What is the outcome in patients with acute leukaemia who survive severe acute graft‐versus‐host disease?

Background

Acute graft‐versus‐host disease (aGVHD ) is a major complication of allogeneic haematopoietic stem cell transplantation (HSCT ). With new promising therapies, survival may improve for severe aGVHD .

Objectives

We wanted to analyze the long‐term outcome in patients who survive severe aGVHD .

Methods

This study was a landmark analysis of 23 567 patients with acute Leukaemia who survived for more than 6 months after HSCT , 2002–2014. Patients alive after severe aGVHD (n = 1738) were compared to controls.

Results

Patients with severe aGVHD had higher non‐relapse mortality (NRM ) and higher rate of extensive chronic GVHD (cGVHD ) than the controls (P < 10^?5). The probability of relapse was significantly lower in the severe aGVHD group, but Leukaemia‐free survival (LFS ) and overall survival were significantly lower than for the controls (P < 10^?5). Five‐year LFS in patients with severe aGVHD was 49%, as opposed to 61% in controls with no or mild GVHD and 59% in patients with moderate GVHD.

Conclusions

HSCT patients who survive severe aGVHD have higher risk of developing extensive cGVHD , a higher NRM , a lower relapse probability, and lower LFS than other HSCT patients. This study is a platform for outcome analysis in patients treated with novel therapies for acute GVHD.

     

Enhanced and aberrant T cell trafficking following total body irradiation: a gateway to graft‐versus‐host disease?

Pre‐transplant conditioning regimens play a major role in triggering graft‐versus‐host disease (GVHD). This study investigated the effect of irradiation on donor T cell trafficking to lymphoid and non‐lymphoid tissues by comparing the migration of carboxy‐fluorescein diacetate succinimidyl ester‐labelled, naïve donor T lymphocytes in vivo in irradiated and non‐irradiated syngeneic mice recipients. Recruitment of adoptively transferred naïve T cells to secondary lymphoid organs was increased in irradiated mice and naïve T cells also aberrantly localized to non‐lymphoid tissues. Irradiation also induced aberrant effector memory T cell migration into lymph nodes and their localization to homing‐privileged non‐lymphoid sites, such as the gut. The presence of a minor histocompatibility mismatch further enhanced the aberrant accumulation of T cells in both lymphoid and non‐lymphoid tissue, whilst their migratory pattern was not modified as compared to fully matched irradiated recipients. These effects correlated with decreased permeability of, and the secretion of chemotactic factors by the endothelium. Our findings are consistent with the possibility that excessive, dysregulated extravasation of T cells induced by irradiation promotes the development of GVHD.     

What predicts high risk acute graft‐versus‐host disease (GVHD) at onset?: identification of those at highest risk by a novel acute GVHD risk score

To define high-risk acute graft-versus-host disease (GVHD) at onset, we examined the initial GVHD stage and grade of 864 patients at the University of Minnesota who received uniform therapy with prednisone 60 mg/m(2) per d. We compared the prognostic utility of the Minnesota (MN; modified from Consensus) versus Center for International Blood and Marrow Transplant Research (CIBMTR) GVHD organ stage-derived grading systems. As neither GVHD grading system optimally predicted outcomes, a novel acute GVHD risk score was devised by combining the MN and CIBMTR systems. Using multiple regression analysis, we could dichotomize patients into high risk (HR, n = 86) acute GVHD with initial grade IIIC, IIID or IVD who were less likely to respond to steroid therapy by day 28 [relative risk (RR), 0·3, P < 0·001] and had a higher risk for transplant-related mortality (RR, 2·0, P < 0·001) than patients with standard risk (SR, initial grade IA-IIIB, n = 778) GVHD. Using this novel acute GVHD Risk Score, HR GVHD is either skin stage 4, lower gastrointestinal (GI) stage 3+, liver stage 3+, or skin stage 3 and lower GI or liver stage 2+ GVHD. Patients with HR acute GVHD have a poor prognosis, require alternative initial therapy and should be the focus of novel therapeutic trials.     

Cytometry in monoclonal B‐cell lymphocytosis and chronic lymphocytic leukaemia – The Hunting of the Snark?

Cytometry has become important in the detection and determination of risk of monoclonal B-cell lymphocytosis; methodology has changed, and will continue to change, as cytometric technology changes.     

rs2072135, a low‐penetrance variant for chronic lymphocytic leukaemia?

