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Click here for the corresponding questions to this CME article. [ABSTRACT FROM AUTHOR]

Background: Outcomes for patients with acute myeloid leukaemia (AML) undergoing allogeneic stem cell transplantation (allo-SCT) have significantly improved in recent years.Objectives: To assess the incremental improvement of transplanted AML patients in the last two decades.Methods: Patients included in this analysis were adult AML patients who underwent allo-SCT from an HLA-matched sibling donor (MSD) or HLA-matched unrelated donor (MUD) in first remission. Patient outcomes were assessed between three cohorts according to the year of transplant (1993-2002, 2003-2007 and 2008-2012).Results: The analysis comprised a total of 20 187 patients of whom 4763 were transplanted between 1993 and 2002, 5835 in 2003 and 2007, and 9589 in 2008 and 2012. In multivariate analysis, leukaemia-free survival (LFS) rates were significantly improved in more recently transplanted patients compared to patients transplanted in 1993-2002 [Hazard ratio (HR) = 0.84, confidence interval (CI) 95%, 0.77-0.92; P = 0.003], a benefit which also extended to improved overall survival (OS; HR = 0.8, CI 95%, 0.73-0.89; P < 0.0001), and decreased nonrelapse mortality (NRM) rates (HR = 0.65, CI 95%, 0.56-0.75; P < 0.0001). Subset analysis revealed that in MSD, the rates of LFS, NRM and OS significantly improved in patients in the more recent cohort with similar results also seen in MUD. Finally, the incidence of acute graft-versus-host disease (GVHD) was significantly reduced leading to improved GVHD-free/relapse-free survival (GRFS) rates in more recently transplanted patients.Conclusion: Outcome of allo-SCT for AML patients has markedly improved in the last two decades owing to decreased nonrelapse mortality and improved rates of leukaemia-free survival resulting in significantly longer survival. [ABSTRACT FROM AUTHOR]

Aplastic anaemia (AA) is frequently associated with other disorders of clonal haemopoiesis such as paroxysmal nocturnal haemoglobinuria (PNH), myelodysplastic syndrome (MDS) and T-large granular lymphocytosis. Certain clones may escape the immune attack within the bone marrow environment and proliferate and attain a survival advantage over normal haemopoietic stem cells, such as trisomy 8, loss of heterozygosity of short arm of chromosome 6 and del13q clones. Recently acquired somatic mutations (SM), excluding PNH clones, have been reported in around 20-25 % of patients with AA, which predispose to a higher risk of later malignant transformation to MDS/acute myeloid leukaemia. Furthermore, certain SM, such as ASXL1 and DNMT3A are associated with poor survival following immunosuppressive therapy, whereas PIGA, BCOR/BCORL1 predict for good response and survival. Further detailed and serial analysis of the immune signature in AA is needed to understand the pathogenetic basis for the presence of clones with SM in a significant proportion of patients. [ABSTRACT FROM AUTHOR]

Bone marrow (BM) genetic abnormalities in myelodysplastic syndrome (MDS) have provided important biological and prognostic information; however, frequent BM sampling in older patients has been associated with significant morbidity. Utilizing single-nucleotide polymorphism array (SNP-A) and targeted gene sequencing (TGS) of 24 frequently mutated genes in MDS, we assessed the concordance of genetic abnormalities in BM and peripheral blood (PB) samples concurrently from 201 MDS patients. SNP-A karyotype in BM was abnormal in 108 (54%) and normal in 93 (46%) patients, with 95% (190/201) having an identical PB karyotype. The median copy number (CN) for deletions was significantly lower in BM (CN:1.4 (1-1.9)) than in PB (CN:1.5 (1-1.95), P<0.001). Using TGS, 71% (130/183) patients had BM somatic mutations with 95% (124/130) having identical mutations in PB. The mutant allele burden was lower in PB (median 27% (1-96%)) compared with BM (median 29% (1-100%); P=0.14) with no significant difference in the number, types of mutations or World Health Organization subtype. In all patients with discordant SNP (n=11) and mutation (n=6) profiles between BM and PB, shared abnormalities were always present irrespective of treatment status. Overall, 86% of patients had a clonal aberration with 95% having identical SNP-A karyotype and mutations in PB, thus enabling frequent assessment of response to treatment and disease evolution especially in patients with fibrotic or hypocellular marrows. [ABSTRACT FROM AUTHOR]

DLIs are frequently used following haematopoietic SCT (HSCT) in patients with risk of relapse but data on GVHD following DLI are scarce. We report on 68 patients who received DLI following HSCT. Most patients developed GVHD following DLI (71%), which was acute in 22 patients (32%) almost half of whom had grade III-IV acute GVHD (aGVHD). Thirty patients (44%) developed cGVHD which followed aGVHD in four patients and was graded severe in nine patients. Corticosteroids were the most common first-line therapy for both acute and chronic GVHD. A wide range of second/third-line agents included cyclosporin, mycophenolate, tacrolimus, imatinib, infliximab and ECP. Relapse of initial malignancy occurred in 37%. Relapse was significantly less frequent in those receiving pre-emptive DLI. Relapse rates were also lower in those with GVHD (31%) than those without GVHD (50%), but this did not reach statistical significance. At 55 months post DLI, 34% of patients had died most commonly from relapse and 22% had on-going GVHD. Although GVHD was an important cause of morbidity post DLI (71%), only 6% died from GVHD. Although most patients develop GVHD post DLI and may require consecutive therapies, mortality from GVHD is infrequent. DLI remains an important option for relapse post transplant and manipulation of the GVT effect needs to be optimised to induce remission without morbidity from GVHD. [ABSTRACT FROM AUTHOR]

The article explores the connection of platelet response criteria and patient outcomes in myelodysplastic syndromes trial with romiplostim. An improvement in platelet count is noted following the use of romiplostim as monotherapy and in combination with azacitidine, decitabine or lenalidomide. The relation of romiplostim treatment with platelet response by all the criteria studied is noted. The likelihood of the patients to require platelet transfusions is also shown in all the criteria.

