RESUMEN
Measurable residual disease (MRD) monitoring independently predicts long-term outcomes in patients with acute myeloid leukemia (AML). Of the various modalities available, multiparameter flow cytometry-based MRD analysis is widely used and relevant for patients without molecular targets. In the transplant (HCT) setting, the presence of MRD pre-HCT is associated with adverse outcomes. MRD-negative remission status pre-HCT was also associated with longer overall (OS) and progression-free survival and a lower risk of relapse. We hypothesize that the combination of disease risk and MRD at the time of first complete remission (CR1) could identify patients according to the benefit gained from HCT, especially for intermediate-risk patients. We performed a retrospective analysis comparing the outcomes of HCT versus non-HCT therapies based on MRD status in AML patients who achieved CR1. Time-dependent analysis was applied considering time-to-HCT as a time-dependent covariate and compared HCT versus non-HCT outcomes according to MRD status at CR1. Among 336 patients assessed at CR1, 35.1% were MRD positive (MRDpos) post-induction. MRDpos patients benefitted from HCT with improved OS and relapse-free survival (RFS), while no benefit was observed in MRDneg patients. In adverse-risk patients, HCT improved OS (HR for OS 0.55; p = 0.05). In intermediate-risk patients, HCT benefit was not significant for OS and RFS. Intermediate-risk MRDpos patients were found to have benefit from HCT with improved OS (HR 0.45, p = 0.04), RFS (HR 0.46, p = 0.02), and CIR (HR 0.41, p = 0.02). Our data underscore the benefit of HCT in adverse risk and MRDpos intermediate-risk AML patients.
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Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Humanos , Citometría de Flujo , Estudios Retrospectivos , Trasplante Homólogo , Recurrencia , Neoplasia Residual , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/terapia , PronósticoRESUMEN
Nucleophosmin-1 (NPM1)-mutated AML is a molecularly defined subtype typically associated with favorable treatment response and prognosis; however, its prognostic significance in AML evolving from an antecedent chronic myeloid malignancy is unknown. This study's primary objective was to determine the impact of mutated NPM1 on the prognosis of AML evolving from an antecedent chronic myeloid malignancy. We conducted a retrospective chart review including patients with NPM1-mutated de novo and sAML. sAML was defined as those with a preceding chronic-phase myeloid malignancy before diagnosis of AML. Of 575 NPM1-mutated patients eligible for inclusion in our study, 51 (8.9%) patients were considered to have sAML. The median time from diagnosis of NPM1-mutated chronic myeloid malignancy to sAML evolution was 3.6 months (0.5-79.3 months). No significant differences in leukemia-free (2-year LKFS 52.0% vs. 51.2%, p = .9922) or overall survival (2-year OS 56.3% vs. 49.4%, p = .4246) were observed between patients with NPM1-mutated de novo versus sAML. Our study suggests that evolution from a preceding myeloid malignancy is not a significant predictor of poor prognosis in the setting of an NPM1 mutation. Our study demonstrated a short time to progression to sAML in most patients, which further supports the consideration of NPM1 as an AML-defining mutation.
RESUMEN
Venous thromboembolism (VTE) is a well-known complication in patients with acute lymphoblastic leukaemia (ALL) receiving asparaginase (ASP)-based chemotherapy, including the ASP-intensive Dana-Farber Cancer Institute (DFCI) 91-01 protocol for adults. Since 2019, native L-ASP is no longer available in Canada and was replaced by pegylated (PEG)-ASP. To determine whether the incidence of VTE has changed since switching from L-ASP to PEG-ASP, we conducted a single-centred retrospective cohort study. We included 245 adult patients with Philadelphia chromosome negative ALL between 2011 and 2021, with 175 from the L-ASP group (2011-2019) and 70 from the PEG-ASP group (2018-2021). During Induction, 10.29% (18/175) of patients who received L-ASP developed VTE, whereas 28.57% (20/70) of patients who received PEG-ASP developed VTE (p = 0.0035; odds ratio [OR] 3.35, 95% confidence interval [CI] 1.51-7.39), after adjusting for line type, gender, history of VTE, platelets at diagnosis. Similarly, during Intensification, 13.64% (18/132) of patients had VTE on L-ASP while 34.37% (11/32) of patients on PEG-ASP developed VTE (p = 0.0096; OR 3.96, 95% CI 1.57-9.96 with multivariable analysis). We found that PEG-ASP is associated with a higher incidence of VTE compared to L-ASP, both during Induction and Intensification, despite the administration of prophylactic anticoagulation. Further VTE mitigation strategies are needed in particular for adult patients with ALL receiving PEG-ASP.
