Pregnancy and assisted reproductive technology use in Australian female transfusion-dependent haemoglobinopathy patients: a 20-year retrospective analysis.

BACKGROUND: In the last few decades, the life expectancy of patients with transfusion-dependent thalassaemia (TDT) and sickle cell disease (SCD) has improved significantly, in part because of improved iron chelation. Fertility challenges and pregnancy complications have historically limited reproductive options in this group; however, improved multi-disciplinary care has made infertility a chronic disease complication requiring attention. Despite this, there are very few reports and no Australian data describing fertility and pregnancy outcomes in this population. AIMS: To identify the rate of assisted reproductive technologies (ART) utilisation in our female transfusion-dependent haemoglobinopathy patients and to establish the nature of maternal and neonatal complications in this cohort. METHODS: A 20-year retrospective analysis (1997-2017) at an Australian centre captured data on conception rates, use of assisted reproductive techniques (ART), and pregnancy and neonatal outcomes in female transfusion-dependent haemoglobinopathy patients. RESULTS: Conception was attempted in 14 women (11 TDT and three SCD) during the study period. A total of 28 pregnancies resulting in 25 live births were recorded. ART supported 13 conceptions. A positive association was not identified between elevated mean serum ferritin and ART use; however, all patients with an established diagnosis of hypogonadotropic hypogonadism (HH) required ART. Maternal complications included gestational diabetes mellitus and post-partum haemorrhage. There were no cardiac complications. Two-thirds of women underwent lower segment caesarean section, with prematurity complicating 20% of births. There were no neonatal or maternal deaths. CONCLUSION: Pregnancy is an achievable goal for women with transfusion-dependent haemoglobinopathies, although the support of ART may be required in a subset of patients.

Immunochemotherapy for life-threatening haematological malignancies in pregnancy: a systematic review of the literature and cross-sectional analysis of clinical trial eligibility.

The management of potentially life-threatening malignancies in pregnancy is complicated by a lack of robust safety and efficacy evidence. This data shortage stems from a historical exclusion of women of childbearing potential from prospective clinical trials due to concerns around potential teratogenicity and toxicity of investigational agents. We conducted a systematic review of published data on immunochemotherapeutic treatment of life-threatening haematological malignancies in pregnancy between 2010 and 2022, and the maternal and neonatal outcomes. We then performed a cross-sectional observational study of clinical trial protocols on ClinicalTrials.gov, between 2016 and 2022, recruiting women of childbearing potential with potentially life-threatening haematological malignancies, collecting trial demographic data, and documenting whether pregnant or lactating women were explicitly excluded, along with the type and duration of contraception required for women of childbearing potential. We included 17 studies for analysis in our systematic review. A total of 595 women were treated with immunochemotherapy during pregnancy, with a median age of 29 years (range 14-48). Of these, 81 women (14%) were treated in the first trimester, and 514 (86%) were treated in the second and third trimesters collectively. In total, 68 trials for acute myeloid leukaemia, acute lymphocytic leukaemia, high-grade non-Hodgkin lymphoma, and Hodgkin lymphoma (40%, 26%, 21%, and 13%, respectively) were included in our ClinicalTrials.gov analysis. Most protocols (66 [97%]) explicitly excluded pregnant women, with 40 (69%) not providing a rationale for exclusion. The potential harm to the fetus from anti-cancer therapy has historically been given greater moral precedence than a pregnant woman's autonomy. This pattern is reflected in the lack of rigorous evidence for immunochemotherapy in pregnancy and a universal exclusion of pregnant and lactating women from clinical trial protocols in this study. Nonetheless, the administration of systemic chemotherapy in the second and third trimesters was not associated with an increased rate of congenital malformations or perinatal mortality in our systematic review cohort, with maternal outcomes broadly comparable to those of the non-pregnant population.

Australia and New Zealand Transplant and Cellular Therapies (ANZTCT) position statement: COVID-19 management in patients with haemopoietic stem cell transplant and chimeric antigen receptor T cell.

