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Summary: Arsenic trioxide is an essential component of therapy for acute promyelocytic leukaemia (APL) and is currently dosed on actual body weight with no upper limit. Arsenic‐induced neurotoxicity is a well‐recognised complication; however, there is uncertainty about its relationship to arsenic dose and obesity. We conducted a large multicentre retrospective study of 487 patients with APL treated with arsenic‐based therapy across 23 sites in Australia from 2008 to 2023. The primary outcome was incidence of neurotoxicity, and secondary outcomes included relationship of neurotoxicity to obesity and cumulative arsenic dose. Any‐grade neurotoxicity occurred in 113 (23%) patients, predominantly peripheral neuropathy (91%). Most events were grade 1–2 severity (85%), with grade 3 events in 12% and grade 4–5 in 3%. The incidence of neurotoxicity increased with BMI (non‐obese: 16%, obesity class I: 25%, obesity class II–III: 41%; p < 0.001). On univariable analysis, obesity class I (OR 1.81, p = 0.036), obesity class II–III (OR 3.93, p < 0.001), weight >100 kg (OR 2.72, p < 0.001), daily arsenic trioxide dose >15 mg (OR 5.05, p < 0.001) and cumulative induction dose >500 mg (OR 3.95, p < 0.001) were all significantly associated with neurotoxicity. Obesity class II–III and induction dose >500 mg remained significant on multivariable analysis. Our study highlights the strong association between BMI, arsenic trioxide dose and neurotoxicity. Pre‐emptive dose reductions should be considered for obese patients receiving high doses of arsenic. [ABSTRACT FROM AUTHOR]

High-dose cytarabine (HDAC) is conventionally delivered on days 1, 3 and 5 (HDAC-135) as acute myeloid leukemia (AML) post-remission therapy. Limited data is available on alternative HDAC schedules such as HDAC-123 (given consecutively for 3 days). We retrospectively compared the tolerability and efficacy of HDAC-135 and HDAC-123 delivered in sequential cohorts of adult AML patients. Seventy-three patients were included with 33% aged ≥60 years. HDAC-123 was associated with faster hematological recovery, reduced bacteremia and shorter hospitalization. No differences in safety profile or hematological recovery were seen between patients ≥60 years and <60 years receiving HDAC-123 except a shorter median time to neutrophil count recovery after cycle 1 in the latter group. Three patients (8%) receiving HDAC-123, all aged <60 years, required a change in schedule to HDAC-135 due to transient cytarabine-related side effects. HDAC-123 consolidation was well-tolerated by AML patients, including those ≥60 years, and associated with tangible reductions in resource utilization. [ABSTRACT FROM AUTHOR]

Variant acute promyelocytic leukaemia with novel NAB2::RARA fusion shows clinical all-trans retinoic acid and arsenic trioxide sensitivity Acute promyelocytic leukaemia (APL) is characterised by reciprocal translocation between the promyelocytic leukaemia ( I PML i ) gene at chromosome 15q24 and the retinoic acid receptor alpha ( I RARA i ) gene at chromosome 17q21. (E) Metaphase FISH using PML:RARA dual fusion translocation probe (Metasystems), which is negative for PML:RARA fusion but displays 3 RARA (green) signals, indicating the presence of a variant RARA translocation. [Extracted from the article]