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Antineoplásicos , Leucemia-Linfoma Linfoblástico de Células Precursoras , Tromboembolia Venosa , Humanos , Adulto , Asparaginasa/efectos adversos , Estudios Retrospectivos , Tromboembolia Venosa/inducido químicamente , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/complicaciones , Incidencia , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Polietilenglicoles/efectos adversos , Antineoplásicos/uso terapéuticoRESUMEN
BACKGROUND: Inconclusive cytogenetic analysis (IC) at baseline has been reported as a predictor of poor prognosis in patients with acute myeloid leukemia (AML). The mutational profile in this group of patients, and its impact on outcomes have not been reported. METHODS: We retrospectively analyzed adult patients (≥18 years) with newly diagnosed AML treated with intensive induction chemotherapy between 2015 and 2019. Patients with any documented cytogenetic abnormalities were excluded. Targeted next generation sequencing (NGS) was performed in all patients. Baseline characteristics, mutation profile, and outcomes were compared between patients with normal cytogenetics(NC) and those with IC. RESULTS: Sixty-one patients (males 39.3%; median age 59 years) had IC at diagnosis. The proportion of patients with mutations in genes with proven prognostic impact were not different between AML patients with IC and NC. AML patients with NC were more likely to harbor the prognostically favorable NPM1mut /FLT3-ITDwt mutational combination conferring "favorable" risk status. As a result, a larger proportion of patients in the IC group underwent allogeneic hematopoietic stem cell transplantation (allo HCT; 54.1% vs. 39.6%; p = .02). The 2-year RFS (55.9% vs. 58.5%; p = .29) and OS (61.9% vs. 66.9%; p = .48) were similar in IC and NC patients. There was no difference in survival of patients who underwent allo HCT when compared with patients who did not (p = .99). CONCLUSIONS: Inconclusive cytogenetic analysis may not be an independent prognostic indicator in AML. In such patients, molecular abnormalities detected through NGS or whole genome sequencing are more likely to be informative.
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Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Masculino , Humanos , Adulto , Persona de Mediana Edad , Estudios Retrospectivos , Nucleofosmina , Mutación , Pronóstico , Análisis Citogenético , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Tirosina Quinasa 3 Similar a fms/genéticaRESUMEN
INTRODUCTION: Care for patients with acute myeloid leukemia (AML) is centralized in the Ontario single-payer public healthcare system, with intensive induction chemotherapy and clinical trials only offered at specialized cancer centers with large catchment areas. METHODS: We therefore conducted a retrospective single-center review of all AML patients assessed at a large specialized cancer center in Ontario, Canada. RESULTS: Between 2012 and 2017, 1,310 patients were assessed by our center for upfront AML therapy. The median distance was 33.1 km, with 29% of patients living more than 50 km away from the center. There was no significant difference in probability of intensive induction chemotherapy or clinical trial by distance from center, both in univariate and multivariable analysis adjusting for age, sex, cytogenetics and molecular testing, and performance status. There was no significant difference in overall survival by distance from center on univariate and multivariable analysis. CONCLUSION: In conclusion, geographic distance from treatment center does not appear to impact choice of upfront therapy, participation in clinical trials, or clinical outcomes in this study of newly diagnosed patients with AML treated in a single-payer environment.
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Quimioterapia de Inducción , Leucemia Mieloide Aguda , Humanos , Resultado del Tratamiento , Estudios Retrospectivos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
PURPOSE: As research on hereditary hematologic malignancy syndromes (HHMS) are accumulating, cancer genetics clinics are identifying more adult hematology patients with an inherited component to their disease. However, investigations for HHMS are complex, and there is no formal consensus on genetic testing criteria. METHODS: We developed genetic testing criteria for adult hematology patients through a comprehensive literature review and our experience at the Princess Margaret Cancer Centre. We validated our criteria by applying them retrospectively to patients referred to our clinic for HHMS assessment. RESULTS: Our genetic testing criteria are comprehensive of myeloid malignancies, lymphoid malignancies, and bone marrow failure, including age at diagnosis, family history, and genetic test results in blood and bone marrow. Of the 104 patients who met the criteria, 26% had at least 1 actionable variant in any gene associated with an increased risk of cancer and 13% had an actionable variant resulting in an HHMS diagnosis. A total of 15 patients had incidental findings, including 11 patients with a pathogenic variant associated with carrier status for an autosomal recessive disorder and 4 patients with a mosaic result. CONCLUSION: Our high gene positivity rate shows the utility of a broad approach to germline testing in an adult hematology population.
