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3.
Cancers (Basel) ; 16(19)2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39409984

RESUMEN

INTRODUCTION: The growing body of evidence around sexual and gender dimorphism in medicine, particularly in oncology, has highlighted differences in treatment response, outcomes, and side effects between males and females. Differences in drug metabolism, distribution, and elimination, influenced by factors like body composition and enzyme expression, contribute to these variations. METHODS: We retrospectively analyzed data of 112 multiple myeloma (MM) patients treated with first-line high-dose chemotherapy (HDCT) with treosulfan and melphalan (TreoMel) followed by autologous stem cell transplantation (ASCT) at a single academic center between January 2020 and August 2022. We assessed response rate, progression-free survival (PFS), overall survival (OS), and toxicities in relation to gender and treosulfan exposure. RESULTS: Our analysis revealed significant gender-specific differences in treosulfan exposure. Females had higher peak levels (343.8 vs. 309.0 mg/L, p = 0.0011) and area under the curve (AUC) (869.9 vs. 830.5 mg*h/L, p = 0.0427) compared to males. Higher treosulfan exposure was associated with increased mortality in females but not in males. Females with treosulfan AUC > 900 mg*h/L had significantly shorter overall survival, while PFS was unaffected by treosulfan exposure. CONCLUSION: Our study demonstrates that female patients undergoing TreoMel HDCT have higher treosulfan exposure than males and that females with higher levels are at increased risk for toxicity and adverse outcomes. These data suggest that higher treosulfan doses do not confer a benefit in terms of better outcomes for females. Therefore, exploring lower treosulfan doses for female MM patients undergoing TreoMel HDCT may be warranted to mitigate toxicity and improve outcomes.

4.
Environ Sci Pollut Res Int ; 31(43): 55490-55506, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39231842

RESUMEN

Stockpiles containing sulfide minerals are subject to oxidation reactions when exposed to atmospheric conditions, which can result in the formation of acid mine drainage (AMD). Reactive waste rock has limited re-use potential due to the contamination risk associated with the generated drainage water. The re-use of reactive waste rock could lead to a significant reduction in the volume of waste rock as it mitigates the environmental impact of mine waste deposition. Acid mine drainage generation rate depends on sulfide weathering kinetics which are controlled by many parameters such as the mineralogy and the particle size. Fine fractions of waste rock have higher specific surface areas and degree of liberation of sulfides, resulting in greater reactivity than the coarse fractions. The objective of this research was therefore to evaluate the potential of re-use by controlling particle size using the sieving method. Two different potentially acid-generating waste rocks were divided into six fractions and subjected to both static and kinetic tests. Prediction of the geochemical behavior using static test did not consider the liberation of the minerals, and the long-term prediction was therefore overestimated. Results of the kinetic columns showed there was less oxidation of the sulfide minerals in the coarse fractions than in the fine fractions. Additionally, the distribution of sulfidic minerals and neutralizing minerals with particle size is influencing the potential of the re-use of the reactive waste rock.


Asunto(s)
Minería , Tamaño de la Partícula , Minerales/química , Cinética
5.
J Contam Hydrol ; 267: 104427, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39265307

RESUMEN

Mine waste rock poses significant environmental challenges. Evaluating management and reclamation options is particularly complex because of the wide particle size distribution, the non-uniform distribution of acid-generating and buffering minerals, and the variable contribution of the different particle size fractions to acid mine drainage (AMD) generation. Reactive transport simulations can be useful to complement and overcome the limitations of laboratory and field experiments. However, predicting field-scale and long-term geochemical behavior of waste rock requires a better understanding of numerical parameters scale-up. In this study, three waste rocks, with different mineral composition and particle size distribution, were separated into different fractions and tested in the laboratory. Kinetic tests were used to calibrate numerical models and adjust minerals' effective kinetic rate constants to match measured pH and metal concentrations. Calibrated reactive transport simulations were able to reproduce accurately the effect of particle size on pH and sulfate and calcium production rates. Experimental and numerical results confirmed that waste rock oxidation and neutralization rates tended to decrease with increasing particle sizes. Several models were tested and the weighted geometric mean of the effective kinetic rate constants as a function of the proportion of each fraction provided the most accurate estimation of the whole specimen kinetic rate constants. A novel approach to predict waste rock geochemical behavior from a single laboratory test also showed promising results. Overall, these results should contribute to improving the extrapolation of laboratory kinetic test results to field predictions.

