A systematic review of qualitative research exploring patient and health professional perspectives of breakthrough cancer pain.

PURPOSE: Breakthrough cancer pain (BtCP) is a prevalent health issue which is difficult to manage. A plethora of quantitative research in this area exists. There is a paucity of research on the perspectives of health professionals and patients surrounding domains impacting effective treatment, including definitions of BtCP, treatment, and education opportunities. This review aims to identify and synthesize the extent of qualitative research exploring health professional and patient perspectives of BtCP. METHODS: A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) approach was undertaken. The approach was registered with Prospero. MEDLINE, EMBASE, and Web of Science were searched for peer-reviewed literature published any date prior to May 19, 2022. Eligible sources must have considered health professional and/or patient perspectives of BtCP. A narrative synthesis approach was utilized. RESULTS: Three sources met the review criteria. One source explored nurse perspectives, while two sources explored patient perspectives. Study quality was moderate to high. Overlapping themes across the three studies included communication, defining BtCP, impact of BtCP, management of BtCP, perceptions of BtCP, analgesia and pain relief, and training and professional development. CONCLUSION: Given limited research investigating clinician and patient perspectives of BtCP, a rich understanding informed by exploratory qualitative methods around identification, best management strategies, professional development, and factors promoting and inhibiting best practice remains unclear. Further qualitative inquiry is warranted, and it is expected such research will inform BtCP clinical guidelines.

Dicer promotes genome stability via the bromodomain transcriptional co-activator BRD4.

RNA interference is required for post-transcriptional silencing, but also has additional roles in transcriptional silencing of centromeres and genome stability. However, these roles have been controversial in mammals. Strikingly, we found that Dicer-deficient embryonic stem cells have strong proliferation and chromosome segregation defects as well as increased transcription of centromeric satellite repeats, which triggers the interferon response. We conducted a CRISPR-Cas9 genetic screen to restore viability and identified transcriptional activators, histone H3K9 methyltransferases, and chromosome segregation factors as suppressors, resembling Dicer suppressors identified in independent screens in fission yeast. The strongest suppressors were mutations in the transcriptional co-activator Brd4, which reversed the strand-specific transcription of major satellite repeats suppressing the interferon response, and in the histone acetyltransferase Elp3. We show that identical mutations in the second bromodomain of Brd4 rescue Dicer-dependent silencing and chromosome segregation defects in both mammalian cells and fission yeast. This remarkable conservation demonstrates that RNA interference has an ancient role in transcriptional silencing and in particular of satellite repeats, which is essential for cell cycle progression and proper chromosome segregation. Our results have pharmacological implications for cancer and autoimmune diseases characterized by unregulated transcription of satellite repeats.

Noninvasive three-state sleep-wake staging in mice using electric field sensors.

STUDY OBJECTIVE: Validate a novel method for sleep-wake staging in mice using noninvasive electric field (EF) sensors. METHODS: Mice were implanted with electroencephalogram (EEG) and electromyogram (EMG) electrodes and housed individually. Noninvasive EF sensors were attached to the exterior of each chamber to record respiration and other movement simultaneously with EEG, EMG, and video. A sleep-wake scoring method based on EF sensor data was developed with reference to EEG/EMG and then validated by three expert scorers. Additionally, novice scorers without sleep-wake scoring experience were self-trained to score sleep using only the EF sensor data, and results were compared to those from expert scorers. Lastly, ability to capture three-state sleep-wake staging with EF sensors attached to traditional mouse home-cages was tested. RESULTS: EF sensors quantified wake, rapid eye movement (REM) sleep, and non-REM sleep with high agreement (>93%) and comparable inter- and intra-scorer error as EEG/EMG. Novice scorers successfully learned sleep-wake scoring using only EF sensor data and scoring criteria, and achieved high agreement with expert scorers (>91%). When applied to traditional home-cages, EF sensors enabled classification of three-state (wake, NREM and REM) sleep-wake independent of EEG/EMG. CONCLUSIONS: EF sensors score three-state sleep-wake architecture with high agreement to conventional EEG/EMG sleep-wake scoring 1) without invasive surgery, 2) from outside the home-cage, and 3) and without requiring specialized training or equipment. EF sensors provide an alternative method to assess rodent sleep for animal models and research laboratories in which EEG/EMG is not possible or where noninvasive approaches are preferred.

Thermoelectric properties of Ag-doped CuS nanocomposites synthesized by a facile polyol method.

