The Cardiovascular Event Risk Associated with Tyrosine Kinase Inhibitors and the Lipid Profile in Patients with Chronic Myeloid Leukemia.

BACKGROUND: Second- and third-generation tyrosine kinase inhibitors (TKIs) are now available to treat chronic-phase chronic myeloid leukemia (CP-CML) in the first and second line. However, vascular adverse events (VAEs) have been reported for patients with CML treated with some TKIs. METHODS: We retrospectively evaluated the cumulative incidence (CI) and cardiovascular risk for 210 patients included in the Canarian Registry of CML. RESULT: With a mean follow up of 6 years, 19/210 (9.1%) patients developed VAEs, all of whom presented at least one cardiovascular risk factor at diagnosis. The mean time to VAE presentation was 54 months from the start of TKI treatment. We found a statistically significant difference between the CI for nilotinib-naïve vs. nilotinib-treated patients (p = 0.005), between dasatinib-naïve and dasatinib-treated patients (p = 0.039), and for patients who received three lines of treatment with first-line imatinib vs. first-line imatinib (p < 0.001). From the multivariable logistic regression analyses, the Framingham risk score (FRS) and patients with three lines of TKI with first-line imatinib were the only variables with statistically significant hazard ratios for VAE development. Significant increases in HDL-C and total cholesterol may also be predictive for VAE. CONCLUSIONS: In conclusion, it is important to estimate the cardiovascular risk at the diagnosis of CML as it can help determine whether a patient is likely to develop a VAE during TKI treatment.

Recovery of uninvolved heavy/light chain pair immunoparesis in newly diagnosed transplant-eligible myeloma patients complements the prognostic value of minimal residual disease detection.

Immunoparesis (IP) in multiple myeloma (MM) patients can be measured by classic assessment of immunoglobulin (Ig) levels or by analysis of the uninvolved heavy/light chain pair of the same immunoglobulin (uHLC) by the Hevylite® assay. In this study we evaluate the prognostic value of recovery from IP measured by classic total Ig and uHLC assessment in newly diagnosed MM transplant-eligible (NDMM-TE) patients with intensive treatment and its association with Minimal Residual Disease (MRD). Patients were enrolled and treated in the PETHEMA/GEM2012MENOS65 trial and continued in the PETHEMA/GEM2014MAIN trial. Total Ig (IgG, IgA and IgM) and uHLC were analyzed in a central laboratory at diagnosis, after consolidation treatment and after the first year of maintenance. MRD was analyzed by next generation flow cytometry after consolidation (sensitivity level 2x10-6). We found no differences in progression free survival (PFS) between patients who recovered and patients who didn't recover from IP after consolidation when examining classic total Ig and uHLC. However, after the first year of maintenance, in contrast to patients with classic IP, patients with recovery from uHLC IP had longer PFS than patients without recovery, with hazard ratio of 0.42 (CI95% 0.21-0.81; p=0.008). Multivariate analysis with Cox proportional-hazards regression models confirmed recovery from uHLC IP after the first year of maintenance as an independent prognostic factor for PFS, with an increase in C-statistic of 0.05 (-0.04-0.14; p<0.001) when adding uHLC IP recovery. Moreover, we observed that MRD status and uHLC IP recovery affords complementary information for risk stratification. In conclusion, recovery from uHLC IP after one year of maintenance is an independent prognostic factor for PFS in NDMM-TE patients who receive intensive treatment. Immune reconstitution, measured as recovery from uHLC IP, provides complementary prognostic information to MRD assessment.

Brain-Derived Neurotrophic Factor (BDNF) and First-Episode Psychosis. A longitudinal one-year prognosis study.

The brain-derived neurotrophic factor (BDNF) is a neurotrophin that has been linked to the schizophrenia neurodevelopmental hypothesis.

Factor neurotrófico derivado del cerebro y primeros episodios psicóticos. Estudio pronóstico de un año / Brain-derived neurotrophic factor (bdnf) and first-episode psychosis. a longitudinal one-year prognosis study