6.
J Stroke Cerebrovasc Dis ; 33(12): 108045, 2024 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-39349265

RESUMEN

BACKGROUND: Cancer is associated with an increased risk of atrial fibrillation. Whether cancer is also associated with atrial cardiopathy, another atrial pathology associated with heightened ischemic stroke risk, is uncertain. METHODS: We conducted a retrospective cross-sectional study among consecutive patients hospitalized with acute ischemic stroke at a quaternary care center in New York, United States from 2011 through 2016. The study exposure was active cancer. The study outcome was atrial cardiopathy, defined as a left atrial volume index ≥35 mL/m2 on echocardiography. We used multivariable logistic regression, adjusting for baseline characteristics, to evaluate the relationship between cancer (active or historical) and atrial cardiopathy. We performed a subgroup analysis among patients with embolic stroke of undetermined source (ESUS). RESULTS: The final cohort included 1104 patients with acute ischemic stroke, of whom 10 % had active cancer and 47 % had atrial cardiopathy. Patients with atrial cardiopathy, compared to those without, were older (median age, 77 versus 68 years), and more frequently had hypertension, coronary disease, and atrial fibrillation. Active cancer was present in 9.6 % of patients with atrial cardiopathy (n = 50/520) and 10.4 % of patients without (n = 61/584). There was no association between active cancer and atrial cardiopathy among the overall ischemic stroke cohort (adjusted odds ratio [OR], 0.91; 95 % confidence interval [CI], 0.60-1.37) nor in patients with ESUS (aOR, 0.64; 95 % CI, 0.30-1.36). When the cancer exposure was broadened to include any history of cancer (n = 236, 21.4 %), there still was no significant association with atrial cardiopathy (aOR, 0.93; 95 % CI, 0.68-1.25). CONCLUSIONS: When defining atrial cardiopathy by left atrial volume, we did not find an association between cancer and atrial cardiopathy in patients with ischemic stroke, including among those with ESUS. Future studies, evaluating other atrial cardiopathy biomarkers and settings, are needed to further investigate any potential link between cancer and atrial cardiopathy.

7.
J Stroke Cerebrovasc Dis ; 33(10): 107899, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39106923

RESUMEN

BACKGROUND: Early diagnosis of previously unknown cancer (i.e., occult cancer) after an acute ischemic stroke (AIS) could result in faster initiation of cancer therapy and potentially improve clinical outcomes. Our study aimed to compare mortality rates between AIS patients with occult cancer diagnosed during the index stroke hospitalization versus those diagnosed after hospital discharge. METHODS: Among consecutive AIS patients treated at our stroke center from 2015 through 2020, we identified new cancer diagnoses made within the year after the AIS. We used multivariable Cox regression analyses to evaluate the association between the timing of occult cancer diagnosis (during the AIS hospitalization versus after discharge) and long-term survival. RESULTS: Of 3894 AIS patients with available long-term follow-up data, 59 (1.5 %) were diagnosed with a new cancer within one year after index stroke. Of these, 27 (46 %) were diagnosed during the index hospitalization and 32 (54 %) were diagnosed after discharge. During a median follow-up of 406 days (interquartile range, 89-1073), 70 % (n = 19) of patients whose cancer was diagnosed during hospitalization had died, compared to 63 % (n = 20) of patients whose cancer was diagnosed after discharge (p= 0.58). In our main multivariable model, there was no difference in long-term mortality between patient groups (adjusted hazard ratio, 1.16; 95 % confidence interval, 0.53-2.52; p= 0.71). CONCLUSIONS: In this analysis, timing of a new cancer diagnosis after AIS did not seem to influence patients' long-term survival. Given the fairly small number of included patients with previously occult cancer, larger multicenter studies are needed to confirm our results.


