Differential responses of nitrifying archaea and bacteria to methylene blue toxicity.

UNLABELLED: Methylene blue, a heterocyclic aromatic chemical compound used to treat fish diseases in the ornamental fish aquaculture industry, is believed to impair nitrification as a side effect. However, very little is known about the toxicity of methylene blue to nitrifying micro-organisms. Here, we report the susceptibility of six bacterial and one archaeal ammonia-oxidizing micro-organisms to methylene blue within the range of 10 ppb to 10 ppm. Remarkably high susceptibility was observed in the archaeal species Nitrosopumilus maritimus compared to the bacterial species. Ammonia oxidation by Nitrosopumilus maritimus was inhibited 65% by 10 ppb of methylene blue. Of the bacterial species examined, Nitrosococcus oceani was the most resistant to methylene blue toxicity. For similar inhibition of Nitrosococcus oceani (75% inhibition), one thousand times more methylene blue (10 ppm) was needed. The examination of single cell viability on Nitrosomonas marina demonstrated that methylene blue is lethal to the cells rather than reducing their single cell ammonia oxidation activity. The level of susceptibility to methylene blue was related to the cell volume, intracytoplasmic membrane arrangement and the evolutionary lineage of nitrifying micro-organisms. Our findings are relevant for effectively using methylene blue in various aquaculture settings by helping minimize its impact on nitrifiers during the treatment of fish diseases. In the future, resistant nitrifiers such as Nitrosococcus oceani may be purposely added to aquaculture systems to maintain nitrification activity during treatments with methylene blue. SIGNIFICANCE AND IMPACT OF THE STUDY: The susceptibility of six bacterial and one archaeal nitrifying micro-organisms to methylene blue was tested. Remarkably high susceptibility was observed in the archaeal species compared to the bacterial species. The level of resistance to methylene blue was related to the cell volume, cytomembrane system and the taxonomic position of the nitrifying micro-organisms. This may be significant in the design and management of engineered nitrification systems and the stability of the nitrification process in various ecosystems if these systems are exposed to harmful chemicals or toxins.

Pharmacophore and binding analysis of known and novel B-RAF kinase inhibitors.

The extensively investigated serine/threonine kinase, B-RAF, is a member of the RAS/RAF/MEK/ERK pathway. It plays important role in the regulation of cell growth, differentiation and survival. The mutation of B-RAF occurs frequently in melanomas and colon tumors; therefore, it is considered as an outstanding therapeutic target. In recent years a great number of B-RAF inhibitors have been reported and this number is expected to increase. The aim of our work was to compare the structures and binding mode of the published B-RAF inhibitors, and then to apply the correlations found for the explanation of our experimental results. In the first part of this paper we describe the main pharmacophore features of the co-crysallized B-RAF inhibitors published in the literature, focusing on the binding modes and common structural elements. In the second part we present and characterize our recently developed B-RAF inhibitor family by application of in silico methods and in vitro kinetic profiling. The inhibitory activity of these compounds was determined in biochemical kinase- and cell-based assays. The docking and assay results support our conclusion that the presented compound family belongs to the type I 1/2 subgroup, they inhibit B-RAF and B-RAF(V600E) mutant in a sub-micromolar range and most of them show selectivity towards B-RAF(V600E) mutant expressing cell lines with equal or even better IC50 values than sorafenib.

Generation of energetic femtosecond green pulses based on an OPCPA-SFG scheme.

Femtosecond green pulses were generated from broadband pulses centered at 800 nm and quasi-monochromatic pulses centered at 532 nm using noncollinear optical parametric chirped pulse amplification (NOPCPA) followed by sum frequency mixing. In addition to amplifying the 800-nm pulses, the NOPCPA stage pumped by a Q-switched, injection seeded Nd:YAG laser also provided broadband idler pulses at 1590 nm. The signal and idler pulses were sum frequency mixed using achromatic and chirp assisted phase matching yielding pulses near 530 nm with a bandwidth of 12 nm and an energy in excess of 200 µJ. The generated pulses were recompressed with a grating compressor to a duration of 150 fs. The technique is scalable to high energies, broader bandwidths, and shorter pulse durations with compensation for higher order chirps and dedicated engineering of the interacting beams.

Novel, selective CDK9 inhibitors for the treatment of HIV infection.

