Directly observed daily mouth care provided to care home residents in one area of Kent, UK.

OBJECTIVE: To gather accurate data on the daily mouth care provided in care homes including tooth brushing, oral health assessment, and recording of care provided. BASIC RESEARCH DESIGN: Direct observation and notes review. CLINICAL SETTING: Both nursing and 'regular' care homes. PARTICIPANTS: 365 Residents living in 16 care homes and their carers underwent observation, notes review or data collection in some form. MAIN OUTCOME MEASURES: Provision of mouth morning care. RESULTS: Of 161 residents observed, most (93, 58%) did not have their teeth/dentures brushed. If performed, brushing was often carried out by the resident themselves (36 cases, 53%), rather than by a carer (32 cases, 44%). Carers used a toothbrush to clean inside a resident's mouth in just 7 cases (4.3% of all personal care routines observed). Smaller care homes were no more likely to brush residents teeth than larger care homes, and nursing homes were no more likely to brush teeth than other care homes. Of the 309 sets of notes available for review, 41 (13%) contained a dedicated oral health needs assessment, and 109 (35%) contained a daily oral care chart in some form. Mouth care was often recorded inaccurately (15% of cases). CONCLUSIONS: This is the first observational study in the UK to assess oral care actually provided to residents by carers in care homes. The findings reveal a substantially different picture of daily mouth care than was previously understood and suggest that many of the nation's care home residents may not be receiving adequate, or any, oral health care.

[How many patient transfer rooms are necessary for my OR suite? : Effect of the number of OR transfer rooms on waiting times and patient throughput in the OR - analysis by simulation]. / Wie viele Patientenschleusen braucht mein OP-Bereich? : Einfluss der Zahl von OP-Schleusen auf Wartezeiten und Patientendurchsatz im OP - Analyse mithilfe einer Simulation.

INTRODUCTION: In most hospitals the operating rooms (OR) are separated from the rest of the hospital by transfer rooms where patients have to pass through for reasons of hygiene. In the OR transfer room patients are placed on the OR table before surgery and returned to the hospital bed after surgery. It could happen that the number of patients who need to pass through a transfer room at a certain point in time exceed the number of available transfer rooms. As a result the transfer rooms become a bottleneck where patients have to wait and which, in turn, may lead to delays in the OR suite. In this study the ability of a discrete event simulation to analyze the effect of the duration of surgery and the number of ORs on the number of OR transfer rooms needed was investigated. METHODS: This study was based on a discrete event simulation model developed with the simulation software AnyLogic®. The model studied the effects of the number of OR transfer rooms on the processes in an OR suite of a community hospital by varying the number of ORs from one to eight and using different surgical portfolios. Probability distributions for the process duration of induction, surgery and recovery and transfer room processes were calculated on the basis of real data from the community hospital studied. Furthermore, using a generic simulation model the effect of the average duration of surgery on the number of OR transfer rooms needed was examined. RESULTS: The discrete event simulation model enabled the analysis of both quantitative as well as qualitative changes in the OR process and setting. Key performance indicators of the simulation model were patient throughput per day, the probability of waiting and duration of waiting time in front of OR transfer rooms. In the case of a community hospital with 1 transfer room the average proportion of patients waiting before entering the OR was 17.9 % ± 9.7 % with 3 ORs, 37.6 % ± 9.7 % with 5 ORs and 62.9 % ± 9.1 % with 8 ORs. The average waiting time of patients in the setting with 3 ORs was 3.1 ± 2.7 min, with 5 ORs 5.0 ± 5.8 min and with 8 ORs 11.5 ± 12.5 min. Based on this study the community hospital needs a second transfer room starting from 4 ORs so that there is no bottleneck for the subsequent OR processes. The average patient throughput in a setting with 4 ORs increased significantly by 0.3 patients per day when a second transfer room is available. The generic model showed a strong effect of the average duration of surgery on the number of transfer rooms needed. CONCLUSION: There was no linear correlation between the number of transfer rooms and the number of ORs. The shorter the average duration of surgery, the earlier an additional transfer room is required. Thus, hospitals with shorter duration of surgery and fewer ORs may need the same or more transfer rooms than a hospital with longer duration of surgery and more ORs. However, with respect to an economic analysis, the costs and benefits of installing additional OR transfer rooms need to be calculated using the profit margins of the specific hospital.