Asunto(s)
Accidente Cerebrovascular Isquémico , Neoplasias , Alta del Paciente , Humanos , Masculino , Femenino , Anciano , Accidente Cerebrovascular Isquémico/mortalidad , Accidente Cerebrovascular Isquémico/diagnóstico , Accidente Cerebrovascular Isquémico/terapia , Factores de Tiempo , Persona de Mediana Edad , Factores de Riesgo , Anciano de 80 o más Años , Neoplasias/mortalidad , Neoplasias/diagnóstico , Neoplasias/terapia , Neoplasias/complicaciones , Medición de Riesgo , Estudios Retrospectivos , Pronóstico , Admisión del Paciente , Hospitalización
8.
Blood ; 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39197072

RESUMEN

Outcomes are poor in triple-class-exposed (TCE) relapsed/refractory multiple myeloma (RRMM). In the phase 3 KarMMa-3 (clinicaltrials.gov; NCT03651128) trial, patients with TCE RRMM and 2-4 prior regimens were randomized 2:1 to idecabtagene vicleucel (ide-cel) or standard regimens (SRs). An interim analysis (IA) demonstrated significantly longer median progression-free survival (PFS; primary endpoint; 13.3 vs 4.4 months; P<.0001) and higher overall response rate (ORR) with ide-cel vs SRs. At final PFS analysis (median follow-up, 30.9 months), ide-cel further improved median PFS vs SRs (13.8 vs 4.4 months; hazard ratio (HR), 0.49; 95% confidence interval (CI), 0.38-0.63). PFS benefit with ide-cel vs SRs was observed regardless of number of prior lines of therapy, with greatest benefit after 2 prior lines (16.2 vs 4.8 months, respectively). ORR benefit was maintained with ide-cel vs SRs (71% vs 42%; complete response, 44% vs 5%). Patient-centric design allowed crossover from SRs (56%) to ide-cel upon progressive disease, confounding overall survival (OS) interpretation. At IA of OS, median (95% CI) was 41.4 (30.9-not reached [NR]) vs 37.9 (23.4-NR) months with ide-cel and SRs, respectively (HR, 1.01; 95% CI 0.73-1.40); median OS in both arms was longer than historical data (9-22 months). Two prespecified analyses adjusting for crossover showed OS favoring ide-cel. This trial highlighted the importance of individualized bridging therapy to ensure adequate disease control during ide-cel manufacturing. Ide-cel improved patient-reported outcomes vs SRs. No new safety signals were reported. These results demonstrate the continued favorable benefit-risk profile of ide-cel in early-line and TCE RRMM. NCT03651128.

10.
Curr Issues Mol Biol ; 46(8): 8197-8208, 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39194701

RESUMEN

Multiple myeloma (MM) first-line treatment algorithms include immuno-chemotherapy (ICT) induction, high-dose chemotherapy (HDCT) and autologous stem cell transplant (ASCT) consolidation, followed by lenalidomide maintenance. After these initial therapies, most patients suffer a disease relapse and require subsequent treatment lines including ICT, additional HDCT and ASCT, or novel immunotherapies. The presence of somatic mutations in peripheral blood cells has been associated with adverse outcomes in a variety of hematological malignancies. Nonsense and frameshift mutations in the PPM1D gene, a frequent driver alteration in clonal hematopoiesis (CH), lead to the gain-of-function of Wip1 phosphatase, which may impair the p53-dependent G1 checkpoint and promote cell proliferation. Here, we determined the presence of PPM1D gene mutations in peripheral blood cells of 75 subsequent myeloma patients in remission after first or second HDCT/ASCT. The prevalence of truncating PPM1D gene mutations emerged at 1.3% after first HDCT/ASCT, and 7.3% after second HDCT/ASCT, with variant allele frequencies (VAF) of 0.01 to 0.05. Clinical outcomes were inferior in the PPM1D-mutated (PPM1Dmut) subset with median progression-free survival (PFS) of 15 vs. 37 months (p = 0.0002) and median overall survival (OS) of 36 vs. 156 months (p = 0.001) for the PPM1Dmut and PPM1Dwt population, respectively. Our data suggest that the occurrence of PPM1D gene mutations in peripheral blood cells correlates with inferior outcomes after ASCT in patients with multiple myeloma.