We report the first thermoelectric properties of Cu1-xAgxS, x = 0-0.75 nanocomposites, synthesized by using a facile polyol method. Systematic characterizations using powder XRD, Rietveld refinement of XRD, EDAX, XPS and Raman spectroscopy confirmed their single phase, hexagonal crystal structure with the space group P63/mmc, nominal elemental composition, valence states of the constituent elements and stoichiometric nature. The TEM images showing the CuS formation of nearly perfect hexagonal disk-like particles of average thickness 26.7 nm and breadth ranging in a few hundreds of nanometers with nanorods stacked from these hexagonal nanodisks (NDs) elongated along the c axis corroborate the FESEM images. Attributed to structural phase transition, an anomaly at 55 K is clearly observed in both the thermopower and Hall resistivity data. By increasing x, a systematic reduction in thermal conductivity was observed near 300 K. Consequently, a 50% enhancement in figure of merit was observed for Cu0.9Ag0.1S as compared to pure CuS at 300 K. These results therefore are expected to provide a new direction in improving ZT near 300 K.

Clodronate exerts an anabolic effect on articular chondrocytes mediated through the purinergic receptor pathway.

OBJECTIVE: Bisphosphonates are commonly used anti-osteoporotic drugs which have controversial effects on joint diseases including osteoarthritis. Certain bisphosphonates have been shown to have anabolic effects on cartilage which could have important ramifications for their proposed effects in vivo; however, the underlying mechanisms are poorly understood. Thus, the purpose of this study was to characterize the effects of clodronate on primary articular chondrocyte metabolism and to determine the underlying signaling pathways responsible. DESIGN: The effects of clodronate and pamidronate on extracellular matrix (ECM) biosynthesis, accumulation and MMP-13 activity were observed in high density, 3D cultures of bovine articular chondrocytes for up to 4 weeks were evaluated. Mechanisms were delineated by measuring intracellular Ca(2+) signaling and the effects of pharmacologic inhibition of the purinergic receptor pathway. RESULTS: Clodronate (100 µM) induced an anabolic effect (increased biosynthesis by 13-14%) which resulted in an 89-90% increase in ECM accumulation after 4 weeks of culture and without an associated effect on matrix turn-over. Stimulation by clodronate resulted in a 3.3-fold increase in Ca(2+) signaling and pharmacological inhibitor experiments suggested that the anabolic effects exerted by clodronate are transduced through the purinergic receptor pathway. CONCLUSIONS: These findings support the previous notion that certain bisphosphonates may be useful as adjunctive therapies to potentially ameliorate progression of cartilage degeneration and improve arthritis management.

Use of nanosilver in consumer products.

Silver nanoparticles (AgNP; many other names such as nanosilver and colloidal silver) have already been used in everyday consumer products requiring broad spectrum antibiotic performance because of their enormous surface area and reactivity. Faunce and Watal [1] recently have critically analyzed the international regulatory issues for medical and domestic use in USA, EU, UK, and Australia. They found that in spite of the fact numerous studies have been made in the past decades, but many scientists are still uncertain of its safety. Very recently, Powers mentioned in her dissertation that her results showed positive that Ag+ and AgNP are developmental neurotoxicants in vitro and in vivo [2]. Therefore, there is a need to conduct a study to identify a global landscape of AgNPs and their products, and their manufacturers. A market- based intellectual property (IP) study has been conducted to examine the current global patent landscape of companies using AgNP in their consumer product development and production from 1980 to 2010. Detailed information in the compositions and formulations is extracted using a "two-stage" stage-gate process from the IP activity in the use of nanosilver. The first stage is in commercial products and the second stage is in consumer products. In the first stage for AgNP and AgNP-based commercial products, there were 7,422 patent families from January 1, 1980 to December 31, 2010. In the second stage for AgNP-based consumer products, 932 patent families from January 1, 1980 to December 31, 2010 were found. Korea, China and USA were found to be the major players in AgNP and AgNP-based commercial and consumer products. However, the recent patenting downturn was observed probably due to rising price in silver metal, regulatory uncertainty, public perception, and health safety & environmental (HS&E) issues.

True vasculitis in lupus nephritis.

