PET assessment of acute gastrointestinal graft versus host disease.

Acute gastrointestinal graft versus host disease (GI-GVHD) is a common complication following allogeneic haematopoietic cell transplantation (HCT), and is characterised by severe morbidity, frequent treatment-refractoriness, and high mortality. Early, accurate identification of GI-GVHD could allow for therapeutic interventions to ameliorate its severity, improve response rates and survival; however, standard endoscopic biopsy is inadequately informative in terms of diagnostic sensitivity or outcome prediction. In an era where rapid technological and laboratory advances have dramatically expanded our understanding of GI-GVHD biology and potential therapeutic targets, there is substantial scope for novel investigations that can precisely guide GI-GVHD management. In particular, the combination of tissue-based biomarker assessment (plasma cytokines, faecal microbiome) and molecular imaging by positron emission tomography (PET) offers the potential for non-invasive, real-time in vivo assessment of donor:recipient immune activity within the GI tract for GI-GVHD prediction or diagnosis. In this article, we review the evidence regarding GI-GVHD diagnosis, and examine the potential roles and translational opportunities posed by these novel diagnostic tools, with a focus on the evolving role of PET.

Dose-adjusted EPOCH-R is a safe and well tolerated outpatient treatment regimen in double-hit lymphoma.

BACKGROUND: Double-hit lymphoma (DHL) is an aggressive subtype of high-grade B-cell lymphoma with inferior prognosis using standard dose chemotherapy. Controversy remains whether more intensive chemotherapy regimens such as dose-adjusted etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin and rituximab (DA-EPOCH-R) provide better outcomes in this cohort. AIMS: To review consecutive cases of DHL treated with DA-EPOCH-R at our institution in comparison to available literature. METHODS: We conducted a retrospective study of 13 consecutive patients with DHL treated with DA-EPOCH-R at our institution. Primary endpoints included complete response (CR), event-free survival (EFS) and overall survival (OS). RESULTS: CR rate with DA-EPOCH-R in DHL was 69% in our cohort. Median EFS and OS duration was 61 months (95% CI: 41-86 months) and 64 months (95% CI: 42-86 months) respectively. One patient discontinued DA-EPOCH-R due to recurrent febrile neutropenia and there were no treatment or infection-related deaths during the study. CONCLUSIONS: This study suggests that DA-EPOCH-R is a well tolerated outpatient regimen for DHL and should be considered for initial treatment in medically fit patients. Further prospective studies are warranted to confirm these findings.

Myeloid somatic mutation panel testing in myeloproliferative neoplasms.

Myeloproliferative neoplasms are characterised by somatic mutations in pathways that regulate cell proliferation, epigenetic modifications, RNA splicing or DNA repair. Assessment of the mutational profile assists diagnosis and classification, but also aids assessment of prognosis, and may guide the use of emerging targeted therapies. The most practical way to provide information on numerous genetic variants is by using massively parallel sequencing, commonly in the form of disease specific next generation sequencing (NGS) panels. This review summarises the diagnostic and prognostic value of somatic mutation testing in Philadelphia-negative myeloproliferative neoplasms: polycythaemia vera, essential thrombocythaemia, primary myelofibrosis, chronic neutrophilic leukaemia, systemic mastocytosis, and chronic eosinophilic leukaemia. NGS panel testing is increasing in routine practice and promises to improve the accuracy and efficiency of pathological diagnosis and prognosis.

Pralatrexate in relapsed/refractory T-cell lymphoma: a retrospective multicenter study.

We present a retrospective multicenter study of pralatrexate treatment outcomes in an Australian practice setting for patients with relapsed/refractory T-cell lymphoma who had failed 1+ systemic therapies, treated via a compassionate access program. Endpoints assessed included response rates, toxicities, and subsequent therapies. Progression-free survival (PFS), time to next treatment (TTNT), event-free survival (EFS), overall survival (OS), and time to best response, were assessed by Kaplan-Meier analysis. The study included 31 patients, with median age 69 years. We demonstrated ORR of 35.5% (n = 11), including 4 complete responses (13%) and 7 partial responses (23%). The predicted median OS was 10 months, with EFS of 9 months, and PFS of 9 months. Median TTNT was 8 months. Mucositis was the most commonly observed toxicity. This study - the second largest real-world cohort reported to date - underscores the importance of pralatrexate in relapsed/refractory T-cell lymphoma, as well as its acceptable toxicity profile.