No proinflammatory signature in CD34+ hematopoietic progenitor cells in multiple sclerosis patients.

Autologous hematopoietic stem cell transplantation (aHSCT) has been used as a therapeutic approach in multiple sclerosis (MS). However, it is still unclear if the immune system that emerges from autologous CD34+ hematopoietic progenitor cells (HPC) of MS patients is pre-conditioned to re-develop the proinflammatory phenotype. The objective of this article is to compare the whole genome gene and microRNA expression signature in CD34+ HPC of MS patients and healthy donors (HD). CD34+ HPC were isolated from peripheral blood of eight MS patients and five HD and analyzed by whole genome gene expression and microRNA expression microarray. Among the differentially expressed genes (DEGs) only TNNT1 reached statistical significance (logFC=3.1, p<0.01). The microRNA expression was not significantly different between MS patients and HD. We did not find significant alterations of gene expression or microRNA profiles in CD34+ HPCs of MS patients. Our results support the use of aHSCT for treatment of MS.

[Autologous peripheral blood hematopoietic cell transplantation in the treatment of AL-amyloidosis].

AIM: To evaluate the efficiency of chemotherapy with standard doses of melfalan and dexamethazone versus autologous peripheral hemopoietic cell transplantation (auto-PHCT) in patients with AL amyloidosis and to reveal poor prognostic factors. SUBJECTS AND METHODS: Of 36 patients diagnosed as having AL-amylodosis, 17 patients underwent auto-PHCT, 11 patients received chemotherapy only; 8 patients died prior to treatment. RESULTS: In patients with AL-amyloidosis after chemotherapy and autotransplantation, 3-year overall survival was 28 and 64%, respectively. Low somatic ECOG status and cardiac lesion were independent poor prognostic factors of the disease. The number of involved organs failed to affect overall survival. CONCLUSION: Auto-PHCT may be proposed as first-line therapy for patients with AL-amyloidosis who have a somatic ECOG score of 0 to 2 and not more than 3 organs involved. Young patients who have a satisfactory somatic status and no benefit from autotransplantation may undergo auto-PHCT. It is expedient to use average-dose melfalan and dexamethasone when treating patients who are ineligible for high-dose chemotherapy.

Active noise control in a pure tone diffuse sound field using virtual sensing.

Local active noise control systems generate a zone of quiet at the physical error sensor using one or more secondary sources to cancel acoustic pressure and its spatial derivatives at the sensor location. The resulting zone of quiet is generally limited in size and as such, placement of the error sensor at the location of desired attenuation is required, which is often inconvenient. Virtual acoustic sensors overcome this by projecting the zone of quiet away from the physical sensor to a remote location. The work described here investigates the effectiveness of using virtual sensors in a pure tone diffuse sound field. Stochastically optimal virtual microphones and virtual energy density sensors are developed for use in diffuse sound fields. Analytical expressions for the controlled sound field generated with a number of control strategies are presented. These expressions allow the optimal control performance to be predicted. Results of numerical simulations and experimental measurements made in a reverberation chamber are also presented and compared.

Waveshape distortion of high frequency acoustic waves in gas media.

In molecular dynamics simulations of an acoustic domain excited by a sinusoidally oscillating plane acoustic source in the frequency range of hundreds of megahertz, the density and velocity perturbations adjacent to the source are observed to be non-sinusoidal in shape. This distortion in the shape of the waves is investigated using a number of simulations of frequencies in the hundred of megahertz range and velocities up to 0.50 Å/ps. The relative distortion of the wave shape is characterised by a developed nested trigonometric function. The distortion is shown to be a function of the Mach number of the acoustic source rather than the source velocity amplitude. Trends in the distortion with source amplitude and frequency indicate that distortion of the velocity and density are independent of frequency. It is shown that the density and velocity perturbation can be approximated for any sound source Mach number within the range examined using the parametrised developed equation. The developed approximation could be used to accurately simulate the influence of an oscillating plane using a stationary analytical source. This could be used to develop a hybrid molecular/continuum model that will allow lower frequency simulations. The improved understanding of the causes of the distorted high frequency waveshape could also improve the fidelity of parametric arrays.

