Dalbavancin for treating prosthetic joint infections caused by Gram-positive bacteria: A proposal for a low dose strategy. A retrospective cohort study.

OBJECTIVE: Gram-positive bacteria are the leading cause of prosthetic joint infection (PJI). Dalbavancin is a lipoglycopeptide with remarkable pharmacokinetic properties and high bactericidal activity against most Gram-positive bacteria. Although clear evidence regarding its effectiveness in bone and joint infections lacks, recent studies suggest a promising role of dalbavancin in PJI. METHODS: From June 1st 2016 to May 1st 2018, all patients diagnosed of PJI and treated with DAL alone or in combination with other drugs were retrospectively evaluated. Dalbavancin susceptibility of every isolate was studied following CLSI criteria. The primary objective was to assess the clinical efficacy and tolerability of the drug in patients with PJI. A cost-analysis was performed following the DALBUSE study methodology. RESULTS: Sixteen patients were treated with dalbavancin, eight with total hip arthroplasty infection (THAi) and eight with total knee arthroplasty infection (TKAi). Staphylococcus spp. and Enterococcus spp. were the microorganisms involved. No major side effects were detected. Infection resolved in 12 patients. In 2 patients the treatment failed, and another patient died due to unrelated causes. One patient is currently being treated for hematogenous-spread knee infection secondary to prosthetic aortic arch endocarditis. After discontinuation of dalbavancin, and excluding patients who died or with clinical failure, the median follow up of the cohort was 503 days (interquartile range IQR, 434.5 to 567 days). We calculate that US$ 264,769 were saved. CONCLUSIONS: This study suggests that dalbavancin treatment for PJI caused by Gram-positive bacteria is a safe and effective option that reduces hospital stay and costs. Future reports are needed to confirm these findings.

[Accuracy of ultrasound estimated fetal weight at term]. / Performance de l'échographie dans l'estimation du poids fœtal à terme.

OBJECTIVES: Our aim was to evaluate the accuracy of estimated fetal weight (EFW) by ultrasound at due date and the factors that could affect it. METHODS: We performed a retrospective study of 233 patients in 2014. An ultrasound was performed at due date consultation around 41 weeks of amenorrhea by midwives sonographer. EFW was calculated using the Hadlock's formula with 3 parameters (biparietal diameter, abdominal circumference and femur length) and then adjusted including the growth from the due date consultation to the day of delivery (25g/day) and finally compared to birth weight (BW). RESULTS: The mean absolute weight difference between EFW adjusted and BW was 256g [0; 910]. The mean absolute percentage error was 7.2 % [0; 24.5] and the proportion of the EFW adjusted within 10 % of BW was 69.1 %. There was a strong correlation between EFW adjusted and BW (R=0.79). Obesity in early pregnancy or childbirth, excessive weight gain, the presence of oligoanamnios and fetal macrosomia had no influence on the estimated fetal weight. Indeed, the mean absolute percentage error of child who were macrosome and those were not, was similars (7.9 % vs 7.1 %, P=0.407). CONCLUSIONS: EFW by ultrasound at due date is performant. However, the adjustment by the effect growth does not improve accuracy. Fetal macrosomia do not decrease the accuracy of ultrasound to estimate the fetal weight at term.

Mesenchymal stromal cells derived from cervical cancer tumors induce TGF-ß1 expression and IL-10 expression and secretion in the cervical cancer cells, resulting in protection from cytotoxic T cell activity.

Cervical cancer (CeCa) tumors are characterized by increased expression of TGF-ß1 and IL-10, which are correlated with downregulated expression of major histocompatibility complex class I antigens (HLA-I) on cancer cells and a reduced immune response mediated by cytotoxic T lymphocytes (CTLs). Mesenchymal stromal cells (MSCs) are important components in the tumor microenvironment that have been suggested to contribute to cancer progression through the induction of TGF-ß1 and IL-10. In this study, we provided evidence that MSCs derived from cervical tumors (CeCa-MSCs) cocultured with CeCa cells induced significant expression of TGF-ß1 and secretion of IL-10 by CeCa cells compared to MSCs derived from the normal cervix (NCx-MSCs) and normal bone marrow (BM-MSCs; gold standard). This increase in expression was associated with a significant downregulation of HLA-I molecules and protection of the cells against specific CTL lysis. Interestingly, the addition of the neutralizing antibody anti-TGF-ß to the CeCa/CeCa-MSCs coculture strongly inhibited the expression and production of IL-10 by CeCa cells. Anti-TGF-ß as well as anti-IL-10 also abolished HLA-I downregulation, and reversed the inhibition of CTL cytotoxicity. These results provide evidence that TGF-ß1 and IL-10 could play an important role in the downregulation of HLA-I molecules on CeCa cells induced by tumor MSCs. Our findings suggest a novel mechanism through which MSCs may protect tumor cells from immune recognition by specific CTLs.