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Pruebas Genéticas , Neoplasias Hematológicas , Adulto , Humanos , Estudios Retrospectivos , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/epidemiología , Anamnesis , Médula Ósea , Predisposición Genética a la EnfermedadRESUMEN
There is limited understanding of the impact of frailty on clinical outcomes in patients with myelofibrosis (MF). In this retrospective cohort study on 439 chronic phase MF patients [mean age: 68·7 ± 12 years; median follow-up: 3·4 years (IQR 0·4-8·6)] from 2004 till 2018, we used a 35-variable frailty index (FI) to categorise patient's frailty status as fit (FI < 0·2, reference), prefrail (FI 0·2-0·29) or frail (FI ≥ 0·3). The association of frailty with overall survival (OS) and cumulative JAK inhibitor (JAKi) therapy failure was measured using hazard ratio (HR, 95% CI). In multivariable analysis, prefrail (HR 1·7, 1·1-2·5) and frail patients (HR 2·9, 1·6-5·5), those with higher DIPSS score (HR 2·5, 1·6-3·9) and transfusion dependency (HR 1·9, 1·3-2·9) had shorter OS. In a subset analysis of patients on JAKi treatment (n = 222), frail patients (HR 2·5, 1·1-5·7), patients with higher DIPSS score (HR 1·7, 1·0-3·1) and transfusion dependence (HR 1·7, 1·1-2·7) had higher cumulative incidence of JAKi failure. Age, comorbidities, ECOG performance status, and MPN driver mutations did not impact outcomes. Thus, higher frailty scores are associated with worse OS and increased JAKi failure in MF, and is a superior indicator of fitness in comparison to age, comorbidities, and performance status.
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Fragilidad/complicaciones , Mielofibrosis Primaria/complicaciones , Mielofibrosis Primaria/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Anciano , Anciano de 80 o más Años , Anciano Frágil , Humanos , Persona de Mediana Edad , Mielofibrosis Primaria/epidemiología , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Core-binding factor acute myeloid leukemia is characterized by t(8;21) or inv(16) and the fusion proteins RUNX1-RUNX1T1 and CBFB-MYH11. International guidelines recommend monitoring for measurable residual disease every 3 months for 2 years after treatment. However, it is unknown if serial molecular monitoring can predict and prevent morphologic relapse. We conducted a retrospective single-center study of 114 patients in complete remission who underwent molecular monitoring with RT-qPCR of RUNX1-RUNX1T1 or CBFB-MYH11 transcripts every 3 months. Morphologic relapse was defined as re-emergence of >5% blasts and molecular relapse as ≥1 log increase in transcript level between 2 samples. Over a median follow-up time of 3.7 years (range 0.2-14.3), remission persisted in 71 (62.3%) patients but 43 (37.7%) developed molecular or morphologic relapse. Patients who achieved <3 log reduction in RUNX1-RUNX1T1 or CBFB-MYH11 transcripts at end of chemotherapy had a significantly higher risk of relapse compared to patients who achieved ≥3 log reduction (61.1% vs. 33.7%, p=0.004). The majority of relapses (74.4%, n=32) were not predicted by molecular monitoring and occurred rapidly with <100 days from molecular to morphologic relapse. Molecular monitoring enabled the detection of impending relapse and permitted pre-emptive intervention prior to morphologic relapse in only 11 (25.6%) patients. The current practice of molecular monitoring every 3 months provided insufficient lead-time to identify molecular relapses and prevent morphologic relapse in the majority of patients with core-binding factor acute myeloid leukemia treated at our institution. Further research is necessary to determine the optimal monitoring strategies for these patients.
