The influence of immunodeficiency, disease features, and patient characteristics on survival in plasmablastic lymphoma.

ABSTRACT: Plasmablastic lymphoma (PBL) is a rare and aggressive non-Hodgkin lymphoma associated with immunodeficiency, characterized by uncertain treatment approaches and an unfavorable prognosis. We conducted a multicenter, international, retrospective cohort study, aiming to characterize the clinical features, risk factors, and outcomes of patients with PBL. Data were collected from 22 institutions across 4 countries regarding patients diagnosed with PBL between 1 January 1999 and 31 December 2020. Survival risk factors were analyzed using both univariate and multivariate regression models. Overall survival (OS) was calculated using Kaplan-Meier statistics. First-line treatment regimens were stratified into standard- and higher-intensity regimens, and based on whether they incorporated a proteasome inhibitor (PI). A total of 281 patients (median age, 55 years) were included. Immunodeficiency of any kind was identified in 144 patients (51%), and 99 patients (35%) had HIV-positive results. The 5-year OS for the entire cohort was 36% (95% confidence interval, 30%-42%). In multivariate analysis, inferior OS was associated with Epstein-Barr virus-negative lymphoma, poor performance status, advanced stage, and bone marrow involvement. In an independent univariate analysis, the international prognostic index was associated with OS outcomes. Neither immunosuppression nor HIV infection, specifically, influenced OS. Among patients treated with curative intent (n = 234), the overall response rate was 72%. Neither the intensity of the treatment regimen nor the inclusion of PIs in first-line therapy was associated with OS. In this large retrospective study of patients with PBL, we identified novel risk factors for survival. PBL remains a challenging disease with poor long-term outcomes.

Death from mantle cell lymphoma limits sequential therapy, particularly after first relapse: Patterns of care and outcomes in a series from Australia and the United Kingdom.

Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma characterised by a heterogeneous clinical course. Patients can often receive sequential treatments, yet these typically yield diminishing periods of disease control, raising questions about optimal therapy sequencing. Novel agents, such as chimeric antigen receptor T-cell therapies and bispecific antibodies, show promise in relapsed MCL, but are often reserved for later treatment lines, which may underserve patients with aggressive disease phenotypes who die early in the treatment journey. To assess the problem of patient attrition from lymphoma-related death limiting sequential treatment, we performed a multicentre retrospective cohort analysis of 389 patients treated at Australian and UK centres over a 10-year period. Deaths from MCL increased after each treatment line, with 7%, 23% and 26% of patients dying from uncontrolled MCL after first, second and third lines respectively. Patients with older age at diagnosis and early relapse after induction therapy were at particular risk of death after second-line treatment. This limitation of sequential treatment by lymphoma-related death provides support for the trial of novel therapies in earlier treatment lines, particularly in high-risk patient populations.

Infection risk and antimicrobial prophylaxis in bendamustine-treated patients with indolent non-Hodgkin lymphoma: An Australasian Lymphoma Alliance study.

Infection and lymphopenia are established bendamustine-related complications. The relationship between lymphopenia severity and infection risk, and the role of antimicrobial prophylaxis, is not well described. This multicentre retrospective study analysed infection characteristics and antimicrobial prophylaxis in 302 bendamustine-treated indolent non-Hodgkin lymphoma patients. Lymphopenia (<1 × 109 /L) was near universal and time to lymphocyte recovery correlated with cumulative bendamustine dose. No association between lymphopenia severity and duration with infection was observed. Infections occurred in 44% of patients (50% bacterial) with 27% hospitalised; 32% of infections occurred ≥3 months post bendamustine completion. Infection was associated with obinutuzumab and/or maintenance anti-CD20 therapy, prior therapy and advanced stage. Twenty-four opportunistic infections occurred in 21 patients: ten varicella zoster virus (VZV), seven herpes simplex virus (HSV), one cytomegalovirus, one progressive multifocal leucoencephalopathy, one nocardiosis, one Pneumocystis jiroveci pneumonia (PJP) and three other fungal infections. VZV/HSV and PJP prophylaxis were prescribed to 42% and 54% respectively. Fewer VZV/HSV infections occurred in patients receiving prophylaxis (HR 0.14, p = 0.061) while PJP prophylaxis was associated with reduced risk of bacterial infection (HR 0.48, p = 0.004). Our study demonstrates a significant infection risk regardless of lymphopenia severity and supports prophylaxis to mitigate the risk of early and delayed infections.