Cyclin Dependent Kinases (CDKs) are important regulators of cell cycle and gene expression. Since an up-to-date review about the pharmacological inhibitors of CDK family (CDK1-10) is not available; therefore in the present paper we briefly summarize the most relevant inhibitors and point out the low number of selective inhibitors. Among CDKs, CDK9 is a validated pathological target in HIV infection, inflammation and cardiac hypertrophy; however selective CDK9 inhibitors are still not available. We present a selective inhibitor family of CDK9 based on the 4-phenylamino-6- phenylpyrimidine nucleus. We show a convenient synthetic method to prepare a useful intermediate and its derivatisation resulting in novel compounds. The CDK9 inhibitory activity of the derivatives was measured in specific kinase assay and the CDK inhibitory profile of the best ones (IC(50) < 100 nM) was determined. The most selective compounds had high selectivity over CDK1, 2, 3, 5, 6, 7 and showed at least one order of magnitude higher inhibitory activity over CDK4 inhibition. The most selective molecules were examined in cytotoxicity assays and their ability to inhibit HIV-1 replication was determined in cellular assays.

Histomorphometric changes by teriparatide in alendronate-pretreated women with osteoporosis.

SUMMARY: The level of increased bone formation after 24 months of treatment with teriparatide (rhPTH (1-34), TPTD) is similar in patients who were either treatment-naïve (TN) or had lower bone turnover initially due to previous alendronate (ALN) therapy. INTRODUCTION: Bone anabolic effects of TPTD in postmenopausal women with osteoporosis may be blunted during the initial phase after switching from ALN to TPTD. To explore the long-term implications, we examined histomorphometric and biochemical markers of bone turnover of patients on TPTD therapy after long-term ALN treatment. METHODS: Paired biopsies were obtained after tetracycline double labeling at baseline and after 24 months of TPTD treatment from 29 ALN-pretreated (64.5 ± 16.4 months) and 16 TN patients. Biochemical markers were measured at baseline, during the treatment, or at study end. RESULTS: Compared with the baseline, after 24-month TPTD, activation frequency (Ac.F.) and osteoid surface (OS) increased in both groups: 0.11-0.34 cycles per year, 3.96-9.8% in the ALN-pretreated group and 0.19-0.33 cycles per year, 6.2-11.3% (p < 0.05) in the TN group, respectively. Biochemical and histomorphometric markers correlated positively both at baseline and endpoint. Serum amino terminal propeptide of type I procollagen (PINP) correlated with Ac.F. (r = 0.57, p < 0.001 and r = 0.48, p < 0.01) and OS (r = 0.51, p < 0.01 and r = 0.56, p < 0.01) at baseline and endpoint, respectively. Following 3 months of treatment, increases in biochemical markers like PINP predicted the increase in Ac.F. (r = 0.52, p < 0.01) and OS (r = 0.54, p < 0.01) after 24 months. CONCLUSIONS: The increased level of formation is similar in patients who were either TN or had lower bone turnover initially due to previous ALN therapy. Elevated bone formation in postmenopausal women with osteoporosis was sustained over a 24-month period by TPTD. Biochemical markers of bone formation are a good surrogate for the assessment of TPTD effects.

Paternal and maternal ages at conception and risk of bipolar affective disorder in their offspring.

BACKGROUND: A consistent association between paternal age and their offspring's risk of schizophrenia has been observed, with no independent association with maternal age. The relationship of paternal and maternal ages with risk of bipolar affective disorders (BPAD) in the offspring is less clear. The present study aimed at testing the hypothesis that paternal age is associated with their offspring's risk of BPAD, whereas maternal age is not. METHOD: This population-based cohort study was conducted with individuals born in Sweden during 1973-1980 and still resident there at age 16 years. Outcome was first hospital admission with a diagnosis of BPAD. Hazard ratios (HRs) were calculated using Cox's proportional hazard regression. RESULTS: After adjustment for all potential confounding variables except maternal age, the HR for risk of BPAD for each 10-year increase in paternal age was 1.28 [95% confidence interval (CI) 1.11-1.48], but this fell to 1.20 (95% CI 0.97-1.48) after adjusting for maternal age. A similar result was found for maternal age and risk of BPAD [HR 1.30 (95% CI 1.08-1.56) before adjustment for paternal age, HR 1.12 (95% CI 0.86-1.45) after adjustment]. The HR associated with having either parent aged 30 years or over was 1.26 (95% CI 1.01-1.57) and it was 1.45 (95% CI 1.16-1.81) if both parents were >30 years. CONCLUSIONS: Unlike schizophrenia, the risk of BPAD seems to be associated with both paternal and maternal ages.