This retrospective national study compared the use of alemtuzumab-based conditioning regimens for hematopoietic SCT (HSCT) in acquired severe aplastic anemia with antithymocyte globulin (ATG)-based regimens. One hundred patients received alemtuzumab and 55 ATG-based regimens. A matched sibling donor (MSD) was used in 87 (56%), matched unrelated donor (MUD) in 60 (39%) and other related or mismatched unrelated donor (UD) in 8 (5%) patients. Engraftment failure occurred in 9% of the alemtuzumab group and 11% of the ATG group. Five-year OS was 90% for the alemtuzumab and 79% for the ATG groups, P=0.11. For UD HSCT, OS of patients was better when using alemtuzumab (88%) compared with ATG (57%), P=0.026, although smaller numbers of patients received ATG. Similar outcomes for MSD HSCT using alemtuzumab or ATG were seen (91% vs 85%, respectively, P=0.562). A lower risk of chronic GVHD (cGVHD) was observed in the alemtuzumab group (11% vs 26%, P=0.031). On multivariate analysis, use of BM as stem cell source was associated with better OS and EFS, and less acute and cGVHD; young age was associated with better EFS and lower risk of graft failure. This large study confirms successful avoidance of irradiation in the conditioning regimens for MUD HSCT patients. [ABSTRACT FROM AUTHOR]

Alemtuzumab, a humanized anti-CD52, IgG1 monoclonal antibody, is used to reduce graft-versus- host disease (GVHD) and aid engraftment after allogeneic haemopoietic stem cell transplant (HSCT). Its associated low incidence of GVHD makes it an attractive alternative to anti-thymocyte globulin (ATG) in transplant conditioning regimen for severe aplastic anaemia (SAA). We have reviewed the use of alemtuzumab-based conditioning regimen for HSCT in SAA and show that it results in sustained haematological engraftment, a very low incidence of chronic GVHD without an increase in viral infections. Intriguingly, alemtuzumab appears to induce tolerance post-HSCT with the findings of stable mixed T cell chimerism with full donor myeloid chimerism and the absence of chronic GVHD, and which persist on withdrawal of post-graft immunosuppression. Finally, its low toxicity profile may permit future application of HSCT to older patients with SAA who fail to respond to immunosuppressive therapy. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic SCT with reduced-intensity conditioning (RIC-HSCT) is increasingly adopted for the treatment of older adults with AML. Our goal was to verify for the first time, if center experience influences outcome of RIC-HSCT. Results of 1413 transplantations from HLA-matched related or unrelated donors for adult patients with AML in first CR were analyzed according to the level of center activity. Transplants were performed in 203 European centers between 2001 and 2007. The 2-year probability of leukemia-free survival (LFS) after RIC-HSCT performed in centers with the lowest activity (15 procedures/7 years) was 43±3% compared with 55±2% in the remainder (P<0.001). The incidence of non-relapse mortality (NRM) was 24±3% and 15±1% (P=0.004), whilst relapse rate was 33±3% and 31±1% (P=0.33), respectively. In a multivariate model, adjusted for other prognostic factors, low RIC-HSCT activity was associated with decreased chance of LFS (hazard ratio (HR)=0.64; P<0.001) and increased risk of NRM (HR=1.47, P=0.04) and relapse (HR=1.41, P=0.01). Center experience is a very important predictor of outcome and should be considered in future analyses evaluating the results of RIC-HSCT. The reasons why centers with low RIC-HSCT activity have worse outcomes should be further investigated. [ABSTRACT FROM AUTHOR]

Extracorporeal photopheresis (ECP) has become a recognised treatment for steroid-refractory chronic GVHD (cGVHD), but the optimal frequency and duration of treatment are yet to be established. We report on 82 consecutive patients with mucocutaneous cGVHD who received a bimonthly regimen of ECP treatment for two consecutive days, which could be subsequently tapered to a monthly regimen depending on response. Patients were steroid-refractory, steroid-dependent or steroid-intolerant, and 29 (35%) had multiorgan involvement. The median duration of treatment was 330 days (42-987). The median number of ECP cycles was 15 (1.5-32). Response was assessed by clinical assessment and reduction in immunosuppression after 6 months. 69/82 (84%) had completed 6 months of ECP and 65/69 (94%) had 50% improvement in symptoms and signs of cGVHD. A total of 77% of patients who completed 6 months of ECP had a reduction in immunosuppression dose and 80% had decreased their steroid dose (27.5% stopped, 30% had 75% reduction, 17.5% had 50% reduction and 25% had <50% reduction). OS at 3 years from the start of ECP was 69%. This study reports the largest series of patients receiving bimonthly ECP treatment for cGVHD, and confirms that ECP allows successful reduction of immunosuppression. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding the long-term transfusion independence in del(5q) chromosomal aberration of myelodysplastic syndrome (MDS) patients who discontinue lenalidomide treatment.

Haematopoietic SCT (HSCT) offers the only potentially curative option in chronic myelomonocytic leukaemia (CMML). In this study, we report on single-centre results of 18 patients with CMML who have undergone allogeneic HSCT. The median age of patients was 54 years. Seven patients had AML, which had transformed from CMML. Overall, 11 patients received stem cells from an unrelated donor. A total of 15 patients received a T-cell-depleted fludarabine/BU-based reduced-intensity conditioning HSCT. The actuarial 3-year OS, non-relapse mortality (NRM) and relapse incidence for the cohort was 31±11%, 31±14% and 47±13%, respectively. Patients with favourable cytogenetics had a 3-year disease-free survival of 65±17%, whereas none of the seven patients with intermediate or poor risk cytogenetics survived beyond 2 years (P<0.01). No patients with favourable risk cytogenetics died from NRM causes, while the 2-year NRM for the intermediate/poor risk cytogenetics subgroup was 71±22% (P<0.02). In terms of disease status at transplantation, patients who had <5% BM blasts had a 3-year disease-free survival of 46.9±19% compared with those with >5% blasts at the time of transplantation (that is, 20.0±13%). Recipient age, type of conditioning regimen or stem cell dose did not have a significant impact on overall outcomes. Our data support existing evidence that allogeneic HSCT is a feasible therapeutic option for CMML, with the ability to attain long-term remission among patient subgroups. [ABSTRACT FROM AUTHOR]

DNA replication is tightly regulated, but paradoxically there is reported to be an excess of MCM DNA replication proteins over the number of replication origins. Here, we show that MCM levels in primary human T cells are induced during the G0→G1 transition and are not in excess in proliferating cells. The level of induction is critical as we show that a 50% reduction leads to increased centromere separation, premature chromatid separation (PCS) and gross chromosomal abnormalities typical of genomic instability syndromes. We investigated the mechanisms involved and show that a reduction in MCM levels causes dose-dependent DNA damage involving activation of ATR & ATM and Chk1 & Chk2. There is increased DNA mis-repair by non-homologous end joining (NHEJ) and both NHEJ and homologous recombination are necessary for Mcm7-depleted cells to progress to metaphase. Therefore, a simple reduction in MCM loading onto DNA, which occurs in cancers as a result of aberrant cell cycle control, is sufficient to cause PCS and gross genomic instability within one cell cycle. [ABSTRACT FROM AUTHOR]