Frey syndrome: factors influencing the time to event.

Frey syndrome is a common complication after parotidectomy. The time from surgery to disease onset may be quite long; therefore, a time-to-event analysis was performed for the occurrence of this syndrome post-parotidectomy. Three hundred and thirty-four patients who underwent a parotidectomy between January 2002 and November 2012 were identified (retrospective study). Of these patients, 102 developed Frey syndrome post-surgery and 232 did not. The time-to-onset analysis enabled us to estimate the risk ratio associated with different types of parotid gland tumours, various parotidectomy procedures, and repeat parotidectomy, which is useful for predicting preoperative and surgical risk. The risk of developing Frey syndrome was lower in patients with malignant tumours than in those with benign tumours (risk ratio 0.351, 95% confidence interval (CI) 0.155-0.594). Risk ratios for lumpectomy PA (pre-auricular area), superficial parotidectomy, and total parotidectomy with respect to lumpectomy T (tail) were 4.378 (95% CI 1.168-16.410), 8.040 (95% CI 3.286-19.670), and 8.174 (95% CI 3.076-21.723), respectively. Repeat parotidectomy also increased the risk of developing Frey syndrome (risk ratio 3.214, 95% CI 1.547-6.678). No effect of the use of a superficial muscular aponeurotic system (SMAS) flap on the risk of developing Frey syndrome was detected (P=0.888).

[Use of chemotherapy and radiotherapy in the treatment of urothelial carcinoma of the upper urinary tract]. / Quelle place pour la radiothérapie et la chimiothérapie dans le traitement adjuvant des carcinomes urothéliaux des voies excrétrices urinaires supérieures ?

Urothelial carcinomas of the upper urinary tract are rare entities. Surgery remains the mainstay of the management. The use of others therapeutic modalities is not clearly defined yet. However, the frequency of local recurrence and locoregional encourage us to evaluate the indication of adjuvant therapies. We conducted a synthesis of key data in the literature on the use of chemotherapy and radiotherapy in the treatment of urothelial carcinoma of the renal pelvis and ureter. A literature search on PubMed was performed using the following keywords (MeSH) "urothelial carcinoma", "upper urinary tract", "radiation", "chemotherapy", and adjuvant.

An annual survey of bacterial production, respiration and ectoenzyme activity in coastal NW Mediterranean waters: temperature and resource controls.

We simultaneously measured bacterial production (BP), bacterial respiration (BR), alkaline phosphatase activity (phos) and ectoaminopeptidase activity (prot) in relation to biogeochemical parameters, nutritive resources and in situ temperature over a 1-year survey at the long-term observatory the SOLEMIO station (Marseille bay, NW Mediterranean Sea). Despite its proximity to the coast, oligotrophic conditions prevailed at this station (yearly mean of Chl a = 0.43 µg dm(-3), NO3 = 0.55 µmol dm(-3) and PO4 = 0.04 µmol dm(-3)). Episodic meteorological events (dominant winds, inputs from the Rhone River) induced rapid oscillations (within 15 days) in temperature and sometimes salinity that resulted in rapid changes in phytoplankton succession and a high variability in C/P ratios within the particulate and dissolved organic matter. Throughout the year, BP ranged from 0.01 to 0.82 µg C dm-(3) h-(1) and bacterial growth efficiency varied from 1 to 39%, with higher values in summer. Enrichment experiments showed that BP was limited most of the year by phosphorus availability (except in winter). A significant positive correlation was found between in situ temperature, BP, BR and phos. Finally, we found that temperature and phosphate availability were the main factors driving heterotrophic bacterial activity and thus play a fundamental role in carbon fluxes within the marine ecosystem.

Per-operative hemodynamic instability in normotensive patients with incidentally discovered pheochromocytomas.

