RESUMEN
In newly diagnosed acute myeloid leukemia (AML), immediate initiation of treatment is standard of care. However, deferral of antileukemic therapy may be indicated to assess comorbidities or pretherapeutic risk factors. We explored the impact of time from diagnosis to treatment on outcomes in newly diagnosed AML undergoing venetoclax-based therapy in two distinct cohorts. By querying the Study Alliance Leukemia database and the global health network TriNetX, we identified 138 and 717 patients respectively with an average age of 76 and 72 years who received venetoclax-based first-line therapy. When comparing patients who started treatment earlier or later than 10 days after initial diagnosis, no significant difference in median overall survival was observed - neither in the SAL cohort (7.7 vs. 9.6 months; P=0.42) nor in the TriNetX cohort (7.5 vs. 7.2 months; P=0.41). Similarly, severe infections, bleeding, and thromboembolic events were equally observed between early and later treatments, both in the overall patient groups and specific subgroups (age ≥75 years or leukocytes ≥20x109/L). This retrospective analysis indicates that delaying the start of venetoclax-based therapy in newly diagnosed AML might be a safe option for selected patients, provided that close clinical monitoring is performed.
Asunto(s)
Compuestos Bicíclicos Heterocíclicos con Puentes , Leucemia Mieloide Aguda , Sulfonamidas , Humanos , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Compuestos Bicíclicos Heterocíclicos con Puentes/administración & dosificación , Sulfonamidas/uso terapéutico , Sulfonamidas/administración & dosificación , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/diagnóstico , Anciano , Masculino , Femenino , Anciano de 80 o más Años , Persona de Mediana Edad , Tiempo de Tratamiento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Resultado del Tratamiento , Adulto , Estudios Retrospectivos , Antineoplásicos/uso terapéuticoRESUMEN
Intensive chemotherapy is the backbone of induction treatment in patients with acute myeloid leukemia (AML). However, AML patients with concomitant cardiac disease may not be eligible for anthracycline-based therapies. In a small cohort of patients, we have previously shown that anthracycline-free, amsacrine-based chemotherapy TAA (thioguanine, cytarabine, amsacrine) may be as effective as cytarabine/daunorubicin for induction therapy in these patients. In this systematic retrospective single-center analysis, we documented the outcome of 31 patients with significant cardiac comorbidities including coronary heart disease or cardiomyopathy receiving TAA as induction chemotherapy. Median (range) ejection fraction (EF) was 48% (30-67%) in this cohort. Patients with EF below 30% were considered unfit for intensive induction therapy. Event-free survival (EFS), overall survival (OS), and relapse-free survival (RFS) were 1.61, 5.46, and 13.6 months respectively. Poor outcome was primarily related to a high early mortality rate within the first 30 days of therapy, mainly caused by infectious complications. TAA cannot be recommended as a substitute of standard induction for AML patients with significant concomitant cardiac disease. In the era of novel agents, alternative strategies (e.g., hypomethylating agents plus venetoclax) should be considered when anthracycline-based regimens are not suitable.
Asunto(s)
Cardiopatías , Leucemia Mieloide Aguda , Humanos , Amsacrina , Quimioterapia de Inducción , Estudios Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/tratamiento farmacológico , Inducción de Remisión , Cardiopatías/epidemiología , Cardiopatías/etiología , Antraciclinas/efectos adversos , CitarabinaRESUMEN
Allogeneic hematopoietic stem cell transplantation (HSCT) is an effective treatment modality for patients with acute myeloid leukemia (AML). Here, we investigated the predictive value of spleen volume on outcome parameters and engraftment kinetics after HSCT in a large cohort of AML patients. A total of 402 patients who received their first HSCT between January 2012 and March 2019 were included in this retrospective study. Spleen volume was correlated to clinical outcome and engraftment kinetics. Median follow-up was 33.7 months (95% confidence interval [CI], 28.9-37.4 months). Patients were subdivided based on median spleen volume of 238.0 cm3 (range 55.7-2693.5 cm3) into a small spleen volume (SSV) and a large spleen volume (LSV) group. LSV was associated with inferior overall survival (OS) after HSCT (55.7% vs. 66.6% at 2 years; P = 0.009) and higher cumulative incidence of NRM (28.8% vs. 20.2% at 2 years; P = 0.048). The adjusted hazard ratio for NRM in the LSV group was 1.55 (95% CI, 1.03-2.34). Time to neutrophil or platelet engraftment and the occurrence of acute or chronic graft-versus-host disease (GVHD) were not significantly different between both groups. Higher spleen volume at the time of HSCT was independently linked to adverse outcomes such as inferior OS and higher cumulative incidence of NRM in AML patients after HSCT. Engraftment kinetics and GVHD were not associated with spleen volume.
Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Humanos , Bazo/diagnóstico por imagen , Estudios Retrospectivos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/etiología , Esplenomegalia/etiología , Acondicionamiento PretrasplanteRESUMEN
PURPOSE: Both exercise and hypoxia cause complex changes in acid-base homeostasis. The aim of the present study was to investigate whether during intense physical exercise in normoxia and hypoxia, the modified physicochemical approach offers a better understanding of the changes in acid-base homeostasis than the traditional Henderson-Hasselbalch approach. METHODS: In this prospective, randomized, crossover trial, 19 healthy males completed an exercise test until voluntary fatigue on a bicycle ergometer on two different study days, once during normoxia and once during normobaric hypoxia (12% oxygen, equivalent to an altitude of 4500 m). Arterial blood gases were sampled during and after the exercise test and analysed according to the modified physicochemical and Henderson-Hasselbalch approach, respectively. RESULTS: Peak power output decreased from 287 ± 9 Watts in normoxia to 213 ± 6 Watts in hypoxia (-26%, P < 0.001). Exercise decreased arterial pH to 7.21 ± 0.01 and 7.27 ± 0.02 (P < 0.001) during normoxia and hypoxia, respectively, and increased plasma lactate to 16.8 ± 0.8 and 17.5 ± 0.9 mmol/l (P < 0.001). While the Henderson-Hasselbalch approach identified lactate as main factor responsible for the non-respiratory acidosis, the modified physicochemical approach additionally identified strong ions (i.e. plasma electrolytes, organic acid ions) and non-volatile weak acids (i.e. albumin, phosphate ion species) as important contributors. CONCLUSIONS: The Henderson-Hasselbalch approach might serve as basis for screening acid-base disturbances, but the modified physicochemical approach offers more detailed insights into the complex changes in acid-base status during exercise in normoxia and hypoxia, respectively.
Asunto(s)
Equilibrio Ácido-Base , Ejercicio Físico , Hipoxia/sangre , Adulto , Humanos , Hipoxia/fisiopatología , Ácido Láctico/sangre , Masculino , Oxígeno/sangreRESUMEN
Flow cytometry-based immunophenotyping is a mainstay of diagnostics in acute myeloid leukaemia (AML). Aberrant CD56 and T-cell antigen expression is observed in a fraction subset of AML cases, but the clinical relevance remains incompletely understood. Here, we retrospectively investigated the association of CD56 and T-cell marker expression with disease-specific characteristics and outcome of 324 AML patients who received intensive induction therapy at our centre between 2011 and 2019. We found that CD2 expression was associated with abnormal non-complex karyotype, NPM1 wild-type status and TP53 mutation. CD2 also correlated with a lower complete remission (CR) rate (47.8% vs. 71.6%, p = 0.03). CyTdT and CD2 were associated with inferior 3-year event-free-survival (EFS) (5.3% vs. 33.5%, p = 0.003 and 17.4% vs. 33.1%, p = 0.02, respectively). CyTdT expression was also correlated with inferior relapse-free survival (27.3% vs. 48.8%, p = 0.04). In multivariable analyses CD2 positivity was an independent adverse factor for EFS (HR 1.72, p = 0.03). These results indicate a biological relevance of aberrant T-cell marker expression in AML and provide a rationale to further characterise the molecular origin in T-lineage-associated AML.