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.

Long-term outcomes of corticosteroid graft versus host disease prophylaxis in peripheral blood allogeneic haemopoietic stem cell transplant: a comparative cohort analysis.

BACKGROUND: Corticosteroids (CSs) have previously been incorporated into graft versus host disease (GVHD) prophylaxis regimens for bone marrow (BM) and haemopoietic stem cell transplant (HSCT). AIMS: To assess the impact of prophylactic CS in HSCT using peripheral blood (PB) stem cells. METHODS: Patients were identified from three HSCT centres receiving a first PB-HSCT between January 2011 and December 2015 from a fully human leukocyte antigen (HLA)-matched sibling or unrelated donor for acute myeloid leukaemia or acute lymphoblastic leukaemia. To enable meaningful comparison, patients were divided into two cohorts. RESULTS: Cohort 1 included only myeloablative-matched sibling HSCT, where the only variation in GVHD prophylaxis was the addition of CS. In these 48 patients, there were no differences in GVHD, relapse, non-relapse mortality, overall survival or GVHD-relapse-free-survival (GRFS) at 4 years after transplant. Cohort 2 included the remaining HSCT recipients, where one group received CS-prophylaxis and the non-CS group received an antimetabolite, ciclosporin and anti-T-lymphocyte globulin. In these 147 patients, those receiving CS-prophylaxis experienced higher rates of chronic GVHD (71% vs 18.1%, P < 0.001) and lower rates of relapse (14.9% vs 33.9%, P = 0.02). Those receiving CS-prophylaxis had a lower 4-year GRFS (15.7% vs 40.3%, P = 0.002). CONCLUSIONS: There does not appear to be a role for adding CS to standard GVHD prophylaxis regimens in PB-HSCT.

Outcomes of human immunodeficiency virus-associated Burkitt lymphoma and diffuse large B-cell lymphoma treated in Australia: A report from the Australasian Lymphoma Alliance.

Antiretroviral therapy (ART) has improved outcomes for human immunodeficiency virus-associated non-Hodgkin lymphoma (HIV-NHL). This is an analysis of 44 patients with HIV with Burkitt lymphoma (HIV-BL) and diffuse large B-cell lymphoma (HIV-DLBCL) treated in Australia over a 10-year period (2009-2019) during the ART and rituximab era. At HIV-NHL diagnosis, the majority of presenting patients had adequate CD4 counts and undetectable HIV viral load <50 copies/mL. More than 80% of patients received chemotherapy with curative intent, rituximab, and concurrent ART with chemotherapy (immunotherapy). R-CODOX-M/IVAC or R-Hyper-CVAD (55%) were most commonly used in HIV-BL. CHOP (58%) was the most commonly used chemotherapy backbone for HIV-DLBCL, although 45% of patients received more intense chemotherapy regimens. Overall, 93% of patients who received curative therapy completed their intended course. The 2-year progression-free survival (PFS) and overall survival (OS) for the HIV-BL cohort was 67% and 67% respectively. The 2-year PFS and OS for the HIV-DLBCL cohort was 77% and 81% respectively. Treatment related mortality was 5%. In all, 83% of patients achieved a CD4 count of >0.2 ×109 /L 6 months after the end of treatment. Current Australian practice favours the treatment of HIV-BL and HIV-DLBCL similarly to the HIV-negative population with the use of concurrent ART, achieving outcomes comparable to the HIV-negative 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.

Efficacy of bortezomib, cyclophosphamide and dexamethasone in cardiac AL amyloidosis.

Cardiac light chain (AL) amyloidosis is a condition with a very poor prognosis. We report a retrospective analysis comparing the traditional melphalan and dexamethasone protocol with cyclophosphamide, bortezomib and dexamethasone in late-stage cardiac AL amyloidosis. The primary end points were overall survival and haematological response. Both regimens provided meaningful responses in this difficult to treat patient group.

Potential intravenous immunoglobulin-induced optic disc edema.

Purpose: To report a case of recurrent and bilateral optic disc edema following intravenous immunoglobulin (IVIG) administration. Observations: A 46 year-old woman received IVIG on 3 separate occasions over 7 years for Non-Hodgkin's Lymphoma (NHL) and each time developed headaches and transient visual disturbance, and was subsequently found to have bilateral optic disc swelling. Lumbar puncture confirmed raised cerebrospinal fluid (CSF) opening pressure and there was resolution following treatment with oral acetazolamide (Diamox). Conclusions and importance: To our knowledge there is no literature on papilledema following administration of IVIG. This case is pertinent for physicians treating patients with IVIG who develop headache, transient visual disturbance and optic disc edema.

Clinical characteristics and prognosis of cardiac amyloidosis defined by mass spectrometry-based proteomics in an Australian cohort.