Introducción. El factor neurotrófico derivado del cerebro(BDNF) es una neurotrofina que se ha relacionado con la hipótesis del neurodesarrollo de la esquizofrenia. Varios estudios confirman que los niveles de BDNF en el primer episodio psicótico (PEP) son más bajos que en los controles sanos. Sin embargo, los datos al respecto de la evolución de los niveles tras un PEP y el valor pronóstico de dichos niveles son controvertidos. Método. Se compararon los niveles séricos de BDNF al ingreso de 28 pacientes hospitalizados con PEP con 28controles sanos. También se midió el BDNF al momento del alta, a los tres, seis, nueve y doce meses. Los niveles de BDNF se presentan en ng/ml. Se buscó correlación con la sintomatología psicótica medida con la Escala de Síndrome Positivo y Negativo (PANSS) y se evaluó en valor pronóstico de los niveles basales para predecir mala funcionalidad (medida por la Evaluación Global del Funcionamiento) y/o recaída, así como el diagnóstico ulterior de un trastorno psicótico crónico. Resultados. Al ingreso, los niveles de BDNF de los pacientes fueron significativamente más bajos que los niveles de los controles sanos (18,52±4,51 vs. 26,55±3,22, p<0,001). Al altalos niveles de PEP aumentaron hasta niveles de los controles sanos (25,95±3,96 vs. 26,55±3,22, p=0,539). En las siguientes determinaciones, los niveles de BDNF en PEP disminuyeron, alcanzando los valores de ingreso y siendo significativamente más bajos que los controles sanos y los niveles al alta(pacientes: tres meses: 19,68±3,88; seis meses: 19,02±4,13;nueve meses: 17,64±5,24; doce meses:17,51±3,45 vs. controles sanos: 26,55±3,22, todos p<0,001). Se encontró una correlación negativa entre el BDNF al ingreso y las puntuaciones de la subescala de síntomas negativos de la PANSS con una tendencia hacia la significación (r=-0,303, p=0,093). ... (AU)

Introduction. The brain-derived neurotrophic factor(BDNF) is a neurotrophin that has been linked to the schizophrenia neurodevelopmental hypothesis. Several studiesconfirm that the BDNF levels in first-episode psychosis (FEP)are lower than in healthy controls (HC). However, data aboutevolution of BDNF levels after a FEP and about the prognostic value of these levels are controversial. Method. Serum BDNF levels at admission of 28 inpatients with FEP were compared with 28 HC. BDNF was also measured at discharge, three, six, nine and twelve months. BDNF levels are presented in ng/ml. We looked for correlation of BDNF levels with the psychotic symptomatology measuredwith the Positive and Negative Syndrome Scale (PANSS) andalso the prognostic value of basal levels was evaluated topredict poor functionality (measured by the Global Assessment of Functioning) and/or relapse, as well as the subsequent diagnosis of a chronic psychotic disorder. Results. At admission, patients BDNF levels were significantly lower than HC levels (18.52±4.51 vs. 26.55±3.22,p<0.001). At discharge FEP levels increase until HC levels(25.95±3.96 vs. 26.55±3.22, p=0,539). Upon the following determinations, BDNF FEP levels decreased, reaching the admission values, and being significantly lower than the HC andthe levels at discharge (patients: three months: 19.68±3.88;six months: 19.02±4.13; nine months: 17.64±5.24; twelve months: 17.51±3.45 vs. HC: 26.55±3.22, all p<0.001). A negative correlation was found between admission BDNF levels and the PANSS negative symptoms subscale score with a trend towards significance (r=-0.303, p=0.093). BDNF levels at admission of patients with por functionality and/orrelapse at 12 months were lower than BDNF levels of patients with goof functionality and without relapse, this difference had a trend towards significance. (15.38±4.72 vs.19.57±4.06; p=0.071). (AU)

Toxicity of Asciminib in Real Clinical Practice: Analysis of Side Effects and Cross-Toxicity with Tyrosine Kinase Inhibitors.

(1) Background: Despite the prognostic improvements achieved with tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML), a minority of patients still fail TKIs. The recent introduction of asciminib may be a promising option in intolerant patients, as it is a first-in-class inhibitor with a more selective mechanism of action different from the ATP-competitive inhibition that occurs with TKIs. Therefore, our goal was to analyze toxicities shown with asciminib as well as to study cross-toxicity with previous TKIs. (2) Methods: An observational, multicenter, retrospective study was performed with data from 77 patients with CML with therapeutic failure to second-generation TKIs who received asciminib through a managed-access program (MAP) (3) Results: With a median follow-up of 13.7 months, 22 patients (28.5%) discontinued treatment: 32% (7/22) due to intolerance and 45% (10/22) due to resistance. Fifty-five percent of the patients reported adverse effects (AEs) with asciminib and eighteen percent grade 3-4. Most frequent AEs were: fatigue (18%), thrombocytopenia (17%), anemia (12%), and arthralgias (12%). None of the patients experienced cardiovascular events or occlusive arterial disease. Further, 26%, 25%, and 9% of patients required dose adjustment, temporary suspension, or definitive discontinuation of treatment, respectively. Toxicities under asciminib seemed lower than with prior TKIs for anemia, cardiovascular events, pleural/pericardial effusion, diarrhea, and edema. Cross-toxicity risk was statistically significant for thrombocytopenia, anemia, neutropenia, fatigue, vomiting, and pancreatitis. (4) Conclusion: Asciminib is a molecule with a good safety profile and with a low rate of AEs. However, despite its new mechanism of action, asciminib presents a risk of cross-toxicity with classical TKIs for some AEs.