Vascular lesions are encountered frequently in renal biopsy specimens of patients with systemic lupus erythematosus (SLE) and can present in a variety of morphologic forms. True renal lupus vasculitis (TRLV) is one of the rare vascular lesions associated with lupus nephritis that has been infrequently reported in the medical literature. The primary focus on glomerular pathology and collective classification of the vascular lesions under lupus vasculopathy is one of the reasons why this form of inflammatory vasculitis has been under-recognized as a separate disease entity. Here we have comprehensively reviewed the literature on renal vascular involvement in SLE for a better understanding of the epidemiology, morphologic features, pathogenesis, clinical course and treatment of TRLV. It can be morphologically differentiated from other forms of renal vascular lesions in lupus nephritis, i.e. arteriosclerosis, uncomplicated vascular immune deposits, non-inflammatory necrotizing vasculopathy, and thrombotic microangiopathy. Despite close similarities with antineutrophil cytoplasmic autoantibody associated vasculitis (AASV), there are certain morphological differences that warrant a thorough investigation of the possible pauci-immune mechanism of pathogenesis. The vasculitis follows a severe clinical course in general with rapid progression to renal failure, although favorable outcomes have been reported in certain cases. The standard use of steroids and cytotoxic drugs has yielded variable results in the treatment of TRLV. Current treatment modalities being used in lupus nephritis and AASV have been compared in this article with focus on drugs acting on the inflammatory cells implicated in TRLV pathogenesis.

Assessment of the potential for soil acidification in North India using the critical load approach and locally derived data for acidic and basic inputs.

Major ions (Cl-, NO3(-), SO4(2-), Ca2+, Mg2+, Na+, K+ and NH4(+)) were analysed in wet and dry deposition samples collected for 2 years using a polyethylene bottle and funnel collector at Agra in India. The deposition of ionic components (Ca2+ and Mg2+) derived from natural sources i.e. soil were higher than those of anthropogenic origin. In rainwater samples, non-sea-salt fraction was found to be 60-90%. In both wet and dry deposition Ca2+ was found to be the dominant ion which may be due to its large particle diameter. Results suggest that most of the acidity, which occurs due to NO3(-), SO4(2-) and Cl- is neutralized by alkaline constituents, which originate from airborne local soil and dust transported from the Thar desert. Acid neutralizing capacity of soil has also been quantified and found to be 33 x 10(3) neqg(-1). Using deposition data, the critical load for acidity of soil with respect to Ashoka and Eucalyptus was evaluated. The present level of deposition of S and N was found to be much lower than critical loads calculated for S and N. Critical load of exceedance in terms of deposition acidity was also calculated and found to be negative. This indicates that with respect to these species, the ecosystem is protected at the current level of deposition.

Viral hemorrhagic fever in Pakistan: awareness among health care personnel.

OBJECTIVE: To assess the level of knowledge regarding viral hemorrhagic fever (VHF) among healthcare personnel at two largest tertiary care hospitals in Karachi, Pakistan. METHODS: A cross sectional convenience survey was conducted in February 2001 among doctors, nurses, laboratory technicians and janitors/orderlies of Jinnah Postgraduate Medical Centre and Civil Hospital, Karachi. The questionnaire included demographic information with their designation and knowledge level regarding VHF management, spread and prevention. Frequencies of the answers to each question were calculated for all questions and scores were assigned. The frequencies were also calculated on the basis of the designation of the respondent so that each group could be examined separately. RESULTS: A total of 187 healthcare personnel (121 doctors, 31 nurses, 19 laboratory technicians and 16 janitors/orderlies) were interviewed. Forty three percent (81) respondents were males and 57% (106) were females. By designation 90% doctors, 71% nurses, 32% laboratory technicians and 6% janitors knew about VHF. Only 57% doctors (69) knew the common signs and symptoms of VHF. Isolation for affected patients was suggested by 65% nurses and 6% janitors. Knowledge regarding burial procedure of dead patients was low in all groups. CONCLUSION: Differences in knowledge of different groups is obvious but it is essential to raise the knowledge regarding VHF at all levels including the housekeeping staff. There is also a need for continuing medical education (CME) for all health care personnel for the emerging health problems in Pakistan.

Measurements of major ion concentration in settled coarse particles and aerosols at a semiarid rural site in India.