Aliment Pharmacol Ther 31, 1330–1336 Background Occult myeloproliferative disorders (MPD) are present in 25% of patients with chronic portal, splenic and mesenteric venous thrombosis (PSMVT). A somatic mutation of JAK2 (JAK2V617F) can be used to identify patients with latent MPD. Aim We evaluated the prevalence and clinical significance of JAK2V617F in patients with chronic PSMVT. Methods Allele-specific polymerase chain reaction was performed to screen for JAK2V617F. Results Thirty-five patients were tested for JAK2V617F. The underlying pro-coagulant condition was MPD in seven of 35 (20.0%) patients; other aetiologies included hereditary thrombophilia ( n = 5), chronic pancreatitis ( n = 2), liver abscess ( n = 1) and umbilical vein sepsis ( n = 3). The remainder were labelled idiopathic, i.e. 17/35 (48.6%) patients. JAK2V617F was detected in 16/35 (45.7%) patients: seven of seven (100%) with MPD, two of 11 (18.1%) with non-MPD acquired conditions and seven of 17 (41.2%) with ‘idiopathic’ chronic PSMVT. Mean haemoglobin concentration ( P = 0.04), haematocrit ( P = 0.04), white cell count ( P = 0.002) and platelet count ( P = 0.05) were significantly higher in patients with JAK2V617F. None of the seven patients with latent MPD have progressed to overt MPD over median follow-up of 85 months. Conclusion JAK2V617F occurs in 41% of patients with idiopathic chronic portal, splenic and mesenteric venous thrombosis, confirming the presence of latent myeloproliferative disorders, and should form part of the routine pro-coagulant screen. [ABSTRACT FROM AUTHOR]

We report a retrospective analysis of 128 consecutive patients with high-risk myelodysplastic syndrome (MDS) and AML who received an alemtuzumab-based reduced-intensity conditioning hematopoietic SCT (RIC HSCT). The median recipient age was 53 years (range 21–72 years). A total of 49 (38%) recipients had a sibling donor and 79 (62%) had a volunteer-unrelated donor. The hematopoietic cell transplantation-specific comorbidity index (HCT-CI) was assigned to all patients with a score of 0 in 40 (31%), of 1–2 in 45 (35%) and 3 in 43 (34%) patients. The 3-year non-relapse mortality (NRM) was 31%, disease-free survival (DFS) was 41% and overall survival (OS) was 46%. The 3-year NRM for patients with a HCT-CI score of 0, 1–2 or 3 was 16, 24 and 42%, respectively. The 3-year DFS and OS by HCT-CI was 58 and 69% (score 0), 39 and 39% (score 1–2) and 24 and 32% (score 3), respectively. On multivariate analysis, HCT-CI was an independent variable affecting 3-year NRM, DFS and OS (P-value=0.04, 0.01 and <0.01, respectively). Although the disease stage at the time of transplant was an additional independent predictive variable on transplant outcomes, recipient age (>/<50 years) did not have a significant predictive impact. In MDS or AML patients with advanced disease receiving alemtuzumab-based RIC HSCT, the HCT-CI provides an important means of stratifying patients with a high risk of inferior transplant outcomes. [ABSTRACT FROM AUTHOR]

Objectives: To identify any seasonal variation in the pattern of referrals to the Surgical Assessment Unit (SAU). Methods: Admission data to the SAU were collected prospectively during two audit periods of 13 weeks each (winter 2004/2005 and summer 2005). The data were analysed comparing numbers of admissions over the two audit periods and variations in the presenting complaint. Results: There were a significantly greater number of referrals to the SAU in the summer compared with winter (999 vs. 849, p = 0.026). Whilst there were no significant differences in the sex distribution of patients presenting with general surgical symptoms, a significantly greater proportion of male patients presented with urological symptoms. Additionally, a significantly greater proportion of patients presented in the summer with scrotal/testicular symptoms compared with the winter (13.9% vs. 8.5%, p = 0.02). There was no significant difference between the two periods in terms of other diagnoses. In both study periods, the SAU was busy during weekdays compared with weekends. Whilst most patients arrived in the SAU between 9 am and midnight a smaller but not insignificant number arrived outside of these hours. Conclusions: Summer compared with winter was a busy period for the SAU. This may be important in managing emergency surgical admissions. A significantly greater proportion of patients presented with scrotal/testicular symptoms during the summer, the reasons for which are unclear. The SAU diverts workload away from busy Accident & Emergency departments. [ABSTRACT FROM AUTHOR]

Disease relapse following an allogeneic transplant remains a major cause of treatment failure, often with a poor outcome. Second allogeneic transplant procedures have been associated with high TRM, especially with myeloablative conditioning. We hypothesized that the use of reduced-intensity conditioning (RIC) would decrease the TRM. We performed a retrospective national multicentre analysis of 71 patients receiving a second allogeneic transplant using RIC after disease relapse following an initial allogeneic transplant. The majority of patients had leukaemia/myelodysplasia (MDS) (N=57), nine had lymphoproliferative disorders, two had myeloma and three had myeloproliferative diseases. A total of 25% of patients had unrelated donors. The median follow-up was 906 days from the second allograft. The predicted overall survival (OS) and TRM at 2 years were 28 and 27%, respectively. TRM was significantly lower in those who relapsed late (>11 months) following the first transplant (2 years: 17 vs 38% in early relapses; P=0.03). Two factors were significantly associated with a better survival: late relapse (P=0.014) and chronic GVHD following the second transplant (P=0.014). These data support our hypothesis that the second RIC allograft results in a lower TRM than using MA. A proportion of patients achieved a sustained remission even when relapsing after a previous MA transplant.Bone Marrow Transplantation (2008) 42, 783–789; doi:10.1038/bmt.2008.255; published online 25 August 2008 [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article related to the contribution of tumor-derived interleukin-6 (IL-6) to the immunological defect of chronic lymphocytic leukemia (CLL) in the November 1, 2007 issue.