Imatinib plasma levels in patients with chronic myeloid leukaemia under routine clinical practice conditions.

INTRODUCTION: The addition of imatinib to the therapeutic arsenal for chronic myeloid leukaemia (CML) has changed the natural course of the disease, in such a way that it is now considered a chronic pathology. However, to achieve therapeutic success, it is necessary to reach adequate plasma concentrations to ensure efficacy and safety.In this study, we aimed to evaluate the plasma concentration of imatinib, analysing its influence on effectiveness and safety in patients with CML. METHODS: We performed a descriptive, multicentre study in which imatinib plasma levels from patients diagnosed with CML between 2019-2020 were analysed. An optimal therapeutic range of 750-1500 ng/mL was established for the stratification of patients, according to their minimum plasma concentrations measured at steady state (Cssmin). RESULTS: A total of 28 patients were included, of whom only 39.3% (n = 11) showed Cssmin within the therapeutic range. 100% of patients with Cssmin >750 ng/mL achieved an optimal molecular response, while only 50% of patients with Cssmin <750 ng/mL achieved an optimal molecular response (p = 0.0004). The toxicity rate was 36.4% for patients with Cssmin >1500 ng/mL and 5.9% for those with Cssmin <1500 ng/mL (p = 0.039). CONCLUSIONS: This study aimed to describe the correlation between the toxicity and effectiveness of imatinib according to its Cssmin in routine clinical practice conditions. Based on our findings, it would be certainly justified to monitor patient plasma concentrations of imatinib on a daily routine basis in our hospitals.

Intramuscular Anti-D treatment for immune thrombocytopenia: A single centre experience.

Intravenous Anti-Rhesus-D immunoglobulin (Anti-D) is a first-line treatment option for immune thrombocytopenia in non-splenectomised and RhD-positive patients. In this report, we retrospectively review our experience with intramuscular (IM) Anti-D treatment in 74 adult patients between 1990 and 2018. We found that 73% of patients showed a response; almost all of them had complete responses (68.9%), and 26% achieved complete responses sustained at least 6 months after treatment discontinuation. [Correction added on 02 December 2022, after first online publication: In the preceding sentence, '(68.89%)' has been corrected to '(68.9%)' in this version.] No significant side effects were observed with no cases of acute haemolysis or anaemia reported. We conclude from this study that IM Anti-D is an effective and safe treatment for immune thrombocytopenia.

Treatment with daratumumab in patients with relapsed/refractory AL amyloidosis: a multicentric retrospective study and review of the literature.

Management of patients with relapsed or refractory (R/R) AL amyloidosis is complex. Some initial reports have shown positive results with daratumumab in heavily pre-treated AL amyloidosis patients. In this retrospective multicentric study, 38 patients (mean age 64 ± 9 years) with R/R AL amyloidosis treated with daratumumab were included. Cardiac and renal involvement was present in 76 and 74% of patients, and 42% had ≥3 organs involved. Median number of previous lines of therapy was 2 (range 1-8). Overall hematological response was 72%, including 28% complete responses. The median time to first hematological response was 2 weeks. A high-quality response (≥very good partial response) was obtained in 65% of patients who had never achieved such depth of response previously. Hematological responses were more frequent among patients receiving daratumumab as second-line therapy compared to subsequent therapies (92 vs. 61%). Cardiac and renal organ response rates were 37 and 59%. At 12 months, overall and progression-free survival were 59% (95%CI: 0.36-0.77) and 52% (95%CI: 0.29-0.70), respectively. Daratumumab is a safe and effective drug in the treatment of R/R AL amyloidosis and should be considered early in the course of the disease.

Biopsia de médula ósea en el linfoma de Hodgkin. Comparación con la PET-TC en 65 pacientes / Bone marrow trephine biopsy in Hodgkin's lymphoma. Comparison with PET-CT scan in 65 patients