BACKGROUND: Cardiac amyloidosis has a very poor prognosis, but it is the nature of the involved precursor protein that ultimately dictates treatment and survival. AIM: Definitively characterise the amyloid subtype by mass spectrometry (MS) in an Australian cohort of patients with cardiac amyloidosis. METHODS: We report the clinical characteristics and survival of 47 cardiac amyloid patients across two Australian centres including 39 patients evaluated for definitive amyloid subtype utilising laser microdissection and tandem mass spectrometry. RESULTS: A quarter (n = 12) of patients were classified as wild-type transthyretin amyloidosis (ATTRwt), 33 patients as light or heavy chain amyloidosis (AL or AH) and two as hereditary mutant transthyretin amyloidosis. Greater left ventricular hypertrophy (interventricular septum 22 vs 15 mm; P = 0.005) and history of cardiac arrhythmia (75% vs 31%; P = 0.016) were significantly associated with ATTRwt patients compared with AL/AH patients. AL patients demonstrated significantly shorter median survival compared with ATTRwt patients (3.5 vs 37 months; P = 0.007). New York Heart Association class III-IV symptoms or plasma cells ≥10% at diagnosis, were the only independent predictors of worse survival in AL patients on multivariate analysis. CONCLUSIONS: AL amyloidosis accounted for 68% of our cohort of patients with cardiac amyloidosis while ATTR accounted for 26%. In the era of novel therapies for both AL amyloid and ATTR, identification of the correct amyloid subtype is essential in making therapeutic decisions and providing accurate prognostic information to patients. Laser microdissection and tandem mass spectrometry plays an important role in identifying amyloid subtype, particularly in complex cases.

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.

Prospective phase II clinical trial of autologous haematopoietic stem cell transplant for treatment refractory multiple sclerosis.

BACKGROUND: Autologous haematopoietic stem cell transplantation (AHSCT) has been explored as a therapeutic intervention in multiple sclerosis (MS) over the last two decades; however, prospective clinical trials of the most common myeloablative conditioning regimen, BEAM, are limited. Furthermore, patient selection, optimal chemotherapeutic regimen and immunological changes associated with disease response require ongoing exploration. We present the outcomes, safety and immune reconstitution (IR) of patients with active, treatment refractory MS. METHODS: This study was a single-centre, phase II clinical trial of AHSCT for patients with active relapsing remitting (RRMS) and secondary progressive MS (SPMS). Patients underwent AHSCT using BEAM (carmustine, etoposide, cytarabine, melphalan)+antithymocyte globulin chemotherapeutic regimen. OUTCOMES: The primary outcome was event-free survival (EFS); defined as no clinical or radiological relapses and no disability progression. Multiparameter flow cytometry was performed for evaluation of post-transplant IR in both MS and lymphoma patients receiving the same chemotherapy regimen. RESULTS: Thirty-five patients (20 RRMS, 15 SPMS) completed AHSCT, with a median follow-up of 36 months (range 12-66). The median Expanded Disability Status Scores (EDSS) was 6 (2-7) and patients had failed a median of 4 (2-7) disease modifying therapies. 66% failed treatment with natalizumab. EFS at 3 years was 60%, (70% RRMS). Sustained improvement in EDSS was seen in 15 (44%) of patients. There was no treatment-related mortality. A sustained rise in CD39+ T regulatory cells, immunosuppressive CD56hi natural killer cells and ablation of proinflammatory mucosal-associated invariant T cells was seen for 12 months following AHSCT in patients with MS. These changes did not occur in patients with lymphoma receiving the same chemotherapy for AHSCT. CONCLUSIONS: The EFS in our MS cohort is significantly greater than other high-efficacy immunosuppressive therapies and similar to other AHSCT studies despite a more heavily pretreated cohort. TRIAL REGISTRATION NUMBER: ACTRN12613000339752.

Impact of Allogeneic Hematopoietic Stem Cell Transplantation on the HIV Reservoir and Immune Response in 3 HIV-Infected Individuals.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) can lead to significant changes to the HIV reservoir and HIV immune responses, indicating that further characterization of HIV-infected patients undergoing HSCT is warranted. METHODS: We studied 3 patients who underwent HSCT after either reduced intensity conditioning or myeloablative conditioning regimen. We measured HIV antigens and antibodies (Ag/Ab), HIV-specific CD4 T-cell responses, HIV RNA, and DNA in plasma, peripheral blood mononuclear cells, isolated CD4 T cells from peripheral blood, and lymph node cells. The patients remained on antiretroviral therapy throughout the follow-up period. RESULTS: All patients have been in continued remission for 4-6 years post-HSCT. Analyses of HIV RNA and DNA levels showed substantial reductions in HIV reservoir-related measurements in all 3 patients, changes in immune response varied with pronounced reductions in 2 patients and a less dramatic reduction in 1 patient. One patient experienced unexpected viral rebound 4 years after HSCT. CONCLUSIONS: These 3 cases highlight the substantial changes to the HIV reservoir and the HIV immune response in patients undergoing allogeneic HSCT. The viral rebound observed in 1 patient indicates that replication competent HIV can re-emerge several years after HSCT despite these marked changes.

Early treatment intensification with R-ICE and 90Y-ibritumomab tiuxetan (Zevalin)-BEAM stem cell transplantation in patients with high-risk diffuse large B-cell lymphoma patients and positive interim PET after 4 cycles of R-CHOP-14.