The presence of clonal gammopathies (CG) has been reported following both conventional myeloablative and autologous haematopoietic stem cell transplantation (HSCT). We monitored the occurrence of CG in a cohort of patients with myeloid malignancies receiving FBC (fludarabine-busulphan-alemtuzumab)-based reduced intensity conditioned (RIC) HSCT, and assessed its correlation with infections, graft-versus-host disease (GvHD) and survival. Serial serum protein electrophoresis was analysed in a total of 138 patients and CG were detected in 49 patients (36%). The predominant Ig isotype was IgG (82%). There was no difference in the incidence of viral infections between patient groups. However, patients with gammopathies were more likely to have had prior chronic GvHD (OR 2.7, 95% CI 1.3–5.5, P<0.001). On multivariate analysis, the only factors that were found to influence overall survival (OS) were presence of gammopathies, which was associated with an improved OS (OR 0.35 95% CI 0.14–0.86, P=0.02) as well as disease stage, patients with advanced disease having a higher risk of death (OR 2.20 95% CI 1.18–4.11, P=0.02). Disease stage was the only variable that influenced relapse incidence on multivariate analysis (OR 4.22 95% CI 1.82–9.78, P<0.01). Clonal gammopathies are a frequent but benign occurrence following alemtuzumab-based RIC HSCT, and their appearance may define a group of patients with a favourable overall outcome.Bone Marrow Transplantation (2007) 40, 747–752; doi:10.1038/sj.bmt.1705805; published online 20 August 2007 [ABSTRACT FROM AUTHOR]

5-Azacytidine, a DNA methyl transferase inhibitor, is effective in patients with myelodysplastic syndromes (MDS). Whether responses to 5-Azacytidine are achieved by demethylation of key genes or by cytotoxicity is unclear. Of 34 patients with MDS or acute myeloid leukaemia (AML) treated with 5-Azacytidine, 7 achieved complete remissions (CR) (21%) and 6 achieved haematological improvement. All six had less than 5% bone marrow (BM) blasts at the time of haematological improvements (HI) (2 had pre-existing refractory anaemia (RA), 4 had refractory anaemia with excess blasts (RAEB)). A further patient with RAEB had blast reduction to less than 5% without HI. Five of the seven (71%) complete responders had chromosome 7 abnormalities. BM CR predicted longer overall survival (OS) (median 23 versus 9 months, P=0.015). Bisulphite genomic sequencing (BGS) of the CDKN2B (p15(INK4b)) promoter showed low level, heterogeneous pretreatment methylation (mean 12.2%) in 14/17 (82%) patients analysed. Lower baseline methylation occurred in responders (9.8% versus 16.2% in non-responders P=0.07). No response was seen in patients with >24% methylation, in whom p15(INK4b) mRNA was not expressed. 5-Azacytidine reduced CDKN2B methylation by mean 6.8% in 8/17 (47%) patients, but this did not correlate with response. At 75 mg/m(2), cell death (reduced BM cellularity (P=0.001) and increased apoptosis (P=0.02)) rather than demethylation of CDKN2B correlates with response. Patients with >24% methylation may benefit from alternative dosing or combination strategies. [ABSTRACT FROM AUTHOR]

Immunosuppressive therapy has been shown to induce sustained hematological responses in a subset of patients with myelodysplastic syndromes (MDS). In particular, antithymocyte globulin (ATG), a polyclonal immunoglobulin induces hematological responses in up to 60% of MDS patients. We report herein on the results of a retrospective multicenter study on the use of ATG in the treatment of 96 patients with MDS. Patients were evaluated for duration of response to ATG, as well as survival after administration of ATG. The median age of the cohort was 54.7 years (range: 19-75 years), with a median follow-up of 33.8 months (range: 0.8-133 months). A total of 40 patients (42%) achieved a hematological response, of which 30 patients (75%) had a durable hematological response lasting a median duration of 31.5 months (range: 6-92 months). On multivariate analysis, both low International Prognostic Scoring System (IPSS) and bone marrow (BM) hypocellularity were independent predictive factors for improved response to ATG (IPSS Int-2/high: odds ratio (OR) 0.08, P=0.018 and BM normo/hypercellularity: OR 0.49, P=0.012). In addition, IPSS was the sole predictor of overall survival, with Int-2/high risk patients having a significantly poorer survival outcome (OR 0.08, P<0.01). In conclusion, this study identifies BM hypocellularity and a low IPSS as important factors predicting response to ATG. [ABSTRACT FROM AUTHOR]

Sclerodermatous graft-versus-host disease (GVHD) is a rare complication of bone marrow transplantation. While GVHD is often associated with the beneficial graft vs. tumour effect, it also contributes towards significant morbidity and mortality. No reliably effective treatment has yet been established. We present 10 patients with haematological malignancies who underwent an allogeneic stem cell transplant and developed sclerodermatous GVHD. Donor lymphocyte infusion administered for relapse or reducing donor T-cell chimerism was a known trigger for sclerodermatous GVHD in four of the patients. Treatment with immunosuppressants, psoralen plus ultraviolet A (PUVA) and extracorporeal photopheresis has been largely unsuccessful in their management. Intensive immunosuppression including the use of anti-CD20 monoclonal antibody may have contributed to relapse of leukaemia in one patient 10 years after her transplant. Sclerodermatous GVHD may occur without a preceding lichenoid stage. Clinical heterogeneity is common, although sclerodermatous GVHD has a predilection for the limbs. Treatment options are largely unsatisfactory if conventional immunosuppression fails. PUVA may give some symptomatic benefit and extracorporeal photopheresis seems to be less efficacious than previously published work suggests. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the long-term results of plication of tunica albuginea in patients with penile curvature secondary to Peyronie’s disease. Patients and methods: A total of 78 men with penile curvature secondary to Peyronie’s disease underwent corporeal plication over a 10 year period. To assess the long-term results, a questionnaire-based study was undertaken on 73 of these patients with a time lapse of > 6 months after the operation. The questionnaire focussed on the presence or absence of penile deformity and pain, erectile function and the ability to perform sexual intercourse. Results: Follow up ranged from 3 to 109 months with a median of 51 months. The cosmetic result was good or excellent (straight or almost straight penis) in 94% by 6 months. A total of 57 replies to the questionnaire were suitable for analysis. A total of 90% patients had a satisfactory cosmetic result, whereas only 71% reported a satisfactory functional result (straight or almost straight penis on erection with pain free penetration and normal sexual intercourse) in the long-term. In patients with > 3 years follow up, the cosmetic and functional success rates were 83% and 67%, respectively, and for patients with > 5 years follow up the corresponding figures were 82% and 71%, respectively. The main causes of functional failure were pain, erectile dysfunction and persisting deformity. There were no major complications associated with the procedure. Conclusions: Corporeal plication is an effective surgical option for the correction of penile deformity in patients with Peyronie’s disease, with good cosmetic results and acceptable functional success rate in the long-term. [ABSTRACT FROM AUTHOR]

