A minority of women of childbearing potential are tested for pregnancy before chemoimmunotherapy: an Australian cancer centre experience.

BACKGROUND: Chemotherapy is potentially harmful to a developing foetus, and there are limited data on the foetal impact of chemoimmunotherapy (CIT). Therefore, determining pregnancy status prior to initiation of CIT should be standard of care. AIMS: To determine how many women of childbearing age are tested for pregnancy prior to immunochemotherapy administration. METHODS: A retrospective chart review at a large Australian metropolitan cancer referral centre, including 304 women aged 18-51 years with a diagnosis of cancer receiving outpatient-based CIT between 1 May 2015 and 12 June 2020. We assessed the uptake of pregnancy screening and contraception counselling prior to and during first-line CIT. RESULTS: Only 17.3% of CIT cycles (n = 416) screened patients for pregnancy no more than 90 days prior to administration, and the median time between pregnancy screening and treatment was approximately 3 weeks. One patient with early breast cancer had a spontaneous miscarriage estimated at 3-4 weeks' gestation, and neither the patient nor the treating oncologist was aware of this event. This was also the only patient who had a pregnancy test beyond the first cycle of CIT during their treatment. CONCLUSIONS: Our results highlight a concerningly low rate of pregnancy screening in women of childbearing age receiving CIT. The implication of missing a positive pregnancy test in this group of women could result in foetal complications, accidental miscarriage, potential bleeding risks and avoidable psychosocial stress. This highlights the urgent need for guidelines to mandate pregnancy testing in women of childbearing age receiving CIT and evidence-based implementation tools.

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.

Rates of Menstrual History-Taking and Counseling With Anticancer Treatments Are Low: People Who Menstruate Deserve Gender-Specific Cancer Care.

BACKGROUND: Chemotherapy predisposes people who menstruate to abnormal uterine bleeding that can be life-threatening and may also damage ovaries, resulting in premature menopause. The purpose of this study was to explore the incidence of menstrual history documentation and counseling before, during, and after cancer treatment. PATIENTS AND METHODS: The medical charts of 137 consecutive females (self-reported) aged 18 to 49 years receiving anticancer treatment at a major tertiary metropolitan hospital in Australia between 2017 and 2020 were reviewed. Data collected included primary diagnosis, stage of cancer, treatment(s) received, rates of remission or progression, documentation of involvement of a specialist gynecologist, reproductive history, menstrual disturbances, menstruation counseling or intervention offered, and diagnosis of early ovarian failure. RESULTS: Only 16.1% of patients had their menstrual history documented at the initial consult, and 49.6% had their menstrual history documented at a subsequent consult with their treating oncologist or hematologist. Most (82.4%) patients with a menstrual history documented experienced menstrual disturbance posttreatment, most commonly amenorrhea (48.0%), followed by menopause or menopause symptoms (20.6%), irregular menstrual bleeding (16.7%), menorrhagia (13.7%), dysmenorrhea (3.9%), and iron deficiency from bleeding (2.9%). Menopause/Menopausal symptoms and iron deficiency were more likely to be treated than other disturbances. CONCLUSIONS: Menstruation disturbance is a common side effect of cancer treatment. Menstrual care should be integral to cancer care for people who menstruate, and higher engagement could be achieved through education of medical and allied health staff, information technology systems automating prompts and referral pathways, regular audits to ensure compliance, better alliances between cancer and fertility specialists, and the creation of accessible patient information to promote awareness and facilitate discussion.

Patients with treated indolent lymphomas immunized with BNT162b2 have reduced anti-spike neutralizing IgG to SARS-CoV-2 variants, but preserved antigen-specific T cell responses.