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Leucemia Mieloide Aguda , Progresión de la Enfermedad , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Neoplasia Residual/genética , Proteínas de Fusión Oncogénica/genética , Recurrencia , Estudios RetrospectivosRESUMEN
Venous thromboembolism (VTE) is a well-known complication in adults receiving asparaginase (ASNase)-based intensification chemotherapy for acute lymphoblastic leukaemia (ALL). The optimal preventative strategy is unclear. Our objective is to determine the effects of low-molecular-weight heparin (LMWH) as primary VTE prophylaxis. A single-centred retrospective cohort study of adult patients with Philadelphia chromosome negative (Ph-) ALL who received ASNase-based intensification from 2001 to 2017, with prophylaxis given from 2011 to 2017. In all, 214 patients were included in this study with 99 in the historical control group and 125 in the prophylaxis group. The mean (range) enoxaparin dose was 0·79 (0·39-1·2) mg/kg. Of the 125 patients in the prophylaxis group 17 (13·6%) developed VTE during the intensification phase, while 27/99 patients (27·3%) in the control cohort experienced at least one thrombotic event (odds ratio [OR] 0·42, 95% confidence interval [CI] 0·21-0·83). Overall, the main sites of VTE incidences included deep vein thrombosis in the lower extremity (54·6%), pulmonary embolism (13·6%) and catheter-related thrombosis (22·7%). In addition, we found that after adjusting for age, T-phenotype ALL was associated with VTE development (OR 3·07, 95% CI 1·04-9·08). There was no documented major bleeding in the prophylaxis group. LMWH prophylaxis reduced the incidence of symptomatic VTE in adult patients with ALL receiving intensification chemotherapy with ASNase.
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Anticoagulantes/administración & dosificación , Asparaginasa , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Tromboembolia Venosa , Adolescente , Adulto , Anciano , Asparaginasa/administración & dosificación , Asparaginasa/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tromboembolia Venosa/inducido químicamente , Tromboembolia Venosa/prevención & controlRESUMEN
Routine VTE prophylaxis is recommended for hospitalized patients, but its effectiveness and safety in cancer patients is unclear. By observation, larger patients seemed poorly covered by the prophylaxis policy. The effectiveness and safety of VTE prophylaxis policy in the hospitalized patients, their potential risk factors such as BMI were examined. A retrospective chart review was conducted to determine VTE incidences, risk factors for VTE and major bleeding events between 2007 and 2016 on the solid tumor units (STU). Patients were divided into pre-policy (Pre-2012) or post-policy implementation groups (Post-2012). Descriptive statistics were used to evaluate effectiveness and safety of prophylaxis, while propensity score matching (1:3, VTE:Non-VTE) was used to reduce selection bias. The VTE incidence per patient was 1.30% (57/4392) pre-policy and 0.56% (18/3210) post-policy (p value = 0.0013). After propensity score matching, a reduction (32.3%) of VTE cases was observed after policy implementation (OR = 0.677, p = 0.32). BMI was found to be a significant predictor of VTE (OR = 1.094, 95% CI 1.021-1.172, p = 0.011). Between July 2014 and July 2016, 1.7% (19/1091) patients who received anticoagulants had a documented bleeding event. The policy positively impacted VTE events on the STU. A significant predictor of VTE was BMI and patients with high BMI may pose a risk of breaking through standard VTE prophylaxis dosing. There was no reported major bleeding for patients who developed an VTE event despite receiving prophylaxis in either the pre-policy or post-policy phase of the study, although a low incidence of minor bleeding was documented in the post-phase.
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Índice de Masa Corporal , Hospitalización , Neoplasias , Tromboembolia Venosa , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Neoplasias/complicaciones , Neoplasias/epidemiología , Neoplasias/terapia , Estudios Retrospectivos , Factores de Riesgo , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/etiología , Tromboembolia Venosa/prevención & controlAsunto(s)
Isocitrato Deshidrogenasa , Leucemia Mieloide Aguda , Humanos , Pronóstico , Factores de Empalme de ARN/genética , Isocitrato Deshidrogenasa/genética , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Mutación , Neoplasia Residual/diagnóstico , Neoplasia Residual/genéticaAsunto(s)
Hipertensión Portal , Trastornos Mieloproliferativos , Neoplasias , Humanos , Trastornos Mieloproliferativos/diagnóstico , Trastornos Mieloproliferativos/genética , Proteínas de Fusión bcr-abl/genética , Endoscopía del Sistema Digestivo , Hipertensión Portal/diagnóstico , Hipertensión Portal/etiologíaRESUMEN
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is incurable with conventional therapies. Limited retrospective data have shown durable remissions after haematopoietic cell transplantation (HCT) [allogeneic (allo) or autologous (auto)]. We conducted a multicentre retrospective study in BPDCN patients treated with allo-HCT and auto-HCT at 8 centres in the United States and Canada. Primary endpoint was overall survival (OS). The population consisted of 45 consecutive patients who received an allo-HCT (n = 37) or an auto-HCT (n = 8) regardless of age, pre-transplant therapies, or remission status at transplantation. Allo-HCT recipients were younger (50 (14-74) vs. 67 (45-72) years, P = 0·01) and had 1-year and 3-year OS of 68% [95% confidence interval (CI) = 49-81%] and 58% (95% CI = 38-75%), respectively. Allo-HCT in first complete remission (CR1) yielded superior 3-year OS (versus not in CR1) [74% (95% CI = 48-89%) vs. 0, P < 0·0001]. Allo-HCT outcomes were not impacted by regimen intensity [3-year OS for myeloablative conditioning = 61% (95% CI = 28-83%) vs. reduced-intensity conditioning = 55% (95% CI = 28-76%)]. One-year OS for auto-HCT recipients was 11% (95% CI = 8-50%). These results demonstrate efficacy of allo-HCT in BPDCN, especially in patients in CR1. Pertaining to auto-HCT, our results suggest lack of efficacy against BPDCN, but this observation is limited by the small sample size. Larger prospective studies are needed to better define the role of HCT in BPDCN.