11.
Int J Mol Sci ; 25(15)2024 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-39125785

RESUMEN

Limited data on treosulfan pharmacokinetics in adults, particularly regarding autologous stem cell transplantation (ASCT) in acute myeloid leukemia (AML), is available to date. Furthermore, correlations between treosulfan exposure, toxicity, and clinical outcome remain understudied. In this single-center retrospective study, we analyzed data from 55 AML patients who underwent HDCT with treosulfan (14 g/m2) and melphalan (140 mg/m2 or 200 mg/m2) (TreoMel) between August 2019 and November 2023 at the University Hospital of Bern. We assessed treosulfan pharmacokinetics and correlations with several physiological parameters with potential impact on its interpatient variability. We further analyzed how treosulfan exposure correlates with toxicity and clinical outcomes. Women above 55 years showed higher area under the curve (AUC) levels (median: 946 mg*h/L, range: 776-1370 mg*h/L), as compared to women under 55 (median: 758 mg*h/L, range: 459-1214 mg*h/L, p = 0.0487). Additionally, women above 55 showed higher peak levels (median: 387 mg/L, range: 308-468 mg/L), as compared to men of the same age range (median: 326 mg/L, range: 264-395 mg/L, p = 0.0159). Treosulfan levels varied significantly with body temperature, liver enzymes, hemoglobin/hematocrit., and treosulfan exposure correlated with diarrhea severity in women over 55 (p = 0.0076). Our study revealed age- and gender-related variability in treosulfan pharmacokinetics, with higher plasma levels observed in female patients above 55. Moreover, our data suggest that treosulfan plasma levels may vary with several physiological parameters and that higher treosulfan exposure may impact toxicity. Our study underlines the need for further research on treosulfan pharmacokinetics, especially in older patients undergoing HDCT in the ASCT setting.


Asunto(s)
Busulfano , Leucemia Mieloide Aguda , Trasplante Autólogo , Humanos , Busulfano/análogos & derivados , Busulfano/farmacocinética , Busulfano/uso terapéutico , Femenino , Leucemia Mieloide Aguda/terapia , Masculino , Persona de Mediana Edad , Adulto , Anciano , Estudios Retrospectivos , Trasplante de Células Madre Hematopoyéticas/métodos , Antineoplásicos Alquilantes/farmacocinética , Antineoplásicos Alquilantes/uso terapéutico
12.
Int J Mol Sci ; 25(16)2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39201242

RESUMEN

In this study, we present the design, implementation, and successful use of digital droplet PCR (ddPCR) for the monitoring of chimeric antigen receptor T-cell (CAR-T) expansion in patients with B-cell malignancies treated with different CAR-T products at our clinical center. Initially, we designed a specific and highly sensitive ddPCR assay targeting the junction between the 4-1BB and CD3ζ domains of tisa-cel, normalized with RPP30, and validated it using blood samples from the first tisa-cel-treated patient in Switzerland. We further compared this assay with a published qPCR (quantitative real-time PCR) design. Both assays showed reliable quantification of CAR-T copies down to 20 copies/µg DNA. The reproducibility and precision were confirmed through extensive testing and inter-laboratory comparisons. With the introduction of other CAR-T products, we also developed a corresponding ddPCR assay targeting axi-cel and brexu-cel, demonstrating high specificity and sensitivity with a limit of detection of 20 copies/µg DNA. These assays are suitable for CAR-T copy number quantification across multiple sample types, including peripheral blood, bone marrow, and lymph node biopsy material, showing robust performance and indicating the presence of CAR-T cells not only in the blood but also in target tissues. Longitudinal monitoring of CAR-T cell kinetics in 141 patients treated with tisa-cel, axi-cel, or brexu-cel revealed significant expansion and long-term persistence. Peak expansion correlated with clinical outcomes and adverse effects, as is now well known. Additionally, we quantified the CAR-T mRNA expression, showing a high correlation with DNA copy numbers and confirming active transgene expression. Our results highlight the quality of ddPCR for CAR-T monitoring, providing a sensitive, precise, and reproducible method suitable for clinical applications. This approach can be adapted for future CAR-T products and will support the monitoring and the management of CAR-T cell therapies.


Asunto(s)
Inmunoterapia Adoptiva , Receptores Quiméricos de Antígenos , Linfocitos T , Humanos , Receptores Quiméricos de Antígenos/genética , Receptores Quiméricos de Antígenos/inmunología , Receptores Quiméricos de Antígenos/metabolismo , Inmunoterapia Adoptiva/métodos , Linfocitos T/metabolismo , Linfocitos T/inmunología , Cinética , Reproducibilidad de los Resultados , Reacción en Cadena de la Polimerasa/métodos , Sensibilidad y Especificidad
13.
Bone Marrow Transplant ; 59(10): 1458-1465, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39095548