Recent multi‐stage genome‐wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) that are robustly associated with chronic lymphocytic leukaemia (CLL) risk. Given that most of these SNPs map to non‐coding regions of the genome, it suggests that the functional basis of many GWAS signals will be through differential gene expression. By referencing publically accessible expression quantitative trait loci (eQTL) data on lymphoblastoid cells lines (LCLs) we have globally demonstrated an association between GWAS P‐values and eQTLs, consistent with much of the variation in CLL risk being defined by variants impacting on gene expression. To explore using eQTL data to select GWAS SNPs for replication, we genotyped rs2072135 (GWAS P‐value = 0·0024, eQTL P‐value = 1·510^?19) in five independent case‐control series totalling 1968 cases and 3538 controls. While not attaining statistical significance (combined P‐value = 1 × 10^?4), rs2072135 defines a promising risk locus for CLL. Incorporating eQTL information offers an attractive strategy for selecting SNPs from GWAS for validation.     

Paediatric lymphoblastic T‐cell leukaemia and lymphoma: one or two diseases?

There is ongoing discussion on whether paediatric acute T‐cell lymphoblastic leukaemia (T‐ALL) and paediatric lymphoblastic T‐cell lymphoma (T‐LBL) are two distinct entities or whether they represent two variant manifestations of one and the same disease and the distinction is arbitrary. Both show overlapping clinical, morphological and immunophenotypic features. Many clinical trials use the amount of blast infiltration of the bone marrow as the sole criterion to distinguish between T‐ALL and T‐LBL. The current World Health Organization classification designates both malignancies as T lymphoblastic leukaemia/lymphoma. However, subtle immunophenotypic, molecular and cytogenetic differences suggest that T‐ALL and T‐LBL might be biologically different in certain aspects. The current review summarizes and discusses the recent advances and understanding of the molecular profile of paediatric T‐ALL and T‐LBL.     

Diabetes in HIV‐infected persons in Cameroon?

In the past, the increased prevalence of diabetes in HIV infection has been attributed to antiretroviral drugs. In this study, Cameroonians with HIV infection were shown in a paper in this issue of the Journal to be more likely to have diabetes if they were not on therapy. Future research should examine if the diabetes is related to the host response to infection or to socioeconomic factors that might both contribute to not being on anti‐retroviral therapy and predispose to diabetes. Copyright © 2016 John Wiley & Sons, Ltd.     

Does stage‐based smoking cessation advice in pregnancy result in long‐term quitters? 18‐month postpartum follow‐up of a randomized controlled trial

AIMS: To evaluate the effect on quitting smoking at 18 months postpartum of smoking cessation interventions based on the Transtheoretical Model (TTM) delivered in pregnancy compared to current standard care. It has been claimed that TTM-based interventions will continue to create quitters after the end of the intervention period. DESIGN: Cluster randomized trial. SETTING: Antenatal clinics in general practices in the West Midlands, UK. PARTICIPANTS: A total of 918 pregnant smokers originally enrolled in the trial, of which 393 women were followed-up at 18 months postpartum. INTERVENTIONS: One hundred general practices were randomized into the three trial arms. Midwives in these practices delivered three interventions: A (standard care), B (TTM-based self-help manuals) and C (TTM-based self-help manuals plus sessions with an interactive computer program giving individualized smoking cessation advice). MEASUREMENTS: Self-reported continuous and point prevalence abstinence since pregnancy. FINDINGS: When combined together, there was a slight and not significant benefit for both TTM arms compared to the control, with an odds ratio (OR) 95% confidence interval (CI) of 1.20 (0.29-4.88) for continuous abstinence. For point prevalence abstinence, the OR (95%CI) was 1.15 (0.66-2.03). Seven of the 54 (13%) women who had quit at the end of pregnancy were still quit 18 months later, and there was no evidence that the TTM-based interventions were superior in preventing relapse. CONCLUSIONS: The TTM-based interventions may have shown some evidence of a short-term benefit for quitting in pregnancy but no benefit relative to standard care when followed-up in the longer-term.     

Is Non‐suicidal Self‐injury Related to Impulsivity in Anorexia Nervosa? Results from Self‐report and Performance‐based Tasks

The present study investigates the association between non‐suicidal self‐injury (NSSI) and impulsivity in anorexia nervosa (AN) patients by means of self‐report and behavioural tasks. In total, 60 female AN patients were included in the study, filled out the Barratt Impulsiveness Scale‐11 (BIS‐11) and performed three performance‐based tasks to assess different facets of impulsivity. Overall, 30% of the AN patients engaged in at least one form of NSSI during their lifetime. AN patients with and without NSSI did not significantly differ on the BIS‐11 impulsiveness scale. On the performance‐based measures, few differences emerged between AN patients with and without NSSI. Patients with NSSI showed more perseverations and perseveration errors (p < .05). The associations between self‐report and performance‐based measures were rather low, except for the association between the BIS‐11 and Wisconsin Card Sorting Task perseveration responses and errors (correlations |r| range between .32 and .42). The implications for theory and treatment of AN patients with and without NSSI will be discussed. Copyright © 2014 John Wiley & Sons, Ltd and Eating Disorders Association.