Three of the most promising antigens for immunotherapy of chronic myelogenous leukaemia (CML) include the specific fusion-protein, Bcr/Abl, and the overexpressed proteins WT1 and Proteinase 3. The clinical significance of Proteinase 3 as a target in myelogenous leukaemias has been bolstered by detection of high frequencies of cytotoxic CD8+ lymphocytes specific for this antigen in patients undergoing immune therapies. Our investigation aimed to directly identify MHC-ligands derived from these antigens and presented on CML blasts by means of affinity-purification and mass spectrometric peptide-sequencing. Although no known or potential new epitopes were discovered for Bcr/Abl or WT1, a novel peptide from Proteinase 3 was detected among the more abundant MHC-ligands. Additionally, MHC-ligands derived from known immunogenic proteins overexpressed as a result of Bcr/Abl transformation were also identified. Our investigation is the second of only a small number of studies to identify a peptide from Proteinase 3 among the more abundant MHC-associated peptides and thus implies that peptides from this antigen are among the more abundantly presented of the known leukaemic antigens. Taken in conjunction with clinical observations of functional Proteinase 3 specific CTL in patients’, these data further support the application of this antigen as an immunotherapeutical target for myelogenous leukaemias.Leukemia (2006) 20, 1067–1072. doi:10.1038/sj.leu.2404234; published online 20 April 2006 [ABSTRACT FROM AUTHOR]

Over more than three decades, The Anthony Nolan Trust (ANT) has provided an unrelated donor (UD) for over 4000 children and adults lacking a suitable family member donor, and has remained at the forefront of developments in haematopoietic stem cell transplantation (HSCT) and bone marrow register management. These three decades have seen major changes in clinical practice of UD-HSCT, including new indications, increased use of alternative haematopoietic cell sources, significant improvement of the outcome as a result of better support care, less-toxic conditioning regimens, and better donor selection, and expansion to older patients with higher comorbidities. In order to foster our goal of improving UD-HSCT availability and outcome in a progressively more complex clinical scenario, a new initiative from ANT was launched in 2005 to convene an experts workshop to address the topical issues in this field. Four consecutive panels addressed factors influencing donor selection and transplant outcome, the use of cord blood, regulatory and accreditation issues, and future developments in this field. This report summarizes the discussions held in this workshop, which will likely develop into a periodic event where transplant clinicians, scientists and registry members will meet to share their experience and vision in the field of UD-HSCT.Bone Marrow Transplantation (2006) 37, 901–908. doi:10.1038/sj.bmt.1705365 [ABSTRACT FROM AUTHOR]

All types of leukaemia can disseminate to the skin, producing cutaneous deposits known as leukaemia cutis (LC). We undertook a retrospective study to review the clinical presentations, treatment and outcome of eight patients with LC managed in our department over a period of 12 years. The clinical phenotype varied, with erythematous papules and nodules occurring with greatest frequency. Infiltrated haemorrhagic plaques and perifollicular acneiform papules were also seen. Although patients were treated aggressively for their underlying leukaemia, and received therapy directed towards LC, they tended to be refractory to treatment and the diagnosis was generally associated with a poor prognosis. The exception was a patient with chronic lymphocytic leukaemia, who survived 3 years after developing LC. [ABSTRACT FROM AUTHOR]

Cardiac involvement as an initial presentation of malignant lymphoma is a rare occurrence. We report the case of an immunocompetent 29-year-old male who presented with syncope and arrythmias secondary to a ventricular cardiac mass. Transcutaneous cardiac biopsy was non-diagnostic, therefore an open cardiac biopsy was performed from which a provisional diagnosis of a cardiac inflammatory pseudotumour was made. Six months after presentation, he developed several subcutaneous lesions with systemic symptoms. Histological and immunophenotypic review of the initial cardiac biopsy revealed features consistent with a diagnosis of CD30, ALK1 positive anaplastic large cell lymphoma (ALCL). Despite intensive treatment with combination chemotherapy, there was significant progression of disease, and he died 11 months after diagnosis. The overall prognosis of cardiac lymphoma remains poor, which may be due to the often late presentation of the tumour. To our knowledge, this is the first reported case of a cardiac ALK positive ALCL. Although rare, cardiac presentation of ALCL should be added to the list of differential diagnoses of cardiac lymphomas. [ABSTRACT FROM AUTHOR]

Objectives: Bladder and prostate cancers occur with increasing prevalence in the ageing population. Our study aims to quantify the incidence of prostate cancer in patients undergoing cystoprostatectomy for bladder cancer and assess the impact of that incidental prostate cancer on oncological outcome. Methods and Materials: We retrospectively reviewed the pathology reports of 128 men who underwent cystoprostatectomy for bladder cancer. Results: Twenty-three men (18%) were found to have incidental prostate cancer. All incidental prostate cancers were organ confined and 91% were well or moderately differentiated. At a mean follow-up of 55 months the prostate cancer-free survival was 96%. Conclusion: The incidence of prostate cancer in cystoprostatectomy specimens is high. When the prostate is removed completely the presence of incidental prostate cancer does not influence the overall oncological outcome. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Presents a letter to the editor related to a study on tumor supernatants.

Objectives: Currently no consensus exists about the role of the foreskin or the effect circumcision has on penile sensitivity and overall sexual satisfaction. Our study assesses the effect of circumcision on sexually active men and the relative impact this may have on informed consent prior to surgery. Materials and Methods: One hundred and fifty men between the ages of 18 and 60 years were identified as being circumcised for benign disease between 1999 and 2002. Patients with erectile dysfunction were excluded from the study. The data was assessed using the abridged, 5-item version of the International Index of Erectile Function (IIEF-5). Questions were also asked about libido, penile sensitivity, premature ejaculation, pain during intercourse and appearance before and after circumcision. IIEF-5 data was analysed using two-tailed paired t test to compare pre-operative and post-operative score changes across the study group. For the rest of the questions, data was analysed using ‘Sign Test’, calculating two-sided p values and 95% confidence intervals. Results: Fifty-nine percent of patients (88/150) responded. The total mean IIEF-5 score was 22.41 ± 0.94 and 21.13 ± 3.17 before and after circumcision, respectively (p = 0.4). Seventy-four percent of patients had no change in their libido levels, 69% noticed less pain during intercourse (p < 0.05), and 44% of the patients (p = 0.04) and 38% of the partners (p = 0.02) thought the penis appearance improved after circumcision. Penile sensation improved after circumcision in 38% (p = 0.01) but got worse in 18%, with the remainder having no change. Overall satisfaction was 61%. Conclusions: Penile sensitivity had variable outcomes after circumcision. The poor outcome of circumcision considered by overall satisfaction rates suggests that when we circumcise men, these outcome data should be discussed during the informed consent process. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

A special unit was set up in an associate teaching hospital to provide a fast-track route for the assessment of acute adult surgical and urological referrals. During an audit period of eight weeks, this surgical assessment unit had 550 referrals, of which 196 (36%) came via the accident and emergency (A&E) department; the other 354 came directly from general practitioners or other hospital departments. Mondays, Tuesdays and Fridays were the busiest days of the week; 57% of all patients arrived between 8 am and 5 pm. 68% were seen by a doctor within 1 hour of their arrival. 68% were either discharged or admitted to the main surgical wards within 4 hours. The study showed that, over the course of a year, the surgical assessment unit might divert some 2301 patients away from the A&E department. To achieve this total it would need to be open and appropriately staffed 24 hours a day. Such a unit offers a strategy for limiting the A&E workload and streamlining the assessment of patients with surgical and urological emergencies. [ABSTRACT FROM AUTHOR]