In the treatment of diffuse large B-cell lymphoma, a persistently positive [18F]fluorodeoxyglucose positron emission tomography (PET) scan typically carries a poor prognosis. In this prospective multi-center phase II study, we sought to establish whether treatment intensification with R-ICE (rituximab, ifosfamide, carboplatin, and etoposide) chemotherapy followed by 90Y-ibritumomab tiuxetan-BEAM (BCNU, etoposide, cytarabine, and melphalan) for high-risk diffuse large B-cell lymphoma patients who are positive on interim PET scan after 4 cycles of R-CHOP-14 (rituximab, cyclophosphamide, doxorubicin, and prednisone) can improve 2-year progression-free survival from a historically unfavorable rate of 40% to a rate of 65%. Patients received 4 cycles of R-CHOP-14, followed by a centrally-reviewed PET performed at day 17-20 of cycle 4 and assessed according to International Harmonisation Project criteria. Median age of the 151 evaluable patients was 57 years, with 79% stages 3-4, 54% bulk, and 54% International Prognostic Index 3-5. Among the 143 patients undergoing interim PET, 101 (71%) were PET-negative (96 of whom completed R-CHOP), 42 (29%) were PET-positive (32 of whom completed R-ICE and 90Y-ibritumomab tiuxetan-BEAM). At a median follow up of 35 months, the 2-year progression-free survival for PET-positive patients was 67%, a rate similar to that for PET-negative patients treated with R-CHOP-14 (74%, P=0.11); overall survival was 78% and 88% (P=0.11), respectively. In an exploratory analysis, progression-free and overall survival were markedly superior for PET-positive Deauville score 4 versus score 5 (P=0.0002 and P=0.001, respectively). Therefore, diffuse large B-cell lymphoma patients who are PET-positive after 4 cycles of R-CHOP-14 and who switched to R-ICE and 90Y-ibritumomab tiuxetan-BEAM achieved favorable survival outcomes similar to those for PET-negative R-CHOP-14-treated patients. Further studies are warranted to confirm these promising results. (Registered at: ACTRN12609001077257).

Adrenal tumours: how to establish malignancy.

Adrenal masses are commonly found in the course of abdominal investigations and present diagnostic challenges. The foremost issue is whether the mass is the cause of the symptoms being investigated. Additional important clinical questions are: (1) is the adrenal mass benign or malignant and (2) whether the adrenal mass is functional or non-functional? We present a case of a 48-year-old man with severe abdominal pain. Imaging revealed a very large adrenal mass. Differential diagnostic procedures were performed and a diagnosis of primary adrenal lymphoma, an extremely rare cause of adrenal malignancy, was made. He proceeded to chemotherapy with cyclical cyclophosphamide, doxorubicin, etoposide and prednisolone, in addition to rituximab. This case illustrates the importance of establishing the nature of adrenal masses, to rapidly facilitate appropriate treatment.

Length of stay variations between rural and urban patients with acute myeloid leukemia: a case-matched study.

BACKGROUND: Keeping patients in hospital longer than medically necessary is costly and occupies resources that could be better utilised. If patients from regional areas remain in hospital longer because of logistical issues such as transport and accommodation, then there is an argument for establishing or expanding appropriate medical services for rural areas. However, if the length of stay (LOS) for rural and urban patients is similar, it could be surmised that current logistic services appropriately meet demand. METHODS: This study reviews the cases of 40 patients with acute myeloid leukemia. This disease was selected as patients are generally required to travel to a metropolitan hospital for treatment, regardless of location. Twenty patients resided within the Sydney metropolitan area and 20 lived in rural New South Wales. Each of the 20 metropolitan patients were case-matched (1:1) with 20 rural patients with reference to sex, specific acute myeloid leukemia subtype (by World Health Organisation ICD-10 classification), and age. RESULTS: Following statistical non-parametric (t-test) analysis, rural and urban medians were found to be very similar with a high t-value and small mean (urban median=29, rural median=29.5, t-value=0.722, m=-0.95, s.d.=15.236, two-tailed P=0.789, 95% CI=-7.89, 5.99). This demonstrates that there was no statistically significant difference between mean LOS for rural or urban patients after case-matching, a conclusion supported by qualitative analysis of the data. CONCLUSION: Logistical issues are therefore unlikely to keep rural patients with AML in hospital beyond their immediate medical treatment. What is known about this topic? A United States-based study found that LOS in hospital for rural patients with human immunodeficiency virus was one-third longer than for urban patients across each of the 6 years analysed (from 1998 to 2003). However it was noted that after adjusting for covariates such as age and sex, differences between LOS for rural and urban residents were not of statistical significance. What does this paper add? This paper provides evidence that current services are utilised appropriately by demonstrating that rural and urban patients spend on average the same amount of time in hospital. Factors such as lack of transport or accommodation are therefore unlikely to keep rural patients in hospital beyond their immediate medical requirements. This paper adds to the limited research base within the Australian context. What are the implications for practitioners? It appears that support organisations adequately fulfil the needs of rural patients in the discharge process. LOS does not appear to correlate with the distance of residence from hospital. Practitioners should continue to support and encourage such support networks.