RESUMEN

Core-binding factor acute myeloid leukemia (CBF-AML) represents 12-15% of all AML cases. Although CBF positivity infers a survival advantage, overall survival (OS) remains dismal. Treatment is with cytarabine/anthracycline-based chemotherapy induction followed by high-dose cytarabine (HiDAC) consolidation. Allogeneic hematopoietic stem cell transplantation (allo-SCT) is reserved for relapse or for patients having not achieved MRD-negativity at high risk for relapse. The role of SCT in first complete remission (CR1) remains controversial and is considered in high risk conditions. In this retrospective, multi-national, European Society for Blood and Marrow Transplantation (EBMT)-based study, we identified 1901 patients with de novo CBF-AML who received an allo-SCT or autologous transplantation (ASCT) in CR1. 65.5% harbored t(8;21) and 34.4% inv(16). In this group, the majority (77%) were treated with allo-SCT in CR1. In multivariate analysis, treatment with allo-SCT was an independent and significant, negative predictor of NRM and OS (HR 4.26, p < 0.0001 and HR 1.67, p = 0.003) and among patients treated with allo-SCT, those treated with MSD had the best outcomes, comparable to those treated with ASCT. There was no interaction between the type of transplant and MRD status at time of SCT. In both, MRD-negative and MRD-positive groups, NRM was worse in the allo-SCT group (MRD-: 12.9% vs 5.2%, p = 0.007; MRD+: 10.6% vs 0%, p = 0.004). We therefore demonstrated that consolidation in CR1 with allo-SCT results in worse outcomes than ASCT. Whether consolidation with ASCT yields better outcomes than chemotherapy alone or chemotherapy in combination with Gemtuzumab Ozogamicin is yet to be investigated.


Asunto(s)
Factores de Unión al Sitio Principal , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Inducción de Remisión , Humanos , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/mortalidad , Adulto , Persona de Mediana Edad , Femenino , Masculino , Trasplante de Células Madre Hematopoyéticas/métodos , Estudios Retrospectivos , Adolescente , Anciano , Adulto Joven , Trasplante Homólogo/métodos , Aloinjertos
14.
Ann Hematol ; 103(10): 4163-4170, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39020041

RESUMEN

Further line treatment of patients with advanced stage AL amyloidosis with cardiac involvement is challenging. Venetoclax is a promising option, especially in t(11;14) and BCL2 expression.In our multicentre observational study, we report the 3-year follow-up of Venetoclax treatment in 9 patients with advanced, relapsed or refractory AL amyloidosis with t(11;14) and BCL-2 expression in > 50% of plasma cells. At baseline, all patients had been previously treated with daratumumab, all had cardiac involvement with revised Mayo stage III or IV/ European modification of Mayo 2004 IIIA or IIIB (1/9 unclassified due to missing troponin T), 5/9 patients had renal involvement.After a median of 35 months (range 25-49) since the start of Venetoclax, 8/9 patients were still alive (OS 89%). First and best hematological responses were observed after a median of 26 days (11-125) and 106 days (35-659), overall response rate was 100% (7/9 CR, 2/9 VGPR). Where observed, organ response was documented within the first 6 months of therapy, including cardiac (6/9) and renal (3/5) improvements. Venetoclax was discontinued in 6/9 patients after a median of 15 months (11-48) due to toxicity (2/9), disease progression (2/9), fixed treatment duration (1/9), or safety concerns (1/9).In conclusion, Venetoclax induces a rapid and deep hematologic response with consistent improvement in organ function with an acceptable safety profile in patients with pretreated, advanced stage AL amyloidosis with cardiac involvement and BCL2 expression with and potentially without detected t(11:14), which warrants further investigation.


Asunto(s)
Compuestos Bicíclicos Heterocíclicos con Puentes , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas , Proteínas Proto-Oncogénicas c-bcl-2 , Sulfonamidas , Translocación Genética , Humanos , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Sulfonamidas/uso terapéutico , Masculino , Femenino , Proteínas Proto-Oncogénicas c-bcl-2/genética , Anciano , Persona de Mediana Edad , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/tratamiento farmacológico , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/genética , Estudios de Seguimiento , Cromosomas Humanos Par 14/genética , Antineoplásicos/uso terapéutico , Cromosomas Humanos Par 11/genética , Anciano de 80 o más Años , Recurrencia
15.
Biomedicines ; 12(7)2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39062189

