The clinical features, management and outcomes of lymphoma in pregnancy: A multicentre study by the Australasian Lymphoma Alliance.

Lymphoma in pregnancy (LIP) presents unique clinical, social and ethical challenges; however, the evidence regarding this clinical scenario is limited. We conducted a multicentre retrospective observational study reporting on the features, management, and outcomes of LIP in patients diagnosed between January 2009 and December 2020 at 16 sites in Australia and New Zealand for the first time. We included diagnoses occurring either during pregnancy or within the first 12 months following delivery. A total of 73 patients were included, 41 diagnosed antenatally (AN cohort) and 32 postnatally (PN cohort). The most common diagnoses were Hodgkin lymphoma (HL; 40 patients), diffuse large B-cell lymphoma (DLBCL; 11) and primary mediastinal B-cell lymphoma (PMBCL; six). At a median follow up of 2.37 years, the 2- and 5-year overall survival (OS) for patients with HL were 91% and 82%. For the combined DLBCL and PMBCL group, the 2-year OS was 92%. Standard curative chemotherapy regimens were successfully delivered to 64% of women in the AN cohort; however, counselling regarding future fertility and termination of pregnancy were suboptimal, and a standardised approach to staging lacking. Neonatal outcomes were generally favourable. We present a large multicentre cohort of LIP reflecting contemporary practice and identify areas in need of ongoing research.

Chromosome microarray characterisation of chromosome arm 12p loss associated with complex molecular karyotype and recurrent adverse cytogenetic markers in multiple myeloma.

Copy number loss within chromosome 12 short arm (12p) has gained attention as an adverse cytogenetic marker in multiple myeloma. The prognostic significance and characterisation of the common minimal deleted region remains controversial between various studies with loss of CD27 proposed as the putative critical gene. We aimed to determine the frequency of 12p loss, its correlation with adverse cytogenetic markers further to define and characterise 12p deletions. Our study included a prospective cohort of 574 multiple myeloma patients referred for cytogenetic testing, including interphase fluorescence in situ hybridisation for IGH (14q32.33) translocations and chromosome microarray. Loss of 12p was detected in 54/574 (9.4%) patients and when compared with the non-12p loss group [520/574 (90.6%)], 12p loss patients demonstrated a statistically significant association with specific recurrent cytogenetic markers: complex molecular karyotypes (98.1% vs 45.2%), 1p loss (50.0% vs 20.2%), t(4;14) (20.4% vs 7.7%), 8p loss (37.0% vs 15.0%), 13/13q loss (70.4% vs 41.7%), and 17p loss (33.3% vs 6.5%). The size and location of 12p losses were heterogeneous with a common 0.88 Mb minimally deleted region that included ~9 genes from ETV6 to CDKN1B in 52/54 (~96.3%) patients but did not include CD27. Our findings support 12p loss being a secondary chromosome abnormality frequently co-occurring with adverse cytogenetic markers and complex molecular karyotypes indicative of chromosome instability.

HOW Collaborative position paper on the management of thrombocytopenia in pregnancy.

Thrombocytopenia in pregnancy is a common occurrence, affecting up to 10% of women by the time of birth. These recommendations aim to provide pragmatic guidance on the investigation, diagnosis and management of thrombocytopenia in pregnancy; including safety of neuraxial anaesthesia and precautions required for birth. Management of neonatal thrombocytopenia is also addressed. The authors are clinicians representing haematology, obstetric medicine, maternal-fetal medicine, and anaesthesia. Each author conducted a detailed literature review then worked collaboratively to produce a series of unanimous recommendations. The recommendation strength is limited by the lack of high-quality clinical trial data, and represents level C evidence.

Managing ITP and thrombocytopenia in pregnancy.

Around 1 in 10 pregnant women will develop thrombocytopenia during an otherwise unremarkable pregnancy. While the most frequent cause is gestational thrombocytopenia, a benign clinical entity which typically induces a mild platelet fall in late pregnancy, a number of important pregnancy-specific causes must be excluded, particularly pre-eclampsia and its severe form hemolysis with elevated liver enzymes and low platelets (HELLP). For women who do not have an identifiable pregnancy-related cause of thrombocytopenia, an underlying medical condition should be considered. The most common of these is immune thrombocytopenia (ITP). Management of ITP in pregnancy can prove particularly challenging. First-line treatment options are limited to intravenous immunoglobulin or corticosteroids; with a higher rate of adverse effects and a lower likelihood of response than in the non-pregnant population. The safety data for commonly employed second-line treatment options is scarce, and there is no international consensus on the optimal second-line treatment in pregnancy. Management of ITP is further complicated by the desire to attain higher platelet thresholds to facilitate the safe administration of neuraxial anesthesia and minimize the risk of postpartum hemorrhage. Finally, the risk of neonatal thrombocytopenia must be considered and appropriate precautions taken at the time of delivery.