The indolent non-Hodgkin's lymphomas are theoretically curable through allogeneic haematopoietic stem cell transplantation (allo-HSCT). The applicability of standard conditioning allo-HSCT is, however, restricted by its toxicity. Recently, reduced-intensity conditioning regimens have demonstrated efficacy with significantly reduced early morbidity and mortality. We examined the safety and efficacy of rituximab-BEAM-CAMPATH as reduced-intensity conditioning for allo-HSCT in follicular lymphomas. Minimal residual disease was assessed by polymerase chain reaction (PCR) for bcl-2/IgH translocations, and chimerism by X,Y-FISH or PCR amplification of short tandem repeat sequences. At a median follow-up of 521 days (371-719), four of five patients were alive and three were in complete molecular remission. Three patients required pre-emptive treatment for CMV reactivation. One succumbed to a perforated viscus and one had slowly progressive disease. A graft-versus-lymphoma effect was demonstrable and quantitative PCR for bcl-2/IgH may allow better accuracy in scheduling post-allograft rituximab and/or donor lymphocyte infusions. Although follow-up is short, reduced-intensity allo-HSCT with BEAM-CAMPATH conditioning appears to be safe, effective in inducing a molecular remission and is potentially curative. Further recruitment and much longer follow-up will be necessary to determine if this impacts favourably upon disease-free and overall survival.Bone Marrow Transplantation (2003) 31, 551-557. doi:10.1038/sj.bmt.1703898 [ABSTRACT FROM AUTHOR]

Background: We report our updated experience of allogeneic transplantation in lympho-proliferative disorders using a reduced-intensity conditioning regimen combining BEAM (plus fludarabine in three cases) with pre-transplant CAMPATH. Post-transplant donor lymphocytes have been infused for persisting disease or relapse, and both chimerism and minimal residual disease have been monitored utilizing molecular techniques. Methods: Thirty patients with median age 47.6 years underwent allogeneic transplantation for relapsed or high-risk lymphoproliferative disease using HLA-identical (sibling n = 25, unrelated n = 2) or one antigen mismatched sibling donors (n = 3). Twenty-one had NHL, three had HD and six had CLL/PLL. Stem-cell source was PBSC (n = 24), BM (n = 5) or both (n = 1) with a median CD34 dose of 4.5 × 10[sup 6]/kg. GvHD prophylaxis was with CYA and MTX. Results: Engraftment was prompt in the majority of patients, with a median of 15 days to both ANC > 0.5 and platelets > 20. There have been three transplant-related deaths secondary to viral pneumonitis or bacterial pneumonia. Seven patients developed Grade I–II acute GvHD post-transplant. Of 28 evaluable patients, 18 achieved a CR at assessment 2–3 months post-transplant and a further patient converted from PR to CR following DLI, to give an overall CR rate of 68%. Three patients had early progressive disease and six have relapsed from CR or progressed from PR (two of whom have achieved CR following DLI therapy). Overall survival is 67% and event-free survival 48% at 3 years. With a median follow-up of 1.3 years 57% of patients are currently alive and lymphoma-free. A molecular remission has been achieved in nine of 12 informative patients. Discussion: These encouraging results show that this reduced-intensity conditioning regimen is effective, with a low-toxicity profile compared with conventional TBI-based conditioning, and certainly merits further evaluation in this setting. [ABSTRACT FROM AUTHOR]

Focuses on a case report wherein remission was obtained using monoclonal antibody rituximab in a woman with low-grade non-Hodgkin's lymphoma after developing a spontaneous deep-vein thrombosis. Details of the treatment; Results of tests after treatment; Analysis and discussion.

Advances in understanding the role of dendritic cells (DCs) as the major antigen (Ag)-presenting cell type of the immune system combined with the recent development of methods for the ex vivo expansion of human DCs have opened the possibility for the transfer of tumor Ags to DCs with a view toward tumor immunotherapy. In this study, we examined the feasibility of Ag transfer to cultured human DCs using the host range-restricted avipoxvirus, fowlpoxvirus (FWPV). FWPV was found to infect and express a lacZ marker gene in a number of mammalian cell lines of fibroblastic, epithelial, and hemopoietic lineage origins. LacZ recombinant FWPV (rFWPV) was found subsequently to infect human DCs that had been cultured ex vivo from peripheral blood monocytes. Using rFWPV containing lacZ under the control of a vaccinia virus (VV) early/late promoter (p7.5K) and a 10 plaque-forming units per cell multiplicity of infection, >80% of cells expressed the lacZ marker gene. Quantitative analysis showed that the level of expression continued to rise for 5 days postinfection, at which point the experiments were terminated. Replication-competent recombinant VV (rVV) was also shown to be capable of transferring the marker gene to primary DC cultures. However, neither rFWPV nor rVV were able to express transgenes under the control of late viral promoters, indicating that both rFWPV and rVV infections are arrested at an early stage in human DCs. Infection of CD83 + DCs by rFWPV was confirmed by double-staining cytochemistry. We conclude that host range-restricted FWPV can be used efficiently to transfer Ag genes to human DCs ex vivo and may have a role in the development of tumor immunotherapy protocols. [ABSTRACT FROM AUTHOR]

Liposomal amphotericin (AmBisome) 2 mg/kg three times weekly was compared with placebo as prophylaxis against fungal infection in patients undergoing chemotherapy or bone marrow transplantation (BMT) for haematological malignancies. Prophylaxis began on day 1 of chemotherapy and continued until neutrophils regenerated or infection was suspected. Of 161 evaluable patients, 74 received AmBisome and 87 received placebo. Proven fungal infections developed in no patients on AmBisome and in three on placebo (3.4%) (P = NS). Suspected fungal infections requiring intervention with systemic antifungal therapy (usually amphotericin B) occurred in 31 patients on AmBisome (42%) and in 40 on placebo (46%) (P = NS). Suspected deep-seated infections developed in 21 (28.3%) and 31 (35.6%) patients, respectively (P = NS). Time to develop a suspected or proven deep-seated infection showed a trend in favour of AmBisome (P = 0.11). Fifty patients had fungal colonisation (48 with Candida spp, two with Aspergillus spp) of at least one body site during prophylaxis; 15 patients while receiving AmBisome (20%) and 35 while on placebo (40%) (P < 0.01). time to colonisation was significantly delayed in the group receiving ambisome (P < 0.05). treatment-related toxicity was modest and no additional toxicity was observed in patients receiving ambisome. ambisome 2 mg/kg three times weekly is safe and reduces fungal colonisation in patients receiving intensive chemotherapy or bmt. however, despite encouraging trends, prophylactic ambisome did not lead to a significant reduction in fungal infection or in requirement for systemic antifungal therapy. [ABSTRACT FROM AUTHOR]

