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.

Integrated molecular and immunological features of human T-lymphotropic virus type 1 infection and disease progression to adult T-cell leukaemia or lymphoma.

The human T-lymphotropic virus type 1 (HTLV-1) retrovirus infects 10-20 million people globally, with endemic regions in southwestern Japan, the Caribbean basin, Africa, and central Australia. HTLV-1 is associated with lifelong infection and immune suppression, resulting in a range of serious sequalae, including adult T-cell leukaemia or lymphoma (ATLL) in 5% of cases. To date, there are no preventive or curative treatments for HTLV-1 and treatment outcomes for ATLL remain generally poor. Depending on the disease subtype, overall survival is 8-55 months. Recent advancements in the past decade have identified genetic, molecular, and immunological events occurring throughout the lives of individuals infected with HTLV-1 and of those who progress to ATLL. In addition, updated guidelines for clinical management have been published. With the aim of focusing research efforts on the development of treatments for both HTLV-1 infections and ATLL, we have conceptualised a four-step disease model for HTLV-1-associated ATLL: (1) viral exposure, (2) establishment of chronic infection, (3) cellular transformation and evolution, and (4) disease presentation and management. For each stage we describe the clinical features, molecular and immunological factors involved, potential biomarkers of disease progression, and the therapeutic applicability of individual targets. We also discuss emerging concepts and novel treatment approaches. Our hope is that this model will promote research interest and guide the testing of new treatments for this neglected virus and its associated rare cancer.

A low-dose rituximab regimen for first-line treatment of acquired haemophilia A.

A low-dose rituximab regimen for first-line treatment of acquired haemophilia A. INTRODUCTION: Acquired haemophilia A (AHA) is a rare disease caused by the development of autoantibodies against FVIII. Diagnosis involves confirmation of FVIII deficiency and the presence of an inhibitor via the Bethesda assay. Severe bleeding is often managed with bypassing agents such as recombinant factor VII. This is then followed by eradication of the inhibitor with immunosuppression which typically includes a corticosteroid backbone. AIM: Review the current management and outcomes of AHA in Queensland, Australia. Determine the incidence, demographics and clinical characteristics of AHA patients. METHODS: Retrospective case series of AHA diagnosed between May 2014 and August 2018. Data were derived from the Australian Bleeding Disorders Registry and state-wide pathology database. Data collection proforma was completed by the treating haematologist and reviewed/compiled centrally. RESULTS: 24 patients were identified (incidence 1 in 1.27 million). The median age was 76.5 years. Median follow-up was 20 months. Index bleed was atraumatic and skin/soft tissue in the majority of patients. Recombinant FVIIa was the most commonly used haemostatic therapy and effective in 85% of patients. Immunosuppression and steroid usage were uniform. Upfront second agent was used in 75% of patients and was most commonly rituximab. 87.5% of patients achieved a complete remission in a median time of 48 days. Low-dose rituximab was frequently used and equally as efficacious as standard dose. CONCLUSION: Immunosuppression with combination therapy, notably rituximab, appears to be non-inferior and has a favourable side effect profile.

Acquired haemophilia and haemostatic control with recombinant porcine factor VIII: case series.

BACKGROUND: Acquired haemophilia A (AHA) is a rare acquired bleeding disorder that can present with life-threatening bleeding. AIMS: To describe recent Australian use of recombinant porcine factor VIII (rpFVIII) replacement therapy as a haemostatic agent in patients with acquired haemophilia. METHODS: Four patients with acquired haemophilia treated in three different institutions around Australia in the past 12 months were included in the study. Haemostatic efficacy of Obizur (Takeda) was assigned by the treating haematologist according to previously published criteria. RESULTS: Six bleeds were treated with rpFVIII, three of which were initially refractory to treatment with recombinant VIIa. rpFVIII was rated efficacious in 100% of bleeds by 24 h. rpFVIII loading dose was 100 U/kg (100-120 U kg-1 ) and this increased the factor VIII level (via one-stage FVIII assay) from <1-1.2% to 54-306% taken 0.5-1.5 h post-infusion. Subsequent doses ranged from 40 to 60 U/kg twice daily or daily for 3 to 13 days. No rpFVIII related adverse events occurred. Three of the four patients achieved complete remission and were weaned from immunosuppression. One patient died prior to achieving partial remission, secondary to an arterial ischaemic event. CONCLUSION: This case series demonstrates that recombinant porcine FVIII is efficacious to treat acute bleeds in acquired haemophilia, including in those who are refractory to bypassing agents. Doses of rpFVIII were able to be titrated based on FVIII level and clinical response.