RESUMEN

Gemtuzumab ozogamicin (GO), a CD33-targeting antibody drug conjugate, previously showed longer relapse-free survival when combined with induction chemotherapy in patients with favorable-risk acute myeloid leukemia (AML). In this patient population, characterized by lower relapse risk as compared to other ELN risk groups, autologous stem cell transplantation (ASCT) can be used as consolidation strategy. However, there are limited data on the impact of GO on the peripheral blood stem cell (PBSC) mobilization potential. We therefore retrospectively analyzed data from 54 AML patients with favorable-risk AML treated with (n = 17) or without (n = 37) GO during induction treatment. We observed no significant differences in the PBSC mobilization rate between patients treated with vs. without GO. The mobilization success in a first attempt directly following cycle 2 was 65% vs. 70% (p = 0.92); and the mobilization success in a subsequent second attempt after hematologic recovery and repeated stimulation procedure was 24% vs. 19% (p = 0.56). No significant impact on treatment outcome in terms of EFS (p = 0.31) or OS (p = 0.99) was observed. Thus, our results suggest that the addition of GO to induction regimens does not negatively impact PBSC mobilization in favorable-risk AML patients. To our best knowledge, this is the first study comparing the stem cell mobilization potential in favorable-risk AML patients treated with vs. without GO.

16.
Pediatr Hematol Oncol ; 41(7): 530-539, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38840569

RESUMEN

Clonal hematopoiesis of indeterminate potential (CHIP) describes recurrent somatic gene mutations in the blood of healthy individuals, associated with higher risk for hematological malignancies and higher all-cause mortality by cardiovascular disease. CHIP increases with age and is more common in adult patients after chemotherapy or radiation for cancer. Furthermore, in some adult patients undergoing autologous stem cell transplantation (ASCT) or thereafter, CHIP has been identified. In children and adolescents, it remains unclear how cellular stressors such as cytotoxic therapy influence the incidence and expansion of CHIP. We conducted a retrospective study on 33 pediatric patients mostly with solid tumors undergoing ASCT for presence of CHIP. We analyzed CD34+ selected peripheral blood stem cell grafts after several cycles of chemotherapy, prior to cell infusion, by next-generation sequencing including 18 "CHIP-genes". Apart from a somatic variant in TP53 in one patient no other variants indicative of CHIP were identified. As a CHIP-unrelated finding, germline variants in CHEK2 and in ATM were identified in two and four patients, respectively. In conclusion, we could not detect "typical" CHIP variants in our cohort of pediatric cancer patients undergoing ASCT. However, more studies with larger patient numbers are necessary to assess if chemotherapy in the pediatric setting contributes to an increased CHIP incidence and at what time point.


Asunto(s)
Hematopoyesis Clonal , Trasplante Autólogo , Humanos , Masculino , Niño , Femenino , Adolescente , Estudios Retrospectivos , Preescolar , Lactante , Quinasa de Punto de Control 2/genética , Trasplante de Células Madre Hematopoyéticas , Proteínas de la Ataxia Telangiectasia Mutada/genética , Mutación , Neoplasias/terapia , Neoplasias/genética
17.
Int J Stroke ; 19(9): 1020-1027, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38816936

RESUMEN

BACKGROUND AND OBJECTIVES: Cancer is associated with an increased risk of acute ischemic stroke (AIS) and venous thromboembolism. The role of a cardiac right-to-left shunt (RLS) as a surrogate parameter for paradoxical embolism in cancer-related strokes is uncertain. We sought to investigate the relationship between the presence of an RLS and cancer in AIS patients. METHODS: We included consecutive AIS patients hospitalized at our tertiary stroke center between January 2015 and December 2020 with available RLS status as detected on transesophageal echocardiography (TEE). Active cancers were retrospectively identified and the association with RLS was assessed with multivariable logistic regression and inverse probability of treatment weighting to minimize the ascertainment bias of having a TEE obtained. RESULTS: Of the 2236 AIS patients included, 103 (4.6%) had active cancer, of whom 24 (23%) were diagnosed with RLS. An RLS was present in 774 out of the 2133 AIS patients without active cancer (36%). After adjustment and weighting, the absence of RLS was associated with active cancer (adjusted odds ratio (aOR) 2.29; 95% confidence interval (CI), 1.14-4.58). When analysis was restricted to patients younger than 60 years of age or those with a high-risk RLS (Risk of Paradoxical Embolism Score ⩾ 6), there was no association between RLS and cancer (aOR, 3.07; 95% CI, 0.79-11.88 and aOR, 0.56; 95% CI, 0.10-3.10, respectively). CONCLUSION: RLS was diagnosed less frequently in AIS patients with cancer than in cancer-free patients, suggesting that arterial sources may play a larger role in cancer-related strokes than paradoxical venous embolization. Future studies are needed to validate these findings and evaluate potential therapeutic implications, such as the general indication, or lack thereof, for patent foramen ovale (PFO) closure in this patient population.