Effect of raloxifene after recombinant teriparatide [hPTH(1-34)] treatment in postmenopausal women with osteoporosis.

UNLABELLED: Loss of bone mineral density occurs after discontinuation of teriparatide, if no subsequent treatment is given. Sequential raloxifene prevented rapid bone loss at lumbar spine and further increased bone mineral density (BMD) at femoral neck, whether raloxifene was started immediately or after a one-year delay following teriparatide treatment. INTRODUCTION: We compared the sequential effects of raloxifene treatment with a placebo on teriparatide-induced increases in bone mineral density (BMD). A year of open-label raloxifene extended the study to assess the response with and without delay after discontinuation of teriparatide. METHODS: Following a year of open-label teriparatide 20 mug/day treatment, postmenopausal women with osteoporosis were randomly assigned to raloxifene 60 mg/day (n = 157) or a placebo (n = 172) for year 2, followed by a year of open-label raloxifene. BMD was measured by dual energy x-ray absorptiometry. RESULTS: The raloxifene and placebo groups showed a decrease in lumbar spine (LS) BMD in year 2 for raloxifene and placebo groups (-1.0 +/- 0.3%, P = 0.004; and -4.0 +/- 0.3%, P < 0.001, respectively); the decrease was less with raloxifene (P < 0.001). Open-label raloxifene treatment reversed the LS BMD decrease with a placebo, resulting in similar decreases 2 years after randomization (-2.6 +/- 0.4% (raloxifene-raloxifene) and -2.7 +/- 0.4% (placebo-placebo). At study end, LS and femoral neck (FN) BMD were higher than pre-teriparatide levels, with no significant differences between the raloxifene-raloxifene and placebo-raloxifene groups, respectively (LS: 6.1 +/- 0.5% vs. 5.1 +/- 0.5%; FN: 3.4 +/- 0.6% vs. 3.0 +/- 0.5%). CONCLUSION: Sequential raloxifene prevented rapid bone loss at the LS and increased FN BMD whether raloxifene was started immediately or after a one-year delay following teriparatide treatment.

The DEBIT trial: an intervention to reduce antipsychotic polypharmacy prescribing in adult psychiatry wards - a cluster randomized controlled trial.

BACKGROUND: Clinical guidelines advise against prescribing more than one antipsychotic with limited exceptions. Despite this, surveys continue to report high antipsychotic polypharmacy rates. The aim of the study was to investigate the effectiveness of a multi-faceted intervention in reducing prescribing of antipsychotic polypharmacy on general adult psychiatry wards, compared with guidelines alone. METHOD: A pragmatic cluster randomized controlled trial recruited 19 adult psychiatric units (clusters) from the South West of England. Participants were all ward doctors and nurses. The multi-faceted intervention comprised: an educational/CBT workbook; an educational visit to consultants; and a reminder system on medication charts. RESULTS: The odds of being prescribed antipsychotic polypharmacy in those patients prescribed antipsychotic medication was significantly lower in the intervention than control group when adjusted for confounders (OR 0.43, 95% CI 0.21-0.90, p=0.028). There was considerable between-unit variation in polypharmacy rates and in the change in rates between baseline and follow-up (5 months after baseline). CONCLUSION: The intervention reduced levels of polypharmacy prescribing compared to guidelines alone although the effect size was relatively modest. Further work is needed to elicit the factors that were active in changing prescribing behaviour.

Advances in renal (patho)physiology using multiphoton microscopy.

Multiphoton excitation fluorescence microscopy is a state-of-the-art confocal imaging technique ideal for deep optical sectioning of living tissues. It is capable of performing ultrasensitive, quantitative imaging of organ functions in health and disease with high spatial and temporal resolution which other imaging modalities cannot achieve. For more than a decade, multiphoton microscopy has been successfully used with various in vitro and in vivo experimental approaches to study many functions of different organs, including the kidney. This study focuses on recent advances in our knowledge of renal (patho)physiological processes made possible by the use of this imaging technology. Visualization of cellular variables like cytosolic calcium, pH, cell-to-cell communication and signal propagation, interstitial fluid flow in the juxtaglomerular apparatus (JGA), real-time imaging of tubuloglomerular feedback (TGF), and renin release mechanisms are reviewed. A brief summary is provided of kidney functions that can be measured by in vivo quantitative multiphoton imaging including glomerular filtration and permeability, concentration, dilution, and activity of the intrarenal renin-angiotensin system using this minimally invasive approach. New visual data challenge a number of existing paradigms in renal (patho)physiology. Also, quantitative imaging of kidney function with multiphoton microscopy has tremendous potential to eventually provide novel non-invasive diagnostic and therapeutic tools for future applications in clinical nephrology.

