JAKCalc: A machine-learning approach to rationalized JAK2 testing in patients with elevated hemoglobin levels.

The demand for Janus Kinase-2 (JAK2) testing has been disproportionate to the low yield of positive results, which highlights the need for more discerning test strategies. The aim of this study is to introduce an artificial intelligence application as a more rational approach for testing JAK2 mutations in cases of erythrocytosis. Test results were sourced from samples sent to a tertiary hospital's genetic laboratory between 2017 and 2023, meeting 2016 World Health Organization criteria for JAK2V617F mutation testing. The JAK2 Somatic Mutation Screening Kit was used for genetic testing. Machine learning models were trained and tested using Python programming language. Out of 458 cases, JAK2V617F mutation was identified in 13.3%. There were significant differences in complete blood count parameters between mutation carriers and non-carriers. Various models were trained with data, with the random forest (RF) model demonstrating superior precision, recall, F1-score, accuracy, and area under the receiver operating characteristic, all reaching 100%. Gradient boosting (GB) model also showed high scores. When compared with existing algorithms, the RF and GB models displayed superior performance. The RF and GB models outperformed other methods in accurately identifying and classifying erythrocytosis cases, offering potential reductions in unnecessary testing and costs.

Single agent vemurafenib or rituximab-vemurafenib combination for the treatment of relapsed/refractory hairy cell leukemia, a multicenter experience.

BACKGROUND: Hairy cell leukemia (HCL) is a rare mature B-cell malignancy that is primarily treated with purine analogues. However, relapse remains a significant challenge, prompting the search for alternative therapies. The BRAF V600E mutation prevalent in HCL patients provides a target for treatment with vemurafenib. PATIENTS AND METHODS: This multicenter retrospective study included nine patients with relapsed/refractory (R/R) HCL from six different centers. Patient data included demographics, prior treatments, clinical outcomes, and adverse events. RESULTS: Patients received different treatment regimens between centers, including vemurafenib alone or in combination with rituximab. Despite the differences in protocols, all patients achieved at least a partial response, with seven patients achieving a complete response. Adverse events were generally mild with manageable side effects. The absence of myelotoxic effects and manageable side effects make BRAF inhibitors attractive, especially for patients ineligible for purine analogues or those with severe neutropenia. CONCLUSION: Single agent vemurafenib or in combination with rituximab appears to be a promising therapeutic option for R/R HCL. Further research is needed to establish standardized treatment protocols and to investigate long-term outcomes.

Experience of Daratumumab in Relapsed/Refractory Multiple Myeloma: A Multicenter Study from Türkiye

Objective: This study aimed to evaluate patients with relapsed/refractory multiple myeloma (RRMM) who underwent daratumumab (DARA) therapy. Materials and Methods: This multicenter retrospective study included 134 patients who underwent at least two courses of DARA from February 1, 2018, to April 15, 2022. Epidemiological, disease, and treatment characteristics of patients and treatment-related side effects were evaluated. Survival analysis was performed. Results: The median age at the start of DARA was 60 (range: 35-88), with 56 patients (41.8%) being female and 48 (58.2%) being male. The median time to initiation of DARA and the median follow-up time were 41.2 (5.1-223) and 5.7 (2.1-24.1) months, respectively. The overall response rate after DARA therapy was 75 (55.9%), and very good partial response or better was observed in 48 (35.8%) patients. Overall survival (OS) and progression-free survival (PFS) for all patients were 11.6 (7.8-15.5) and 8.0 (5.1-10.9) months, respectively. OS was higher for patients undergoing treatment with DARA and bortezomib-dexamethasone (DARA-Vd) compared to those undergoing treatment with DARA and lenalidomide-dexamethasone (DARA-Rd) (16.9 vs. 8.3 months; p=0.014). Among patients undergoing DARA-Rd, PFS was higher in those without extramedullary disease compared to those with extramedullary disease (not achieved vs. 3.7 months; odds ratio: 3.4; p<0.001). The median number of prior therapies was 3 (1-8). Initiation of DARA therapy in the early period provided an advantage for OS and PFS, although it was statistically insignificant. Infusion-related reactions were observed in 18 (13.4%) patients. All reactions occurred during the first infusion and most reactions were of grade 1 or 2 (94.5%). The frequency of neutropenia and thrombocytopenia was higher in the DARA-Rd group (61.9% vs. 24.7%, p<0.001 and 42.9% vs. 15.7%, p<0.001). Conclusion: Our study provides real-life data in terms of DARA therapy for patients with RRMM and supports the early initiation of DARA therapy.

Immune Thrombotic Thrombocytopenic Purpura in Elderly Patients: The Roles of PLASMIC and French Scores

Objective: In recent years, new developments have been incorporated into daily practice in the management of immune thrombotic thrombocytopenic purpura (iTTP). In particular, clinical scoring systems could help clinicians with clinical decision-making and early recognition. However, older patients frequently present with more organ involvement and in unusual ways. The ways in which age could affect these clinical prediction scoring systems remain unclear. We evaluated the use of PLASMIC and French scores in patients over 60 years of age. Materials and Methods: We performed a retrospective cross-sectional analysis of patients over 60 years of age with a presumptive diagnosis of iTTP between 2014 and 2022 at 10 centers. We calculated PLASMIC and French scores and compared our data with a single-center analysis of younger patients presenting with thrombotic microangiopathy. Results: Our study included 30 patients over 60 years of age and a control group of 28 patients younger than 60 years. The diagnostic sensitivity and specificity of a French score of ≥1 were lower in older patients compared to the control group (78.9% vs. 100% and 18.2% vs. 57.1%, respectively). The diagnostic sensitivity and specificity of a PLASMIC score of ≥5 were 100% vs. 95% and 27.3% vs. 100% for the study group and control group, respectively. Our study showed a higher mortality rate in older patients compared to the control group (30% vs. 7.1%, p=0.043). Conclusion: For a limited number of patients (n=6), our results showed that rituximab can reduce mortality. Given that the reliability of clinical prediction scores for iTTP in older patients may be lower, more caution must be undertaken in interpreting their results.

Adherence to hemophilia patients with prophylaxis: Veritas-Pro and psychometric properties adapted to Turkish.

The Validated Hemophilia Regimen Treatment Adherence Scale-Prophylaxis (VERITAS-Pro) assesses adherence to prophylaxis treatment recommendations in hemophilia patients. This study aimed to adapt the VERITAS-Pro into Turkish and evaluate its reliability and validity. The research design used is a psychometric study. A convenience sample of 102 patients with hemophilia A or B was followed by the Aegean Adult Hemophilia and Thrombosis Center. The VERITAS-Pro was adapted to Turkish in six steps, including forward- and back-translation, committee review, and reliability and validity analysis. Based on the confirmatory factor analysis, modification indices suggested discrepancies amongst items, which were improved upon the removal of items 11 and 15. Findings from this alternative model are: χ2/df = 1.34; RMSEA = 0.05; SRMR = 0.09; and IFI = 0.92. The alternative model showed high adherence rates. Cronbach's alpha value for the Turkish version was found to be 0.83. The test-retest reliability of the Turkish scale ranged from 0.31 to 0.78. All items discriminated significantly between participants who were more adherent and those who were less adherent (t = 23.53; p<0.01). Translation of the VERITAS-Pro into local languages enables more accurate measurement of treatment adherence among people with hemophilia and facilitates cross-cultural comparison studies. According to the validity and reliability evidence obtained, the psychometric properties of the Turkish version of the VERITAS-Pro are suitable.