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Células Dendríticas/patología , Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Mieloide Aguda/terapia , Enfermedad Aguda , Adolescente , Adulto , Anciano , Enfermedad Crónica , Progresión de la Enfermedad , Supervivencia de Injerto , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Estimación de Kaplan-Meier , Leucemia Mieloide Aguda/patología , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Acondicionamiento Pretrasplante/métodos , Trasplante Autólogo/efectos adversos , Trasplante Autólogo/métodos , Trasplante Homólogo/efectos adversos , Trasplante Homólogo/métodos , Resultado del Tratamiento , Adulto JovenRESUMEN
Reduced-intensity conditioning (RIC) has been shown to have similar overall survival (OS) but higher relapse rates compared with myeloablative (MAC) regimens in patients with myeloid malignancies undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Using propensity score matching (PSM) analysis, well-balanced pairs of different variables can be compared effectively. We retrospectively compared allo-HSCT recipients with acute myeloid leukemia or myelodysplasia receiving a RIC regimen (FBT200; fludarabine 30 mg/m2/day for 4 days, busulfan 3.2 mg/kg/day for 2 days, and total body irradiation [TBI] 200 cGy) or MAC regimen (FBT400; fludarabine 50 mg/m2/day for 4 days, busulfan 3.2 mg/kg/day for 4 days, and TBI 400 cGy). A total of 248 patients (121 in the RIC group and 127 in the MAC group) were included in the analysis. No statistically significant difference was observed in 2-year OS (RIC group, 45.2 ± 5.0%; MAC group, 51.7 ± 5.2%; P = .541), nonrelapse mortality (NRM; RIC group, 28.7 ± 2.8% MAC group, 34.7 ± 4.6%; P = .368), and acute graft-versus-host disease (GVHD) (P = .171) or chronic GVHD (P = .605) at 1 year. The cumulative incidence of relapse (CIR) at 2 years was statistically significantly different between the 2 groups, however (RIC, 26.1 ± 2.6%; MAC, 14.2 ± 3.5%; P = .033). When PSM was applied to the study population, 42 case-control pairs were evenly matched. PSM analysis confirmed no statistically significant difference in 2-year OS (RIC, 49.0 ± 9.1%; MAC, 54.9 ± 7.7%; P = .718), NRM (RIC, 22.2 ± 2.3%; MAC, 33.3 ± 2.8%; P = .238), or CIR (RIC, 25.7 ± 2.6%; MAC, 9.5 ± 1.1%; P = .315) in the PSM pairs. Our findings demonstrate that after applying PSM, FBT 200 RIC conditioning has comparable OS, NRM, and CIR to FBT 400 MAC conditioning before allo-HSCT.