Deposition rates and deposition velocities of water-soluble ions (F, Cl, NO3, SO4, NH4, Ca, Mg, Na and K) were measured at a rural site (Gopalpura, Agra). Dry deposition samples were collected throughout the year from December 1995 to August 1997, while the aerosol samples were collected only during the winter season of 1996. Surrogate technique was used to collect the dry deposition samples, while aerosol samples were collected on PTFE membrane filter. Deposition velocities (Vd) of SO4 and NO3 are < or = 0.01 m s(-1) while Ca, Mg, Na, K, NH4, F and Cl exhibit greater than 0.01 m s(-1) Equivalent concentration ratios of K/Na, Ca/Na and Mg/Na conform with the corresponding ratios of local soil, indicating the dominant contribution of local sources. Deposition rates are maximum in winter, followed by summer and monsoon. No significant differences are found in dry deposition rates of all ions or in atmospheric concentrations of soil-derived elements with respect to wind direction. However, in aerosols, concentrations of F, Cl, NO3 and SO4 are higher with winds from southwesterly and westerly directions corresponding to pollution sources located in these directions. Deposition data have been used to calculate the critical load of S and N for soil with respect to Triticum vulgaris. The critical load of actual acidity was found to be 622.4 eq ha(-1) year(-1) within the range of 500-1,000 eq ha(-1) year(-1) as assessed by the RAINS-Asia model for this region. The present load of S and N (77.4 and 86.4 eq ha(-1) year(-1)) was much lower than the critical load of S and N (622.4 and 2,000 eq ha(-1) year(-1)), indicating that at present there is no harmful effect on ecosystem structure and function.

Addressing semen loss concerns: towards culturally appropriate HIV/AIDS interventions in Gujarat, India.

A situation analysis of sexual networking and sexual health in an industrial area of Gujarat, India, identified anxiety about masturbation and other semen loss concerns as major preoccupations among young men. This paper describes how the Deepak Charitable Trust addressed these concerns in their HIV prevention programme for young men aged 15 to 30. Flowcharts were used as participatory learning tools and to obtain data on the perceived consequences of masturbation, both before and after intervention activities. Research was also done on the relation between semen-related anxieties and sexual risk behaviour by DCT and two other NGOs among young men engaging in unsafe sexual behaviour. DCT advocates addressing masturbation and other semen loss concerns in all sexual health campaigns in South Asia, based on the magnitude of these concerns, their potential to confound syndromic management of STIs and their significance as an idiom of psychosocial distress. Masturbation and associated anxieties about sexual performance are seen as health issues and discussed as such by the programme. There is immediate identification among young men, whether or not they are already sexually active, and it provides an excellent entry point for sexual health and safer sex education. The community response to these efforts has been entirely positive.

The incidences of trisomy 8, trisomy 9 and D20S108 deletion in polycythaemia vera: an analysis of blood granulocytes using interphase fluorescence in situ hybridization.

We have used interphase fluorescence in situ hybridization (IFISH) to detect trisomy 8, trisomy 9 and 20q deletion in circulating granulocytes from patients with polycythaemia vera (PV). Out of 64 PV patients, 15 (23%) exhibited an abnormality. Two patients had trisomy 9, three had trisomy 8 and 10 patients had hemizygous deletion of D20S108 (a locus in the 20q common deleted region). Aberrant nuclei ranged from 10% to 80% in these 15 cases. There was no correlation between the presence of a marker and sex, age, interval between presentation and IFISH analysis, neutrophil or platelet count or therapy. Conventional marrow cytogenetic karyotype results were available in 23 cases and there was concurrence between these and blood IFISH in 16 cases (13 normal and three with 20q/D20S108 deletion by both methods). Three patients with D20S108 deletion by IFISH were normal by previous marrow cytogenetic testing and four cases with 20q deletion by previous marrow cytogenetics had normal blood granulocytes according to IFISH. Thus, we confirm that trisomies 8 and 9 and deletion of 20q are diagnostically useful markers of PV. IFISH analysis of blood granulocytes is a practical method for detecting these markers, but as an adjunct to, not as a substitute for, conventional marrow cytogenetics.

Prospective cohort study to determine if trial efficacy of anticoagulation for stroke prevention in atrial fibrillation translates into clinical effectiveness.