The cardiovascular and respiratory health of people with schizophrenia.

OBJECTIVE: To examine the cardiovascular and respiratory health of people with severe mental illness (SMI) and compare findings with the Health Surveys for England. METHOD: A prospective, multi-centre observational prevalence study of 602 patients with schizophrenia-related psychoses carried out in six locations across the UK over 24 months. RESULTS: Compared with general population subjects, people with SMI reported higher rates of angina and respiratory symptoms and had poor lung function. Much of this increased risk could be explained by lifestyle risk factors; there were increased levels of obesity among younger people with SMI. CONCLUSION: Key indicators of the cardiovascular and respiratory health of people with SMI are poor compared with those of the general population. Care plans should prioritize interventions to attenuate lifestyle risk factors. Evidence of increasing obesity in younger patients is of particular concern, predicting even greater health needs in the future.

Is the season of birth association with psychosis due to seasonal variations in foetal growth or other related exposures? A cohort study.

OBJECTIVE: To investigate the association between season of birth and psychosis, and to assess whether any association is caused by seasonal fluctuations in foetal growth or other related exposures. METHOD: Cohort of 747 432 Swedish males and females born between 1973 and 1980 and followed up from 16 years of age to 31 December 1999. Psychiatric admissions were identified using the Swedish Inpatient Discharge Register. The analysis is based on the 696 025 subjects with complete data. RESULTS: A total of 506 (0.07%) subjects developed schizophrenia and 879 (0.13%) non-affective non-schizophrenic psychoses. There was a moderate increased risk of schizophrenia amongst winter births, hazard ratio 1.23 (95% confidence interval 0.96-1.59), but this did not reach conventional levels of statistical significance. There was no association with non-affective psychoses. We found no evidence that associations were confounded by measures of foetal growth or maternal socioeconomic position. There was no evidence that seasonal effects on schizophrenia differed in men and women. CONCLUSION: Season of birth associations with schizophrenia do not appear to be confounded by birth-related exposures.

Association between psychotic disorder and urban place of birth is not mediated by obstetric complications or childhood socio-economic position: a cohort study.

BACKGROUND: Although urban place of birth has been identified as a risk factor for schizophrenia, the extent to which this association is mediated by socially patterned risk factors such as obstetric complications and childhood socio-economic position is unclear. The diagnostic specificity of the association within the clinical psychotic syndromes is also unclear. METHOD: A population cohort of 696025 males and females, born in Sweden between 1973 and 1980 and with linked birth and socio-economic data was followed up from age 16 for up to 9.8 years. Hospitalized cases of schizophrenia and other non-affective psychosis were identified from the Swedish Inpatient Discharge Register. We examined associations of these disorders with a three-level measure of urbanicity of birthplace before and after controlling for measures of foetal nutrition, obstetric complications and level of maternal education. RESULTS: Urban compared to rural birthplace was associated both with increased risk of adult onset schizophrenia (hazard ratio 1.34, CI 0.91-1.96) and other non-affective psychoses (hazard ratio 1.63, CI 1.18-2.26). None of these associations was greatly affected by adjustment for obstetric complications or maternal educational level. In the group of other non-affective psychoses urban-rural differences in disease risk were strongest among those born in the winter months. CONCLUSION: Urbanization of birthplace is associated with increased risk of non-affective psychosis but this is not confined to narrowly defined cases. The magnitude of the association in Sweden is lower than that reported in other studies. Causal factors underlying this association appear to operate independently of risks associated with obstetric complications and parental educational status.

Patterns and predictors of hospitalisation in first-episode psychosis. Prospective cohort study.

