CAR T in patients with large B-cell lymphoma not fit for autologous transplant.

Large B-cell lymphoma (LBCL) patients with comorbidities and/or advanced age are increasingly considered for treatment with CD19 CAR T, but data on the clinical benefit of CAR T in the less fit patient population are still limited. We analysed outcomes of consecutive patients approved for treatment with axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) by the UK National CAR T Clinical Panel, according to fitness for autologous stem cell transplant (ASCT). 81/404 (20%) of approved patients were deemed unfit for ASCT. Unfit patients were more likely to receive tisa-cel versus axi-cel (52% vs. 48%) compared to 20% versus 80% in ASCT-fit patients; p < 0.0001. The drop-out rate from approval to infusion was significantly higher in the ASCT-unfit group (34.6% vs. 23.5%; p = 0.042). Among infused patients, response rate, progression-free and overall survival were similar in both cohorts. CAR T was well-tolerated in ASCT-unfit patients with an incidence of grade ≥3 cytokine release syndrome and neurotoxicity of 2% and 11%, respectively. Results from this multicentre real-world cohort demonstrate that CD19 CAR T can be safely delivered in carefully selected older patients and patients with comorbidities who are not deemed suitable for transplant.

Quantum dots light up pathology.

Quantum dots (QDs) are novel nanocrystal fluorophores with extremely high fluorescence efficiency and minimal photobleaching. They also possess a constant excitation wavelength together with sharp and symmetrical tunable emission spectra. These unique optical properties make them near-perfect fluorescent markers and there has recently been rapid development of their use for bioimaging. QDs can be conjugated to a wide range of biological targets, including proteins, antibodies, and nucleic acid probes, rendering them of particular interest to pathology researchers. They have been used in multiplex immunohistochemistry and in situ hybridization, which when combined with multispectral imaging, has enabled quantitative measurement of gene expression in situ. QDs have also been used for live in vivo animal imaging and are now being applied to an ever-increasing range of biological problems. These are detailed in this review, which also acts to outline the important advances that have been made in their range of applications. The relative novelty of QDs can present problems in their practical use and guidelines for their application are given.

Effective use of oral ribavirin for respiratory syncytial viral infections in allogeneic haematopoietic stem cell transplant recipients.

BACKGROUND: Respiratory syncytial virus (RSV) is a frequent cause of respiratory viral infections, increasing the morbidity and mortality in allogeneic haematopoietic stem cell transplantation (HSCT) recipients. Little is known about the best management strategy in this immunocompromised group and there are very few data on oral ribavirin treatment. AIM: To evaluate the effectiveness of oral ribavirin in allogeneic HSCT patients with RSV infection. METHODS: Twenty-three RSV cases treated with oral ribavirin were analysed retrospectively. RSV diagnosis was established by polymerase chain reaction assay. Oral ribavirin was initiated at 15 mg/kg/day in three divided doses for 10 days, with no subsequent dose escalation, as per centre policy. FINDINGS: At diagnosis, seven patients presented with lower respiratory tract infection (RTI), whereas 16 had upper RTI. Oral ribavirin was well tolerated with minor adverse effects. The median treatment duration was 10 days (range: 5-47). After a median follow-up of 17 months (range: 4-48), 17 patients are alive. We recorded one RSV-related and five non-related deaths. CONCLUSION: To our knowledge, this is the largest single centre study yet performed on adult allogeneic HSCT recipients with RSV infection treated with oral ribavirin. Prompt initiation of treatment is essential and may avoid hospital admission. Our experience supports the use of oral ribavirin, but large prospective studies are needed to determine the optimal therapy in this patient group.

Comparison of gene-expression profiles in parallel bone marrow and peripheral blood samples in acute myeloid leukaemia by real-time polymerase chain reaction.

