Clinical and cytogenetic features of pediatric dic(9;20)(p13.2;q11.2)-positive B-cell precursor acute lymphoblastic leukemias: a Nordic series of 24 cases and review of the literature

Although dic(9;20)(p13.2;q11.2) is a characteristic abnormality in childhood B-cell precursor acute lymphoblastic leukemias (BCP ALL), little is known about its clinical impact or the type and frequency of additional aberrations it may occur together with. We here review the clinical and cytogenetic features of a Nordic pediatric series of 24 patients with dic(9;20)-positive BCP ALL diagnosed 1996-2006, constituting 1.3% of the BCP ALL, as well as 47 childhood cases from the literature. Consistent immunophenotypic features of the Nordic cases included positivity for HLA-DR, CD10, CD19, CD20, and CD22 and negativity for T-cell and myeloid markers; no detailed immunophenotypes were reported for the previously published cases. In the entire cohort of 71 cases, the modal chromosome distribution was 45 (62%), 46 (21%), 47 (7%), 48 (4%), 49 (3%), 44 (1%), and 50 (1%). Additional changes were present in 63%, the most frequent of which were homozygous loss of CDKN2A (33%) and gains of chromosomes 21 (28%) and X (10%). The median patient age was 3 years, the female/male ratio was 2.0, the median white blood cell count was 24 x 10(9)/l, 11% had central nervous system involvement, and 5% had a mediastinal mass at diagnosis. Risk group stratification was nonstandard risk in 79%. The event-free survival and overall survival at 5 years for the 24 Nordic cases was 0.62 and 0.82, respectively. Thus, although relapses are quite common, postrelapse treatment of many patients is successful.     

Somatic,hematologic phenotype,long‐term outcome,and effect of hematopoietic stem cell transplantation. An analysis of 97 Fanconi anemia patients from the Italian national database on behalf of the Marrow Failure Study Group of the AIEOP (Italian Association of Pediatric Hematology–Oncology)

We analyzed 97 Fanconi anemia patients from a clinic/biological database for genotype, somatic, and hematologic phenotype, adverse hematological events, solid tumors, and treatment. Seventy‐two patients belonged to complementation group A. Eighty percent of patients presented with mild/moderate somatic phenotype and most with cytopenia. No correlation was seen between somatic/hematologic phenotype and number of missense mutations of FANCA alleles. Over follow‐up, 33% of patients improved or maintained mild/moderate cytopenia or normal blood count, whereas remaining worsened cytopenia. Eleven patients developed a hematological adverse event (MDS, AML, pathological cytogenetics) and three developed solid tumors. 10 years cumulative risk of death of the whole cohort was 25.6% with median follow‐up 5.8 years. In patients eligible to hematopoietic stem cell transplantation because of moderate cytopenia, mortality was significantly higher in subjects transplanted from matched unrelated donor over nontransplanted subjects, whereas there was no significant difference between matched sibling donor transplants and nontransplanted patients. In patients eligible to transplant because of severe cytopenia and clonal disease, mortality risk was not significantly different in transplanted from matched unrelated versus matched sibling donor versus nontransplanted subjects. The decision to transplant should rely on various elements including, type of donor, HLA matching, patient comorbidities, impairment, and clonal evolution of hematopoiesis. Am. J. Hematol. 91:666–671, 2016. © 2016 Wiley Periodicals, Inc.     

Effect on cytokine release and graft-versus-host disease of different anti-T cell antibodies during conditioning for unrelated haematopoietic stem cell transplantation.

Three different types of anti-T cell antibody were used in patients undergoing haematopoietic stem cell transplantation (HSCT) with an HLA-A, -B and -DR compatible unrelated donor: ATG-Fresenius (ATG-F) (n = 26), Thymoglobuline (TMG) (n = 61) and OKT-3 (n = 45). The groups were comparable regarding diagnosis, stage, age, conditioning and GVHD prophylaxis, Adverse events were less frequent after ATG-F treatment. Levels of IL-2, IL-6, IFN-gamma, TNF-alpha and GM-CSF were increased after OKT-3 infusion. In multivariate analysis OKT-3 treatment (P = 0.01), G-CSF treatment (P = 0.02) and a cell dose >/=2.7 x 108/kg (P = 0.03) gave a faster engraftment. Acute GVHD grades II-IV occurred in 25% of the ATG-F patients, 12% of the TMG-patients and 43% (P < 0.001 vs TMG) of the OKT-3 patients. OKT-3 was associated with acute GVHD in multivariate analysis. TRM was 26% using TMG as compared to 43% in the OKT-3 group (P = 0.03). Patient survival at 4 years was 63%, 50% and 45% in the ATG-F, TMG and OKT-3-treated patients, respectively (NS). Relapses were 8%, 49% and 34%, respectively (ATG-F vs TMG, P = 0.03). Relapse-free survivals were 61%, 40% and 37% (NS). Among CML patients the probability of relapse was 61% in TMG-treated patients, while no patients relapsed in the other two groups. To conclude, the type of anti-T cell antibody affects GVHD and relapse after HSCT using unrelated donors.     