Multiple myeloma: from diagnosis to treatment.

BACKGROUND: Multiple myeloma is characterised by the proliferation of malignant plasma cells within the bone marrow, which produce an abnormal monoclonal paraprotein and evidence of end organ damage. OBJECTIVE: Multiple myeloma can pose a diagnostic challenge and this article highlights issues in diagnosis and provides an overview of management. DISCUSSION: Multiple myeloma can present with a wide constellation of symptoms including hypercalcaemia, anaemia, renal impairment and/or bony pain. A combination of these symptoms, particularly if unexpected or unexplained, should prompt diagnostic evaluation for myeloma. Work up of plasma cell disorders involves establishing the presence of a monoclonal paraprotein, baseline bloods and radiological investigations. Haematology referral is required for bone marrow biopsy and ongoing management. Newer treatments such as the immunomodulators thalidomide or lenalidomide, or the proteasome inhibitor bortezomib, administered in combination with steroids and occasionally cytotoxic agents have improved outcomes in patients with myeloma. Autologous stem cell transplant is offered to younger patients with few comorbidities. Some patients are offered maintenance therapy with thalidomide or lenalidomide.

Recommendation on the nomenclature for anticoagulants: updated communication from the International Society on Thrombosis and Haemostasis Scientific and Standardization Commitee on the Control of Anticoagulation.

Oral anticoagulation therapy has evolved beyond vitamin K antagonists to include oral direct thrombin inhibitors and factor Xa inhibitors. Collectively known as "direct oral anticoagulants," this class of medications represents the current standard of care for the prevention and treatment of common thrombotic disorders, including atrial fibrillation and venous thromboembolism. Medications that target factors XI/XIa and XII/XIIa are currently under investigation for several thrombotic and nonthrombotic conditions. Given that these emerging medications will likely have distinct risk-benefit profiles to the current direct oral anticoagulants, may have different routes of administration, and could be used for unique clinical conditions (e.g., hereditary angioedema), the International Society on Thrombosis and Haemostasis Subcommittee on Control of Anticoagulation assembled a writing group to make recommendations on the nomenclature of anticoagulant medications. With input from the broader thrombosis community, the writing group recommends that anticoagulant medications be described by the route of administration and specific targets (e.g., oral factor XIa inhibitor).

Capturing the lived experiences of women with lymphoma in pregnancy: a qualitative study.

Lymphoma in pregnancy is a rare and challenging diagnosis that complicates ∼1:6000 pregnancies; posing a series of unique therapeutic, social, and ethical challenges to the patient, her family, and the medical professionals involved. These difficulties are compounded by the paucity of real-world data on the management of LIP, and a lack of relevant support systems for women in this setting. We conducted a retrospective multicenter qualitative study, interviewing women aged ≥18 years of age diagnosed with Hodgkin (HL) or non-Hodgkin lymphoma (NHL) during pregnancy or within 12 months postpartum, between 1 January 2009 and 31 December 2020 from 13 Australasian sites. Semi-structured telephone interviews were conducted, recorded, and analyzed using QSR Int NVivo 12 Pro (March 2020, USA) to quantify salient themes. Of the 32 women interviewed, 20 (63%) were diagnosed during pregnancy (16, 34, and 13% in the 1st, 2nd, and 3rd trimesters, respectively), while 12 (37%) were diagnosed post-partum. Women recalled that their chief concerns at diagnosis were the welfare of their child (n = 13, 41%) and a fear of dying (n = 9, 28%). Perceived diagnostic delay attributed to pregnancy was reported by 41% of participants. Other key themes were communication, educational materials, psychosocial supports, and oncofertility issues. To our knowledge this is the first report capturing the lived experiences of survivors of lymphoma during pregnancy, affording a unique opportunity to consider the management, psychosocial supports, and delivery of care to meet the needs of these women.What is the NEW aspect of your work? To our knowledge, this is the first report capturing and analyzing the healthcare experiences of survivors of Lymphoma in Pregnancy (LIP).What is the CENTRAL finding of your work? Women valued clear and empathic communication, provision of tailored educational materials, access to psychosocial supports (particularly childcare and financial supports), and timely oncofertility management in their healthcare journey.What is (or could be) the SPECIFIC clinical relevance of your work? Women's personal accounts of positive and negative experiences of LIP care provide insights into their specific concerns and needs which can shape healthcare policy and development of a specific framework for managing and supporting patients with LIP (and other cancers).