Patients with post-haemopoietic stem cell transplant or chimeric antigen receptor T -cell (CAR-T) therapy face a significant risk of morbidity and mortality from coronavirus disease 2019 because of their immunosuppressed state. As case numbers in Australia and New Zealand continue to rise, guidance on management in this high-risk population is needed. Whilst we have learned much from international colleagues who faced high infection rates early in the pandemic, guidance relevant to local health system structures, medication availability and emerging therapies is essential to equip physicians to manage our patients optimally.

Innovative strategies to improve hematopoietic stem cell transplant outcomes in myelofibrosis.

Myelofibrosis (MF) is a clonal myeloproliferative neoplasm characterized by inflammation, marrow fibrosis, and an inherent risk of blastic transformation. Hematopoietic allogeneic stem cell transplant is the only potentially curative therapy for this disease, however, survival gains observed for other transplant indications over the past two decades have not been realized for MF. The role of transplantation may also evolve with the use of novel targeted agents. The chronic inflammatory state associated with MF necessitates pretransplantation assessment of end-organ function. Applying the transplant methodology employed for other myeloid disorders to patients with MF fails to acknowledge differences in the underlying disease pathophysiology. Limited understanding of the causes of poor transplant outcomes in this cohort has prevented refinement of transplant eligibility criteria in MF. There is increasing evidence of heterogeneity in molecular disease grade, beyond the clinical manifestations which have traditionally guided transplant timing. Exploring the physiological consequences of disease chronicity unique to MF, acknowledging the heterogeneity in disease grade, and using advanced prognostic models, molecular diagnostics and other organ function diagnostic tools, we present an innovative review of strategies with the potential to improve transplant outcomes in this disease. Larger, prospective studies which consider the impact of molecular-based disease grade are needed for MF transplantation.

Management and Outcomes of Diffuse Large B-cell Lymphoma Post-transplant Lymphoproliferative Disorder in the Era of PET and Rituximab: A Multicenter Study From the Australasian Lymphoma Alliance.

There are limited data on post-transplant lymphoproliferative disorder (PTLD) in the era of positron emission tomography (PET) and rituximab (R). Furthermore, there is limited data on the risk of graft rejection with modern practices in reduction in immunosuppression (RIS). We studied 91 patients with monomorphic diffuse large B-cell lymphoma PTLD at 11 Australian centers: median age 52 years, diagnosed between 2004 and 2017, median follow-up 4.7 years (range, 0.5-14.5 y). RIS occurred in 88% of patients. For patients initially treated with R-monotherapy, 45% achieved complete remission, rising to 71% with the addition of rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone (R-CHOP) for those not in complete remission. For patients initially treated with R-CHOP, the complete remission rate was 76%. There was no difference in overall survival (OS) between R-monotherapy and R-chemotherapy patients. There was no difference in OS for patients with systemic lymphoma (n = 68) versus central nervous system (CNS) involvement (n = 23) (3-y OS 72% versus 73%; P = 0.78). Treatment-related mortality was 7%. End of treatment PET was prognostic for patients with systemic lymphoma with longer OS in the PET negative group (3-y OS 91% versus 57%; P = 0.01). Graft rejection occurred in 9% (n = 4 biopsy-proven; n = 4 suspected) during the entire follow-up period with no cases of graft loss. RIS and R-based treatments are safe and effective with a low likelihood of graft rejection and high cure rate for patients achieving complete remission with CNS or systemic PTLD.

Use of direct oral anticoagulants for treatment of atrial fibrillation in patients with HIV: a review.

PURPOSE OF REVIEW: Atrial fibrillation is increasingly common in the ageing population. Patients with atrial fibrillation and HIV have a higher stroke risk, with guidelines recommending anticoagulation in the majority. Whilst anticoagulation options have diversified in the last decade for the general population, there is limited evidence for the safety and efficacy of these medications when used concurrently with antiretroviral therapy. We review the potential for patients with HIV on antiretroviral therapy to have direct-acting oral anticoagulations (DOACs). RECENT FINDINGS: Several case reports have been published in the past 5 years, as well as theoretical analyses of anticipated drug interactions, which provide a starting point to guide use of DOACs with antiretroviral medications. SUMMARY: Caution is needed when prescribing DOACs in patients with atrial fibrillation and HIV due to potential drug interactions. Studies are lacking and current advice is based on case reports, expert opinion and knowledge of theoretical interactions.