We performed flow cytometric analysis of CD34+ cell apoptosis in 59 patients with myelodysplastic syndrome (MDS) or acute myeloid leukaemia (AML) secondary to MDS (MDS-AML) using annexin V-FITC, which binds to exposed phosphatidylserine on apoptotic cells. Apoptosis was significantly increased in FAB subtypes RA, RARS and RAEB (<10% blasts) (56.5% (15.1–86.5%)) compared to normal controls (18.5% (3.4–33.4%), P < 0.0001) and RAEB-t/MDS-AML (16% (2.1–43.2%), P < 0.0001). There was no correlation between % apoptosis, Full blood count or cytogenetics in any disease category. Two-colour cytometric analysis of permeabilized CD34+ cells stained with antibodies to Bcl-2, Bcl-X (anti-apoptotic), Bax and Bad (pro-apoptotic), demonstrated significantly higher ratios of pro- v anti-apoptotic proteins in early MDS (2.47 (1.19–9.42) compared to advanced disease (1.14 (0.06–3.32), P = 0.0001). Moreover, using repeated measures of variants (ANOVA), we found that variations between individual Bcl-2-related proteins differed significantly according to disease subtype (P < 0.0005). Our results confirm that CD34+ cell apoptosis was significantly increased in MDS subtypes RA and RARS and fell with disease progression. Early MDS was also associated with a significantly higher CD34+ cell pro- v anti-apoptotic Bcl-2-family-protein ratio than advanced disease. Furthermore, patterns of expression of individual Bcl-2 related proteins differed significantly between different disease categories. However, no correlation between pro- v anti-apoptotic Bcl-2-family-protein ratios and the degree of apoptosis was observed. [ABSTRACT FROM AUTHOR]

Interstitial cystitis is an uncommon disease reported predominantly in females. Recently we were involved in the management of 4 men who had the clinical, endoscopic and pathological features consistent with the diagnosis of interstitial cystitis. The rarity of occurrence of the disease in males prompted us to report these cases. [ABSTRACT FROM AUTHOR]

Modification of autologous tumour cells to express the immune costimulator B7.1 is a potential strategy for immunotherapy of cancer. Previously, this has involved introduction of genetic material into cells, in vitro culture, and confirmation of the protein product on the cell surface. This is possible only if sufficient tumour is obtainable and efficiently modified in a short time. Whilst progress has been made on ex vivo tumour cell culture and transfection/infection procedures there are still tumour types for which the present means of gene transfer are not efficient enough. We describe a highly efficient in vitro procedure for the modification of over 99% of the cells in a population, allowing the expression of cell surface proteins with potential immune modulatory activities. This procedure, which can be completed in as little as 24 h with no upper limit on cell number, utilizes succinimide esters to label cell surface proteins with biotin covalently. Biotinylated cell membrane proteins then anchor an avidin bridge for immobilizing protein G′-biotin. This can serve to bind immunoglobulin (Ig) molecules via their Fc region such that the variable region of the antibody is freely and functionally available. In the present study the binding of a stimulatory mouse anti-human CD28 monoclonal antibody to the surface of tumour cells is used to show that the modified cells are capable of co-stimulating T cells in vitro. The simplicity of the method, and the use of common reagents, represents a further step towards a realistic, truly ‘off-the-shelf’, nongene immunotherapy protocol. [ABSTRACT FROM AUTHOR]

Gene modification of malignant cells to express immune stimulators (cytokines and immune costimulators) has provided the basis for a novel form of immunotherapy. Using a MPSV-based retroviral vector with hygromycin resistance gene as a selectable marker, we have studied retrovirus-mediated gene transfer of an immune costimulator, B7.1, into primary human acute myeloid leukaemia (AML) cells and the subsequent induction of immune costimulatory function. AML blasts from 10 patients were transduced by co-culture for 48 h with or without haemopoietic growth factors (HGFs). In the absence of HGFs, transduction efficiency (TE), as judged by % B7.1 expressing cells, was low, varying from 0.3 to 8.2% (median 1.5%). Addition of HGFs increased the median TE 1.8-fold with stem cell factor alone and 2.6-fold with SCF, interleukin-3 and GM-CSF. Effects on cell cycling alone could not explain this difference, suggesting other factors such as virus binding and promoter activity, are also involved. CFU-AL assays indicated a higher transduction efficiency of clonogenic cells, which was not improved by growth factors. Limited duration of cell growth prevented significant expansion of transduced populations by culture in the presence of hygromycin. Although not increasing transduction efficiency, CD34 enrichment enhanced drug selection, by targeting cells with the greatest self-renewal capacity. Immunoselection of B7.1 expressing cells produced transduced populations with 30–60% expressing B7.1. In an allogeneic mixed leukaemic cell/T lymphocyte reaction (MLLR), transduced AML cells enriched by immunoselection were able to stimulate allogeneic T cells (CD4 and CD8 positive), which could be inhibited by a solubilised B7 receptor, CTLA4.Ig. Our results demonstrate that using a replication incompetent retroviral vector, it is possible to introduce the immune costimulator B7.1 into primary AML blasts and, by immunoselection, enrich the transduced cells, which may be used for... [ABSTRACT FROM AUTHOR]

- The records of 111 patients with multiple superficial grade 1-2 transitional cell tumours of the bladder treated with intravesical Epodyl and followed up for a mean period of 6.4 years were retrospectively analysed. The study showed that 65% of patients responded completely after 12 weekly instillations and 46% of these remained continuously free of disease for 5 years. An initial complete response to therapy and lower pathological grade seemed to indicate a long-term successful response to treatment. In patients who failed to respond by 1 year, further therapy was of no benefit. Clearance of bladder disease by 1 year carried a 14% risk of subsequent tumour invasion by 5 years. This risk increased to 75% in those who failed to respond by 1 year. [ABSTRACT FROM AUTHOR]

- In a retrospective study of 185 patients with transitional cell carcinoma of the renal pelvis and ureter, of whom 127 were treated by total nephroureterectomy and 58 by conservative resection, the survival of those with superficial well differentiated tumours was > 90% in each group. When urothelium was left behind after conservative resection, there was a 22% rate of recurrence on the same side but this almost only occurred when the original tumour had been multifocal. Post-operative radiotherapy did not improve survival. [ABSTRACT FROM AUTHOR]