Patients with indolent lymphoma undertaking recurrent or continuous B cell suppression are at risk of severe COVID-19. Patients and healthy controls (HC; N = 13) received two doses of BNT162b2: follicular lymphoma (FL; N = 35) who were treatment naïve (TN; N = 11) or received immunochemotherapy (ICT; N = 23) and Waldenström's macroglobulinemia (WM; N = 37) including TN (N = 9), ICT (N = 14), or treated with Bruton's tyrosine kinase inhibitors (BTKi; N = 12). Anti-spike immunoglobulin G (IgG) was determined by a high-sensitivity flow-cytometric assay, in addition to live-virus neutralization. Antigen-specific T cells were identified by coexpression of CD69/CD137 and CD25/CD134 on T cells. A subgroup (N = 29) were assessed for third mRNA vaccine response, including omicron neutralization. One month after second BNT162b2, median anti-spike IgG mean fluorescence intensity (MFI) in FL ICT patients (9977) was 25-fold lower than TN (245 898) and HC (228 255, p = .0002 for both). Anti-spike IgG correlated with lymphocyte count (r = .63; p = .002), and time from treatment (r = .56; p = .007), on univariate analysis, but only with lymphocyte count on multivariate analysis (p = .03). In the WM cohort, median anti-spike IgG MFI in BTKi patients (39 039) was reduced compared to TN (220 645, p = .0008) and HC (p < .0001). Anti-spike IgG correlated with neutralization of the delta variant (r = .62, p < .0001). Median neutralization titer for WM BTKi (0) was lower than HC (40, p < .0001) for early-clade and delta. All cohorts had functional T cell responses. Median anti-spike IgG decreased 4-fold from second to third dose (p = .004). Only 5 of 29 poor initial responders assessed after third vaccination demonstrated seroconversion and improvement in neutralization activity, including to the omicron variant.

Consensus guidelines for the diagnosis and management of invasive aspergillosis, 2021.

Invasive aspergillosis (IA) in haematology/oncology patients presents as primary infection or breakthrough infection, which can become refractory to antifungal treatment and has a high associated mortality. Other emerging patient risk groups include patients in the intensive care setting with severe respiratory viral infections, including COVID-19. These guidelines present key diagnostic and treatment recommendations in light of advances in knowledge since the previous guidelines in 2014. Culture and histological-based methods remain central to the diagnosis of IA. There is increasing evidence for the utility of non-culture methods employing fungal biomarkers in pre-emptive screening for infection, as well as for IA diagnosis when used in combination. Although azole resistance appears to be uncommon in Australia, susceptibility testing of clinical Aspergillus fumigatus complex isolates is recommended. Voriconazole remains the preferred first-line antifungal agent for treating primary IA, including for extrapulmonary disease. Recommendations for paediatric treatment broadly follow those for adults. For breakthrough and refractory IA, a change in class of antifungal agent is strongly recommended, and agents under clinical trial may need to be considered. Newer immunological-based imaging modalities warrant further study, while surveillance for IA and antifungal resistance remain essential to informing the relevance of current treatment recommendations.

Integrated electronic health record facilitates a safer and more efficient rural outreach haematology service.

BACKGROUND: Rural Australian oncology patients are known to have inferior mortality rates compared to metropolitan patients, possibly related to access to appropriate healthcare services and treatments. Electronic systems improve the safety of chemotherapy administration and allow easily accessible patient information and data collection. AIMS: To integrate the electronic healthcare delivery systems at a metropolitan hospital and a rural outreach haematology clinic to facilitate streamlined and safe outpatient care. METHODS: The MOSAIQ v2.64(Elekta) system utilised at St Vincent's Hospital was introduced at a linked rural outreach haematology clinic. The two separate comprehensive practice management systems incorporating all patient information were consolidated into one, becoming accessible from both sites. RESULTS: The electronic systems were successfully integrated between the two sites in October 2017. Electronic chemotherapy prescribing at the Griffith site is now guided by inbuilt, pharmacist-reviewed protocols thereby improving the safety and flexibility of remote prescribing. The centralised electronic health record has improved streamlined care during patient transitions between the two hospitals with enhanced continuity of documentation and management. Increases in total clinic patients and appointment numbers are demonstrable since implementation, and sustained during the COVID-19 pandemic. CONCLUSION: The present study provides a novel example of the successful implementation of a centralised electronic healthcare record and chemotherapy prescribing system in a haematology setting shared between a metropolitan service and a rural outreach hospital clinic. This has positive implications for the safety and efficiency of healthcare delivery at the rural site applicable to all linked rural Australian clinics, as well as allowing data collection to assist future planning of the service.

