Arsenic-induced neurotoxicity in patients with acute promyelocytic leukaemia.

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.

The association of mobilising regimen on immune reconstitution and survival in myeloma patients treated with bortezomib, cyclophosphamide and dexamethasone induction followed by a melphalan autograft.

G-CSF only mobilisation has been shown to enhance immune reconstitution early post-transplant, but its impact on survival remains uncertain. We undertook a retrospective review of 12 transplant centres to examine overall survival (OS) and time to next treatment (TTNT) following melphalan autograft according to mobilisation method (G-CSF only vs. G-CSF and cyclophosphamide [CY]) in myeloma patients uniformly treated with bortezomib, cyclophosphamide and dexamethasone induction. Six centres had a policy to use G-CSF alone and six to use G-CSF + CY. Patients failing G-CSF only mobilisation were excluded. 601 patients were included: 328: G-CSF + CY, 273: G-CSF only. Mobilisation arms were comparable in terms of age, Revised International Staging System (R-ISS) groups and post-transplant maintenance therapy. G-CSF + CY mobilisation generated higher median CD34 + yields (8.6 vs. 5.5 × 106/kg, p < 0.001). G-CSF only mobilisation was associated with a significantly higher lymphocyte count at day 15 post-infusion (p < 0.001). G-CSF only mobilisation was associated with significantly improved OS (aHR = 0.60, 95%CI 0.39-0.92, p = 0.018) and TTNT (aHR = 0.77, 95%CI 0.60-0.97, p = 0.027), when adjusting for R-ISS, disease-response pre-transplant, age and post-transplant maintenance therapy. This survival benefit may reflect selection bias in excluding patients with unsuccessful G-CSF only mobilisation or may be due to enhanced autograft immune cell content and improved early immune reconstitution.

Hydroa Vacciniforme-Like Lymphoproliferative Disorder in an Adult Patient With Chronic Lymphocytic Leukemia.

Hydroa vacciniforme-like lymphoproliferative disorder (HV-LPD) is a rare Epstein-Barr virus (EBV)-positive T-cell lymphoproliferative disorder (LPD) which primarily affects children from Latin America and Asia. Typical features include vesicles and ulceration in sun-exposed areas which may be accompanied by systemic symptoms such as fever, lymphadenopathy and hepatosplenomegaly. We report a 73-year-old man diagnosed with HV-LPD in the context of zanubrutinib (oral Bruton tyrosine kinase (BTK)-inhibitor) treatment for chronic lymphocytic leukemia (CLL). The patient presented with slowly progressive peri-orbital edema and erythema non-responsive to topical therapies which eventually progressed to focal crusting and erosion. Prednisolone was subsequently introduced, which led to a good response in the patient's symptoms.

An unusual case of plasmablastic lymphoma presenting as dermatomyositis.

We report a rare case of aggressive plasmablastic lymphoma with an initial presentation of dermatomyositis. The challenges associated with the diagnosis and treatment approach are also highlighted in this case report.

Determinants of 6-month survival of critically ill patients with an active hematologic malignancy.

PURPOSE: This study assessed the determinants of 6-month survival of critically ill patients with an active hematologic malignancy (HM). METHODS: All patients with an active HM defined by either receiving ongoing or due to receive antineoplastic therapy, admitted to 2 tertiary intensive care units between 2010 and 2015, were included in this retrospective cohort study. RESULTS: Of the 273 patients included in the study (median age, 63[interquartile range, 54-71] years; 40.7% female), 116 (42.5%; 95% confidence interval, 36.8-48.4) died in hospital. The 6-month mortality was 56.4% (95% confidence interval, 50.5-62.2). Mechanical ventilation, intensive care unit admission source, and the type of active HM were significantly associated with hospital mortality and 6-month survival, after adjusting for severity of acute illness. The type of active HM was the most important prognostic factor, with over a 10-fold difference in 6-month survival between HM with the best and worst prognosis. In addition, recent hematopoietic stem cell transplant (<30 days) was associated with a better 6-month survival. CONCLUSION: Differences in 6-month survival between critically ill patients with different types of active HM were substantial. Recent hematopoietic stem cell transplant, severity of illness, and use of mechanical ventilation were additional important determinants of 6-month survival in patients with an active HM.