Randomized trial of high-dose adjuvant chemotherapy with autologous hematopoietic stem-cell support versus standard-dose chemotherapy in breast cancer patients with 10 or more positive lymph nodes: overall survival after 6 years of follow-up.

Investigation of high-dose chemotherapy (HD-CT) compared with standard-dose chemotherapy (SD-CT) as adjuvant treatment in patients with primary breast cancer and >/=10 axillary lymph nodes. From November 1993 to September 2000, 307 patients were randomized to receive after four cycles of epirubicin (90 mg/m(2)), cyclophosphamide (600 mg/m(2)) i.v. (every 21 days) and either HD-CT of cyclophosphamide (1500 mg/m(2)), thiotepa (150 mg/m(2)) and mitoxantrone (10 mg/m(2)) i.v. for four consecutive days followed by stem cell transplantation or a SD-CT of three cycles CMF (cyclophosphamide 500 mg/m(2), methotrexate 40 mg/m(2), 5-fluorouracil 600 mg/m(2), i.v. on day 1 and 8, respectively, every 28 days). After a median follow-up of 6.1 years, 166 events with respect to event-free survival (EFS) (SD-CT: 91, HD-CT: 75) have been observed. The hazard ratio of HD-CT versus SD-CT is estimated as 0.80 [95% confidence interval (0.59, 1.08)], P = 0.15. The trend to a superiority of HD-CT as compared with SD-CT with respect to EFS seems to be more pronounced in premenopausal patients as compared with postmenopausal patients and in patients with tumor grade 3 as compared with patients with tumor grade 1/2. With a follow-up of 6 years, there was a trend in favor of HD-CT with respect to EFS not being significant. A proper meta-analysis needs to be undertaken for an evaluation of subgroups of patients who might benefit from HD-CT.

Minimal residual disease diagnostics in myeloid malignancies in the post transplant period.

Allogeneic SCT is important in myelodysplastic syndrome, the BCR-ABL-negative chronic myeloproliferative diseases (CMPDs) and in poor-risk AML. Techniques to monitor the minimal residual disease, for example, by PCR or immunophenotyping gain increasing importance in the post transplantation period as basis for improved and earlier therapeutic interventions in impending relapse. Recent markers such as the NPM1 mutations in AML or the JAK2V617F mutation in the CMPD can be exactly quantified by real-time PCR and were evaluated for their prognostic value in the post transplantation phase and for their utility to plan adoptive immunotherapy in case of molecular relapse. With respect to chimerism, new and very sensitive methods were introduced, for example, quantitative assessment of genetic polymorphisms by real-time PCR, but also methods here are still highly individualized. Only in CML, where SCT focuses now on poor-risk cases or cases of tyrosine kinase inhibitor failure, follow-up schedules are standardized. Standardization of the different diagnostic techniques and of the intervals in the post transplantation period is urgently needed also in other myeloid malignancies and should be focus of future studies.

Transportation and cryopreservation may impair haematopoietic stem cell function and engraftment of allogeneic PBSCs, but not BM.

Recent data suggest that the practice of using frozen allogeneic grafts is becoming increasingly common among transplant centres. Therefore, we retrospectively analysed 31 frozen allogeneic PBSC and 8 BM grafts by flow cytometry with regard to their CD34+ content, membrane integrity (7-AAD) and stem cell-specific enzyme activity (aldehyde dehydrogenase, ALDH) in relation to individual transplantation results. Membrane integrity of CD34+ cells was significantly impaired in cryopreserved PBSC but not in BM compared to unfrozen allografts. In 9 out of 31 frozen PBSC (but none of the BM) grafts numbers of SSC(lo)ALDH(br) cells per kg body weight (BW) were significantly reduced while in the same grafts the numbers of CD34+ cells per kg BW were close to normal. Overall, 9 out of 33 patients (27%) who received unrelated PBSC allografts cryopreserved after transportation did not achieve engraftment. For comparison, primary graft failure was observed in our centre in only 7 out of 493 recipients (1.4%) of fresh allogeneic PBSC grafts. Moreover, we did not see any graft failure in patients receiving frozen/thawed BM or autologous PBSC transplants. We, therefore, conclude that PBSC grafts become much more sensitive to cryopreservation after transport and/or storage. Importantly, the engraftment potential of frozen HSC grafts may reliably be predicted by measuring ALDH activity.