CONTEXT: The per-operative hemodynamic behavior of normotensive incidentally discovered pheochromocytomas is poorly documented. OBJECTIVE: To compare the per-operative hemodynamic instability and early postoperative outcome of normotensive pheochromocytomas, hypertensive pheochromocytomas, and benign non-pheochromocytoma adrenal incidentalomas (AIs). DESIGN: Retrospective cohort treated in a single center. PATIENTS AND METHODS: Fifty patients (10 normotensive pheochromocytomas, 24 hypertensive pheochromocytomas, and 16 AIs) were anesthetized and operated on by the same team, using laparoscopy in 78% of cases. Before surgery, 60% of normotensive and 95.8% of hypertensive pheochromocytomas received pretreatment with α-receptor or calcium channel blockers. All of the patients received the same intraoperative hemodynamic monitoring, including continuous direct intra-arterial pressure recording. RESULTS: All the features of hemodynamic instability, with the exception of the diastolic pressure nadir and fluid volume requirements, differed between hypertensive pheochromocytomas and AIs. Conversely, all features of hemodynamic instability were similar in hypertensive and normotensive pheochromocytomas. More specifically, by comparison with AIs, normotensive pheochromocytomas displayed higher maximal systolic pressure; more hypertensive, severe hypertensive, and hypotensive episodes; and a higher minimal heart rate, and also required more interventions to treat undesirable blood pressure elevations. Postoperative complications, all of which were mild, were more frequent in hypertensive pheochromocytomas than in normotensive pheochromocytomas (P < .03). CONCLUSIONS: Normotensive pheochromocytomas have roughly comparable per-operative hemodynamic instability to hypertensive pheochromocytomas and differ markedly from non-pheochromocytoma AIs. It is therefore crucial to identify normotensive pheochromocytomas among AIs when surgery is scheduled and to apply the standard of care for pheochromocytoma anesthesia.

Overexpression of hypoxia-inducible factor 1 alpha impacts FoxP3 levels in mycosis fungoides--cutaneous T-cell lymphoma: clinical implications.

Mycosis fungoides (MF) is the most common variant of primary cutaneous T-cell lymphoma, and decreased forkhead box P3 (FoxP3) expression has been reported in MF late stages. Hypoxia-inducible factor 1 alpha (HIF-1α) may regulate FoxP3 expression; however, it is unknown whether HIF-1α is expressed in the CD4(+) T cells of MF patients and how it could affect the expression of FoxP3. Therefore, we evaluated the expression of HIF-1α and FoxP3 in CD4(+) T cells obtained from the skin lesions of MF patients. We found increased cell proliferation and an increase in CD4(+) T cells with an aberrant phenotype among early stage MF patients. HIF-1α was overexpressed in these CD4(+) T cells. In addition, we found a decrease in the percentage of FoxP3(+) cells both in the skin of MF patients, when compared with control skin samples, and with disease progression. In addition, a negative correlation was established between HIF-1α and FoxP3 expression. Skin HIF-1α expression in MF patients correlated with the extent of the affected area and increased with the disease progression. Finally, we showed that ex vivo inhibition of HIF-1α degradation increases the percentage of FoxP3(+) T cells in skin lesions. Our results suggest that overexpression of HIF-1α affects the levels of FoxP3 in MF patients, which could have relevant implications in terms of disease outcome.

Effect of glycophosphopeptide on the lymphocytes and IgA of Olympic platform divers.

AIM: The aim of this paper was to evaluate the effect of a treatment with glycophosphopeptide on Olympic high platform divers during training and competition by measuring lymphocytes and cortisol in peripheral blood, and secretory immunoglobin A in saliva (sIgA). METHODS: Two groups of 8 divers were given a 14-day treatment of capsules (Gp or placebo) three times per day. Measurements of the peripheral blood lymphocytes (TCD3+, TCD4+ and T CD8+), plasma cortisol and IgA levels in saliva were made on day 0, 21 and 150. RESULTS: There was no significant difference found between the Gp- and placebo-treated groups regarding the increase in IgA between basal and first, or first and second measurements. The fact that there was a significant increase in S-IgA (9.89 ± 0.44 to 10.59±0.55, P=0.001) and B CD19+ (345.13±108.24 to 484.75±120.54, P=0.025) in the Gp- and not in the placebo-treated group between the basal and first measurement was due to the variation among the athletes of the latter group, and not the increase itself, indicating that Gp acted as an immunomodulator. It was apparently the exercise and not the Gp treatment that caused the increase in S-IgA and B CD19+ at the first and second measurements. CONCLUSION: The current study reports that with athletes who practiced moderately intense exercise, which stimulated the immune response, a Gp treatment of two weeks seems to have acted only as an immunomodulator that reduced the variation in the increased levels of IgA and B CD19+.