Asunto(s)
Ecocardiografía Transesofágica , Foramen Oval Permeable , Accidente Cerebrovascular Isquémico , Neoplasias , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Neoplasias/complicaciones , Neoplasias/epidemiología , Prevalencia , Estudios Retrospectivos , Accidente Cerebrovascular Isquémico/epidemiología , Accidente Cerebrovascular Isquémico/complicaciones , Foramen Oval Permeable/complicaciones , Foramen Oval Permeable/epidemiología , Foramen Oval Permeable/diagnóstico por imagen , Embolia Paradójica/epidemiología , Embolia Paradójica/diagnóstico por imagen , Factores de Riesgo , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/complicaciones
18.
Open Forum Infect Dis ; 11(5): ofae263, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38798896

RESUMEN

Data on posaconazole serum levels of patients on prophylaxis with delayed-release tablets or oral suspension during intensive chemotherapy for acute myeloid leukemia and myelodysplastic syndrome are scarce. In this analysis, the proportion of patients with acute myeloid leukemia/myelodysplastic syndrome achieving posaconazole target concentrations with delayed-release tablets was higher than with oral suspension.

19.
Cancer Med ; 13(10): e7289, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38770551

RESUMEN

BACKGROUND: Mantle cell lymphoma (MCL) is a type of B-cell lymphoma that is currently incurable. Pirtobrutinib shows promising response rates in heavily pretreated MCL patients according to the approval study, but the real-world data are scarce. METHODS: In this study, we retrospectively analyzed the efficacy and safety profile of pirtobrutinib in 10 relapsed/refractory MCL patients from compassionate use program (CUP). RESULTS: On average, the patients underwent three lines of systemic therapy prior to pirtobrutinib and were predominantly BTKi exposed (9/10). The best overall response rate (BORR) was 67%. In a median follow-up of 8.6 months, the mean duration of response (DOR), progression-free survival (PFS), and overall survival (OS) were not reached. No new safety signals were documented. CONCLUSIONS: In summary, pirtobrutinib represented a safe and effective treatment option in a small real-world population.


Asunto(s)
Ensayos de Uso Compasivo , Linfoma de Células del Manto , Humanos , Linfoma de Células del Manto/tratamiento farmacológico , Masculino , Femenino , Anciano , Persona de Mediana Edad , Estudios Retrospectivos , Europa (Continente) , Resultado del Tratamiento , Recurrencia Local de Neoplasia/tratamiento farmacológico , Anciano de 80 o más Años , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/efectos adversos , Supervivencia sin Progresión , Adulto , Resistencia a Antineoplásicos
20.
Cancers (Basel) ; 16(10)2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38791933

RESUMEN

Daratumumab is being increasingly integrated into first-line multiple myeloma (MM) induction regimens, leading to improved response depth and longer progression-free survival. Autologous stem cell transplantation (ASCT) is commonly performed as a consolidation strategy following first-line induction in fit MM patients. We investigated a cohort of 155 MM patients who received ASCT after first-line induction with or without daratumumab (RVd, n = 110; D-RVd, n = 45), analyzing differences in stem cell mobilization, apheresis, and engraftment. In the D-RVd group, fewer patients successfully completed mobilization at the planned apheresis date (44% vs. 71%, p = 0.0029), and more patients required the use of rescue plerixafor (38% vs. 28%, p = 0.3052). The median count of peripheral CD34+ cells at apheresis was lower (41.37 vs. 52.19 × 106/L, p = 0.0233), and the total number of collected CD34+ cells was inferior (8.27 vs. 10.22 × 106/kg BW, p = 0.0139). The time to recovery of neutrophils and platelets was prolonged (12 vs. 11 days, p = 0.0164; and 16 vs. 14 days, p = 0.0002, respectively), and a higher frequency of erythrocyte transfusions (74% vs. 51%, p = 0.0103) and a higher number of platelet concentrates/patients were required (4 vs. 2; p = 0.001). The use of daratumumab during MM induction might negatively impact stem cell mobilization and engraftment in the context of ASCT.

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