EBV reactivation and post transplant lymphoproliferative disorders following allogeneic SCT.

Fatal problems encountered in allogeneic stem cell transplantation include EBV reactivation and post transplant lymphoproliferative disorders (PTLDs) with high mortality rates. We performed a retrospective analysis in all consecutive adult and pediatric EBV reactivations and PTLD during a period of 8.5 years. There were 26 patients with EBV reactivation/PTLD out of a total of 854 transplantations giving an overall incidence of 3.0%. Specifically, the incidence of EBV-PTLD was 1.3%, whereas that of EBV reactivation was 1.8%. Median age was 46.0 and 11.0 years in the adult and pediatric patients, respectively. There were high rates (54%) of concomitant bacterial, viral, fungal and parasitic infections at the time of EBV manifestation. Variable treatment regimens were applied including in most cases an anti-CD20 regimen often in combination with virustatic compounds, polychemotherapy or donor lymphocytes. The mortality rates were 9 of 11 (82%) in patients with EBV-PTLD and 10 of 15 (67%) in patients with reactivation. Only 7 of 26 patients (27%) are alive after a median follow-up of 758 days (range 24-2751). The high mortality rates of EBV reactivation and of EBV-PTLD irrespective of multimodal treatment approaches emphasize standardization and optimization of post transplant surveillance and treatment strategies to improve control of these often fatal complications.

Cognitive function in the acute course of allogeneic hematopoietic stem cell transplantation for hematological malignancies.

The aim of the study was to assess cognitive performance in patients with hematological malignancies before, and 3 months after, allogeneic hematopoietic stem cell transplant (HSCT). A consecutive sample of 39 patients was assessed before admission with a comprehensive neuropsychological test battery and health-related quality-of-life (HRQoL) questionnaires; 19 of these patients were retested around 100 days post HSCT. Test results were compared with normative data and revealed minimal differences at both time points in the level of group-means. One parameter - simple reaction time - was significantly worse (prolonged) at second measurement after HSCT. According to the definition of an impairment score (more than three impaired functions), 26% of patients were classified as impaired before as well as after HSCT. Neuropsychological test results did not vary systematically according to medical variables such as extent of pretreatment, graft-versus-host-disease (GvHD) and kind of conditioning protocol. As a dimension of HRQoL, self-rated cognitive function was in the normal range before and after HSCT. Significant correlations between HRQoL and neuropsychological parameters were related to symptom scales. This study showed impairments of neuropsychological performance for a subgroup of patients before and after allogeneic HSCT. Systematic effects of conditioning, medical variables or self-rated HRQoL could not be observed.

[Recovery of peripheral blood lymphocytes in patients with hematological diseases after allogenic non-relative transplantation of hemopoietic stem cells].

AIM: To define impact of lymphopoiesis state on the results of transplantation of hemopoietic stem cells (THSC) by assessment of kinetics of lymphocyte count recovery in early posttransplantation period; to study correlation between THSC results and changes in composition of lymphocyte subpopulation. MATERIAL AND METHODS: Recipients of 122 non-relative THSC entered the trial. The recipients were adults with various hematological malignancies. RESULTS: Allogenic non-relative THSC leads to deep and long-lasting lymphopenia, low count of all lymphocyte subpopulations and, as a result, to marked impairment of antiinfectious and antitumor immune response. Kinetics of lymphopoiesis recovery depended on some clinical factors. Of most importance were duration of the disease before THSC, HLA donor and recipient compatibility, the source of stem cells, lymphocyte count in the transplant, administration of immunosuppressive drugs. Conduction of non-myeloablative regimens of conditioning did not reduce severity and duration of lymphopoiesis suppression. The time of lymphoid subpopulations count recovery had a significant influence on THSC results. Long-term lymphopenia increased the risk of severe infectious complications and recurrence. Low (under 500 lymphocytes in 1 mcl) lymphocyte level in peripheral blood one month after the transplantation was a death risk factor for patients after THSC. CONCLUSION: Dynamics of the recovery of lymphocyte subpopulations can be used for formulating policy of adaptive immunotherapy in patients after THSC.