Favourable survival in "Discordant" acute gastrointestinal graft versus host disease (GI-GVHD) is explained by mild clinical course and treatment-responsive disease.

We have previously reported that haematopoietic progenitor cell transplantation recipients with biopsy-negative acute Gastrointestinal Graft versus Host Disease (Discordant GVHD) demonstrate superior survival compared to "True Positive" cases. We aimed to elucidate this discrepancy by examining clinical and laboratory predictors of survival among patients treated for True Positive or Discordant GVHD. Data were obtained by retrospective chart review. At diagnosis, the incidence of severe symptoms, hypoalbuminaemia, hyperbilirubinaemia, and poor performance status were recorded. Following treatment, the incidence of non-response to first-line corticosteroids was assessed. Differences between cohorts were compared using Fisher's exact test. 74 patients were identified, comprising 55 (74%) True Positive and 19 (26%) Discordant GVHD cases. True Positive cases were significantly more likely to have baseline severe symptoms (84% vs. 36%; p = 0.0002) and hypoalbuminaemia (94% vs. 75%; p = 0.023). There was no significant difference between cohorts in terms of hyperbilirubinaemia or performance status. Non-response to corticosteroid therapy was observed significantly more frequently in the True Positive cohort (55% vs. 11%; p = 0.001). In summary, the superior survival observed in Discordant GVHD is explained by a less severe GI-GVHD phenotype at diagnosis and a greater likelihood of response to corticosteroids. Further research is warranted to explain biological mechanisms for these findings.

Diagnostic Utility of Endoscopy and Biopsy in Suspected Acute Gastrointestinal Graft-versus-Host Disease after Hematopoietic Progenitor Cell Transplantation.

Acute gastrointestinal graft-versus-host disease (GI-GVHD) after hematopoietic progenitor cell transplantation (HPCT) is a common and life-threatening complication. Endoscopic biopsy of the GI tract (GIT) is required for diagnosis. However, clear evidence to optimize this diagnostic approach is lacking, leading to variation in diagnostic sensitivity between institutions. We aimed to assess the clinical, endoscopic, and histologic findings of endoscopies performed for suspected acute GI-GVHD at our institution to better define the optimal use of this strategy. We performed a retrospective cohort study of adults who had undergone endoscopy for suspected acute GI-GVHD within 180 days after allogeneic HPCT for hematologic malignancy between 2011 and 2016. Details included symptoms at time of referral for endoscopy, type of procedure performed, macroscopic findings on endoscopy, and histologic findings after gut biopsy. Correlation was made with clinical GVHD severity scores. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated and compared for each procedure. Predictors of histologic GVHD and overall survival were also compared. Of the 123 patients included, acute GI-GVHD occurred in 59 (48%). Lower endoscopy demonstrated greater sensitivity than upper endoscopy (50% versus 39%). Single upper endoscopy for upper symptoms alone had the lowest yield of GI-GVHD (14%). Combination upper and lower endoscopy demonstrated strong histologic concordance between upper and lower procedures. The addition of upper endoscopy to lower endoscopy only identified an extra 2 (4%) cases of GVHD. Advanced age and the presence of lower GIT symptoms were the only pre-endoscopy predictors of histologic GVHD on multivariate analysis. Patients with isolated upper histologic GVHD showed similar survival to patients with negative biopsies. Endoscopy and biopsy only identified 74% of those ultimately requiring treatment for acute GI-GVHD. Acute GI-GVHD remains a clinical diagnosis supported by available histologic evidence. Isolated upper GI-GVHD is rare, and in the absence of lower GIT symptoms, routine upper endoscopy does not significantly improve diagnostic yield for histologic GVHD. Overall, endoscopy and biopsy underdiagnoses 26% of clinical GI-GVHD, highlighting a need for research into novel diagnostic strategies.

