with control PBMC (P = .036). IL-10 mRNA levels were also fivefold higher in isolated G-PBMC-derived CD14 cells compared with control CD14 cells. This corresponded to increased constitutive production of IL-10 by isolated G-PBMC-derived CD14 cells compared with control CD14 cells (357.2 +/- 104.5 v 51.7 +/- 30.5, P = .051). In conclusion, these data suggest that monocytes contained within G-PBMC, which, in comparison to marrow, are increased in absolute number and relative proportion to T cells, may suppress T-cell responsiveness by secretion of IL-10.

Impaired induction of the CD28-responsive complex in granulocyte colony-stimulating factor mobilized CD4 T cells.

Use of the CD28/B7 costimulatory signal for T-cell activation was analyzed in granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood mononuclear cells (G-PBMCs) and in peripheral blood mononuclear cells obtained before administration of G-CSF (preG-PBMCs). CTLA4Ig inhibition of OKT3-stimulated proliferation was significantly lower in G-PBMCs compared with preG-PBMCs (39.9% +/- 5.6% and 72.2% +/- 5.4%, respectively; P < .001). Furthermore, as shown in electrophoretic mobility-shift assays, the inducible level of the T-cell transcription factor CD28 responsive complex (CD28RC) was suppressed in CD4 cells derived from G-PBMC. However, depletion of CD14 cells from G-PBMCs restored CD28RC induction to normal levels. Taken together, these findings suggest that the large number of CD14 monocytes in G-PBMCs may limit T-cell responsiveness by suppressing the induction of the CD28RC.

Differential modulation of adhesion markers with ex vivo expansion of human umbilical CD34+ progenitor cells.

The effect of different expansion protocols on the expression levels of CD49dw/CD29 (VLA-4), CD11a/CD18 (LFA-1), CD31 (PECAM-1), CD44, and CD34 was determined after cord blood CD34+ cells were cultured for defined periods with the following: 1) A growth factor mix (GFmix) containing interleukin (IL)-1, IL-3, IL-6, kit ligand (KL), G-CSF, GM-CSF, and erythropoietin (Epo); 2) IL-3 + KL; and 3) HS-5 (a human stromal cell line supernatant) + KL. Before culturing, cord blood CD34+ cells (> 95% purity) were 94 +/- 5% CD31+, 98 +/- 1% CD44+, 66 +/- 29% VLA-4+, and 68 +/- 18% LFA-1+ (mean +/- SEM). Immunophenotyping and morphological examination of pre- and post-cultured cells indicated that GFmix preferentially supported erythroid development, while IL-3+KL and HS-5+KL preferentially supported myeloid development. Similar to what other investigators have reported, there was an absolute increase in CD34+ cell numbers as well as clonogenic precursors with ex vivo expansion. However, the majority of clonogenic precursors post-expansion expressed CD34 antigen at reduced levels. Examination of adhesion molecules indicated that a majority of cells cultured with GFmix expressed PECAM-1 and LFA-1 at undetectable levels, but PECAM-1 and LFA-1 levels remained essentially unchanged when cells were cultured with IL-3+KL and HS-5+KL. Overall VLA-4 expression levels slightly increased and CD44 expression levels were more heterogeneous with ex vivo expansion. Nevertheless, LFA-1, VLA-4, PECAM-1, and CD44 expression levels remained essentially unchanged on cultured progeny retaining a CD34 phenotype, independent of the culture system used. Together these results indicate that differential modulation of adhesion markers occur with different culture conditions, yet adhesion receptor expression levels on progeny cells retaining a CD34 phenotype are essentially maintained independent of the culture conditions. And although there is an absolute increase in CD34+ cells after ex vivo expansion, a majority of clonogenic precursors have reduced levels of CD34 antigen.

Phenotype and engraftment potential of cytokine-mobilized peripheral blood mononuclear cells.

Cytokine-mobilized peripheral blood stem cell products are increasingly used for hematopoietic reconstitution after myeloablative therapy. Favorable engraftment kinetics, the ease of harvest, and the large number of CD34+ cells obtained that allow for graft manipulations (ie, tumor cell or T-cell depletion) have made this stem cell source an attractive alternative to marrow. More recent data suggest that in addition to the increased number of CD34 cells, there may be also qualitative differences between leukapheresis products and marrow. In the allogeneic transplantation setting, the one log more T cells contained in granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells compared with marrow has not translated into more severe graft-versus-host disease, indicating possible differences in T-cell or accessory-cell function. Whether such differences will compromise graft-versus-leukemia effects and disease-free survival remains to be seen. Nevertheless, it is reasonable to speculate that cytokine-mobilized peripheral blood products may eventually replace marrow as a source for hematopoietic stem cells. However, each new mobilization strategy needs to be evaluated carefully, as comparable increases in CD34 cell numbers may not necessarily affect the same, as yet underlined, qualitative changes that make this product so attractive.

Suppression of alloantigen-induced T-cell proliferation by CD14+ cells derived from granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells.

The proliferative responsiveness of granulocyte colony-stimulating factor (G-CSF)-mobilized blood was studied in uni-directional mixed leukocyte cultures. Unfractionated mononuclear cells from mobilized blood obtained by leukapheresis at day 4 after initiation of G-CSF (G-PBMC) were hyporesponsive (31.5% +/- 9.2% response, P = .003) compared to mononuclear cells obtained from the peripheral blood before administration of G-CSF (preG-PBMC). There was great variability among donors when purified preG- and G-CD4 cells were compared. In eight of 10 donors, G-CD4 cells were equally responsive or moderately hyporesponsive; in two of 10 donors, G-CD4 cells were more strikingly hyporesponsive. CD14 cells derived from leukapheresis products (G-CD14 cells) suppressed alloantigen-induced proliferation by 48.6% +/- 7.5% when added to preG-PBMC or preG-CD4 cells at responder-CD14 ratios of 2:1 (P < .001). Suppression was evident (14.4% +/- 5.0%) even at responder-CD14 ratios of 8:1 and was largely contact-independent. PreG- and G-CD14 cells had equivalent potency in suppressing proliferative responses. Given that G-CSF-mobilized blood cell grafts contain 50-fold more CD14 cells and only 10-fold more T cells than marrow, we propose that suppression of donor T cells by the large proportion of monocytes present in leukapheresis products could contribute to the unexpectedly low incidence and severity of graft-versus-host disease after peripheral blood stem cell transplantation.