Depression and anxiety following hematopoietic stem cell transplantation: a prospective population-based study in Germany.

In this prospective multicenter study, we investigated the course of depression and anxiety during hematopoietic stem cell transplantation (HSCT) until 5 years after transplantation adjusting for medical information. Patients were consulted before HSCT (n=239), at 3 months (n=150), 12 months (n=102) and 5 years (n=45) after HSCT. Depression and anxiety were assessed with the Hospital Anxiety and Depression Scale (HADS). Detailed medical and demographic information was collected. Prevalence rates were compared with an age- and gender-matched control group drawn from a large representative sample (n=4110). The risk of depression before HSCT was lower for patients than for the control group (risk ratio (RR), 0.56; 95% confidence interval (CI), 0.39/0.81). Prevalence rates of depression increased from 12 to 30% until 5 years post HSCT. Anxiety rates were most frequently increased before HSCT (29%, RR, 1.31; 95% CI, 1.02/1.68) and then reached a stable level comparable to the background population (RR 0.83, 95% CI, 0.56/1.22). This study confirms the low levels of depression in the short term after HSCT and identifies depression as a long-term effect. Furthermore, it confirms previous results of heightened anxiety before HSCT. Surveillance of symptoms of anxiety during the short-term phase of HSCT and of depression during the following years is crucial.

Impact of molecular residual disease post allografting in myelofibrosis patients.

We screened 136 patients with myelofibrosis and a median age of 58 years who underwent allogeneic stem cell transplantation (AHSCT) for molecular residual disease for JAKV617F (n=101), thrombopoietin receptor gene (MPL) (n=4) or calreticulin (CALR) (n=31) mutation in peripheral blood on day +100 and +180 after AHSCT. After a median follow-up of 78 months, the 5-year estimated overall survival was 60% (95% confidence interval (CI): 50-70%) and the cumulative incidence of relapse at 5 years was 26% (95% CI: 18-34%) for the entire study population. The percentage of molecular clearance on day 100 was higher in CALR-mutated patients (92%) in comparison with MPL- (75%) and JAKV617F-mutated patients (67%). Patients with detectable mutation at day +100 or at day +180 had a significant higher risk of clinical relapse at 5 years than molecular-negative patients (62% vs 10%, P<0.001) and 70% vs 10%, P<0.001, respectively) irrespectively of the underlying mutation. In a multivariate analysis, high-risk diseases status (hazard ratio (HR) 2.5; 95% CI: 1.18-5.25, P=0.016) and detectable MRD at day 180 (HR 8.36, 95% CI: 2.76-25.30, P<0.001) were significant factors for a higher risk of relapse.

Investigating the temporal course, relevance and risk factors of fatigue over 5 years: a prospective study among patients receiving allogeneic HSCT.