BACKGROUND: Little is known about predictors of hospitalisation in patients with first-episode psychosis. AIMS: To identify the pattern and predictors of hospitalisation of patients with a first psychotic episode making their first contact with specialist services. METHOD: Three-year follow-up of a cohort of 166 patients with a first episode of psychosis making contact with psychiatric services in Nottingham between June 1992 and May 1994. RESULTS: Eighty-eight (53.0%) patients were admitted within 1 week of presentation; 32 (19.3%) were never admitted during the 3 years of follow-up. Manic symptoms at presentation were associated with an increased risk of rapid admission and an increased overall risk of admission; negative symptoms and a longer duration of untreated illness had an increased risk of late admission. CONCLUSIONS: Community-oriented psychiatric services might only delay, rather than prevent, admission of patients with predominantly negative symptoms and a longer duration of untreated illness. First-episode studies based upon first admissions are likely to be subject to selection biases, which may limit their representativeness.

Remarkably reduced transplant-related complications by dibromomannitol non-myeloablative conditioning before allogeneic bone marrow transplantation in chronic myeloid leukemia.

A non-myeloablative conditioning protocol containing dibromomannitol (DBM/cytosine arabinoside/cyclophosphamide) has been applied to 36 chronic myeloid leukemia (CML) patients followed by bone marrow transplantation (BMT) from sibling donors. Risk factors include: accelerated phase (10 patients), older age (17 patients over >40 years) and long interval between diagnosis and BMT (27 months on average). Severe mucositis did not occur. Venoocclusive liver disease was absent. Infectious complications were rare. Although grade II-IV acute graft-versus-host disease (GVHD) was present in 9 (25%) cases, there were only 2 serious (III-IV) ones. Chronic GVHD occurred in 25 (69%) cases, preceded by acute GVHD in 9 of the 25 affected patients. Early hematological relapse, 7-29 weeks after BMT, developed in 6 patients (17.6%). No relapse was noted in the completely chimeric patients, however molecular genetic residual disease was observed in 6 patients, in most of them after transient short-term mixed chimeric state. Overall actual survival rate is 83.3% for the 36 cases, and leukemia-free survival is 72.2% for the 34 engrafted patients.

[Restricted antibody diversity after bone marrow transplantation--homogeneous immunoglobulins]. / A csontveló-átültetés után kialakuló korlátozott ellenanyagkészlet--homogén immunglobulinok.

After bone marrow transplantation, a prolonged dysregulation of humoral immunity, including restricted electrophoretic heterogeneity of serum immunoglobulins and the appearance of homogeneous immunoglobulin components, can be observed. The current study was undertaken to characterize further and define the posttransplantational incidence of monoclonal and oligoclonal immunoglobulins, as well as the clinical and laboratory correlations of these phenomena. For this purpose, serial serum protein (IgM, IgG, IgA and CRP) quantification, electrophoresis and immunofixation were performed on 29 patients undergoing allogeneic bone marrow transplantation for chronic myeloid leukemia. 23 out of the 29 patients developed transient oligoclonal and/or monoclonal gammopathies that appeared between 20 and 1750 posttransplantational days. No correlation, however, between the development of graft versus host disease, EBV or CMV infections, or any other symptoms and development of homogeneous immunoglobulin components was seen. Therefore, the development of oligoclonal and monoclonal gammopathies after bone marrow transplantation may be an ubiquitous finding reflecting the inadequacy, i.e. oligoclonality of the recovering B-cell system.

[Clinical and immunopathological significance of chimerism in bone marrow and organ transplantations] / A kimerizmus immunpatológiai és klinikai jelentosége csontvelô-transzplantációban és szervátültetésekben.

Chimerism is an exceptional immunogenetic state, characterized by the survival and collaboration of cell populations originated from two different individuals. The prerequisites to induce chimerism are immunosuppression, myeloablation or severe immunodeficiency of the recipients on one side and donor originated immuno-hematopoietic cells in the graft on the other. Special immunogenetic conditions to establish chimerism are combined with bone marrow transplantation, transfusion and various kinds of solid organ grafting. There are various methods to detect the type of chimera state depending on the immunogenetic differences between the donor and recipient. The chimera state seems to be one of the leading factors to influence the course of the post-transplant period, the frequency and severity of graft-versus-host disease (GVHD), and the rate of relapse. However, the most important contribution of the chimeric state is the development of graft versus leukemia (GVL) effect. A new conditioning protocol (DBM/Ara-C/Cy) for allogeneic BMT in CML patients and its consequence on chimera state and GVL effect is demonstrated.