Update on inherited disorders of haemostasis and pregnancy.

Inherited bleeding disorders have the potential to cause bleeding complications during pregnancy, childbirth and the postpartum period as well as effect fetal outcomes. There is an evolving understanding of the need for specialised and individualised care for affected women during these times. The aim for each patient is to estimate the risk to mother, fetus and neonate; to implement measures to minimise these risks; and to anticipate complications and develop contingencies for these scenarios. This includes accurate diagnosis, preconceptual care, prenatal diagnostic options, antenatal care, delivery and postpartum care as well as care of an affected neonate. An understanding of the physiologic haemostatic changes associated with pregnancy as well as the scope of defects, inheritance and management of inherited bleeding disorders is paramount when caring for these women. Collaborative and prospective management in conjunction with haematology services underpins the approach advocated. This review draws on the available literature, and outlines the principles of care for women with inherited bleeding disorders before, during and after pregnancy, as well as their babies, based on both available data and collective clinical experience.

Post-transplant lymphoproliferative disease in heart and lung transplantation: Defining risk and prognostic factors.

BACKGROUND: Heart and lung transplant recipients have among of the highest incidence rates of post-transplant lymphoproliferative disease (PTLD). Despite this, there is a paucity of data specific to this group. We collated data on heart, lung and heart-lung transplant recipients with PTLD to identify disease features and prognostic factors unique to this group of patients. METHODS: Seventy cases of PTLD were identified from a single institution (41 heart, 22 lung, 6 heart-lung and 1 heart-kidney transplant) from 1984 to 2013. Demographics, immunosuppression, treatment, response, complications and survival data were analyzed. Uni- and multivariate Cox regression analyses were performed to identify prognostic factors. RESULTS: The incidence of PTLD was 7.59% in heart-lung, 5.37% in heart and 3.1% in lung transplant recipients. Extranodal disease (82%) with diffuse large B-cell lymphoma (72%) was the most common presentation. Bone marrow involvement (13%) and central nervous system disease (3%) were uncommon. Heart transplant recipients had later onset of PTLD (>1 year post-transplant), with less allograft involvement, compared with lung and heart-lung recipients. Poor prognostic markers were bone marrow involvement (HR 6.75, p < 0.001) and serum albumin <30 g/liter (HR 3.18, p = 0.006). Improved survival was seen with a complete response within 3 months of treatment (HR 0.08, p < 0.001). Five-year overall survival was 29%. CONCLUSION: This analysis is the largest to date on PTLD in heart and lung transplant recipients. It provides a detailed analysis of the disease in this group of patients and identifies unique prognostic features to aid risk stratification and guide treatment allocation.

Antenatal haemoglobinopathy screening: Patterns within a large obstetric service. Working towards a standard of care.

BACKGROUND: Antenatal screening can predict clinically significant haemoglobinopathies, however in Australia, practices are not standardised and are evolving as the population becomes more ethnically diverse. This study describes antenatal screening practices in a large Australian laboratory/antenatal service. METHODS: Data were collected retrospectively on consecutive antenatal haemoglobin electrophoresis over 16 months and correlated with obstetric data, obtained from the local obstetric database. RESULTS: 462 patients were included, with an average gestation of 25.8 weeks. 'Pregnancy' was the most common stated indication, with absent indication/clinical information in 8%. Gestational age was documented in 54%. In 15%, no contact details of the referrer were documented and partner screening was traceable in only 25 cases (5.4%). In 82% of cases, no abnormalities were detected. Beta thalassemia trait was the most common positive result. Only 52% of patients had recent iron studies. The mean haemoglobin was 111.6 g/L and mean cell volume was 80.5 fl at the time of testing. Ethnicity was documented on the request form in 3%. After Australasia, the most common ethnicity of patients was South East Asia and the Middle East. CONCLUSION: Referral patterns in our health service are diverse and reflect our changing population and care practices. Detailed guidelines are required and we propose a comprehensive algorithm for general use where selective screening is practiced within an Australasian population or one with similar demographics.