Although allogeneic hematopoietic stem cell transplantation (HSCT) features severe physical and psychological strain, no previous study has prospectively investigated fatigue beyond 3 years after transplantation. We investigated the temporal course of fatigue over 5 years, compared patients with the general population (GP) and tested for treatment- and complication-related risk factors. Patients were assessed before conditioning (T0, N=239) and at 100-day (T1, N=150), 1-year (T2, N=102) and 5-year (T3, N=45) follow-up. We measured fatigue with the Multidimensional Fatigue Inventory-20. Patients were compared with the GP at T0 and at T3. Global fatigue increased from T0 to T1 (t=3.85, P<0.001), decreased from T1 to T2 (t=-2. 92, P=0.004) and then remained stable (t=0.45, P=0.656). No difference in global fatigue was found between T0 and T3 (t=0.68, P=0.497). Compared with the GP, patients showed higher global fatigue at T0 (t=-6.02, P<0.001) and T3 (t=-2.50, P=0.014). These differences reached meaningful effect sizes (d⩾0.5). Acute and chronic GvHD predicted global fatigue at T1 (γ=0.34, P=0.006) and T2 (γ=0.38, P=0.010), respectively. To conclude, fatigue among allogeneic HSCT patients improves with time, finally returning to pretransplantation levels. However, even after 5 years, the difference from the GP remains relevant. Patients with GvHD are at risk for increased fatigue.

Autologous stem cell transplantation for therapy-related acute myeloid leukemia and myelodysplastic syndrome.

We report the results of 65 patients with treatment-related myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML) who were transplanted from an autograft and reported to the EBMT. The median age was 39 years (range, 3-69), and stem cell source was bone marrow (n = 31), or peripheral blood progenitor cells (n = 30), or the combination of both (n = 4). The primary disease was solid tumors (n = 37), Hodgkin's disease (n = 13), non-Hodgkin's lymphoma (n = 10), acute lymphoblastic leukemia (n = 2) or myeloproliferative syndromes (n = 3). The types of MDS were as follows: RAEB (n = 1; 2%), RAEB-t (n = 3; 5%), or AML (n = 56; 87%). The median time between diagnosis and transplantation was 5 months (range, 3-86). The Kaplan-Meier estimates of the probability of 3-year overall and disease-free survival were 35% (95% CI: 21-49%) and 32% (95% CI: 18-45%), respectively. The median leukocyte engraftment was faster after transplantation with peripheral blood stem cells than with bone marrow: 12 (range, 9-26) vs 29 (range, 11-67) days (P<0.001). The cumulative incidence of relapse was 58% (95% CI: 44-72%) and of treatment-related mortality 12% (95% CI: 6-38%). Lower relapse rate was seen in patients transplanted in first complete remission (CR1 vs non-CR1: 3 years: 48 vs 89%; P = 0.05). Furthermore, age beyond 40 years resulted in a higher treatment-related mortality (47 vs 7%; P = 0.01). In a multivariate analysis, transplantation in CR1 age as well as their interaction influenced overall survival significantly. Autologous transplantation may cure a substantial number of patients with treatment-related MDS/AML, especially if they are in CR1 and of younger age.

Allogeneic stem-cell transplantation in patients with refractory acute leukemia: a long-term follow-up.

We examined retrospectively 44 patients with refractory acute leukemia (acute myeloid leukemia (AML)/acute lymphoblastic leukemia=25/19) who underwent allogeneic transplantation at our center between 11/1990 and 04/2004. The median leukemic blasts was 25% and age 28 years (range, 3-56). Twenty-one patients had untreated relapse, 13 failed reinduction, eight in partial remission and two aplastic. Conditioning was myeloablative using cyclophosphamide, busulfan, total-body irradiation and etoposide (Bu/Cy/VP, n=22; TBI/Cy/VP, n=17; others, n=5) followed by marrow or peripheral blood transplant (n=23/21) from unrelated or related donors (n=28/16). All patients had graft-versus-host disease (GVHD) prophylaxis with cyclosporin and methotrexate. One patient experienced late graft failure. Severe acute-GVHD and chronic-GVHD appeared in eight and 14 patients, respectively. Thirteen patients (30%) remain alive after a median of 25.3 months (range, 2.4-134.1); with 31 deaths, mostly from relapse (n=15) and infections (n=12). Overall survival (OS) and progression-free survival (PFS) at 5 years was 28 and 26%, respectively. OS and PFS were significantly better with blasts < or =20% and time to transplant < or =1 year while transplant-related mortality was less with the use of TBI. We conclude that patients with refractory leukemia can benefit from allogeneic BMT, especially with < or =20% marrow blast.