Prolactin down-regulates CD4+CD25hiCD127low/- regulatory T cell function in humans.

Among its many functions, prolactin (PRL) participates in immune responses and promotes the activation, differentiation and proliferation of T cells. However, the mechanisms by which PRL regulates regulatory T (T(reg)) cells are still unknown. Our goal was to determine whether PRL plays a role in T(reg) function. We measured the expression of PRL and its receptor in T(reg) and effector T (T(eff)) cells from 15 healthy individuals. We also evaluated the functional activity of T(reg) cells by examining proliferation and cytokine secretion in cells activated with anti-CD3/CD28 in the presence or absence of PRL. We report that T(reg) cells constitutively expressed PRL receptor, whereas T(eff) cells required stimulation with anti-CD3/CD28 to induce PRL receptor expression. Expression of PRL was constitutive in both populations. We found that the addition of PRL inhibited the suppressor effect (proliferation) mediated by T(reg) cells in vitro, reducing suppression from 37.4 to 13% when PRL was added to co-cultures of T(reg) and T(eff) cells (P<0.05). Cultures treated with PRL favoured a Th1 cytokine profile, with increased production of TNF and IFNγ. We report for the first time that PRL receptor expression was constitutive in T(reg) cells but not in T(eff) cells, which require stimulation to induce PRL receptor expression. PRL inhibited the suppressive function of T(reg) cells, apparently through the induced secretion of Th1 cytokines.

In search of effective bioassessment of urban stormwater pond sediments: enhancing the 'sediment quality triad' approach with oligochaete metrics.

Stormwater ponds have been widely used to control increased volumes and rates of surface runoff resulting from urbanization. As receiving waters, they are under the influence of intermittent pollution from urban wet-weather discharges. Meanwhile they offer new aquatic habitats balancing the transformation of initial ecosystems and their associated biodiversity. Bioassessment of stormwater facilities is therefore crucial to insure the preservation and rehabilitation of biodiversity in urban areas. Nonetheless, the application of traditional bioassessment methodologies such as the sediment quality triad (SQT), based on the comparisons with reference sites, is challenged by the artificial and atypical features of urban stormwater ponds. Our concern in finding a more specific and effective bioassessment methodology led us to consider associating the Oligochaete Index Methodology (OIM) with the SQT. This study shows that although some adjustments were needed, the OIM brought new and complementary information to the SQT assessment on the effects of contaminants and on the biological quality status of the sediment in a test urban stormwater pond.

Bioassessment of wet-weather pollution impacts on fine sediments in urban waters by benthic indices and the sediment quality triad.

Benthic invertebrate assessments can be used to gauge the impact of urban wet-weather flows in receiving waters. Experiences from Cemagref in France have shown that standardized benthic indices (e.g. Oligochaete Index of Sediment Bioindication - IOBS) can be used to reliably determine the ecological status of urban streams and can be incorporated into the new European Water Framework Directive. The Canadian studies on streams and stormwater ponds using chemical analyses, benthic toxicity testing and benthic invertebrate community structure (i.e. the sediment quality triad) comparisons have shown that toxicity was more likely to occur in ponds at sites with higher concentrations of heavy metals and heavier polycyclic aromatic hydrocarbons, and at greater water depths, where fine sediments from urban runoff accumulated. A more comprehensive evaluation of wet-weather flow impacts could be obtained by combining approaches from both countries.

Peripheral blood CD161+ T cells from asthmatic patients are activated during asthma attack and predominantly produce IFN-gamma.

In humans, T cells expressing the CD161 molecule NKR-P1A constitute around 20% of the circulating CD3(+) cells and are potentially immunoregulatory in several diseases. Their role in asthma is not well known, but they could participate in asthma attacks. To determinate whether activation of CD161(+) T cells and their cytokine production correlate with clinical status of asthma, we analysed blood samples from asthma attack patients (AAP) and stable asthma patients (SAP) in comparison with healthy non-atopic controls (HC). There was a significant higher baseline expression of CD69 on T cells from AAP and the difference was more notorious on CD161(+) T cells; upregulation of CD69 was observed on both CD161(-) and CD161(+) T cells driven by Dermatophagoides pteronyssinus crude extract, whereas polyclonal stimulation with phorbol 12-myristate 13-acetate plus ionomycin predominantly induced IFN-gamma but no IL-4, IL-5 and IL-13 by CD161(+) T cells in all groups; upon polyclonal stimulation, there were more CD161(+) T cells producing IFN-gamma and less CD161(-) T cells producing this cytokine, contrasting with the opposite results observed in SAP and HC groups. Our results indicate that, during asthma attack, CD161(+) T cells are activated and are able to produce predominantly IFN-gamma but no Th2 cytokines. We hypothesize that during an asthma attack, IFN-gamma produced by CD161(+) T cells could help to reestablish the Th1/Th2 equilibrium. These observations may contribute to the understanding of the immune mechanisms involved in asthma attacks.