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.

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.

Clinical consequences of the extremely rare anti-PP1Pk isoantibodies in pregnancy: a case series and review of the literature.

BACKGROUND: The absence of the red cell antigens P, P1 and Pk , known as 'p', represents an extremely rare red cell phenotype. Individuals with this phenotype spontaneously form anti-PP1Pk isoantibodies, associated with severe haemolytic transfusion reactions, recurrent spontaneous abortion and haemolytic disease of the fetus and newborn (HDFN). METHODS: We report a series of four successful pregnancies in three women with anti-PP1Pk isoantibodies, one complicated by HDFN, another by intrauterine growth restriction, all managed supportively. We also review the literature regarding the management of pregnancy involving anti-PP1Pk isoimmunization. RESULTS: The literature surrounding anti-PP1Pk in pregnancy is limited to a very small number of case reports. The majority report management with therapeutic plasma exchange (TPE) with or without intravenous immunoglobulin. The relationship between titre and risk of pregnancy loss remains unclear, though a history of recurrent pregnancy loss appears important. Although a positive cord blood direct antiglobulin test is frequently noted, clinically significant HDFN appears uncommon, though possible. CONCLUSION: Early initiation of TPE in high risk patients should be strongly considered. If possible, pregnancies should be managed in a high-risk obstetric or maternal fetal medicine service. The fetus should be monitored closely with interval fetal ultrasound and middle cerebral artery peak systolic volume Doppler to screen for fetal anaemia. Timely sourcing of compatible blood products is likely to be highly challenging, and both directed and autologous donation should be contemplated where appropriate. The International Red Cell Donor Panel may also provide access to compatible products.

Successful treatment of CMV, EBV, and adenovirus tissue infection following HLA-mismatched allogeneic stem cell transplant using infusion of third-party T cells from multiple donors in addition to antivirals, rituximab, and surgery.

Viral infections, principally cytomegalovirus, Epstein Barr virus (EBV) and adenovirus, are a leading cause of morbidity and mortality after allogeneic stem cell transplantation. The use of systemic antivirals is limited by limited efficacy and organ toxicities. Inability to clear infection is exacerbated by transplant-related immunosuppression and prophylaxis or treatment of acute graft versus host disease. We report the first patient to clear three serious viral infections after stem cell transplant using third-party donor partially human leukocyte antigen (HLA) matched virus-specific cytotoxic T cells. The patient, a 53 year old female with transplanted for relapsed leukemia, with severe graft versus host disease received five T cell infusions from three separate donors that ultimately cleared serious systemic infections with cytomegalovirus and adenovirus, and an EBV-driven lymphoma. Systemic antivirals had resulted in failed clinical responses. Use of repeated infusions of partially HLA matched virus-specific T cells from banks containing cryopreserved cells should be strongly considered in transplant recipients with single or multiple refractory viral infections.

Qualitative study of nuclear medicine physicians' perceptions of positron emission tomography/computed tomography in pregnant patients with cancer.

Staging using positron emission tomography/computed tomography (PET/CT) is standard of care in many cancers that occur most frequently in pregnancy, particularly lymphoma. While expert guidelines generally recommend against PET/CT in pregnant women, there is emerging evidence that likely absorbed foetal doses in pregnancy are relatively low, and as such in certain circumstances PET/CT may be acceptable when balancing benefit and risk. We conducted a qualitative survey of nuclear medicine physicians in Australia and New Zealand to assess practice and attitudes with respect to PET/CT in pregnancy women, finding that most respondents considered PET/CT in pregnancy may be an appropriate modality in carefully selected clinical contexts with appropriate modifications. It is important to continue to define the role of PET/CT in pregnancy into the future, particularly as this imaging modality has emerged as the standard of care in staging and response assessment for many cancers.

