Positive pion absorption on 3He using modern trinucleon wave functions

We study pion absorption on 3He employing trinucleon wave functions calculated from modern realistic NN interactions (Paris, CD Bonn). Even though the use of the new wave functions leads to a significant improvement over older calculations with regard to both cross section and polarization data, there are hints that polarization data with quasifree kinematics cannot be described by just two-nucleon absorption mechanisms.Comment: 14 pages, 6 figure

Genetic and genomic analysis of acute lymphoblastic leukaemia in older adults reveals a distinct profile of abnormalities: analysis of 210 patients from the UKALL14 and UKALL60+ clinical trials

Despite being predominantly a childhood disease, the incidence of ALL has a second peak in adults aged 60 years and over. These older adults fare extremely poorly with existing treatment strategies and very few studies have undertaken a comprehensive genetic and genomic characterisation to improve prognosis in this age group. We performed cytogenetic, single nucleotide polymorphism (SNP) array and next generation sequencing (NGS) analyses on samples from 210 patients aged ≥60 years from the UKALL14 and UKALL60+ clinical trials. BCR-ABL1 positive disease was present in 26% (55/210) of patients, followed by low hypodiploidy/near triploidy in 13% (28/210). Cytogenetically cryptic rearrangements in CRLF2, ZNF384 and MEF2D were detected in 5%, 1% and 1% of patients respectively. Copy number abnormalities were common and deletions in ALL driver genes were seen in 77% of cases. IKZF1 deletion was present in 51% (40/78) of samples tested and the IKZF1plus profile identified in over a third (28/77) of BCP-ALL cases. The genetic good risk abnormalities high hyperdiploidy (n=2), ETV6-RUNX1 (no cases) and ERG deletion (no cases) were exceptionally rare in this cohort. RAS pathway mutations were seen in 17% (4/23) of screened samples. KDM6A abnormalities, including biallelic deletions, were discovered in 5% (4/78) of SNP array and 9% (2/23) of NGS samples, and represent a novel, potentially therapeutically actionable lesions using EZH2 inhibitors. Outcome remained poor with five-year event-free (EFS) and overall survival (OS) rates of 17% and 24% respectively across the cohort indicating a need for novel therapeutic strategies

In-vivo T-cell depleted reduced-intensity conditioned allogeneic haematopoietic stem-cell transplantation for patients with acute lymphoblastic leukaemia in first remission: results from the prospective, single-arm evaluation of the UKALL14 trial

Background The outcome of chemotherapy in patients older than 40 years with acute lymphoblastic leukaemia is poor and myeloablative allogeneic haematopoietic stem-cell transplantation (HSCT) has a high transplant-related mortality (TRM) in this age cohort. The aim of this study was to assess the activity and safety of reduced-intensity conditioned allogeneic HSCT in this patient population. Methods This was a single-arm, prospective study within the UKALL14 trial done in 46 centres in the UK, which recruited patients to the transplantation substudy. Participants in UKALL14 had B-cell or T-cell acute lymphoblastic leukaemia, were aged 25–65 years (BCR-ABL1-negative) or 18–65 years (BCR-ABL1-positive), and for this subcohort had a fit, matched sibling donor or an 8 out of 8 allelic matched unrelated donor (HLA-A, HLA-B, HLA-C, and HLA-DR). On June 20, 2014, the protocol was amended to allow 7 out of 8 matched unrelated donors if the patient had high risk cytogenetics or was minimal residual disease (MRD)-positive after the second induction course. Patients were given fludarabine, melphalan, and alemtuzumab (FMA; intravenous fludarabine 30 mg/m2 on days –6 to –2, melphalan 140 mg/m2 on day –2, and alemtuzumab 30 mg on day –1 [sibling donor] and days –2 and –1 [unrelated donor]) before allogeneic HSCT (aged ≥41 years patient pathway). Donor lymphocyte infusions were given from 6 months for mixed chimerism or MRD. The primary endpoint was event-free survival and secondary and transplantation-specific endpoints included overall survival, relapse incidence, TRM, and acute and chronic graft-versus-host disease (GVHD). This study is registered with ClinicalTrials.gov, NCT01085617. Findings From Feb 22, 2011, to July 26, 2018, 249 patients (236 aged ≥41 years and 13 younger than 41 years) considered unfit for a myeloablative allograft received an FMA reduced-intensity conditioned HSCT. 138 (55%) patients were male and 111 (45%) were female. 88 (35%) participants received transplantations from a sibling donor and 160 (64%) received transplantations from unrelated donors. 211 (85%) participants had B-precursor acute lymphoblastic leukaemia. High-risk cytogenetics were present in 43 (22%) and another 63 (25%) participants were BCR-ABL1-positive. At median follow-up of 49 months (IQR 36–70), 4-year event-free survival was 46·8% (95% CI 40·1–53·2) and 4-year overall survival was 54·8% (48·0–61·2). 4-year cumulative incidence of relapse was 33·6% (27·9–40·2) and 4-year TRM was 19·6% (15·1–25·3). 27 (56%) of 48 patients with TRM had infection as the named cause of death. Seven (15%) of 48 patients had fungal infections, 13 (27%) patients had bacterial infections (six gram-negative), and 11 (23%) had viral infections (three cytomegalovirus and two Epstein-Barr virus). Acute GVHD grade 2–4 occurred in 29 (12%) of 247 patients and grade 3–4 occurred in 12 (5%) patients. Chronic GVHD incidence was 84 (37%) of 228 patients (50 [22%] had extensive chronic GVHD). 49 (30%) of 162 patients had detectable end-of-induction MRD, which portended worse outcomes with event-free survival (HR 2·40 [95% CI 1·46–3·93]) and time-to-relapse (HR 2·41 [1·29–4·48]). Interpretation FMA reduced-intensity conditioned allogeneic HSCT in older patients with acute lymphoblastic leukaemia in first complete remission provided good disease control with moderate GVHD, resulting in better-than-expected event-free survival and overall survival in this high-risk population. Strategies to reduce infection-related TRM will further improve outcomes. Funding Cancer Research UK

Virtual Compton Scattering and Neutral Pion Electroproduction in the Resonance Region up to the Deep Inelastic Region at Backward Angles

We have made the first measurements of the virtual Compton scattering (VCS) process via the H$(e,e'p)\gamma$ exclusive reaction in the nucleon resonance region, at backward angles. Results are presented for the $W$-dependence at fixed $Q^2=1$ GeV$^2$, and for the $Q^2$-dependence at fixed $W$ near 1.5 GeV. The VCS data show resonant structures in the first and second resonance regions. The observed $Q^2$-dependence is smooth. The measured ratio of H$(e,e'p)\gamma$ to H$(e,e'p)\pi^0$ cross sections emphasizes the different sensitivity of these two reactions to the various nucleon resonances. Finally, when compared to Real Compton Scattering (RCS) at high energy and large angles, our VCS data at the highest $W$ (1.8-1.9 GeV) show a striking $Q^2$- independence, which may suggest a transition to a perturbative scattering mechanism at the quark level.Comment: 20 pages, 8 figures. To appear in Phys.Rev.