Peripheral blood mobilization of different lymphocyte and dendritic cell subsets with the use of intermediate doses of G-CSF in patients with non-Hodgkin's lymphoma and multiple myeloma.

Between June 2003 and November 2004, we collected mobilized peripheral blood units from 29 patients with non-Hodgkin's lymphoma and multiple myeloma for autologous peripheral blood stem cell transplantation. They received granulocyte colony-stimulating factor (G-CSF) (16 micro g/kg/day) for a total of 5 days. Immediately before and 3 h after the fourth and fifth dose of G-CSF, we performed flow cytometry analysis to quantify: T cells (CD3+CD4+, CD3+CD8+), B cells (CD19+), NK cells (CD3-CD16+CD56+), NKT cells (CD3+CD16+CD56+), type 1 dendritic cells (DC1) (lin-HLA-DR+CD11c+), type 2 dendritic cells (DC2) (lin-HLA-DR+CD123+), regulatory T cells (Tregs) (CD4+CD25+), and activated T cells (CD3+HLA-DR+). All cell subsets were mobilized after G-CSF treatment with the exception of B, NK, and NKT lymphocytes. The median number of Treg cells before and after G-CSF was statistically different (29+/-14.9x10(6)/l vs 70.1+/-46.1x10(6)/l, P<0.02). DCs were mobilized significantly with a 5.9-fold increase in DC2 (15.1+/-30.3x10(6)/l vs 89.8+/-81.0x10(6)/l, P<0.02) and a 2.6-fold increase for DC1 (41+/-42.5x10(6)/l vs 109.5+/-58.0x10(6)/l, P<0.04). Patients received a mean of 3.1+/-1.2x10(7)/kg NK cells, 1.3+/-0.9x10(7)/kg NKT cells, 0.41+/-0.29x10(7)/kg DC1, 0.2+/-0.22x10(7)/kg DC2, and 1.8+/-1.9x10(7)/kg Tregs. In conclusion, intermediate doses of G-CSF induce mobilization of different lymphocyte subsets, with the exception of B, NK, and NKT cells. The mobilization of certain suppressive populations (DC2 and Treg) could be in theory deleterious, at least in patients with cancer.

Clinical relevance of NK, NKT, and dendritic cell dose in patients receiving G-CSF-mobilized peripheral blood allogeneic stem cell transplantation.

To analyze the relationship between the cellular composition of peripheral blood allografts and clinical outcome, we performed a prospective study in 45 adult patients who underwent allogeneic peripheral blood hematopoietic stem cell transplantation (HSCT) from a histocompatibility leukocyte antigen identical sibling donor for different hematological malignancies. The dose of CD34+, CD3+, CD4+, CD8+, and CD19+ lymphocytes, natural killer (NK) cells, natural killer T (NKT) cells, type 1 and type 2 dendritic cells (DC1 and DC2), as well as regulatory T (Treg) lymphocytes was analyzed. All patients were conditioned with busulphan and cyclophosphamide (BuCy2) +/- VP-16 and received a short course of methotrexate and cyclosporin-A as graft-versus-host disease (GVHD) prophylaxis. Acute GVHD (aGVHD) was present in 9 of 43 (21%) patients, and chronic GVHD (cGVHD) developed in 18 of 39 (46%) patients. There was a significantly higher incidence of aGVHD in patients receiving more than 6x10(6)/kg CD34+ cells. In univariate analysis, variables associated with better survival were as follows: a dose of less than 1.5x10(7)/kg NKT cells and less than 1.7x10(6)/kg DC2 for disease-free survival (DFS), and a dose of less than 3x10(7)/kg NK cells, less than 1.5x10(7)/kg NKT cells, less than 3x10(6)/kg DC1, and less than 1.7x10(6)/kg DC2 for overall survival (OS). In the Cox regression analysis, the dose of NKT cells was the only variable associated with better DFS, while the doses of NK, NKT, and CD34+ cells (less than 8x10(6)/kg) were associated with better OS. In conclusion, different circulating cell populations, other than CD34+ cells, are also of relevance in predicting the clinical outcome after allogeneic peripheral blood HSCT.