OBJECTIVE: To determine whether trial efficacy of prophylaxis with warfarin for patients with atrial fibrillation at high risk of stroke translates into effectiveness in clinical practice. DESIGN: Two year prospective cohort study. SETTING: District general hospital. PARTICIPANTS: 167 patients with atrial fibrillation and at high stroke risk who were eligible for anticoagulation. INTERVENTIONS: Long term anticoagulation with warfarin at adjusted doses to maintain an international normalised ratio of 2.0-3.0. MAIN OUTCOME MEASURES: Comparison of patient characteristics, comorbidity, anticoagulation control, stroke rate, and haemorrhagic complications with pooled data from five randomised controlled trials. RESULTS: Patients in the study group were seven years older (95% confidence interval 4 to 10) and comprised 33% more women than patients in the pooled trials. The international normalised ratio was in the target range for 61% of the time (range 37%-85%), below for 26% of the time (range 8%-32%), and above for 13% of the time (range 6%-26%). The time that patients in the study group spent in the target range was significantly less than in the pooled analysis. The incidence of stroke in the study group (2.0% per year, 0.7% to 4. 4%) was comparable to that of patients receiving warfarin in pooled studies (1.4%, 0.8% to 2.3%). Per year the incidence of major (1.7% v 1.6%) and minor (5.4% v 9.2%) bleeding complications was also similar. CONCLUSION: Rates of stroke and major haemorrhage after anticoagulation in clinical practice were comparable to those obtained from pooled data from randomised controlled studies for patients with atrial fibrillation at high risk of stroke.

High dose methyl prednisolone in refractory chronic lymphocytic leukaemia.

We treated 14 patients with advanced, resistant chronic lymphocytic leukaemia (CLL) including three with >10% prolymphocytes (CLL/PL) with high dose methyl prednisolone (HDMP). All patients had stage C CLL or bulky stage B disease. There were 11 males and 3 females with a median age of 58.5 years (range: 49-69). Six out of eleven CLL patients had a partial response as defined by the NCI guidelines, no patient had a complete remission. The mean duration of PR was 19.6 months with a median of 8 months (range 6-78). Seven patients have died including the 5 non-responders. None of the 3 patients with CLL/PL had a measurable response. Previous treatments included chlorambucil, fludarabine, deoxycoformycin, anthracycline containing regimens such as CHOP and Campath-1H. HDMP was given at a dose of 1 g/m2 for five days, at monthly intervals for one to seven courses depending on the response. H2 antagonists and antimicrobial prophylaxis were given concurrently. Acyclovir prophylaxis was given if there was a recent history of herpes infection. HDMP was generally well tolerated. Side effects included fluid retention, hyperglycaemia, bradycardia (1 patient), herpes simplex (1), and pneumonia (1) in a patient with a previous history of recurrent chest infection and pneumonia. These results suggest that HDMP may be beneficial in the treatment of refractory CLL but is of no value in CLL/PL.

Intravesicular instillation of E-aminocaproic acid for patients with adenovirus-induced hemorrhagic cystitis.

Hemorrhagic cystitis (HC) is a known complication of allogenic BMT. We report a case of a 28-year-old female with CML in chronic phase, which was treated with a matched unrelated donor (MUD) transplant, complicated by hemorrhagic cystitis on day +42 after the transplant. Adenovirus was isolated from the urine and she was treated with ribavirin, 1 g twice a day for 8 days. We report the use of Amicar (E-aminocaproic acid), 2.5 g solution as bladder instillation to treat the intractable hematuria.

Issues that influence patient/physician discussion of complementary therapies.

This article explores what patients expect from physicians when discussing complementary therapies. Counsellors at four cancer centres, under the auspices of the British Columbia Cancer Agency, discuss their clinical observations in working with oncology patients. They present perspectives of factors that influence the patient/physician discussion of complementary therapies. Some of the common themes include desire for collaboration and control, need for understanding treatment information, maintenance of hope, and trust of the physician.

The use of intravenous intermediate dose melphalan and dexamethasone as induction treatment in the management of de novo multiple myeloma.

The variable absorption of melphalan from the gastrointestinal tract results in response rates between 40 and 60%. High dose melphalan increases response rates but at the cost of increased morbidity and mortality. We have investigated intravenous intermediate dose melphalan and dexamethasone in the treatment of patients presenting with de novo multiple myeloma with the object of reducing toxicity while preserving an improved response rate compared to oral melphalan and prednisolone. The results show that this treatment can be delivered safely on an outpatient basis in patients up to the age of 78 yr; 82% of patients achieved an objective response and 30% a complete haematological and clinical remission. Median overall survival for the whole group is 37 months.

Rapid progression of fibrosing alveolitis and thyrotoxicosis after antithymocyte globulin therapy for aplastic anemia.