Outdoor gyms and older adults - acceptability, enablers and barriers: a survey of park users.

Issue addressed Increasing the proportion of older adults meeting current recommendations for physical activity is important. This study aimed to determine the acceptability of outdoor gym use among older adults by assessing their outdoor gym use, intention to use, motivators, frequency and preference for use, and barriers and enablers to use. Methods Interviews were conducted with 438 consenting English speaking park users≥50 years after installation and promotion of an outdoor gym. Results Forty-two percent of older adults interviewed had used the outdoor gym. Outdoor gym users had a significantly higher proportion of local residents (χ2=10.43; P<0.01), were more frequent park users (χ2=8.75; P<0.01) and spoke a language other than English (χ2=15.44; P<0.0001) compared with general park users. Shade and different equipment types were the most cited enablers. Conclusions Outdoor gyms may be an acceptable form of physical activity for older adult park users. Installations should offer a variety of equipment types and shade. So what? Outdoor gyms are a potential equitable approach to engaging older adults in a variety of physical activity types. Social and physical benefits of outdoor gym use in high risk groups for physical inactivity should be explored.

Pretransplant platelet transfusion refractoriness is not associated with platelet nonengraftment in T-replete hematopoietic progenitor cell transplantation for hematologic malignancies.

BACKGROUND: Cellular engraftment after allogeneic hematopoietic progenitor cell transplantation (HPCT) can be affected by pre-HPCT antibodies against donor human leukocyte antigen (HLA; donor-specific antibodies [DSAs]), which are commonly acquired by either pregnancy or transfusion. Issues regarding high assay sensitivity and variable interpretation limit routine screening for DSAs. Platelet (PLT) transfusion refractoriness (PTR) is relatively common in patients with hematologic malignancies, and anti-HLA alloantibodies can be identified in up to 20% of cases. For patients with PTR undergoing subsequent allogeneic HPCT, however, the effect if any on subsequent PLT nonengraftment is unknown. STUDY DESIGN AND METHODS: We conducted a retrospective study of 480 adults who underwent T-replete HPCT for hematologic malignancy and compared the posttransplantation clinical outcomes between patients who were PTR before HPCT and those who were not. RESULTS: Multivariate analysis demonstrated that PTR was not directly associated with PLT nonengraftment or graft failure, but did predict for early intensive care unit admission, which was the only variable associated with these outcomes (p < 0.0001). CONCLUSION: Our findings suggest that PTR before HPCT identifies patients at higher risk of early clinical rather than immunologic complications.

Impact of an outdoor gym on park users' physical activity: A natural experiment.

This study assessed the impact of an outdoor gym installation on park users' physical activity levels and examined the characteristics of outdoor gym users. A before-after time series design was employed, consisting of nine data collection periods: three each at baseline, post outdoor gym installation, and at 12-month follow-up. Repeated observational surveys and park intercept interviews were conducted. There was a small but significant increase in senior park users engaging in moderate to vigorous physical activity at follow-up (1.6 to 5.1%; p<0.001). There were significant increases from baseline to follow-up in the outdoor gym area for: MVPA (6 to 40%; p<0.001); and seniors' use (1.4 to 6%; p<0.001). The study contributes to the limited evidence on the impact of outdoor gyms on physical activity outcomes.

Acute ST-elevation myocardial infarction in a 24-year-old woman with atheromatous coronary artery disease.

We report the case of a 24-year-old Torres Strait Islander woman who presented to a rural hospital ED with chest pain suspicious for myocardial ischaemia and was found to have an anterior ST-elevation myocardial infarction. She was thrombolysed and transferred to a tertiary centre where subsequent angiography revealed atheromatous disease of the left anterior descending coronary artery. We believe this to be one of the youngest reported cases of myocardial infarction due to atheromatous coronary artery disease, and demonstrates important learning points regarding the demographics and risk factors of indigenous patients with chest pain.