Characterising vincristine-induced peripheral neuropathy in adults: symptom development and long-term persistent outcomes.

BACKGROUND: Decades following the introduction of vincristine as treatment for haematological malignancies, vincristine-induced peripheral neuropathy (VIPN) remains a pervasive, untreatable side-effect. However there remains a gap in understanding the characteristics of VIPN in adults. This study presents a comprehensive phenotyping of VIPN. METHODS: Adult patients (n = 57; age = 59.8 ± 14.6) were assessed cross-sectionally following completion of vincristine (months post treatment = 16.3 ± 15.6, cumulative dose = 7.6 ± 4.4), with a subset of 20 patients assessed prospectively during treatment. Patient reported measures (EORTC-QLQ-CIPN20, R-ODS) were used to profile symptoms and disability. Neurological assessment was undertaken using the Total Neuropathy Score and nerve conduction studies. Sensory threshold and fine motor tasks were also undertaken. Comparisons of data between timepoints were calculated using paired-sample t tests or Wilcoxon matched-pairs signed-rank test. Comparisons between outcome measures were calculated with independent sample t tests or Mann-Whitney U tests for non-parametric data. RESULTS: The majority of patients developed VIPN by mid-treatment (77.8%, 7.0 ± 3.3 weeks post baseline) with the prevalence remaining stable by end-of-treatment (75%, 8.1 ± 1.7 weeks post mid-treatment). By 3 months post-completion, 50% of patients still reported VIPN although there were significant improvements on neurological grading and functional assessment (P < 0.05). VIPN presented with sensorimotor involvement in upper and lower limbs and was associated with decreased sensory and motor nerve amplitudes, reduced fine-motor function and increased disability. CONCLUSION: VIPN in adults presents as a sensorimotor, upper- and lower-limb neuropathy that significantly impacts disability and function. Neuropathy recovery occurs in a proportion of patients; however, VIPN symptoms may persist and continue to affect long-term quality of life.

VEXAS syndrome: lessons learnt from an early Australian case series.

VEXAS is a newly recognised adult-onset autoinflammatory syndrome resulting from a somatic mutation in the UBA1 gene. Herein, we present three cases of VEXAS syndrome in Sydney, Australia, that capture key clinical features and the refractory nature of the condition. They highlight the importance of multidisciplinary collaboration for early diagnosis and the need for new therapeutic options.

Balance Deficits and Functional Disability in Cancer Survivors Exposed to Neurotoxic Cancer Treatments.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) persists after treatment in up to 40% of cancer survivors and has been linked with increased balance deficits, disabilities, and fall occurrences. This study aimed to comprehensively assess the links between CIPN, balance deficits, and functional disability and to inform the development of clinical screening tools for patients at risk of these events. PATIENTS AND METHODS: A total of 190 cancer survivors exposed to neurotoxic chemotherapies (age, 57 ± 13 years; average time from completion of neurotoxic therapy, 12 ± 11 months) attended a neurology research clinic for a single cross-sectional assessment of patient-reported and objective CIPN, standing balance in 4 conditions of increasing difficulty, and functional disability. RESULTS: Most patients (68%) reported CIPN symptoms at assessment. Symptomatic patients displayed increased functional disability (F=39.4; P<.001) and balance deficits (F=34.5; P<.001), with degree of balance impairments consistent with a healthy elderly population (age ≥65 years) reporting multiple falls over the subsequent year. Increasing CIPN severity correlated with increasing functional disability (clinically assessed R2=0.46; patient-reported R2=0.49; P<.001) and balance deficits (clinically assessed R2=0.41; patient-reported R2=0.30; P<.001). A 5-factor model of key independent correlates-patient-reported numbness/tingling, weakness, and balance deficit; age; and vibration perception-was strongly linked to balance deficits (R2=0.46; P<.001) and functional disability (R2=0.56; P<.001). CONCLUSIONS: This study confirms links between increasing CIPN severity and increasing balance deficits and functional disability using comprehensive CIPN assessment methodology. The extent of balance deficits in patients with CIPN underscores the functional consequences of neurotoxicity. A 5-factor model provides a foundation for clinical screening tools to assess balance deficits and functional disability in patients exposed to neurotoxic chemotherapies.

Optimizing Clinical Screening for Chemotherapy-Induced Peripheral Neuropathy.

