Summary:Chronic myeloid leukaemia (CML) can be treated sucAllogeneic bone marrow transplantation (BMT) is a successful treatment modality for patients with chronic myeloid leukaemia (CML). Sixty to 80 percent of patients cessfully with allogeneic bone marrow transplantation transplanted with unmanipulated BM in first chronic phase (BMT) leading to long-term disease-free survival. Leu-(CP) achieve long-term disease-free survival. 1 However, kemia relapse, however, remains a significant clinical relapse rates of 10-20% are still the most frequent cause problem. Relapse following BMT presumably results of treatment failure. 2,3 Leukaemia relapse following BMT from the expansion of small numbers of recipient leupresumably results from the inability of the conditioning kaemic cells which have survived the conditioning therregimen to eliminate all recipient leukaemic cells. Ideally, apy. In order to define patients who are at a high risk following BMT, the recipient's bone marrow should be of leukaemia relapse, a variety of techniques have been completely ablated by the conditioning regimen, facilitating employed to detect persistence of host haemopoiesis the engraftment of donor haemopoietic stem cells giving (mixed chimaerism, MC) or residual leukaemia rise to a complete donor haemopoietic chimaera. 4(minimal residual disease, MRD). However, the precise The true incidence and significance of the detection of relationship between the detection of MC and MRD mixed haemopoietic chimaerism (MC) post-BMT remains post-BMT is unknown. We have investigated chimaerunclear. 4,5 MC was initially thought to indicate an impendism and MRD status in 22 patients who were in clinical ing relapse, however, using more sensitive molecular techand haematological remission post-allogeneic BMT for niques it has become clear that MC post-BMT is not chronic phase CML. Chimaerism was assessed using uncommon, with varying percentages of recipient cells short tandem repeat PCR (STR-PCR) while BCR-ABL being detected in different study groups. [6][7][8][9][10] This variation mRNA detection using reverse transcriptase polymerase in the degree of MC is influenced by a number of factors chain reaction (RT-PCR) was performed to detect the including the sensitivity and timing of the assay, the disease presence of MRD. Seventeen patients received unmanindication for BMT, the stage of disease at time of BMT ipulated marrow (non-TCD) while in five patients a T and the choice of conditioning regimen. Several studies cell-depleted transplant (TCD) was performed as indicated that low levels of persisting recipient cells are not additional GVHD prophylaxis. Chimaerism was evaluassociated with an increased risk of leukaemic relapse. 7-10ated in 18 patients (14 non-TCD, four TCD). Mixed However, increasing levels of recipient cells over time chimaerism was an uncommon finding in recipients of (progressive mixed chimaerism) appear to predict relapse, unmanipulated BMT (21%) when compared to TCD especially in recipients of a T cell-depleted (TCD) trans-BMT (100...

Summary:A total of 75 patients underwent sibling allogeneic stem cell transplantation (SCT) for chronic myeloid leukaemia in first chronic phase from 1984 to 2000. Of these patients, 51 (68%) were alive at a median follow-up of 98 months (range 34-217 months). Nine (18%) patients relapsed and seven (14%) received donor lymphocyte transfusions. Quality of life (QoL) was assessed crosssectionally using the EORTC QLQ-C30, a Leukaemia-BMT-specific module and questionnaires on sexual functioning, fertility and late effects. A total of 46 (90%) replied. Scores for Role (P ¼ 0.018) and Cognitive (Po0.001) function were significantly lower when compared to an age-adjusted general population. Dyspnoea (P ¼ 0.022) and Financial Difficulties (Po0.001) were significantly more common in the SCT group. No difference was found for scores in the Physical, Emotional and Social domains or the overall Global Health Status/ QoL. Decreased sexual functioning was found in one-third of respondents. Although most BMT recipients reported a good QoL, a minority have difficulty with reintegration into professional roles and consequent monetary problems. Identified cognitive and sexual impairments highlight the need for long-term access to psychosocial support. Bone Marrow Transplantation (2004) 34, 545-556. doi:10.1038/sj.bmt.1704638 Published online 9 August 2004 Keywords: chronic myeloid leukaemia; quality-of-life; allogeneic SCT Recent years have seen an increase in the therapeutic options available for the treatment of patients with chronic myeloid leukaemia (CML). 1 Allogeneic stem cell transplantation (SCT), however, remains the standard of care for younger patients with an HLA-compatible donor. The most recent EBMT registry survey reported that the median survival of patients who underwent non-T-celldepleted transplantation for CML in first chronic phase (CP) from an HLA-matched sibling donor had not been reached at 10 years. 2 Health-related quality of life (QoL) has been defined as referring 'to the extent to which one's usual or expected physical, emotional and social well-being are affected by a medical condition or its treatment'. 3 Most of the previous studies are cross-sectional in design, apply one of several available instruments and pool all patients transplanted for different diagnoses at a single centre. [4][5][6][7][8][9][10][11][12] Although marked morbidity in the first few years is evident, there is a clear trend to improved QoL in long-term survivors of transplantation. 6,8 Nonetheless, aggregated studies confirm that a minority of individuals continue to suffer from the effects of chronic graft-versus-host disease (GvHD) and sexual dysfunction. Our observations confirm and extend those of Kiss et al 12 in a group of 24 patients receiving SCT for CML in first CP.The European Organisation for Research and Treatment of Cancer (EORTC) QoL questionnaire -QLQ-C30 13 -was used in this study. Both EORTC population reference data and CML-specific data have been generated using this instrument. [14][15][16] In addition to t...

