RESUMEN
FLT3-ITD and NPM1 mutations are key to defining the genetic risk profile of acute myeloid leukemia (AML). We aimed to assess the prognostic features of the FLT3-ITD and NPM1 mutations in old and/or unfit individuals with AML treated with non-intensive therapies in the era before azacitidine-venetoclax approbation. The results of various non-intensive regimens were also compared. We conducted a retrospective analysis that included patients treated with different non-intensive regimens, between 2007 and 2020 from PETHEMA AML registry. We compiled 707 patients with a median age of 74 years and median follow-up time of 37.7 months. FLT3-ITD patients (N = 98) showed a non-significant difference in overall survival (OS) compared to FLT3-ITD negative-patients (N = 608) (P = 0.17, median OS was 5 vs 7.3 months respectively). NPM1-mutated patients (N = 144) also showed a non-significant difference with NPM1 wild type (N = 519) patients (P = 0.25, median OS 7.2 vs 6.8 respectively). In the Cox regression analysis neither NPM1 nor FLT3-ITD nor age were significant prognostic variables for OS prediction. Abnormal karyotype and a high leukocyte count showed a statistically significant deleterious effect. Azacitidine also showed better survival compared to FLUGA (low dose cytarabine plus fludarabine). NPM1 and FLT3-ITD seem to lack prognostic value in older/unfit AML patients treated with non-intensive regimens other than azacitidine-venetoclax combination.
Asunto(s)
Leucemia Mieloide Aguda , Mutación , Proteínas Nucleares , Nucleofosmina , Tirosina Quinasa 3 Similar a fms , Anciano , Femenino , Humanos , Masculino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Tirosina Quinasa 3 Similar a fms/genética , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/diagnóstico , Proteínas Nucleares/genética , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Vidarabina/análogos & derivados , Vidarabina/uso terapéutico , Vidarabina/administración & dosificaciónRESUMEN
Studies that analyze the epidemiology and risk factors for invasive fungal disease (IFD) after engraftment in alloSCT are few in number. This single-center retrospective study included 404 alloSCT adult recipients surviving >40 days who engrafted and were discharged without prior IFD. All patients who received ⩾20 mg/day of prednisone were assigned to primary oral prophylaxis (itraconazole or low-dose voriconazole). The primary end point was the cumulative incidence (CI) of probable/proven IFD using the European Organization for Research and Treatment of Cancer and Mycoses Study Group (EORTC/MSG) criteria. The independent prognostic factors after multivariate analyses were used to construct a post-engraftment IFD risk score. The 1-year CI of IFD was 11%. The non-relapse mortality was 40% in those developing IFD and 16% in those who did not. The intent-to-treat analysis showed that 17% of patients abandoned the assigned prophylaxis. Age >40 years, ⩾1 previous SCT, pre-engraftment neutropenia >15 days, extensive chronic GVHD and CMV reactivation were independent risk factors. The post-engraftment IFD score stratified patients into low risk (0-1 factor, CI 0.7%), intermediate risk (2 factors, CI 9.9%) and high risk (3-5 factors, CI 24.7%) (P<0.0001). The antifungal prophylaxis strategy failed to prevent post-engraftment IFD in 11% of alloSCT. Our risk score could be useful to implement risk-adapted strategies using antifungal prophylaxis after engraftment.