CONTEXT: Efficient and accurate clinical screening for treatment-related toxicities is a critical component of optimal patient management. A number of alternate screening tools for chemotherapy-induced peripheral neuropathy (CIPN) have been proposed in response to demonstrated limitations with standard clinical screening, although their relative diagnostic value is unclear. OBJECTIVES: The aim of this study is to evaluate the relative construct validity and discriminant properties of available CIPN screening tools. METHODS: Patients treated with known potentially neurotoxic therapies underwent CIPN evaluation at one or multiple timepoints (N = 316 patients; age = 56 ± 13 years). At each testing session (N = 644 testing sessions), patients were evaluated using screening tools and comprehensive CIPN assessments. Comprehensive assessments were clinician-rated (Total Neuropathy Score, reduced) or patient-reported outcome (PRO; Functional Assessment of Cancer Therapy-Gynecologic Oncology Group/Neurotoxicity questionnaire). Similarly, screening tools were clinician-rated (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE]) or PRO (Patient Neurotoxicity Questionnaire, PRO-CTCAE). RESULTS: Analyses revealed moderate-to-high correlations between screening tools and comprehensive assessments (0.55 ≤ rho ≤ 0.75; P < 0.001) and similar discriminant properties across screening tools (P > 0.01). Screening tool grading corresponding to clinically significant (grade 2/3) vs. low-grade (grade 0/1) CIPN would correspond to greater ratings of CIPN severity by more comprehensive assessments in a predicted 77%-91% of cases (c-statistic = 0.77-0.91; P < 0.01). CONCLUSIONS: PRO screening tools provide adequate CIPN screening while avoiding potential biases demonstrated to limit currently used clinician-rated screening tools. Addition of a brief objective test did not add value to PRO screening. Up to 23% of patients would be misidentified through screening, providing quantitative evidence of the limitations of available screening tools. More extensive CIPN evaluations are critical in patients at risk of serious neurotoxicity.

Concomitant Prostate Carcinoma and Follicular Lymphoma: "Flip-Flop" Appearances on PSMA and FDG PET/CT Scans.

We report a case of a 75-year-old man with concomitant metastatic prostate cancer and progressive follicular lymphoma and the utility of molecular imaging in differentiating these 2 conditions. F-FDG PET/CT can offer accurate staging in many cancers, although its role in prostate cancer is limited. The role of F-DCFPyL (PSMA) PET/CT in prostate cancer is evolving and has been demonstrated to have a higher sensitivity than conventional bone scan and CT scan. Together, FDG and PSMA PET/CT studies may offer a noninvasive approach to individually characterize concomitant malignancies, aiding optimization of management and follow-up.

An autoanti-Kp b immunoglobulin M that simulates antigen suppression.

BACKGROUND: Patients may present with an antibody against a blood group antigen, a negative direct antiglobulin test (DAT), and a null phenotype. Typically, this represents an alloantibody in a null individual. However, on occasion, the antibody disappears coincident with conversion to a positive red blood cell (RBC) phenotype. This has been called antigen loss, antigen suppression, or weakened antigenicity. Herein, a unique serologic profile that mimics this pattern, when in fact antigen loss did not occur, is described. STUDY DESIGN AND METHODS: RBCs and serum were analyzed using a gel microtyping system and flow cytometry. Genomic DNA was amplified by polymerase chain reaction and sequenced. RESULTS: Initially, an anti-Kp(b) was detected in MTS gel, RBCs typed K-k-Kp(b-), and the DAT was negative for immunoglobulin G (IgG). Later, the anti-Kp(b) disappeared and RBCs phenotyped as K-k+Kp(b+). Analysis of initial specimens by flow cytometry identified an immunoglobulin M (IgM) anti-Kp(b) with a positive IgM-specific DAT; eluates contained an anti-Kp(b) at immediate spin. Supporting the presence of the Kell glycoprotein, RBCs agglutinated with anti-Js(b). Sequencing showed homozygosity for Kp(b) with no mutations surrounding the Kp(b) polymorphism. CONCLUSION: In antigen loss, antibody masking is excluded by a negative DAT. However, because typical DAT reagent does not detect IgM, such reasoning was inaccurate in the current case. In addition, an anti-Kp(b) resulted in RBCs typing k-, even though no anti-k was detected. Overall, this case suggests that an IgM may mask adjacent epitopes and illustrates the potential to mistake a non-IgG autoantibody as antigen loss.

Aggressive natural killer cell leukemia presenting with hemophagocytic lymphohistiocytosis.

Aggressive natural killer cell leukemia (ANKL) is a very rare condition and when reported occurs almost exclusively in adults. We report a pediatric case of ANKL that presented with hemophagocytic syndrome, preceding the onset of leukemia by 12 weeks. Clinical and laboratory findings are discussed, along with morphology, immunophenotyping and cytogenetics, as well as the association with Epstein-Barr virus (EBV). This case is noteworthy for the expression of CD8 on the malignant cells, the cytogenetic findings that include abnormalities of chromosomes 6 and 7, as well as the age of the patient.

Treatment of acquired factor X inhibitor by plasma exchange with concomitant intravenous immunoglobulin and corticosteroids.

A patient with spontaneous hemorrhage from multiple body sites was found to have markedly prolonged international normalized ratio (INR) and activated partial thromboplastin times (aPTT) with incomplete correction of aPTT on mixing studies using normal plasma. The cause of this severe hemorrhage was due to a specific factor X inhibitor. No underlying or associated diseases were found. Initial treatment with fresh frozen plasma, vitamin K, and recombinant activated factor VII (rFVIIa) was unsuccessful. However, therapy utilizing plasma exchange with concomitant intravenous immunoglobulin and corticosteroids resulted in a rapid and sustained normalization of factor X levels with a clinical hemostatic response.