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Leucemia Mieloide/terapia , Puntaje de Propensión , Acondicionamiento Pretrasplante/métodos , Adulto , Anciano , Busulfano/administración & dosificación , Estudios de Casos y Controles , Relación Dosis-Respuesta a Droga , Relación Dosis-Respuesta en la Radiación , Femenino , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/mortalidad , Humanos , Leucemia Mieloide/complicaciones , Leucemia Mieloide/mortalidad , Masculino , Persona de Mediana Edad , Agonistas Mieloablativos/uso terapéutico , Síndromes Mielodisplásicos/complicaciones , Síndromes Mielodisplásicos/mortalidad , Síndromes Mielodisplásicos/terapia , Recurrencia , Estudios Retrospectivos , Análisis de Supervivencia , Vidarabina/administración & dosificación , Vidarabina/análogos & derivados , Irradiación Corporal Total , Adulto JovenAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Tirosina Quinasa 3 Similar a fms/genética , Anciano , Aloinjertos , Anemia Refractaria con Exceso de Blastos/fisiopatología , Compuestos de Anilina/administración & dosificación , Azacitidina/administración & dosificación , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Compuestos Bicíclicos Heterocíclicos con Puentes/administración & dosificación , Ensayos Clínicos Fase III como Asunto , Citarabina/administración & dosificación , Daunorrubicina/administración & dosificación , Resultado Fatal , Femenino , Humanos , Leucemia Mieloide Aguda/etiología , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Liposomas , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/fisiopatología , Neoplasia Residual , Neoplasias Inducidas por Radiación/tratamiento farmacológico , Neoplasias Inducidas por Radiación/genética , Neoplasias Inducidas por Radiación/mortalidad , Neoplasias Inducidas por Radiación/patología , Proteínas de Fusión Oncogénica/antagonistas & inhibidores , Proteínas de Fusión Oncogénica/genética , Trasplante de Células Madre de Sangre Periférica , Mutación Puntual , Inhibidores de Proteínas Quinasas/administración & dosificación , Pirazinas/administración & dosificación , Inducción de Remisión , Terapia Recuperativa , Estaurosporina/administración & dosificación , Estaurosporina/análogos & derivados , Sulfonamidas/administración & dosificación , Tirosina Quinasa 3 Similar a fms/antagonistas & inhibidoresRESUMEN
PURPOSE: The aim of this study was to describe the incidence of venous thromboembolism (VTE) and major bleeding among hospitalized patients with hematologic malignancy, assessing its association with critical illness and other baseline characteristics. METHODS: We conducted a population-based cohort study of hospitalized adults with a new diagnosis of hematologic malignancy in Ontario, Canada, between 2006 and 2017. The primary outcome was VTE (pulmonary embolism or deep venous thrombosis). Secondary outcomes were major bleeding and in-hospital mortality. We compared the incidence of VTE between intensive care unit (ICU) and non-ICU patients and described the association of other baseline characteristics and VTE. RESULTS: Among 76,803 eligible patients (mean age 67 years [standard deviation, SD, 15]), 20,524 had at least one ICU admission. The incidence of VTE was 3.7% in ICU patients compared to 1.2% in non-ICU patients (odds ratio [OR] 3.08; 95% confidence interval [CI] 2.77-3.42). The incidence of major bleeding was 7.6% and 2.4% (OR 3.33; 95% CI 3.09-3.58), respectively. The association of critical illness and VTE remained significant after adjusting for potential confounders (OR 2.92; 95% CI 2.62-3.25). We observed a higher incidence of VTE among specific subtypes of hematologic malignancy and patients with prior VTE (OR 6.64; 95% CI 5.42-8.14). Admission more than 1 year after diagnosis of hematologic malignancy (OR 0.64; 95% CI 0.56-0.74) and platelet count ≤ 50 × 109/L at the time of hospitalization (OR 0.63; 95% CI 0.48-0.84) were associated with a lower incidence of VTE. CONCLUSION: Among patients with hematologic malignancy, critical illness and certain baseline characteristics were associated with a higher incidence of VTE.
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Neoplasias Hematológicas , Tromboembolia Venosa , Adulto , Humanos , Anciano , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/etiología , Estudios de Cohortes , Enfermedad Crítica , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/epidemiología , Ontario/epidemiología , HemorragiaRESUMEN
This retrospective report presents the outcomes and adverse events (AEs) observed in 73 patients aged 60 years or older diagnosed with Philadelphia Chromosome-negative Acute Lymphoblastic Leukemia (Ph-negative ALL) treated with a pediatric-inspired protocol incorporating either Pegylated (PEG-ASP) or Native Asparaginase (EC-ASP). Notably, 61% of patients experienced AEs of Grade III-IV severity. The most prevalent AEs included thrombosis (35.6%), febrile neutropenia (38.4%), and transaminitis (34.2%). AEs did not translate into significant differences concerning overall survival, leukemia-free survival, or early mortality. Furthermore, we observed a reduction in early mortality rates (11% vs. 20%) and an increase in median overall survival (54 vs. 48 months) compared to our previous data. These findings suggest that the utilization of a pediatric-inspired chemotherapy protocol, with ASP, is an effective and well-tolerated therapeutic option for older patients with Ph-negative ALL. However, it emphasizes the importance of diligent monitoring and close follow-up throughout treatment.