Immunological importance of chimerism in transplantation: new conditioning protocol in BMT and the development of chimeric state.

Chimerism is an exceptional immunogenetic state, characterized by the survival and collaboration of cell populations originated from two different individuals. The prerequisits to induce chimerism are immuno-suppression, myeloablation, or severe immunodeficiency of the recipients on the one side and donor originated immuno-hematopoietic cells in the graft on the other. The pathologic or special immunogenetic conditions to establish chimerism are combined with bone marrow transplantation, transfusion, and various kinds of solid organ grafting. Different types of chimerism are known including complete, mixed and mosaic, or split chimerism. There are various methods used to detect the type of chimera state, depending on the immunogenetic differences between the donor and recipient. The induction of complete or mixed chimerism is first determinated by the effect of myeloablative therapy. The chimera state seems to be one of the leading factors to influence the course of the post-transplant period, the frequency and severity of GVHD, and the rate of relapse. However, the most important contribution of the chimeric state is in development of graft versus leukemia effect. A new conditioning protocol (DBM/Ara-C/Cy) for allogeneic BMT in CML patients and its consequence on chimera state and GVL effect is demonstrated.

[A new radiation-free conditioning in bone marrow transplantation and dibromo-mannitol therapy in chronic myeloid leukemia]. / Uj, sugárzásmentes csontvelö-transzplantációs kondicionáló kezelés dibróm-mannitollal krónikus myeloid leukaemiában.

A new, radiation-free, conditioning protocol, containing the original Hungarian mitobronitol (DBM) (DBM/ cytosine arabinoside/cyclosphosphamide) has been applied to 36 chronic myeloid leukemia (CML) patients followed by bone marrow transplantation (BMT) from HLA identical sibling donors between 1990-1997. In spite of some prognostically disadvantageous factors (half of them were above 40 years, 10 out of 36 patients were in accelerated phase, the disease history was longer than 2 years in average) the overall survival (30/36) and the leukemia free survival rate (26/36) were in accordance with the best international results. Transplantation-related toxicity was remarkably reduced in comparison to bone marrow transplantation performed by total body irradiation/cyclophosphamide (TBI/Cy) or busulphan/cyclophosphamide (Bu/Cy) conditioning protocols. Acute graft versus host disease was present in lower percentage (9/36) and the number of serious cases was only 2/36. Chronic GVH disease, generally known to be associated with antileukemic effect (GVL), occurred in 25 of cases. Early haematological relapse among the 34 patients with functioning graft occurred in 6 patients which rate is slightly higher than reported after TBI/Cy or Bu/Cy conditioning treatment. There was no relapse among patients transplanted within one year post-diagnosis and patients having CML with accelerated phase. The leukemia free post-transplant period was in association with the chronic GVH disease and full chimeric state.

Haemopoietic cell transplantation activity and results: a single institution experience.

Between February 1993 and November 1997, 62 patients with severe aplastic anaemia (SAA), acute myeloid (AML), acute lymphoid (ALL), or chronic myeloid leukaemia (CML) as well as two patients with NHL underwent allogeneic marrow transplantation (BMT) from HLA-identical or one-antigen mismatched sibling or unrelated donors. Patients received preparative regimens according to the baseline disease. Patients with SAA were conditioned with ATG/Cy (2 cases) and TAI/Cy (3 cases), AML, ALL and NHL with TBI/Cy (21 cases including two retransplantations) and CML with Mitobronitol/Ara-C/Cy except two patients conditioned traditionally with Bu/Cy. For GVHD prevention, patients received cyclosporin-A (CsA) with short course methotheraxe according to the Seattle protocol. Significantly better overall survival rates were associated with the Mitobronitol (DBM)/Ara-C/Cy conditioning regarded the patients as a whole. Autologous stem cell transplantation (bone marrow and/or peripheral blood) were performed in ten cases including 2 AML, 4 non-Hodgkin's lymphoma (NHL), 3 Hodgkin's disease (HD) and 1 patient with multiple myeloma (MM). Patients with AML and two patients with NHL were conditioned with TBI/Cy and the others with BEAM combined chemotherapy. Eight out of ten patients are leukaemia- or lymphoma-free survivors. One patient relapsed having conventional chemotherapy and interferon maintenance therapy. One patient died in a rapid relapse five months post-BMT.