An open, randomized study was performed at 18 European centres to compare the efficacy, safety and tolerance of oral fluconazole with oral polyenes for the prophylaxis of fungal colonization and infection in adults at high risk of developing neutropenia. Five hundred and thirty-six hospitalized patients with malignant disease, about to receive chemotherapy, radiotherapy, or bone marrow transplantation, and who were already neutropenic or were expected to develop neutropenia were included in the study. Before therapy or transplantation, patients commenced either oral fluconazole therapy (50 mg/day as a single dose) or oral polyenes therapy (amphotericin B 2 g/day and/or nystatin 4×10 units/day in four or more divided doses), for a mean of 29·3 days and 31· days, respectively. After baseline clinical and mycological testing, patients were re-evaluated at least weekly during prophylaxis, at the end of prophylaxis and two to six weeks later to identify proven or suspected fungal infection and to determine rates of colonization with fungi. Fungal infection was diagnosed in 41 of 511 evaluable patients, 10 (3·9%) of 256 in the fluconazole group and 31 (12·2%) of 255 in the polyene group (=0·001). This total included four patients (1·6%) in the fluconazole group who developed oropharyngeal candidiasis compared with 22 (8·6%) in the polyene group (<0·001) Systemic infections comprised 6(2·3%) in the fluconazole group and 9 (3·5%) in the polyene group ( = not significant), and included three infections in each group. Parenteral amphotericin B therapy was given empirically for persistent fevers in an additional 62 (24·2%) patients receiving fluconazole and 59 (23·1%) receiving polyenes ( = not significant). Colonization with fungi was generally similar in each treatment group, although an increased proportion of patients receiving fluconazole developed colonization of the faeces (<0·01). Adverse reactions, possibly related to treatment, were recorded in 15 (5·6%) of 269 patients in the fluconazole group and 14 (5·2%) of 267 in the polyene group; these necessitated discontinuation of therapy in seven patients in each group. Once-a-day fluconazole was therefore more effective than oral polyenes for the prevention of oropharyngeal fungal infection and as effective for the prevention of infections at other sites in patients with neutropenia. [ABSTRACT FROM PUBLISHER]

In a randomized multicentre study ciprofioxacin combined with aziocillin was compared with gentamicin and aziocillin for the treatment of febrile episodes in neutropenic patients. In 147 evaluable episodes in 108 patients, 80 patients received ciprofioxacin/aziocillin and 67 received gentamicin/azlocillin. The two treatment groups were comparable in terms of age, underlying diagnosis, and duration of neutropenia. Microbiologically documented infections were the cause of fever in 34 (42.5%) and 29 (43.3%) episodes in the ciprofloxacin/aziocillin and gentamicin/azlocallin groups respectively. At the end of therapy, 46 patients (57.5%) receiving eiprofioxacin/azlocillin showed complete resolution compared with 30 (44.7%) for the gentamicin/azlociuin group (P = 0.14). The clinical response rate for microbiologically documented episodes was 58.8% and 43.3% respectively (P = 0.45). Among the microbiologically documented infections with follow-up cultures available, 24(92.3%) of 26 isolates from patients receiving ciprofioxacin/aziociflin were eradicated, in comparison with 19 (86.4%) of 22 in the gentamicin/azlocillin group (P = 0.65). There were five superinfections, all in the gentamicin/azlocillin group. Significant resistance to the study drugs was not seen. Of all evaluable patients, including those subsequently withdrawn because of early modification of therapy, there were 12 deaths within the study period six (6.8%) of these occurred in 88 patients randomized to the ciprofloxacin/azlocillin group, compared with two of 80(2.5%) in the gentamicin/azlocillin group. Both treatments were generally well-tolerated; one patient in the ciprofioxacin/azlocillin group developed convulsions, probably related to ciprofloxacin. The combination of ciprofloxacin and azlocillin is as effective as gentamicin plus azlocillin and offers a useful alternative for the empirical treatment of febrile neutropenic patients. [ABSTRACT FROM PUBLISHER]

Angiodysplasia of the colon is a relatively common cause of blood loss in the elderly. Electrocoagulation through a colonscope is a common mode of treatment for this condition. Three patients are presented who had associated hemostatic defects and electrocoagulation resulted in life threatening secondary hemorrhage. In two of these patients a right hemicolectomy was performed. On the basis of these findings we suggest that patients with angiodysplasia and associated hemostatic disorders have a greatly increased risk of secondary hemorrhage following electrocoagulation treatment. These patients should be followed closely for two-three weeks following this treatment. [ABSTRACT FROM AUTHOR]

The myelodysplastic syndromes (MDS) constitute a heterogeneous group of clonal disorders arising from a multipotent haemopoietic progenitor which share a leukaemic propensity, 30% of cases culminating in acute myeloid leukaemia (AML). Their pathogenesis probably entails multiple steps, phenotypic progression being determined by either expansion or evolution of the abnormal clone. The clonal origin of certain cases of de novo AML is analogous to that of MDS and evidence that they share a common pathogenesis and distinct biological characteristics is beginning to emerge. [ABSTRACT FROM AUTHOR]

A 71-year-old woman presented with intractable cardiac failure 10 years after receiving treatment for lymphoma. Extensive investigations failed to demonstrate a recurrence of her disease, but resolution of her cardiac failure following a trial of chemotherapy and subsequently a cross-sectional echocardiogram suggested intracardiac relapse. This was later confirmed at autopsy. Cardiac metastases should be suspected in patients with malignant disease who develop signs or symptoms related to the heart. [ABSTRACT FROM PUBLISHER]

The clinical, biochemical, and haematological aspects of a recent outbreak of lead poisoning, in which exposure was related to the oxyacetylene cutting of red lead painted ironwork, were investigated. Initial suspicion was raised when a blood film showed punctate basophilia which remains a simple and useful method of picking up lead toxicity. Estimations of blood lead concentration and conventional laboratory data confirmed the diagnosis. Although there was prominent punctate basophilia, spectrophotometric analysis showed only negligible accumulation of pyrimidine-5'-nucleotides despite severe suppression of pyrimidine-5'-nucleotidase activity. The pattern of the red cell glycolytic intermediates, investigated for the first time, suggested that lead may also affect glycolysis at the hexokinase step. Once the diagnosis was made intravenous chelation treatment was begun with a rapid improvement in symptoms. Long term follow up is required to assess any sequelae of intoxication. These cases emphasise the classic features of lead poisoning, and despite the currently available diagnostic tests, lead intoxication may still go unrecognised unless a thorough occupational history is taken. [ABSTRACT FROM PUBLISHER]