Reduced-toxicity conditioning with treosulfan, fludarabine and ATG as preparative regimen for allogeneic stem cell transplantation (alloSCT) in elderly patients with secondary acute myeloid leukemia (sAML) or myelodysplastic syndrome (MDS).

We investigated a dose-reduced conditioning regimen consisting of treosulfan and fludarabine followed by allogeneic stem cell transplantation (SCT) in 26 patients with secondary AML or MDS. Twenty patients were transplanted from matched or mismatched unrelated donors and six from HLA-identical sibling donors. The median age of the patients was 60 years (range, 44-70). None of the patients was eligible for a standard myeloablative preparative regimen. No graft-failure was observed, and leukocyte and platelet engraftment were observed after a median of 16 and 17 days, respectively. Acute graft-versus-host disease (GvHD) grade II-IV was seen in 23% and severe grade III GvHD in 12% of the patients. No patients experienced grade IV acute GvHD. Chronic GvHD was noted in 36% of the patients, which was extensive disease in 18%. The 2-year cumulative incidence of relapse was 21%. The relapse rate was higher in patients beyond CR1 or with intermediate two or high risk MDS (P = 0.02). The treatment-related mortality at day 100 was 28%. The 2-year estimated overall and disease-free survival was 36-34%, respectively. No difference in survival was seen between unrelated and related SCT.

Comparable results in patients with acute lymphoblastic leukemia after related and unrelated stem cell transplantation.

We report the results of 84 patients with ALL after related (n = 46) or unrelated (n = 38) allogeneic SCT. Mean recipient age was 23 years (range: 1-60) and median follow-up was 18 months (range: 1-133). Forty-three patients were transplanted in CR1; 25 in CR2 or CR3; four were primary refractory; four in PR; eight in relapse. The conditioning regimen consisted of TBI/VP16/CY (n = 76), TBI/VP16 (n = 2), TBI/CY (n = 2), Bu/VP16/CY (n = 4). The OS at 3 years was 45% (44% unrelated, 46% related). Univariate analysis showed a significantly better OS for patients <18 years (P=0.03), mismatched sex-combination (P = 0.03), both with a stronger effect on increasing OS after unrelated SCT. Factors decreasing TRM were patient age <18 years (P = 0.004), patient CMV-seronegativity (P = 0.014), female recipient (P = 0.04). There was no significant difference in TRM and the relapse rate was similar in both donor type groups. Multivariate analysis showed that factors for increased OS which remained significant were mismatched sex-combination (RR: 0.70,95% CI: 0.51-0.93, P = 0.015), patient age < 18 years (RR: 0.66, 95% CI: 0.47-0.93, P = 0.016). A decreased TRM was found for female patients (RR: 0.56, 95% CI: 0.33-0.98, P=0.042), negative CMV status of the patient (RR: 0.57, 95% CI: 0.36-0.90, P = 0.015). Unrelated stem cell transplantation for high-risk ALL patients with no HLA-compatible family donor is justifiable.

Retroviral vector insertions in T-lymphocytes used for suicide gene therapy occur in gene groups with specific molecular functions.

Graft-versus-host disease (GvHD) is a severe complication in the context of allogeneic stem cell transplantation and adoptive immunotherapy. The transfer of a suicide gene into donor T-lymphocytes (TLCs) allows selective elimination of GvHD-causing cells. As retroviral gene transfer into hematopoietic stem cells can induce leukaemia, there is an urgent need also to analyze retroviral integration sites in TLCs. We examined suicide gene-transduced TLCs in four grafts and from four transplanted patients. One-hundred and fifteen integration sites were detected in vitro. Of these 90 could be mapped to the human genome; 50% (45) were located in genes and 32% (29) were detected 10 kb upstream or downstream of transcription start sites. We found a significant overrepresentation of genes encoding for proteins with receptor activity, signal transducer activity, transcription regulator activity, nucleic acid binding activity and translation regulator activity. Similar data were obtained from patient samples. Our results point to preferred vector integration patterns, which are specific for the target cell population and probably independent of selection processes. Thus, future preclinical analysis of the integration repertoire with abundant amounts of transduced cells could allow a prediction also for the in vivo situation, where target cells are scarce.