BACKGROUND: Gene signatures (Indicator genes) in bone marrow that provide more precise prognostication in haematological malignancy have been identified by microarray expression studies. It would be beneficial to measure these diagnostic signatures in peripheral blood. AIMS: To determine the degree of correspondence of gene expression for a set of Indicator genes between bone marrow and peripheral blood in acute myeloid leukaemia (AML). METHODS: Parallel bone marrow aspirate and peripheral blood samples were obtained from 19 patients diagnosed with AML and mononuclear cells isolated from both sample types. mRNA was globally amplified by polyadenylated real-time polymerase chain reaction (polyA RT-PCR); the expression of 15 AML Indicator genes, identified from previous microarray studies, was measured by RT-PCR. All values were normalised to the mean expression of three housekeeping genes (IF2-beta, GAP and RbS9) and were statistically compared using SPSS software. RESULTS: No significant difference in expression between bone marrow and peripheral blood was observed for 10 of the genes (leptin receptor, CD33, adipsin, proteoglycan 1, MB-1, cyclin D3, hSNF2b, proteasome iota, HkrT-1 and E2A), indicating its possible use in monitoring disease activity in peripheral blood samples, whereas c-myb, HOXA9, LYN, cystatin c and LTC4s showed significantly different expression between bone marrow and peripheral blood samples. CONCLUSION: These results indicate a possible use for the method in monitoring AML in peripheral blood by RT-PCR measurement of Indicator genes. In addition, the initial use of polyA PCR facilitates translation to very small clinical samples, including fractionated cell populations, of particular importance for monitoring haematological malignancy.

[Compassion as a mediator between stressful events and perceived stress in Greek students].

Compassion is closely related with human's survival as a mammal and has been developed through evolution for pain reduction, for forming affiliative bonds and alliances with non kin in order to increase protection and cope with external threats. Compassion seems to influence people's ability to deal with life's adverse situations such as stress and it is linked with lower psychopathology and greater wellbeing. Compassion is closely related to empathy and altruism and it is defined as the recognition of the pain of the self or others' that is accompanied with the will to take action in order to relieve the person from pain. Its main features are kindness instead of self-judgment and indifference, the recognition of common humanity instead of the feeling of separation and mindfulness when facing adverse conditions instead of over-identification with one's pain or disengagement with the pain of others. According to the biopsychosocial approach, stress can be defined by three dimensions such as the cause or stressful factors that can be major life events or daily hassles, the perception of stress that is manifested through cognitive, emotional and behavioural reactions and the physiological response for achieving homeostasis. The purpose of the present study was to investigate the role of compassion for self and others in the occurrence of stressful events and levels of perceived stress in students. Participants were 280 undergraduate students from two Greek universities. Results indicated that students who had experienced a greater amount of stressful events during the past year reported having higher levels of perceived stress and that higher self-compassion was correlated with less perceived stress. Moreover, the adverse effect of stressful events on perceived stress was partially explained by the mediating role of self-compassion. Students who reported more stressful events showed higher compassion for others in opposition to compassion towards themselves but compassion for others was not significantly correlated with perceived stress. Since compassion is not considered being a fixed personality trait but it is seen as a capacity that can be developed by appropriate training it was suggested that enhancing self-compassion's stress buffering properties can be useful for dealing with stressful events and reducing stress responses. Moeover, it was suggested that it is interesting to explore the relationship between compassion for others and positive characteristics such as sense of coherence, quality of life and social support that may enhance stress resilience indirectly. The above findings imply that it is important to investigate further the role of compassion in coping with stress in qualitative, longitudinal studies as well as randomized control trials. Compassion may be an alternative mechanism for coping with stressful events and stress, other than fight or flight that has been shaped by evolution.

Impact of pre-transplant co-morbidities on outcome after alemtuzumab-based reduced intensity conditioning allo-SCT in elderly patients: a British Society of Blood and Marrow Transplantation study.

The advent of reduced intensity conditioning (RIC) regimens has permitted the extension of allo-SCT to selected patients into their eighth decade but GVHD remains a major cause of morbidity and mortality. Alemtuzumab is increasingly used to reduce the risk of severe GVHD, but there are concerns that T-cell depletion may compromise outcome particularly in older patients. We therefore studied the impact of pre-transplant factors on the outcome of 187 patients with a haematological malignancy over the age of 60 transplanted using an alemtuzumab-based RIC regimen of whom co-morbidity scoring was possible in 169. Of the patients, 120 had a haematopoietic cell transplantation co-morbidity index (HCT-CI) of 0 or 1 and 49 had a score of 2 or more. The 5-year OS was 33%. In multivariable analysis, OS was determined by co-morbidity score (P=0.001) and disease status at transplant (P=0.004) but not by patient age. Non-relapse mortality was determined by co-morbidity score (P=0.001). Two-year OS for patients with a HCT-CI of 0-1 was 59 versus 6% for patients with a higher score. Alemtuzumab-based RIC allografts can be delivered safely in patients aged over 60 but co-morbidity scoring is mandatory to identify patients who will benefit.

A multicentre UK study of GVHD following DLI: rates of GVHD are high but mortality from GVHD is infrequent.

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.