COVID-19 vaccination in haematology patients: an Australian and New Zealand consensus position statement.

Australia and New Zealand have achieved excellent community control of COVID-19 infection. In light of the imminent COVID-19 vaccination roll out in both countries, representatives from the Haematology Society of Australia and New Zealand and infectious diseases specialists have collaborated on this consensus position statement regarding COVID-19 vaccination in patients with haematological disorders. It is our recommendation that patients with haematological malignancies, and some benign haematological disorders, should have expedited access to high-efficacy COVID-19 vaccines, given that these patients are at high risk of morbidity and mortality from COVID-19 infection. Vaccination should not replace other public health measures in these patients, given that the effectiveness of COVID-19 vaccination, specifically in patients with haematological malignancies, is not known. Given the limited available data, prospective collection of safety and efficacy data of COVID-19 vaccination in this patient group is a priority.

Australian and New Zealand consensus statement on the management of lymphoma, chronic lymphocytic leukaemia and myeloma during the COVID-19 pandemic.

The COVID-19 pandemic poses a unique challenge to the care of patients with haematological malignancies. Viral pneumonia is known to cause disproportionately severe disease in patients with cancer, and patients with lymphoma, myeloma and chronic lymphocytic leukaemia are likely to be at particular risk of severe disease related to COVID-19. This statement has been developed by consensus among authors from Australia and New Zealand. We aim to provide supportive guidance to clinicians making individual patient decisions during the COVID-19 pandemic, in particular during periods that access to healthcare resources may be limited. General recommendations include those to minimise patient exposure to COVID-19, including the use of telehealth, avoidance of non-essential visits and minimisation of time spent by patients in infusion suites and other clinical areas. This statement also provides recommendations where appropriate in assessing indications for therapy, reducing therapy-associated immunosuppression and reducing healthcare utilisation in patients with specific haematological malignancies during the COVID-19 pandemic. Specific decisions regarding therapy of haematological malignancies will need to be individualised, based on disease risk, risks of immunosuppression, rates of community transmission of COVID-19 and available local healthcare resources.

Second Primary Cancers in People With HIV/AIDS: A National Data Linkage Study of Incidence and Risk Factors.

BACKGROUND: Evidence regarding the characteristics of second primary cancer (SPC) in people living with HIV (PLWHIV) is limited. SETTING: We performed a national population-based data linkage study to determine the incidence and risk factors of SPC in PLWHIV in Australia between 1982 and 2012. METHODS: We conducted a probabilistic data linkage study to compare the incidence of SPC over time, defined using HIV treatment eras, for SPCs related to oncogenic viral infection in comparison with non-infection-related SPCs. Risk factors considered included age at diagnosis of cancer, sex, HIV exposure modality, and CD4 + count. RESULTS: Of 29,383 individuals diagnosed with HIV, 3123 individuals who developed a first primary cancer were included in the analysis. Among them, 229 cases of SPC were identified across 27,398 person-years of follow-up. The most common SPCs were non-Hodgkin lymphomas (n = 71, 31%). The incidence of SPC overall did not change over time; however, there was an increase in individuals diagnosed with HIV in later eras ( P trend =0.001). The incidence of non-infection-related SPC increased over time and was associated with older age ( P trend = 0.005) and the acquisition of HIV in later eras ( P trend <0.001). Conversely, the incidence of infection-related SPC decreased ( P trend <0.001), but this was no longer significant after adjustment for age ( P trend = 0.14). CONCLUSIONS: The risk of SPC in PLWHIV in Australia remains high, with a temporal increase observed in non-infection-related cancer, likely due to aging of the population. Optimal screening and prevention strategies for SPC in PLWHIV are increasingly important.

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.

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).