Illustrated State-of-the-Art Capsules of the ISTH 2022 Congress.

The ISTH London 2022 Congress is the first held (mostly) face-to-face again since the COVID-19 pandemic took the world by surprise in 2020. For 2 years we met virtually, but this year's in-person format will allow the ever-so-important and quintessential creativity and networking to flow again. What a pleasure and joy to be able to see everyone! Importantly, all conference proceedings are also streamed (and available recorded) online for those unable to travel on this occasion. This ensures no one misses out. The 2022 scientific program highlights new developments in hemophilia and its treatment, acquired and other inherited bleeding disorders, thromboinflammation, platelets and coagulation, clot structure and composition, fibrinolysis, vascular biology, venous thromboembolism, women's health, arterial thrombosis, pediatrics, COVID-related thrombosis, vaccine-induced thrombocytopenia with thrombosis, and omics and diagnostics. These areas are elegantly reviewed in this Illustrated Review article. The Illustrated Review is a highlight of the ISTH Congress. The format lends itself very well to explaining the science, and the collection of beautiful graphical summaries of recent developments in the field are stunning and self-explanatory. This clever and effective way to communicate research is revolutionary and different from traditional formats. We hope you enjoy this article and will be inspired by its content to generate new research ideas.

Effectiveness and safety of thromboprophylaxis with enoxaparin for prevention of pregnancy-associated venous thromboembolism.

Essentials Thromboprophylaxis is offered to women considered to be at risk from pregnancy-associated venous thromboembolism (PA-VTE) but there is a suggestion that standard doses of low-molecular-weight heparin may not be effective. We conducted a large observational cohort study reviewing maternal outcomes in women who received extended thromboprophylaxis with enoxaparin for prevention of PA-VTE. We report a low rate of breakthrough VTE in women, the majority of whom received standard doses of enoxaparin. High rates of postpartum hemorrhage are reported in our cohort. Our data do not strongly support a move to increase doses of thromboprophylaxis for prevention of PA-VTE and raise the possibility that higher doses may increase bleeding complications and limit women's access to neuraxial analgesia/anesthesia. BACKGROUND: Low-molecular-weight heparin is used to prevent pregnancy-associated venous thromboembolism (PA-VTE), but there are limited data to inform which women require thromboprophylaxis in pregnancy and debate about which low-molecular-weight heparin dose is effective and safe. AIMS: To evaluate the efficacy and rate of complications using enoxaparin for thromboprophylaxis in a cohort of women at risk of PA-VTE managed between 1999 and 2014 at National Women's Hospital, a tertiary obstetric referral center in Auckland, New Zealand. METHODS: A retrospective, observational study of women who received thromboprophylaxis with enoxaparin for prevention of PA-VTE while under the care of the obstetric or maternal fetal medicine team. RESULTS: A total of 172 pregnancies in 123 women were identified. A single daily dose of 40 mg enoxaparin was used in 94.8% of pregnancies. Two breakthrough PA-VTEs occurred (1.2% [95% confidence interval, 0.32-4.14]). Postpartum hemorrhage ≥500 mL was reported in 36.6% of births and postpartum hemorrhage ≥1000 mL in 9.3% of births. Only four women were transfused. Neuraxial analgesia/anesthesia was used in 52.4% of births, including 39.6% of vaginal births. CONCLUSION: Use of standard doses enoxaparin thromboprophylaxis in our cohort was effective at preventing PA-VTE. Neuraxial analgesia/anesthesia was used frequently during labor and birth;, using higher doses of enoxaparin may limit access to this. Postpartum hemorrhage was common and higher doses of thromboprophylaxis may increase obstetric bleeding complications. These data do not suggest an urgent need to consider higher doses of enoxaparin for thromboprophylaxis in this clinical setting.