Summary:Donor lymphocyte infusions (DLI) have been shown to enhance the graft-versus-leukaemia (GVL) effect and induce haematological and molecular remission in patients with relapsed CML following allogeneic bone marrow transplantation (BMT). The potent donor cellmediated cytolysis following DLI may lead to a short period of aplasia before the re-establishment of donor haematopoiesis. The absence of detectable donor cells in patients prior to DLI infusion may result in permanent aplasia in certain patients. We report on four patients who relapsed 1, 3, 6.5 and 7 years post-BMT for chronic phase CML and were treated with DLI from their original BMT donor. Polymorphic short tandem repeats (STRs) were used to assess haematological chimaerism both prior to and following DLI. At the time of relapse, STR-PCR indicated the presence of donor cells in all four patients, at levels ranging from 1-40%. A clinical and molecular response was seen in 4/4 patients following a short period of cytopenia and all patients remain in clinical remission with a follow-up of 2 months-3 years post-DLI. STR-PCR indicated that a response was occurring during the period of pancytopenia when metaphase analysis was unsuccessful. Lineage-specific analysis of the cellular response to DLI was monitored using STR-PCR of peripheral blood (PB) and bone marrow (BM) lymphocyte-enriched fractions and CD2-positive and -negative T cell fractions. In one patient BM and PB CD34-positive and -negative fractions were also assessed. A change in the ratio of donor:recipient cells in the PB lymphocyte fraction was the earliest molecular indication of an anti-leukaemic response. Subsequent conversion to donor chimaerism occurred in the other lineages and the granulocyte fraction was the last lineage to convert. In conclusion, lineage-specific STR-PCR permits detailed monitoring of subtle changes in donor/recipient cell dynamics in specific lineages following DLI during the crucial pancytopenic phase and may be a useful predictor of haematological response to DLI therapy.

BackgroundThere is currently conflicting evidence surrounding the effects of obesity on postoperative outcomes. Previous studies have found obesity to be associated with adverse events, but others have found no association. The aim of this study was to determine whether increasing body mass index (BMI) is an independent risk factor for development of major postoperative complications.MethodsThis was a multicentre prospective cohort study across the UK and Republic of Ireland. Consecutive patients undergoing elective or emergency gastrointestinal surgery over a 4‐month interval (October–December 2014) were eligible for inclusion. The primary outcome was the 30‐day major complication rate (Clavien–Dindo grade III–V). BMI was grouped according to the World Health Organization classification. Multilevel logistic regression models were used to adjust for patient, operative and hospital‐level effects, creating odds ratios (ORs) and 95 per cent confidence intervals (c.i.).ResultsOf 7965 patients, 2545 (32·0 per cent) were of normal weight, 2673 (33·6 per cent) were overweight and 2747 (34·5 per cent) were obese. Overall, 4925 (61·8 per cent) underwent elective and 3038 (38·1 per cent) emergency operations. The 30‐day major complication rate was 11·4 per cent (908 of 7965). In adjusted models, a significant interaction was found between BMI and diagnosis, with an association seen between BMI and major complications for patients with malignancy (overweight: OR 1·59, 95 per cent c.i. 1·12 to 2·29, P = 0·008; obese: OR 1·91, 1·31 to 2·83, P = 0·002; compared with normal weight) but not benign disease (overweight: OR 0·89, 0·71 to 1·12, P = 0·329; obese: OR 0·84, 0·66 to 1·06, P = 0·147).ConclusionOverweight and obese patients undergoing surgery for gastrointestinal malignancy are at increased risk of major postoperative complications compared with those of normal weight.