Depression, Anxiety, and Stress Among People With Chronic Hepatitis C Virus Infection and a History of Injecting Drug Use in New South Wales, Australia.

OBJECTIVE: The aims of this study were to assess symptoms of depression, anxiety, and stress and associated sociodemographic factors among people living with chronic hepatitis C virus (HCV) infection with a history of injecting drug use and to assess the association between symptoms of depression, anxiety, or stress and HCV treatment intent, specialist assessment, or treatment uptake. METHODS: The Enhancing Treatment for Hepatitis C in Opioid Substitution Settings was an observational cohort study evaluating the provision of HCV assessment and treatment among people with chronic HCV and a history of injecting drug use, recruited from 9 community health centers and opioid substitution therapy (OST) clinics (New South Wales, Australia). Symptoms were assessed using the Depression Anxiety Stress Scales (DASS-21). Analyses were performed using logistic regression. RESULTS: Among 415 participants (mean age 41 years, 71% male), 47%, 52%, and 36% demonstrated moderate to extremely severe symptoms of depression, anxiety, and stress, respectively. In adjusted analyses, depression symptoms were associated with recent injecting drug use [adjusted odds ratio (aOR) 1.63, 95% confidence interval (CI) 1.07-2.49), whereas stress symptoms were associated with unemployment (aOR 2.99, 95% CI 1.09-8.15) and not living with a spouse or other relatives/friends (aOR 1.55, 95% CI 1.01-2.39). Symptoms of depression, anxiety, or stress or having a history of treated mental illness were not independently associated with HCV treatment intent, specialist assessment, or treatment uptake. CONCLUSIONS: Findings suggest a need for improved interventions and care regarding mental health among people living with chronic HCV with a history of injecting drug use, but suggest that symptoms of depression, anxiety, and stress should not be immediate contraindications to HCV assessment and treatment.

Potentially inappropriate medications (PIMs) in older hospital in-patients: Prevalence, contribution to hospital admission and documentation of rationale for continuation.

AIM: To establish prevalence, sequelae and documentation of potentially inappropriate medication (PIM) use in older hospital in-patients. METHODS: Notes of all patients ≥65 years old, admitted to our tertiary teaching hospital (January 2013), were retrospectively reviewed, and the Screening Tool of Older Persons' potentially inappropriate Prescriptions applied. RESULTS: Amongst 534 patients, 54.8% (284) were on ≥1 PIM at admission, 26.8% on multiple; 60.8% were discharged on a PIM. Six percent of all admissions were potentially attributable to a PIM; falls associated with risk therapies were commonest (23/30), and often (65.2%) associated with serious injury. Pre-specified subgroup analysis (n = 100) identified 101 PIMs-at-discharge amongst 47 patients. In 82.2%, a clinical rationale for continued prescription was documented, with this communicated to the GP by letter in 71.1%. CONCLUSION: PIMs were common, and contributed to admission and injury. Hospitalisation provides an opportunity for medication rationalisation, and documentation of rationale for any PIM use.

Novel oral anticoagulants and HIV: dabigatran use with antiretrovirals.

Compatibility of novel oral anticoagulants in patients with HIV taking combined antiretroviral therapy has not been established, with no published reports of successful concurrent use. We present a case where chronic anticoagulation was indicated in a patient with treated HIV and non-valvular atrial fibrillation who refused warfarin therapy. The patient tolerated the combination, with dabigatran blood levels within the expected range at a standard dosing regimen, without evidence of bleeding or other adverse outcomes. While further research is needed to establish the role of novel oral anticoagulants in patients taking antiretrovirals, this case suggests that dabigatran may be a viable option for selected patients.

A Novel Case of Symptomatic BK Viraemia in a Patient Undergoing Treatment for Hodgkin Lymphoma.

Symptomatic BK viral infection in the immunocompromised host is well described, most commonly seen in renal transplant recipients, bone marrow transplant recipients, and HIV positive patients. The present case describes a novel clinical scenario of symptomatic urological BK virus infection in a patient receiving treatment for Hodgkin lymphoma. This case highlights the importance of casting a wide diagnostic net for adverse events encountered with novel therapeutic agents or regimens.