CD4+ CD25+ lymphocyte and dendritic cell mobilization with intermediate doses of recombinant human granulocyte colony-stimulating factor in healthy donors.

We prospectively conducted a quantitative and phenotypic analysis of T, B, natural killer (NK), NKT, type 1 and 2 dendritic cells (DC), and regulatory T cells, before and after mobilization with intermediate doses of granulocyte colony-stimulating factor (G-CSF) (16 microg/kg per day). Between November, 2003, and December, 2004, we collected stem cells from 25 HLA identical sibling donors for allogeneic hematopoietic stem cell transplantation. Before mobilization and 3 h after the fourth and fifth doses of G-CSF, blood samples were taken for blood counts and flow cytometry. The median number of regulatory T cells before and after G-CSF was statistically different (69 +/- 41 x 10(6)/L versus 161 +/- 159 x 10(6)/L, p < 0.01). We observed a 1.7-fold increase in NK and NKT cells (p < 0.009 and p < 0.02, respectively). DC were mobilized with a 11.5-fold increase in type 2 (p < 0.004) and a 8.5-fold increase in type 1 DC (p < 0.003). The patients received a mean of: 2.2 x 10(7)/kg +/- 1.4 x 10(7)/kg of NK cells, 0.95 x 10(7)/kg +/- 0.81 x 107/kg of NKT cells, 0.43 x 107/kg +/- 0.53 x 10(7)/kg of type 1 DC, 0.3 v 10(7)/kg +/- 0.45 x 10(7)/kg of type 2 DC and 1.4 x 10(7)/kg +/- 1.2 x 10(7)/kg of regulatory T cells. Using intermediate doses of G-CSF, we have demonstrated the mobilization of different lymphocyte subsets, in particular regulatory T cells and DC, which can be expanded later and used in the treatment of cancer and autoimmune diseases.

[Variability of HIV-1 viral load in patients cared along 4 years]. / Variabilidad de la carga vírica de VIH-1 en individuos atendidos a lo largo de 4 años.

BASIS: Analysis of the variations of HIV-1 viral load (VL) in a cohort of patients. MATERIAL AND METHODS: A retrospective study was designed for the calculation and analysis of the differences between two consecutive measurements of VL in a cohort of 1,336 patients along a 48 months follow-up. RESULTS: At the beginning of the follow-up period the highest proportion of patients with decreases of VL (54.2% in their first measurement, at 0-75 days) as well as the least proportion of patients both without changes (30.7%) and with increases of their VL (15.1%), were registered. The proportion of patients with decreases was declining along the study period. More than half of the patients did not experience significant variations in the measurements carried out. CONCLUSIONS: The significant decreases of VL appeared in our series at the beginning of the follow-up period, and a growing proportion of individuals showed elevations of the VL along the period studied.

Donor lymphocyte infusions for relapse of chronic myeloid leukemia after allogeneic stem cell transplantation: prognostic significance of the dose of CD3(+) and CD4(+) lymphocytes.

Between December 1993 and November 2001, 30 patients with chronic myeloid leukemia who relapsed after stem cell transplantation were studied. Seventeen patients were not treated before donor lymphocyte infusion (DLI), eight patients received interferon-alpha (IFN-alpha), and five underwent chemotherapy. The method of DLI was the bulk dose regimen. The median time between DLIs was 6 weeks. The median number of infusions was three; the median time from transplant to relapse was 17 months and from relapse to DLI 2 months. Eleven patients (37%) were in molecular/cytogenetic relapse, 14 (47%) in chronic phase, and five (16%) in accelerated or blastic phase. Seventeen patients (57%) developed acute graft-versus-host disease (GVHD). Chronic GVHD was observed in 15 of 24 (62%) patients. Four (13%) patients developed cytopenia after a median of 30 days. Nineteen (63%) patients achieved response, 15 of them developed GVHD. The response rate according to the disease phase was molecular or cytogenetic relapse: 91%, chronic phase: 57%, and accelerated or blastic phase: 20%. The median time to response was 6 months. Patients treated with IFN-alpha or no treatment as well as those who were in molecular/cytogenetic relapse and those who received a CD3(+) cell dose <1 x 10(8)/kg and CD4(+) <8 x 10(7)/kg had better survival. We conclude that patients who receive lower doses of lymphocytes have better survival. In some patients IFN-alpha seems to be a good choice to potentiate the graft-versus-leukemia (GVL) effect.