Fundamento y objetivo: Comparar la biopsia de médula ósea (BMO) y la PET/CT en la detección de la afectación medular en el linfoma de Hodgkin. Material y métodos: Análisis retrospectivo de 65 pacientes con realización de ambas pruebas en la estadificación inicial o en recaída con especial atención al patrón de la PET/CT. Resultados: En 3 pacientes (4,6%) la BMO mostró afectación medular, siendo la PET/CT positiva en todos ellos: 2 con patrón difuso+multifocal y uno solo difuso. En 11 pacientes más (total 14/65, 21%) se estimó que había afectación medular ósea por PET/CT al tener un consumo de médula ósea superior al hepático. El patrón fue focal único en 2 casos, multifocal en 5, difuso en 3 casos y difuso+multifocal en uno. En estos últimos 4 casos la BMO mostró una mielopatía inespecífica. Conclusiones: La PET/CT detecta todos los casos con BMO afectada y muchos que se escapan a la biopsia; sin embargo, cuando el patrón de captación es difuso puede ser por afectación o por hiperplasia reactiva y en esos casos debería mantenerse la BMO (AU)

Background and objectives: To compare bone marrow biopsy (BMB) and PET/CT in detecting bone marrow involvement in Hodgkin's lymphoma. Material and methods: Retrospective analysis of 65 patients with both tests in the initial staging or in relapse with special attention to the PET/CT uptake pattern. Results: In 3 patients (4.6%), the BMB showed bone marrow involvement with the PET/CT being positive in them all: 2 with diffuse+multifocal pattern and one diffuse only. In 11 additional patients (total 14/65, 21%), bone marrow involvement was diagnosed by PET/CT because bone marrow uptake was above hepatic one. The pattern was focal only in 2 cases, multifocal in 5, diffuse in 3 and diffuse+multifocal in one. In these last 4 cases the BMB showed an unspecific myelopathy. Conclusions: PET/CT detects all cases with BMB affected and many that escape to biopsy, however when the uptake pattern is diffuse it could be by involvement or reactive hyperplasia and in those cases the BMB should be done (AU)

Bone marrow trephine biopsy in Hodgkin's lymphoma. Comparison with PET-CT scan in 65 patients. / Biopsia de médula ósea en el linfoma de Hodgkin. Comparación con la PET-TC en 65 pacientes.

BACKGROUND AND OBJECTIVES: To compare bone marrow biopsy (BMB) and PET/CT in detecting bone marrow involvement in Hodgkin's lymphoma MATERIAL AND METHODS: Retrospective analysis of 65 patients with both tests in the initial staging or in relapse with special attention to the PET/CT uptake pattern. RESULTS: In 3 patients (4.6%), the BMB showed bone marrow involvement with the PET/CT being positive in them all: 2 with diffuse+multifocal pattern and one diffuse only. In 11 additional patients (total 14/65, 21%), bone marrow involvement was diagnosed by PET/CT because bone marrow uptake was above hepatic one. The pattern was focal only in 2 cases, multifocal in 5, diffuse in 3 and diffuse+multifocal in one. In these last 4 cases the BMB showed an unspecific myelopathy. CONCLUSIONS: PET/CT detects all cases with BMB affected and many that escape to biopsy, however when the uptake pattern is diffuse it could be by involvement or reactive hyperplasia and in those cases the BMB should be done.

Outbreak of vancomycin-resistant enterococcus on a haematology ward: management and control.

Vancomycin-resistant enterococci (VRE) infections and outbreaks are still infrequent in Spain. A six-month outbreak, which took place in a haematology ward, its control and management are described in this study. A total of 22 patients were colonised and two bloodstream infections occurred during this period. Even though there were two waves of new colonised patients, a multidisciplinary approach, quick interventions and enhanced infection control policies were required in order to control this outbreak.

Thrombopoietin receptor agonist switch in adult primary immune thrombocytopenia patients: A retrospective collaborative survey involving 4 Spanish centres.

OBJECTIVE: To describe the reasons for and result of thrombopoietin receptor agonists (TPO-RA) switching in adult immune thrombocytopenia (ITP) patients of 4 Spanish centres. METHODS: We retrospectively analysed all patients who received sequential treatment with both TPO-RA between 2010 and 2015 recording clinical and biological parameters. RESULTS: Twenty-six patients were included; 17 received first romiplostim and 9 received first eltrombopag. Reasons for switching were inefficacy (n = 10), patient preference (n = 8), side effects (n = 5) and excessive platelet count fluctuation (n = 3). When the switch was due to inefficacy, 100% of patients who received romiplostim first and 66% who received eltrombopag first responded to the second drug. It is significant that none of the patients who received romiplostim first reached the maximum recommended dose before switching. When the change was due to patient preference or because of side effects, 100% of the patients responded to both TPO-RA. Three patients changed from romiplostim to eltrombopag due to platelet count fluctuation; one did not respond and the fluctuation persisted in the remaining 2 patients. We also found 4 sustained remissions after administering the second TPO-RA, 2 of these with inefficacy of the first drug. CONCLUSION: TPO-RA switching is a feasible strategy in different scenarios with high probability of success.