Antithymocyte globulin (ATG) therapy is an established form of treatment for aplastic anaemia and has also been used as prophylaxis against graft rejection of bone marrow and renal allografts. Administration of ATG preparations has been associated with many mild clinical reactions, as have other forms of immunomodulatory therapy. However, serious adverse effects appear to be rare. We report a case of rapidly progressive fibrosing alveolitis and thyrotoxicosis in relation to ATG therapy, highlighting its potential toxicity and emphasising that its administration should be undertaken by experienced physicians in specialised centres.

VAPEC-B chemotherapy in the treatment of aggressive non-Hodgkin's lymphoma: a retrospective analysis of 45 patients.

We performed a retrospective analysis on 45 patients who, between January 1989 and October 1993, received VAPEC-B chemotherapy for high and intermediate grade non-Hodgkin's lymphoma. The aim was to assess response and tolerance to treatment. The weekly regimen consisted of: doxorubicin 35 mg/m2 i.v. weeks 1,3,5,7,9,11; cyclophosphamide 350 mg/m2 i.v. weeks 1, 5, 9; etoposide 100 mg/m2 p.o. daily for 5 days, weeks 3, 7, 11; vincristine 1.4 mg/m2 i.v. (2 mg max.) weeks 2, 4, 6, 8, 10; bleomycin 10 mg/m2 i.v. weeks 2, 6, 10; methotrexate 12.5 mg i.t. weeks 1, 5, 9; prednisolone 50 mg p.o. daily for 6 weeks, reduced to 25 mg daily for 6 weeks. The patients treated were aged 22-71 years, 34 (75%) had high grade (Working Formulation) non-Hodgkin's lymphoma (NHL); 11 (24%) had intermediate grade NHL; 25 had Stage III/IV disease; and 14 (31%) had marrow involvement. The majority of patients (76%) received VAPEC-B as first line chemotherapy; the remainder received it for relapsing disease. Follow-up time from completion of VAPEC-B chemotherapy ranged from 6 months to 50 months (median 25). VAPEC-B, as first line therapy, induced a complete response (CR) and partial response (PR) in 79% and 18% respectively, whilst 3% had no response to treatment. VAPEC-B used for relapsing disease produced CR and PR in 64% and 27% respectively, whilst 9% failed to respond. Six patients in PR and five patients in CR have subsequently undergone an autologous bone marrow transplant or a peripheral blood stem cell transplant. In the group who received VAPEC-B first line but did not proceed to transplant (27 patients), five relapsed (three with CNS disease who had not had CNS prophylaxis). Tolerance to treatment was measured by WHO toxicity scores. The haemoglobin (Hb) toxicity median score for all patients was grade 1 (Hb 9.5-10.9 g/dl), and the white cell count (WCC), toxicity score was grade 2 (WCC 2.0-2.9 x 10(9)/l). No platelet toxicity was observed. Ten per cent of patients suffered grade 3 severity infections requiring antibiotics and there was one treatment related death. The majority of patients received VAPEC-B on time, however, 24% patients had a 2-week delay. VAPEC-B chemotherapy is an effective regimen for malignant lymphoma, either as a first line or as a salvage treatment. Although chemotherapy was given weekly, the tolerance to treatment was acceptable, thus making this short regimen a good alternative to CHOP chemotherapy.

Detection of residual leukaemia more than 10 years after allogeneic bone marrow transplantation for chronic myelogenous leukaemia.

The clinical status of a homogeneous cohort of long-term survivors of allogeneic marrow transplantation was assessed and residual leukaemia was studied by reverse transcription polymerase chain reaction for leukaemia specific BCR-ABL mRNA. The group comprised 34 consecutive patients with CML in chronic phase treated by chemoradiotherapy and transplantation of bone marrow from HLA-identical sibling donors between February 1981 and December 1983 in the joint Hammersmith-Northwick Park programme. The probability of survival at 10 years was 59 +/- 17%. Eighteen of the 19 surviving (95%) patients have Karnofsky scores of 90 or 100% indicative of a good performance status. One of the survivors had evidence of relapse 6.5 years after transplant but has since been restored to complete remission by treatment with interferon-alpha followed by donor leucocyte transfusions. Surprisingly, 2 of the 19 patients who have been in remission for over 10 years have molecular evidence of persisting leukaemic cells. Quantification by competitive PCR indicated that the malignant clone persisted at low levels. The data suggest that the majority of long-term survivors after BMT for CML are in good health and may be regarded as cured. Some long-term survivors, however, may still harbour residual leukaemic cells and continued monitoring for late relapse is warranted. Late relapse is amenable to further therapy with leukocyte transfusions from the original marrow donor.