Asunto(s)
Antifúngicos/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Micosis/epidemiología , Premedicación , Triazoles/uso terapéutico , Administración Oral , Adulto , Anciano , Aloinjertos , Anfotericina B/uso terapéutico , Antifúngicos/administración & dosificación , Aspergilosis/tratamiento farmacológico , Aspergilosis/epidemiología , Aspergilosis/etiología , Caspofungina , Causas de Muerte , Quimioterapia Combinada , Equinocandinas/uso terapéutico , Femenino , Fungemia/tratamiento farmacológico , Fungemia/epidemiología , Fungemia/etiología , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Neoplasias Hematológicas/terapia , Humanos , Huésped Inmunocomprometido , Incidencia , Lipopéptidos , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Micosis/tratamiento farmacológico , Micosis/etiología , Micosis/prevención & control , Neutropenia/prevención & control , Cooperación del Paciente , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Análisis de Supervivencia , Acondicionamiento Pretrasplante/efectos adversos , Insuficiencia del Tratamiento , Triazoles/administración & dosificación , Adulto JovenRESUMEN
We describe incidence, clinical features, serological data, response to therapy and outcome of autoimmune cytopenias (ACs), including autoimmune hemolytic anemia (AIHA) and autoimmune thrombocytopenia (AIT) in a series of 281 consecutive adults with hematological malignancies that received single-unit umbilical cord blood transplantation (UCBT) at a single institution. AIHA was diagnosed in 15 patients at a median time of 181 days (range, 25-543), 12 of them had cold antibodies (IgM). The 3-year cumulative incidence (CI) of AIHA was 5.4% (CI 95% 2.7-8.1). Concomitant infections at the time of AIHA were present in 10 patients. Five out of nine patients that received corticosteroids achieved either a PR or a CR, whereas six out of eight patients that received rituximab responded. Four patients developed AIT giving a 3-year CI of 1.4% (CI 95% 0-2.8), concomitant infections were present in three of them. Multivariable analysis showed that development of chronic GVHD (relative risk (RR) 4; 95% CI 1.1-13.7; P=0.03) and diagnosis of CML (RR 4.3; 95% CI 1.5-12.7; P=0.008) were associated with an increased risk of AC. In conclusion, AIHA and AIT are relevant and clinically significant complications in UCBT recipients, especially among those that develop chronic GVHD. Response to therapy is sub-optimal, and rituximab should be considered as a therapeutic option, in this setting were most patients had cold AIHA and a serological profile similar to that seen in cold agglutinin disease.
Asunto(s)
Corticoesteroides/administración & dosificación , Anemia Hemolítica Autoinmune , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Trasplante de Células Madre de Sangre del Cordón Umbilical , Neoplasias Hematológicas/terapia , Factores Inmunológicos/administración & dosificación , Púrpura Trombocitopénica Idiopática , Adolescente , Adulto , Aloinjertos , Anemia Hemolítica Autoinmune/tratamiento farmacológico , Anemia Hemolítica Autoinmune/etiología , Enfermedad Crónica , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedad Injerto contra Huésped/etiología , Neoplasias Hematológicas/patología , Humanos , Masculino , Persona de Mediana Edad , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Púrpura Trombocitopénica Idiopática/etiología , Estudios Retrospectivos , RituximabRESUMEN
We analyzed the incidence, clinicopathological features, risk factors and prognosis of patients with EBV-associated post-transplant lymphoproliferative disorder (EBV-PTLD) in 288 adults undergoing umbilical cord blood transplantation (UCBT) at a single institution. Twelve patients developed proven EBV-PTLD at a median time of 73 days (range, 36-812). Three-year cumulative incidence (CI) of EBV-PTLD was 4.3% (95% CI: 1.9-6.7). All patients presented with extranodal involvement. Most frequently affected sites were the liver, spleen, central nervous system (CNS), Waldeyer's ring and BM in 7, 6, 4, 3 and 3 patients, respectively. One patient had polymorphic and 11 had monomorphic EBV-PTLD (7 diffuse large B-cell lymphomas not otherwise specified, 4 plasmablastic lymphomas). We confirmed donor origin and EBV infection in all histological samples. EBV-PTLD was the cause of death in 11 patients at a median time of 23 days (range, 1-84). The 3-year CI of EBV-PTLD was 12.9% (95% CI: 3.2-22.5) and 2.6% (95% CI: 0.5-4.7) for patients receiving reduced-intensity conditioning (RIC) and myeloablative conditioning, respectively (P<0.0001). In conclusion, adults with EBV-PTLD after UCBT showed frequent visceral and CNS involvement. The prognosis was poor despite routine viral monitoring and early intervention. An increased risk of EBV-PTLD was noted among recipients of RIC regimens.