Multi‐parametric flow cytometry (MFC) has a well‐established role in measurable residual disease (MRD) monitoring in patients with B‐lymphoblastic leukemia (B‐ALL). However, the optimal time‐point (TP) for early MRD testing and associated prognostic impact remain undefined in adult B‐ALL patients receiving Hyper‐CVAD induction chemotherapy. To evaluate the utility of MRD analysis after one cycle (TP1) in comparison to MRD analysis after two cycles (TP2) of induction treatment with Hyper‐CVAD chemotherapy, we studied 49 adult B‐ALL patients over a 10‐year period (2010–2020) who had available bone marrow samples for morphological and MFC MRD assessments at the two separate TPs. Median times to TP1 and TP2 relative to start of treatment were 21 and 45 days, respectively. When censored at transplant, achievement of MRD negativity at TP1 was not associated with a statistically significant improvement in either event‐free survival (EFS) (p =.426) or overall survival (OS) (p =.335) when compared to patients with MRD positivity. In contrast, achieving MRD negativity at TP2 was associated with a statistically significant improvement in both EFS (p = ·005) and OS (p =.047) over patients who remained MRD positive. Multivariate analysis demonstrated that KMT2A‐rearrangement and MRD positivity at TP2 were the only significant predictors of outcome, correlating with worse EFS and OS. Therefore, in the absence of residual morphologic disease, MRD analysis after one cycle of Hyper‐CVAD induction chemotherapy did not provide additional benefit with regard to risk stratification or correlation with survival outcomes when compared to MRD testing after two cycles of Hyper‐CVAD in adult B‐ALL patients. [ABSTRACT FROM AUTHOR]

Thrombopoietin (TPO)-receptor agonists have heralded a paradigm shift in the treatment of refractory immune thrombocytopenia (ITP). Reactive thrombocytosis has been described as a secondary effect of such therapies. However, the phenomenon of extreme thrombocytosis with morphology mimicking a myeloproliferative neoplasm (MPN) followed by fatal thromboembolism is unusual in this setting. Caution is required in the diagnosis of refractory ITP as well as TPO-receptor agonist dosing in such cases. [ABSTRACT FROM AUTHOR]

Thrombopoietin (TPO)-receptor agonists have heralded a paradigm shift in the treatment of refractory immune thrombocytopenia (ITP). Reactive thrombocytosis has been described as a secondary effect of such therapies. However, the phenomenon of extreme thrombocytosis with morphology mimicking a myeloproliferative neoplasm (MPN) followed by fatal thromboembolism is unusual in this setting. Caution is required in the diagnosis of refractory ITP as well as TPO-receptor agonist dosing in such cases. [ABSTRACT FROM AUTHOR]

Although reactive large granular lymphocytosis due to diverse etiologies is not an uncommon finding in clinical practice, isolated natural killer (NK)‐cell lymphocytosis is unusual and its association with immunotherapy has not been described thus far. We provide a brief analysis of a patient with this unique hematological corollary of immunotherapy being increasingly used in the setting of both solid organ and hematological malignancies, and highlight this as an additional differential to consider in the diagnosis of large granular lymphocytosis. Also explored is the importance of recognizing and monitoring the potential hematological manifestations of experimental immunotherapies, as well as the possible implicated mechanisms of action. It is hypothesized that quantification of large granular lymphocytosis may potentially be used as a surrogate marker of therapeutic efficacy in this setting. [ABSTRACT FROM AUTHOR]

Despite the absence of previous thrombosis, these clinicopathological features were consistent with triple-positive antiphospholipid syndrome (APS) and bilateral adrenal haemorrhage. Although uncommon, there have been reports of bilateral adrenal haemorrhage as the first presentation of APS.[[4]] It is possible that the patient's recent antecedent viral illness triggered his initial thrombotic manifestation of APS. Keywords: Thrombosis EN Thrombosis 250 251 2 04/04/23 20230401 NES 230401 Clinical record A 39-year-old man presented to the emergency department with a three-day history of anorexia and severe abdominal pain, which was worse in the right lower quadrant. [Extracted from the article]

The article presents a case study of a young Australian-born 28 year old gentleman was diagnosed with a stage 1 non-seminomatous testicular cancer, for which he underwent a left radical orchidectomy followed by a single cycle of adjuvant chemotherapy with bleomycin, etoposide and cisplatin. The article discuss the appearance of bilateral swollen, erythematous tonsils with exudates, associated with bilateral tender cervical lymphadenopathy.