The effect of group-based cognitive behavioral therapy on inflammatory biomarkers in patients with coronary heart disease—results from the SUPRIM-trial

Abstract

Background: The Secondary Prevention in Uppsala Primary Healthcare Project (SUPRIM) is a prospective randomized controlled trial of a group-based cognitive behavioral therapy (CBT) stress management program for coronary heart disease (CHD) patients. The intervention reduced the risk of fatal or non-fatal first recurrent cardiovascular (CV) events. The aim of the present study was to analyze if the positive effects of the CBT program on clinical outcomes could have been mediated by changes in biomarkers for inflammation.

Methods: Altogether 362 patients with CHD were randomly assigned to intervention or usual care. The inflammatory biomarkers (VCAM-1, TNF-R1, TNF-R2, PTX3, and hs-CRP) were serially assessed at five time points every six months from study start until 24 months later, and analyzed with linear mixed models.

Results: Baseline levels of the inflammatory markers were near normal, indicating a stable phase. The group-based CBT stress management program did not significantly affect the levels of inflammatory biomarkers in patients with CHD. Three out of five (VCAM-1, TNF-R2, and PTX3) inflammatory biomarkers showed a slight increase over time in both study groups, and all were positively associated with age.

Conclusion: Group-based CBT stress management did not affect biomarkers for inflammation in patients with CHD. It is therefore unlikely that inflammatory processes including these biomarkers were mediating the effect the CBT program had on the reduction in CV events. The close to normal baseline levels of the biomarkers and the lack of elevated psychological distress symptoms indicate a possible floor effect which may have influenced the results.     

Randomised controlled trial of a complex intervention by primary care nurses to increase walking in patients aged 60–74 years: protocol of the PACE-Lift (Pedometer Accelerometer Consultation Evaluation - Lift) trial

Background

Physical activity is essential for older peoples’ physical and mental health and for maintaining independence. Guidelines recommend at least 150 minutes weekly, of at least moderate intensity physical activity, with activity on most days. Older people’s most common physical activity is walking, light intensity if strolling, moderate if brisker. Less than 20% of United Kingdom 65–74 year olds report achieving the guidelines, despite most being able to. Effective behaviour change techniques include strategies such as goal setting, self-monitoring, building self-efficacy and relapse prevention. Primary care physical activity consultations allow individual tailoring of advice. Pedometers measure step-counts and accelerometers measure physical activity intensity. This protocol describes an innovative intervention to increase walking in older people, incorporating pedometer and accelerometer feedback within a primary care nurse physical activity consultation, using behaviour change techniques.

Methods/Design

Design: Randomised controlled trial with intervention and control (usual care) arms plus process and qualitative evaluations. Participants: 300 people aged 60–74 years registered with 3 general practices within Oxfordshire and Berkshire West primary care trusts, able to walk outside and with no restrictions to increasing their physical activity. Intervention: 3 month pedometer and accelerometer based intervention supported by practice nurse physical activity consultations. Four consultations based on behaviour change techniques, physical activity diary, pedometer average daily steps and accelerometer feedback on physical activity intensity. Individual physical activity plans based on increasing walking and other existing physical activity will be produced. Outcomes: Change in average daily steps (primary outcome) and average time spent in at least moderate intensity physical activity weekly (secondary outcome) at 3 months and 12 months, assessed by accelerometry. Other outcomes include quality of life, mood, exercise self-efficacy, injuries. Qualitative evaluations will explore reasons for trial non-participation, the intervention’s acceptability to patients and nurses and factors enhancing or acting as barriers for older people in increasing their physical activity levels.

Discussion

The PACE-Lift trial will determine the feasibility and efficacy of an intervention for increasing physical activity among older primary care patients. Steps taken to minimise bias and the challenges anticipated will be discussed. Word count 341.

Trial registration number

ISRCTN42122561     

Formation and adhesion of biomimetic hydroxyapatite deposited on titanium substrates

This study has been carried out to investigate the bioactivity of rutile and to deposit hydroxyapatite (HA) on heat-treated titanium through a biomimetic method. Biomimetic deposition of HA has gained large interest because of its low deposition temperature and good step coverage; however, it demands a substrate with bioactive properties. Commercially pure titanium is not bioactive but it can acquire bioactive properties through various surface treatments. In the present study, titanium plates were heat-treated at 800 °C to achieve rutile TiO₂ surfaces. These samples were immersed in a phosphate-buffered saline solution for seven days in order to deposit a HA layer on the surface. The rutile TiO₂ surfaces were found to be highly bioactive: after seven days of immersion, a layer of HA several micrometers thick covered the plates. The HA surfaces were confirmed by electron microscopy and X-ray diffraction. A scratch test was used to assess the adhesion of the HA coatings. This is a standard method to provide a measure of the coating-to-substrate adhesion and was found to be a useful method to test the thin HA coatings deposited on the bioactive surfaces. The critical pressure of the layer was estimated to be 2.4 ± 0.1 GPa.